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Calming magnesium, amino acids and herbs. Sleep Relief contains magnesium, a gentler muscle relaxer. The amino acids L-Tryptophan, L-Theanine, glycine and GABA and herbs such as Hops (Humulus lupulus) and Skullcap (Scutellaria lateriflora) all contribute to the calming effects of Sleep Relief by targeting different neurological and biochemical pathways.

  • L-Tryptophan is converted to serotonin and melatonin. Serotonin is a mood-elevating hormone and melatonin is a circadian modulator that helps regulate your body’s day and night cycle. 
  • L-Theanine promotes alpha wave brain activity, which is associated with alert relaxation.
  • Glycine and GABA are nutrients that acts as naturally calming neurotransmitters that promote relaxation.
  • Hops and Skullcap are ancient plants that have long histories of use in traditional healing systems. Native Americans relied on them for a wide variety of medicinal purposes, and extensive research has validated many of their traditional applications, including promoting healthy sleep.   

Adaptogenic herbs like Ashwagandha (Withania somnifera) and Jujube (Ziziphus jujuba). Adaptogens are a unique class of healing plants. They help balance, restore and protect the body. Ashwagandha and Jujube are ancient plants that have been used in traditional Asian medicine for thousands of years and can promote a healthy stress response.

Nutritional Biochemistry, Inc. (NBI) formulates and manufactures products that give results. Started by John Neustadt, ND, in 2006 when he couldn’t find formulas he needed to help his patients and family, NBI products solve 2 problems he was having. Existing products didn’t contain the dose or combination of nutrients used in clinical trials and actually shown to work. Equally frustrating, other companies would cite studies on their websites, but then use lower amounts of nutrients than what was used in the study, or use entirely different nutrients that weren’t supported by the research.

Neustadt’s latest creation is Sleep Relief [3]. NBI’s Sleep Relief is a breakthrough in sleep technology. Its bi-phasic, time-release technology delivers NBI’s proprietary formula with clinically validated nutrients in two stages—a quick-release first stage and a slow-release second stage to help you gently fall asleep, stay asleep and wake refreshed and ready for your day. NBI’s Osteo-K [5] delivers the clinical dose of nutrients shown in more than 25 clinical trials to grow stronger bones and reduce fractures more than 80%.

NBI is and always has been a family-owned company. We don’t manufacture anything we wouldn’t take ourselves or give to our own family. No matter what we do, our promise to physicians using our products is to help their patients, and to customers purchasing directly from NBI, is uncompromising quality.

NBI is a name you can trust. But don’t take our word for it. Spend some time on our website [6], learn about our products, and educate yourself on the hundreds of research citations and studies that they’re based on.

Transcript

Karolyn Gazella: Hello. I’m Karolyn Gazella, publisher of the Natural Medicine Journal. Thank you so much for joining me. Today, our topic is the integrative approach to insomnia. During this interview, we will learn that insomnia is a significant problem for many patients that can have far reaching physical, mental and emotional health ramifications. We will also learn how to successfully treat this condition by using a combination of diet, lifestyle recommendations, and dietary supplements.

My expert guest today is Dr. John Neustadt. Dr. Neustadt received his naturopathic doctorate from Bastyr University and he was the founder and medical director of Montana Integrative Health.

Before we begin, I’d like to thank the sponsor of this topic who is Nutritional Biochemistry Incorporated, or NBI, manufacturers of high-quality dietary supplements for health care professionals.

Dr. Neustadt, thank you so much for joining me today.

John Neustadt, ND: Thank you for having me on.

Gazella: Well, so the Centers of Disease Control and Prevention calls lack of sleep a public health epidemic. Now, that seems pretty significant so today we’re going to talk specifically about insomnia. How common is insomnia in particular?

Neustadt: Well, the CDC is absolutely correct. It is a public health epidemic. Up to 80% of people struggle at some point with what’s considered transient insomnia, less than two weeks of duration and insomnia effects 10 to 15 percent of the general population.

In primary care settings, it’s estimated that up to almost 70 percent of primary care patients have insomnia so it is incredibly common.

Gazella: Oh, yeah that is. So how does lack of sleep impact a patient’s overall health from like a physical, mental, emotional standpoint?

Neustadt: It has devastating impacts. There are two ways to think of it. One is short-term impacts and the other are the long-term impacts. So, short term it can impact decreased job performance, impact social and family life by creating greater fatigue. I mean, just you’re more tired during the day. Decreased mood and depression, increases in anxiety and stress. Decreased vigor and just not being able to cope with the demands of daily life and be able to complete tasks. That’s only short term. Devastating just in the short term.

But in the long term, it can be a killer. There, if people are sleeping an average of less than six hours per night, it can increase the … or decrease the quality of life at the same magnitude of a similar condition such as congestive heart failure and major depressive disorder. It’s an early symptom for Alzheimer’s Disease and Parkinson’s Disease and Huntington’s Disease and there’s a sweet spot for sleeping of about eight hours. That research shows is the healthiest, and if you’re sleeping less than six, or longer than nine hours, it increases your risk for diabetes, metabolic syndrome, and death and, in fact, for metabolic syndrome, there’s a 45 percent increase in risk compared to people who are sleeping seven to eight hours a night.

Gazella: Wow, so yeah, so this is a very important topic for clinicians to have on their radar. So, when you’re evaluating a patient with a sleep disorder such as insomnia, how do you approach the work up?

Neustadt: Well, insomnia’s really a qualitative diagnosis. It’s how are they … how do they feel that they’re sleeping? How do they feel that it’s impacting their health? Now the DSM official diagnosis, there is a quantitative or a couple of quantitative aspects to that and that is it’s occurring at least three nights per week, and present for at least three months. So understand the difference between transient insomnia, less than two weeks, versus the diagnosis, official diagnosis, needs to be going on for greater than three months.

So there’s a huge discrepancy there and in time periods and clinically it’s important to be aware of that because these detrimental and dangerous effects of insomnia and sleep deprivation definitely are occurring in shorter than three months period of time. They’re happening pretty quickly if someone’s not getting enough sleep and even over a few days the short term consequences.

And so what I ask people about is how many hours, on average, do they think they’re sleeping a night? Do they have any difficulty with falling asleep or staying asleep called sleep phase delay or sleep phase advance? Are they waking refreshed in the morning? What’s going on with them psychosocially? Are there any stresses going on at work or in relationships or financially that’s increasing their anxiety and could be impacting their sleep? Are they are risk for any hormonal abnormalities or imbalances because the research is clear that low estrogen, low or high testosterone, elevated TSH, those are all things that can create insomnia. Abnormal progesterone, as well.

And then looking at medications because there are some medications that can impact sleep, as well.

Gazella: Yeah, let’s talk about the medications that can impact sleep. What are some of those medications that can impact sleep?

Neustadt: Well, prednisone, that can cause hyper-arousal, or can cause somebody to not sleep, not be able to fall asleep, or have fragmented sleep. Beta-blockers, very common heart medications, can decrease melatonin production. So we know what the mechanism of action … their interaction of sleep is they decrease melatonin and can cause poor sleep.

Some antidepressants, actually, can cause poor sleep. Antidepressants can, depending on the antidepressants, can either cause somebody to not be able to sleep enough or can cause hypersomnolence, somebody to be sleeping too much. So looking at those, looking up … it’s very easy to look up whatever medication they’re taking quickly and see, besides the ones that I mentioned, could it be potentially interfering and impacting with their sleep.

Gazella: So I’ve been hearing about hyperarousal, or the hyperarousal hypothesis, which I find quite fascinating. What is the hyperarousal hypothesis and how can it affect what is recommended to patients?

Neustadt: Great question. So the hyperarousal hypothesis I like to refer to as “wired-but-tired.” And it occurs to people typically who are under a lot of stress, they have elevated cortisol, and when they end up trying to fall asleep they just can’t turn their mind off, or even if their mind isn’t racing, they just can’t calm down. Their body can’t relax and settle into sleep. They’re staring at the ceiling, it can cause fragmented sleep. And that wired-but-tired, again, typically occurs in people who are under chronic stress.

Gazella: Yeah. And you know the other day when you and I were talking as it related to the hyperarousal hypothesis, you were telling me about something else that was new to me and it was called social jet lag. Talk a little bit about social jet lag and the research associated with social jet lag.

Neustadt: I’m so happy you brought this up because I love this as well. Fitbit, that maker of the wearable tracking devices, and tracking people’s sleep as well, they had access, because of their users, to over six billion data points of sleep. And they looked at those. And they looked at the data and determined that the biggest predictor of healthy sleep, restful sleep, is going to bed at about the same time every night. Basically training our body that it’s bedtime, getting that routine.

Social jet lag occurs when people are going to bed at about the same time every night during the week but then the weekend comes. Friday night they go out, hang out with friends, stay out late. Saturday night maybe do the same thing, and then Sunday comes around and they try to go to bed again at their weekday, or their work week time, and they can’t fall asleep. And essentially what they’ve done is it’s as if they’ve flown to another time zone and their body thinks that it’s not time to go to sleep yet. And they’ve induced their own jet lag called social jet lag.

And so one of the things that Fitbit found, and I think one of the most impactful things, is showing that getting that regular bedtime, being in that routine, going to bed at about the same time every night is one of the best things people can do for improving their sleep.

Gazella: And even on the weekend, and I’ll tell, you, when you put this on my radar I, of course, had to do a little research and there’s a lot of studies on this that actually show that the physical effects that you talked about with sleep deprivation earlier also occur with this social jet lag. So I think it’s really important for clinicians to be aware of that. So thank you for bringing this to my attention.

So now doctors often prescribe benzodiazepine or benzodiazepine-like drugs to help patients sleep. What are some of the potential risks of these particular medications?

Neustadt: Well, the potential risks are very well documented and they increase risk for falling, dizziness, light-headedness, those risks are increased in people who are 60 years or older because their ability to metabolize the drug tends to decrease. And so because it increases the risk for falls and dizziness and light-headedness, it then increases the risk for fall-related injuries, such as osteoporotic fractures, such as concussions, such as death, even. But even beyond those risks associated with increased risks for falling, the research has shown that cancer risk is actually increased in people who take over about 132 doses of benzodiazepine a year. So that’s even … that’s less than half of a year worth.

And in fact some of these risks are increased with very small and limited exposure. So you know from half a dose to 18 doses per year, the hazard risk for death is increased 3.6 times. 18 to 132 doses, the hazard risk for death increased 4.43 times in a study that looked at this. And for greater than 132 doses, it increases 5.32 times. That’s 532 percent greater than somebody not taking these medications for death. And the research has shown to actually get one benefit, the number needed to treat, to have one patient benefit is 13 patients. But the number to treat to create harm is only 6 patients.

Gazella: Yeah, that’s problematic. So what about the newer class of medications, like the orexin receptor antagonist Belsomra?

Neustadt: Belsomra came on the market in 2015, it’s a schedule 4 drug and it’s a CNS depressant. So, like other CNS depressants, like benzodiazepine, it can have similar adverse effects. Some of the benzodiazepine drugs like Lunesta or Ambien can also cause, like Belsomra, can cause daytime impairment including impaired driving skills, risk of falling asleep while driving, abnormal thinking and behavioral changes are part of the adverse events spectrum, including amnesia, anxiety, hallucinations, other neuropsychiatric symptoms, even complex behaviors like sleep-driving. I mean, you’re driving while not fully awake, after taking the hypnotic. Or other complex behaviors have been documented, like preparing and eating food, making phone calls, or even having sex, without remembering it.

And so the drug has some serious risks, including worsening of depression and suicidal ideation, and the benefits of that, it can increase … or the benefits of the medication, because all medication, it’s a risk-reward calculation … it can decrease sleep latency, that is, the amount of time to fall asleep by about eight to 10 minutes and increase sleep duration by 17 to 20 minutes.

So at the most beneficial end of that, maybe it’s 30 extra minutes of sleep. But you get all of those risks associated with it.

Gazella: And are patients getting good sleep when they’re on these prescription and over-counter medications? Are they getting good quality sleep?

Neustadt: Well, you raise a great point. That’s one of the problems with all of these medications is they tend to increase sleep duration, sleep quantity, but they’re not increasing sleep quality. They’re not getting patients into that deep, restorative phrases of sleep, the slow-wave sleep, phase 3 and into phase 4, to get that good, restorative sleep.

So the quantity of the sleep may be increased but the quality has not been shown to be increased.

Gazella: So you’ve made a pretty compelling case that a more integrated, holistic approach is needed. And integrative practitioners often recommend melatonin for insomnia with their patients. Can you talk a little bit about melatonin and why for some patients, many even many patients, it may not be enough?

Neustadt: Melatonin is one of the first things I find that people with whom I speak, they’ve tried. They’ve reached for that. If they’re going to try a natural product, they’ve reached for the melatonin, you know, first, almost universally.

The challenge with melatonin is that it’s got a very short half life, 40 to 50 minutes. And so while melatonin is considered a circadian modulator, meaning it helps the body recognize day from night, and it is a natural hormone, a natural product that our body uses to help us fall asleep, it’s not really used for sleep maintenance. And so when somebody takes melatonin to help them fall asleep, because it’s got such a short half life, well 50 percent of the melatonin is eliminated from the body in less than an hour, so let’s just be generous and say an hour for easy calculations. So common doses out there is a 3 mg dose. So in an hour, they’ve got a one and a half milligrams left. An hour later they’ve got .75 milligrams left. And on down.

And so 3, 4 hours later, essentially most of that melatonin is out of their body and they wake up again. I hear so often people who take melatonin, they end up waking up in the middle of the night, still. And so what do they do? Well, they might need more melatonin. And so they keep taking higher and higher doses until they’re sleeping through the night and then they wake up feeling drugged in the morning. Groggy, hungover and it takes them hours to actually feel fully awake.

So the natural rhythm of melatonin in our body is that the rise in melatonin occurs around 10 PM and then it peaks at about 2 AM in the morning, and it declines at approximately 6 AM, it’s declined back to baseline. And that makes sense because that’s sort of the rhythm of when we start to fall asleep and when our body then starts to wake up. Of course melatonin is balanced with other hormones as well that the body is producing during sleep, but the immediate release of melatonin that people are taking is not mimicking the body’s cycle of melatonin production during the night. And it’s also not a complete solution because it’s not dealing with the other phases of sleep, we’re looking at the other hormones in sleep, GABA for example. Or the other variables that can impact sleep such as poor blood sugar. When blood sugar can drop, hormones are secreted like cortisol and epinephrine to increase the body’s blood sugar and we wake up.

And so that’s why melatonin for a lot of people doesn’t work, because it’s just not a complete enough solution.

Gazella: I think that’s a really good point, that it’s not a complete solution for many people and that’s why you use such an integrative approach. So I’d like to really dig into your integrative approach, I’d like to talk about dietary supplements, diet, and other lifestyle factors. So as long as we’re talking about melatonin, let’s keep on that subject and talk about dietary supplements. Are there specific dietary supplements that you use in your clinical practice specifically for insomnia?

Neustadt: There are and it depends typically on the clinical picture. So for example if somebody has muscle aches or tight muscles that’s keeping them from sleeping, magnesium can help, that can be a gentle muscle relaxant. If there’s some anxiety that may keep them from sleep, well, glycine is an amino acid that’s also an inhibitory neurotransmitter, that can be helpful. GABA also an inhibitory neurotransmitter used in the body available as a dietary supplement. That can be helpful. Botanical extracts such as alphianine increases alpha-wave production in the brain which is associated with calming, alert calmness. Then there are some sedative botanicals that can be helpful such as hops or skullcap, also called Scutellaria. And others.

So that’s part of it and for potential, looking at decreasing the response to stress, I like using, if they’re under a lot of stress, some adaptogenic herbs like ashwagandha, or jujube, magnolia bark extract. If there is vaso … if there’s an issue with hot flashes and perimenopause, pine back extract. There’s a clinical trial on that showing that it improved sleep quality and sleep quantity.

And so I typically, you know, this monotherapy approach of one symptom, 1 pill, it really doesn’t work when we’re looking at complex pathologies like insomnia or many other chronic issues. And so I tend to like products that combine those different nutrients shown in clinical trials to work that target the underlying pathology, the underlying biochemical pathways at work and sleep and affected by insomnia in a time release or a biphasic time release delivery system because it more closely mimics the body’s natural rhythm of the 2 major categories of your sleep. One is helping somebody fall asleep, you know how do we do that, and the other, over … you know, the subsequent 6, 7 hours later after they’ve fallen asleep, how do we help them stay asleep?

And so that’s how I conceptualize it and that’s the overall approach with dietary supplements when they’re indicated.

Gazella: So before I move on to diet, I know that you helped formulate and create a specific sleep supplement. I want you to tell me the name of that supplement but I also want you to tell me why you created it, because let’s face it, there are a lot of sleep supplements in the market. So why did you want to create the supplement that you created?

Neustadt: So the name of the product is NBI’s, my company, NBI’s Sleep Relief is the name of the product. And I created it for a couple reasons.

One, just like all the products that I’ve created in NBI and formulated, I couldn’t find the combination of nutrients or the dose and form of nutrients in a product shown in clinical trials to actually work. And I personally suffered from insomnia for years and years. And I tried a lot of different things. It wasn’t helping me. I’d work with a lot of my patients trying to different things, having to dispense different bottles of products, in addition of course to working with diet and lifestyle and other psychosocial factors involved. And I couldn’t find something that worked consistently.

And so I started digging into the sleep research, the pathophysiology of sleep, the clinical trials, what are the underlying mechanisms affecting sleep. And after over a year of research and formulating and working, trying over a dozen different combinations and doses, that’s when I created Sleep Relief.

Gazella: Okay perfect, Sleep Relief. So now let’s talk a little bit about diet. What are some of the things that you recommend to your patients when it comes to sleep, associated with diet that may not be on the radar of some practitioners?

Neustadt: So one of the big things that I see over and over is a lot of people have, may have acid reflux and they don’t know about it. And because maybe it’s not … maybe they have a cough when they lay down, maybe they are just not aware that that’s going on. And so evaluating for that because that can wake people up.

The other thing that I find with diet that’s very important, and with acid reflux, you know, that can be diet related. There are 5 most common foods that can contribute to that and interrupt sleep, that’s raw garlic and onion, chocolate, coffee, and citrus. Although other things can do it for other people. An infection can do that, H. Pylori can cause that as well. And then if they have a hernia, a hiatal hernia, that can cause it as well. So looking at that, looking at those underlying potential causes if that is involved.

The other thing is poor blood sugar control which I already mentioned. And one of the things I like to ask that can indicate if they might have poor blood sugar control is if they get that afternoon, postprandial tiredness. You know, about 3, 4 o’clock in the afternoon, a couple hours after lunch do they just get that energy slump. And that can be an indication that they’re having a little bit of blood sugar control issues. Or are they waking up at the same time every night. Both of those questions can give clues.

And if that does seem to be involved, one thing that I love to try with patients … it doesn’t work very often but when it does, it’s really a home run, and that is ask them to eat 8 to 10 grams of protein before bed. Protein’s one of the best ways to regulate blood sugar. And so if they do that and it stabilizes their blood sugar and they then are sleeping through the night, well, again, it’s a home run. I mean, there are no pills, no powders, it’s just natural doing it with food and it also opens the door for even more discussions with helping them understand how they can improve their diet during the day to help, to eat, to promote … to help them understand how they can eat, changes they can make to eat, the promote their health for the rest of their life.

Gazella: Yeah, those are some great suggestions when it comes to diet. Now let’s talk a little bit about lifestyle. What are some things that may not be on the radar of some practitioners when it comes to lifestyle aspects?

Neustadt: So we talked about going to sleep at about the same time every night, that’s really important. The other thing is … and most practitioners, or hopefully all of them have heard of sleep hygiene. The research shows that about the 69 to 70 degrees for most people is the ideal temperature for sleep. Some people who, if they’re in a relationship with their partner, they may like different temperatures may be most comfortable for them.

So there are wonderful things out there now, it’s call the ChiliPad, that you can get, it’s a pad you can put on your bed, where you can control the temperature on each side of the bed. So that can be really helpful.

Stress of course is a big issue in our society, a lot of people are under chronic stress, so anything that we can do to help people decrease their stress or better deal with stress is really important. And a fantastic study came out recently that showed that a lot of the impact of stress is not the actual event happening to us, it’s how we view it. So if people view stress as a good thing, meaning “I gotta learn something from it and what can I take from this,” the health impacts from stress are mitigated. If somebody sees a stressful event and they’re internalizing it and they’re not seeing it as a growth opportunity, then it magnifies the negative stress impacts.

So, A) getting them to just understand that mindset is really important, just when it comes to stress happening, and then what can they do to have more control over those events that may be causing them stress to decrease that stress. And that could mean creating healthy boundaries for themselves. That could mean doing any yoga or mind-body techniques. You know there’s lots of things that we can offer to patients that can be incredibly, incredibly helpful.

Gazella: Yeah, I would agree. And now your approach focuses on diet, lifestyle, and dietary supplements. How important is it to focus on all 3? So some practitioners might be really focused on the person’s diet, or some might be looking at their stress level, and some might be focused on just melatonin. Why is it so important to look at this from an integrative standpoint?

Neustadt: Well I think if we want to do the best job we possibly can for our patients and give them the best results, looking at it through a more integrative approach is important. And I like the approach of trying dietary supplements to give people benefit quickly. So if somebody is sleep deprived, it’s gonna increase their tendency to reach for those comfort foods. I think we’ve probably all experienced that. And especially because what happens with insomnia and sleep deprivation, it decreases mood. It can cause depression. And sugary foods, for example, when we reach for those, it can increase our serotonin production and temporarily lift mood. But it causes this rollercoaster of insulin and blood sugar that’s hard to get off of.

So just getting people sleep can help improve their mood. So I like the dietary supplement approach for triage to get them feeling better so they can make healthier decisions, have a more present mindset, be more proactive instead of reactive, while I’m working with them also on improving their diet. Transitioning to a healthier way of eating, which, the research has shown, unambiguously is the Mediterranean pattern of eating. And also stress reduction and exercise and those things as well.

Gazella: Yeah, I mean that all makes a lot of sense. And this is a very important topic and I want to thank you, Dr. Neustadt for a very interesting conversation and once again, I’d also thank today’s sponsor, Nutritional Biochemistry Incorporated, or NBI. Thanks again, Dr. Neustadt, for joining me.

Neustadt: Thank you for the opportunity.

The above was from: https://www.naturalmedicinejournal.com/journal/2019-02/insomnia-integrative-approach

Naltrexone could alleviate depression symptoms in patients who relapsed while taking antidepressants

The drug naltrexone is approved for use in the treatment of opioid use disorders and alcohol use disorders, but preliminary research suggests it could also aid the treatment of depression.

The double-blind, randomized study found that low dose naltrexone reduced depression severity in 12 depressed subjects who had relapsed on dopamine-enhancing antidepressants. The study will be published in the January 2017 issue of the Journal of Affective Disorders.

Mischoulon: Our group studies a wide variety of treatments for depression. We are especially interested in the underlying biology of antidepressants and mechanisms by which depression develops. This study of low dose naltrexone (LDN) was based on a model proposed by Bear and Kessler, originally for restless leg syndrome for which it was patented. During treatment of patients with RLS, they observed anecdotally that LDN seemed to benefit depression as well.

Because one of the apparent mechanisms of low dose naltrexone is through dopamine, which is a neurotransmitter associated with mood regulation, Dr Bear’s company, PharmoRx, was interested in funding a pilot study on this agent for people with depression who had relapsed on dopaminergic antidepressants. They spoke with us about running such a study at MGH, and we agreed to do it.

What should the average person take away from your study?

The main finding is that if you have depression and relapsed while taking a previously effective antidepressant that works primarily by dopaminergic mechanisms, addition of LDN could potentially alleviate the depression in combination with the original antidepressant.

PsyPost interviewed the study’s corresponding author, David Mischoulon of Massachusetts General Hospital/Harvard Medical School. Read his explanation of the research below:

he main limitation of this work is the small patient sample. We only treated 12 patients and this is too few to draw firm conclusions. We need to replicate this work in a larger group of patients. The study included only antidepressants that work by dopaminergic mechanisms, and so we don’t know how well it would work with other types of antidepressants, such as those that are primarily serotonergic (e.g. SSRIs) or noradrenergic (e.g. tricyclic antidepressants).

Also, LDN may involve a range of different doses that are defined as “low,” and so a dose-finding study to determine the optimal “low” dose would also be valuable to do. Clinicians who wish to prescribe LDN for depressive relapse should realize that this is considered an experimental therapy, and should inform their patients about the risks of trying a relatively unproven therapy.

Is there anything else you would like to add?

While LDN is obtainable by prescription from a licensed physician, it cannot be bought in most drugstores, because commercially available forms of naltrexone come in much higher doses. To obtain LDN you will need to take your prescription to a compounding pharmacy where they can prepare it for you in the appropriate dosage form. Most insurance plans will cover it, however, so LDN should be accessible to most people.

In addition to Mischoulon, the study “Randomized, proof-of-concept trial of low dose naltrexone for patients with breakthrough symptoms of major depressive disorder on antidepressants” was co-authored by Lindsay Hylek, Albert S. Yeung, Alisabet J. Clain, Lee Baer, Cristina Cusin, Dawn Flosnik Ionescu, Jonathan E. Alpert, David P. Soskin and Maurizio Fava.

Kresser Institute

Clinicians are increasingly using low-dose naltrexone to treat challenging illnesses such as autoimmune conditions and neurodegenerative disease. LDN is extremely safe and well tolerated, especially compared to the drugs typically used to treat these conditions, making LDN a valuable tool for clinicians and an important focus for ongoing research.


naltrexone
istock.com/baona

As a practitioner, you may be familiar with the drug naltrexone, which was approved by the FDA in 1984 for treating addiction patients. In doses of 50 to 100 milligrams, naltrexone completely blocks opioid receptors in the brain, preventing patients from experiencing a high when they take opioid drugs.

Soon after the drug’s initial approval, Dr. Bernard Bihari discovered a potential alternate application for naltrexone. He noticed that in AIDS and cancer patients, a much lower dose of naltrexone (about 3 milligrams) had beneficial immune-modulating effects. This discovery gave rise to a grassroots movement of patients and practitioners who had seen LDN work and were calling for additional research and mainstream attention.

Despite the promise of this new treatment, formal research on LDN has been slow to happen, likely because LDN is off patent and therefore not as profitable to drug companies. Even so, our understanding of the mechanisms behind LDN’s effectiveness in various conditions continues to progress, and results from preliminary clinical trials are slowly being published.

In this article, I’ll describe our current understanding of LDN’s mechanisms and review the clinical trials that have been conducted thus far. I’ll also give you a more practical take on LDN from my perspective as a clinician and cover concerns that might be relevant for other clinicians who want to prescribe LDN to their patients.

How Does LDN Work?

As research on LDN progresses, it appears more and more likely that it functions through a variety of different mechanisms and that the most relevant mechanism might differ depending on the disease that is being treated. But at this point, the two most well-characterized functions of LDN are as an opioid antagonist and an anti-inflammatory.

Increasing Endogenous Opioid Activity

Like its full-dose counterpart, low-dose naltrexone blocks opioid receptors in the brain, the major difference being that LDN is cleared from the system after only a few hours. Most researchers believe that this temporary opioid receptor blockade creates a “rebound effect,” resulting in up-regulated production of the endogenous opioids beta-endorphin and met-enkephalin, as well as increased expression of opioid receptors (1).

How these adaptive changes affect the disease processes that LDN influences is less established. However, several mechanisms have been proposed. First, endogenous opioids are known to have analgesic and stress-relieving effects, which alone could account for some of the symptom relief seen with LDN.

What the latest research says about low-dose naltrexone

Second, we know that immune cells possess opioid receptors, and both endogenous and exogenous opioids have long been considered important immune modulators (2, 3). The exact effects of endogenous opioids on the immune system, however, remain unclear; both increases and decreases in immune cell activity and proliferation have been observed in response to LDN, as well as beta-endorphin and met-enkephalin (4, 5, 6).

These endogenous opioids may also exert therapeutic benefits based on their regulation of cellular proliferation. Met-enkephalin, also known as opioid growth factor (OGF), has been found to regulate the cell cycle by suppressing DNA synthesis via its action on the OGF receptor (7, 8). This so-called “OGF–OGFr axis” is the focus of research on LDN for treating cancer and may also be another mechanism by which LDN modulates immune function.

Reducing Inflammation in the CNS

LDN appears to have a second mechanism of action that is independent from the opiate-antagonist pathway described above: suppression of microglial activity. Microglia are the primary immune cells in the central nervous system and are responsible for creating inflammation in response to pathogens or injury. When activated, microglia secrete factors such as pro-inflammatory cytokines, prostaglandins, nitric oxide, and excitatory amino acids (9).

The activation of the microglia and the subsequent release of cytokines—though essential to protecting the brain and CNS—cause symptoms such as fatigue, reduced pain tolerance, sleep and mood disturbances, cognitive disruption, and general malaise, all classically referred to as “sickness behaviors” (10). While these adaptive symptoms may make sense in the short term for promoting rest and recovery, ongoing CNS inflammation is maladaptive and can contribute to a wide range of diseases and syndromes.

Evidence indicates that LDN can suppress microglial activation, likely via its antagonistic effect on toll-like receptor 4 (TLR4), a non-opioid receptor that is found on macrophages such as microglia (11). This mechanism may explain LDN’s effectiveness for conditions like fibromyalgia and other chronic pain disorders, which involve chronic activation of microglial cells.

LDN in the Scientific Literature

Unfortunately, research on LDN as a treatment for human disease is still extremely sparse. Most of the trials that have been conducted thus far were primarily intended to test the tolerability and safety of LDN, rather than the efficacy, so keep that in mind, but the initial research does show promise. I’ve summarized the existing studies below, and hopefully additional research won’t be far behind.

Crohn’s Disease

A small open-label pilot study from 2007 had remarkable results, reporting that 89 percent of participants responded to LDN, and a whopping 67 percent achieved remission (12). This was the first published LDN trial in humans.

Results from two subsequent randomized controlled trials were less dramatic, but still extremely promising. One study from 2011 reported significant improvement in 88 percent of the participants in the LDN group, compared to 40 percent in the placebo group (13). And 33 percent of participants in the LDN group achieved remission, compared to 8 percent in the placebo group, although this difference was not statistically significant.

The second RCT was published in 2013 and looked at the effectiveness of LDN in children with Crohn’s disease (14). They found that of those treated with LDN, 67 percent exhibited improvement, and 25 percent went into remission. In all of these studies, LDN was very well tolerated with no significant difference in side effects compared to placebo.

Fibromyalgia and Other Conditions

In 2009, a pilot study involving 10 fibromyalgia patients reported a greater than 30 percent reduction in symptoms over placebo in those taking LDN (15). Interestingly, they found that patients with a higher erythrocyte sedimentation rate (ESR) at baseline had greater symptom reduction in response to LDN treatment. ESR is a marker for inflammation, so this observation lends credence to the theory that LDN works by reducing inflammation in the central nervous system.

The second study, a randomized controlled trial involving 31 fibromyalgia patients, was published in 2013. They reported significant improvements in pain, mood, and general satisfaction with life in the LDN group compared to placebo (16). And again, LDN was well tolerated in these studies.

LDN has also been studied in and shown potential efficacy for autism (17), pain (18, 19), depression (20), multiple sclerosis (21, 22, 23), systemic sclerosis (24), and complex regional pain syndrome (25). Additionally, preliminary evidence in vitro and in animal models indicates that LDN may be an effective treatment for cancer, including ovarian cancer and pancreatic cancer (26, 27).

Clinical Success Using LDN for Autoimmune and Neurodegenerative Diseases

As I mentioned at the beginning of this article, LDN is unusual in that its use has spread as a result of grassroots efforts by patients themselves, rather than the typical top-down marketing of new drugs by pharmaceutical companies. Because of this, clinical and anecdotal evidence for the drug’s effectiveness in a wide variety of conditions still vastly outpaces the scientific literature.

This is initially a cause for concern because we obviously want any treatment we use on patients to be as evidence based and extensively studied as possible. But we do have ample safety data from the approval process of full-dose naltrexone, and all of the evidence we have so far on LDN shows that it is extremely safe and well tolerated. It’s still a judgment call, but the fact that existing treatments for many of these illnesses are demonstrably toxic with significant side effects certainly makes LDN an attractive option.

Conditions that have clinically responded well to LDN but have not been formally studied include autoimmune diseases such as Hashimoto’s thyroiditis, Graves’ disease, rheumatoid arthritis, lupus, psoriasis, and ulcerative colitis, as well as neurodegenerative diseases like Parkinson’s and Alzheimer’s, and other conditions like chronic fatigue syndrome and even infertility. Because these conditions share the same underlying disease processes of immune dysregulation and inflammation, it’s not a huge surprise that LDN can be an effective treatment, despite the differences in disease presentation.

Practical Concerns for Prescribing LDN

LDN is generally very well tolerated, but patients may experience insomnia, headaches, or unusually vivid dreams when first starting the medication. These side effects are usually minor and dissipate after a week or two of taking LDN.  

Because naltrexone is only produced in 50-milligram tablets, prescriptions for LDN do need to be filled at a compounding pharmacy. And, because LDN is off label, it’s unlikely that insurance companies will cover it, but the out-of-pocket cost of LDN is only about $40 per month, making it more affordable than many drugs on the market.

One downside of LDN is that there’s not a standardized dose, and the most effective dose for a given patient may be anywhere from 1.25 to 4.5 milligrams. We typically start patients on 1 to 1.5 milligrams, then gradually increase to 4.5 milligrams and see how they do. From my experience, I’ve seen most people end up around 2.5 to 3 milligrams.

Note that in patients with Hashimoto’s or Graves’, their previous dose of thyroid medication could suddenly be too high as their thyroid function improves on LDN. It may be necessary to reduce their normal thyroid medication to prevent them from becoming hypo- or hyperthyroid.

Finally, be aware that while LDN can be miraculous for some patients, others may see no benefits at all. Unfortunately we don’t know enough yet to determine if there’s a subset of patients that LDN is most likely to help, so the best we can do is try and hope for the best. It can sometimes take a little while for patients to notice improvement on LDN, so we typically allow about three months as a trial period before deciding whether to continue treatment.

Ketamine – Psycom

8 herbs and supplements for depression

Depression is a serious mood disorder with symptoms that range from mild to debilitating and potentially life-threatening. Some people look to manage depression with herbal remedies, rather than with medication a doctor prescribes.

The most recent data from the National Institute of Mental Health suggest that in the United States, 6.7 percent of people experienced a major depressive episode in 2016.

Medications and counseling are conventional ways to alleviate the symptoms of depression. However, some herbs and supplements may also help.

In this article, we look at the common herbs and supplements with links to the treatment of depression and discuss their safety and effectiveness.

Herbs and supplements

herbs for depression

Some herbs, essential oils, and supplements have shown promising effects for people with depression.

The use of complementary therapies continues to gain popularity, as people look for more natural methods of managing their health.

However, herbal does not always mean safe or effective, and knowing which products to choose can save a lot of time and money.

In the United States, the Food and Drug Administration (FDA) do not monitor herbs in the same way as food and drugs. As a result, manufacturers are not always 100 percent clear about the quality or purity of their product.

Research suggests promise for some supplements in treating mild-to-moderate depression. These are some of the supplements that people most widely use:

1. St. John’s wort

St. John’s wort is also known as Hypericum perforatum. This plant has been a common herbal mental health treatment for hundreds of years. However, people must use caution if they chose to try it as a potential treatment for depression.

2016 systematic review found that St. John’s wort was more effective than a placebo for treating mild to moderate depression and worked almost as well as antidepressant medications.

However, this review of eligible studies did not find research on the long-term effects of St. John’s wort on severe depression.

The authors also advised caution against accepting the results wholesale, as the herb has adverse effects that many of the studies did not consider.

St John’s wort can also interfere with the effects of antidepressant medication, meaning that it may make symptoms worse or reduce the effectiveness of conventional treatment.

While St. John’s wort might help some people, it does not show consistently beneficial effects.

For these reasons, people should not use St. John’s wort instead of conventional treatment. Neither should they try St. John’s wort to treat moderate to severe depression.St. John’s Wort: Should I use it?Should I take St. John’s wort? Click here to find out more.READ NOW

2. Ginseng

This supplement comes from the gnarled root of the American or Asian ginseng plant. Siberian, Asian, and Eleuthero ginseng are different plants with different active ingredients.

Practitioners of Chinese medicine have used ginseng for thousands of years to help people improve mental clarity and energy and reduce the effects of stress.

Some people associate these properties of ginseng with potential solutions for the low energy and motivation that can occur with depression.

However, the National Center for Complementary and Integrative Health (NCCIH) advise that none of the many studies that people have conducted on ginseng have been of sufficient quality to form health recommendations.

3. Chamomile

study in 2012 reviewed data about chamomile, which comes from the Matricaria recutita plant, and its role in helping to manage depression and anxiety.

The results show that chamomile produced more significant relief from depressive symptoms than a placebo. However, further studies are necessary to confirm the health benefits of chamomile in treating depressive symptoms.

4. Lavender

Lavender oil is a popular essential oil. People typically use lavender oil for relaxation and reducing anxiety and mood disturbances.

2013 review of various studies suggested that lavender might have significant potential in reducing anxiety and improving sleep.

Lavender has mixed results in studies that assess its impact on anxiety. However, its effectiveness as a treatment for ongoing depression has little high-quality evidence in support at the current time.

5. Saffron

Some studies cite using saffron as a safe and effective measure for controlling the symptoms of depression, such as this non-systematic review from 2018.

However, more research would help confirm the possible benefits of saffron for people with depression. Scientists also need to understand any possible adverse effects better.

6. SAMe

man looks at drugs

Some supplements have shown promising effects on depression symptoms. However, many investigations confirming their benefits are low quality.

SAMe is short for S-adenosyl methionine. It is a synthetic form of a chemical that occurs naturally in the body.

In 2016, researchers reviewed all the randomized controlled trials on record for the use of SAMe to treat depression in adults. They found no significant difference between the effects of SAMe on depression symptoms and those of a placebo.

However, they also found that SAMe had about the same effectiveness as the common antidepressants imipramine or escitalopram. Furthermore, it was better than a placebo when the researchers mixed SAMe with selective serotonin reuptake inhibitor medications.

As with many other studies into herbs and supplements, the investigations into the safety and efficacy of SAMe are of low quality. More research is necessary to determine its exact effect.

People use the supplement in Europe as a prescription antidepressant. However, the FDA have not yet approved this for use in the U.S.

7. Omega-3 fatty acids

In a 2015 systematic review, researchers concluded that omega-3 fatty acid supplements are not useful across the board as a depression treatment.

While the study authors reported no serious side effects from the supplement, they also advised that it would only be an effective measure in treatment for depression that was due to omega-3 deficiency.

8. 5-HTP

Also known as 5-hydroxytryptophan, this supplement may be useful in regulating and improving levels of serotonin in the brain. Serotonin is the neurotransmitter that affects a person’s mood.

5-HTP has undergone a number of animal studies, and some, such as this review from 2016, cite its potential as an antidepressant therapy. However, evidence of its effects in human subjects is limited.

5-HTP is available as an over-the-counter (OTC) supplement in the U.S. but may require a prescription in other countries.

More research is necessary, especially regarding concerns that it may cause serotonin syndrome, a serious neurological complication if a person takes 5-HTP in excess.

Supplement manufacturers do not have to prove that their product is consistent. The dose on the bottle may also be inaccurate.

People should ensure they purchase herbs and supplements from a trusted manufacturer.

FOODS for Depression:

https://www.medicalnewstoday.com/articles/318428.php

Important foods and nutrients

The following foods and nutrients may play a role in reducing the symptoms of depression.

Selenium

Selenium can be a part of reducing symptoms of depression in many people. Low selenium levels have been linked to poor moods.

Selenium can be found in supplement form or a variety of foods, including whole grains, Brazil nuts, and some seafood. Organ meats, such as liver, are also high in selenium.

Vitamin D

Vitamin D deficiency is associated with many mood disorders, including depression. It is important to get enough vitamin D to help in the fight against depression.

This vitamin is obtained easily through full body exposure to the sun, and there are also many high-quality supplements on the market that contain vitamin D.

Food sources of vitamin D include fatty fish such as salmon, tuna, and mackerel.

Omega-3 fatty acids

Nuts and seeds are a source of omega fats

Nuts and seeds are sources of omega fats, which can help treat mood disorders and improve cognitive function.

In a study posted to the Indian Journal of Psychiatry, researchers observed that populations that do not eat enough omega-3fatty acids might have higher rates of depressive disorders.

Good sources of omega-3s may include:

  • cold water fish, such as salmon, sardines, tuna, and mackerel
  • flaxseed, flaxseed oil, and chia seeds
  • nuts, such as walnuts and almonds

The quality of these foods can affect the levels of omega-3s they contain.

Eating omega-3 fatty acids may increase the level of healthful fats available to the brain, preserve the myelin sheath that protects nerve cells, and keep the brain working at the highest level. In turn, this can reduce the risk of mood disorders and brain diseases occurring.

Antioxidants

Antioxidants have become popular as they fight free radicals. Free radicals are damaged molecules that can build up in different cells in the body and cause problems, such as inflammation, premature aging, and cell death.

The brain may be more prone to this type of damage than other areas of the body. As a result, it needs a good way to get rid of these free radicals and avoid problems. Foods rich in antioxidants are believed to help reduce or reverse the damage caused by free radicals.

Everyday antioxidants found in a variety of whole foods include:

These nutrients may help reduce stress-related symptoms of psychiatric disorders.

B vitamins

Some B vitamins are also key in mood disorders such as depression. Vitamin B12 and folate, or vitamin B9, have both been linked to a reduced risk of mood disorders.

Sources of B vitamins include:

  • eggs
  • meat
  • poultry
  • fish
  • oysters
  • milk
  • whole grains

Fortified cereals may also contain vitamins B12 and folate. Other foods that have folate in them include:

  • dark leafy vegetables
  • fruit and fruit juices
  • nuts
  • beans
  • whole grains
  • dairy products
  • meat and poultry
  • seafood
  • eggs

Eating a varied diet is an easy way to ensure there is enough folate in the diet.

Zinc

Zinc helps the body perceive taste, boosts the immune system, and may also influence depression. Zinc levels may be lower in people with clinical depression, and zinc supplementation may also improve the effectiveness of antidepressants.

Zinc is found in supplements. Foods, including whole grains, oysters, beans, and nuts, are also good sources of zinc.

Protein-rich foods

High-quality proteins are the building blocks of life. Getting adequate protein is essential for everyone, but some forms of protein, in particular, may be more helpful for people with depression.

Foods such as tuna, turkey, and chickpeas have good levels of tryptophan, which is needed to form serotonin.

Serotonin deficiency was once thought to be a major cause of depression. We now know that the link between serotonin and depression is very complex, but it does seem to influence depression in many people. Including foods rich in tryptophan in a diet may help relieve symptoms.

Foods to avoid

Just as certain foods and nutrients may be of benefit to people with depression, there are also some that should be avoided.

Caffeine

For people with depression that is linked to anxiety, it may be important to avoid caffeine. Caffeine can make it difficult to sleep and may trigger symptoms of anxiety in many people.

Caffeine also affects the system for hours after it is consumed. It is best for people with depression to avoid caffeine if possible, or reduce consumption and stop consuming it after noon.

Alcohol

Though occasional alcohol drinking is seen as an acceptable distraction, it may make depression symptoms worse.

Excessive alcohol consumption may increase the risk of panic attacks or depressed episodes. Alcohol also alters a person’s mood and may turn into a habit, which could influence depression symptoms.

Refined foods

High-calorie foods with few nutrients in them may also influence depression symptoms. Foods high in sugar and refined carbs can promote a crash, as the energy from them is depleted. This can make a person feel mood swings or energy swings.

Nutrient-dense whole foods are a much better approach to balancing mood and energy levels.

Processed oils

Highly processed or refined oils, such as safflower and corn oil, are very high in omega-6 fatty acids. Having too many omega-6s in the diet can cause an imbalance in the body that may promote inflammation in the brain and influence depression symptoms.

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Other factors in depression

Woman walking.

Regular physical activity and spending time outdoors are proven ways to help improve the symptoms of depression.

There are other factors that link to both diet and depression and play a role in this mental healthillness.

Emerging research has shown gut bacteria to play an integral role in major mood disorders, including depression and bipolar disease. A 2016 meta-analysis reported that probiotics, in both supplement form and in fermented foods such as yogurt and kefir, resulted in significant reductions in depression.

More research is needed to identify the therapeutic value of specific strains, but so far Lactobacillus and Bifidobacterium show potential.

Obese people may be more likely to be depressed, and depressed people are more likely to become obese. This may be due to hormone changes and immune system imbalances that come with depression.

Spending time outdoors and at least 150 minutes of physical activity weekly have been shown to improve mood and depressive symptoms.

Some people with depression also have substance abuse problems. Alcohol or other drugs can interfere with sleep patterns, decrease motivation, and alter a person’s mood.

Sleep may also play a role in depression. The body’s natural sleep cycle creates mood-altering chemicals to match the time of day. Altering this natural cycle may affect how well the body can use these chemicals.

Most adults respond well when they get 7 to 8 hours of sleep, though the number varies from person to person. It may also help to reduce exposure to blue light, during the hours leading up to sleep. Blue light is emitted by electronic devices and low-energy light bulbs.

LDN for psychiatric disorders:

LDn Information

When I have to describe my patient population, I often say that “my patients are normal people with some problems.” A significant number of my patients also have a chronic medical illness, such as an autoimmune disorder. Since I added it to my prescribing armamentarium many years ago, LDN has become a frequently used tool that I offer to my patients along with the other therapeutic strategies.

…LDN has become a frequently used tool that I offer to my patients along with the other therapeutic strategies.

For what kinds of conditions do you prescribe LDN?

In my practice, I use LDN for these conditions because I see it work:

  • Some subtypes of depression (subtypes that seem to be triggered by inflammation, seasonal type, postpartum, or related to deficiency of dopamine or endorphins);
  • Some subtypes of anxiety (for example, that come with obsessive ruminations or intrusive thoughts);
  • Obsessive-compulsive disorder and OCD-spectrum disorders;
  • Post Traumatic Stress Disorder (PTSD);
  • Modulation of sleep architecture;
  • A variety of sexual problems, including problems of desire, performance and satisfaction;
  • What I call “LDN assisted psychotherapy”. (I think I found how to use it to help extinguish unwanted behaviors and reinforce wanted alternative behaviors. This work is done with therapists I teach and then collaborate with);
  • Appetite control;
  • Addiction to internet, sex, gambling;
  • Alcohol and drug dependence. (While we probably need a “traditional dose” of naltrexone for treatment of alcohol dependence, some other types are doing great on LDN);
  • Helping patients stop opioids and then recover quicker from the prolonged post-opioid use problems, or just decreasing the amount of pain pills they are taking.

You mention prescribing LDN for certain subtypes of depression/anxiety. What subtypes are you referring to?

In my opinion, depression is not a single disorder. It is rather a generic name that was chosen to describe a number of diverse conditions, just because they share a few common symptoms. There were many attempts in academic psychiatry to separate the clearly heterogeneous group of disorders collectively called “depression” into subtypes. Unfortunately, for a long time, this work had no impetus, as most of the medications that came to market during the last 20-30 years were inspired by the same theory – that depression is related to the imbalance in one or more principal neurotransmitters in the brain – serotonin, norepinephrine and dopamine. In my view, in the nearest future, we will see that new medications will seek approval to treat specific symptoms of depression, such as sadness, racing thoughts, obsessive ruminations and changes in energy, rather than for the generic indication “depression”.Which subtypes of depression are more responsive to LDN?

Although not always, patients whose depression comes with tiredness, inability to feel any excitement, no motivation, no enthusiasm, slowed movements and thinking, decreased appetite, etc. are more likely to respond to LDN. This is compared to patients who describe their depression as “painful”, who feel discontent, antsy, and/or pessimistic. There are no strict rules; some of the depression types can overlap in their symptoms. I also want to add that it is very uncommon for LDN to worsen depression.

Although not always, patients whose depression comes with tiredness, inability to feel any excitement, no motivation, no enthusiasm, slowed movements and thinking, decreased appetite, etc. are more likely to respond to LDN.

What effects did you see LDN providing?

Since the majority of my patients are already taking at least a few, if not more, medications, I do not have a luxury to stop all their medications suddenly and switch them only to LDN. I usually start by adding LDN, along with making some other changes to the cocktail of their medications. I can only say that the result of adding LDN is sometimes spectacular and sometimes there is no obvious change.In your experience, who can benefit from LDN?

LDN works on opioid receptors. Everybody who has opioid receptors can benefit from LDN. Although at this point there are no recommendations to take LDN prophylactically, knowing how much LDN can do, and how many autoimmune conditions remain undetected for long time, a trial of LDN is probably warranted for most of the cases of “vague symptoms”, for the cases of incomplete resolution of an illness, etc.What do you advise your patients about the timing of taking their LDN?

In psychiatry, we frequently adjust dosages and schedules. Of course, I am aware of the traditional way to take low dose naltrexone before bed and I always recommend that patients start taking it this way. If, however, we do not get a desirable result – and, in the case of psychiatry, the patient, not the lab value is the best judge of the result – the dosage can be changed or the timing can be changed. I have patients who take LDN once a day and others who sip an LDN solution throughout the day. In some cases of addiction, or if my goal is to modify an unwanted behavior, I might instruct the patient to take naltrexone every time they think they might find themselves engaged in the behavior they want to extinguish.Have you observed long-term effects of LDN yet?

As far as I understand, there is no official information related to the long term use of LDN. A lot of patients feel that they “returned back to step one” when they stopped taking LDN. Because of this, especially taking in consideration practically negligible side effects, the risk-benefit ratio of LDN is clearly supporting long-term use. Even when I treat illnesses with episodic courses, such as depression, I still recommend that patients continue taking LDN because of the high risk of recurrence. On the other hand, I had patients who felt strongly about stopping all medications as soon as they improved; it made no sense, but they had strong philosophical disagreement with taking any medications in general. In their cases, I just made sure that they have a strategic supply of LDN which can be started when the next episode begins. Unfortunately, this kind of patient is not always able to catch the first signs of the illness and start the treatment before it becomes severe.

…especially taking in consideration practically negligible side effects, the risk-benefit ratio of LDN is clearly supporting long-term use.

Do you think there is a risk of receptors becoming adjusted to LDN and creating the potential for either tolerance or addiction to it?

Some of my patients who say, “If I forget to take my LDN, I feel it” wonder the same. They feel they are “missing something”, and they might become more irritable, tired, have difficulty concentrating, and complain of “brain fog”. This makes sense because LDN works on the opioid receptors, after all. At the same time, I do not know a case when a patient could not stop LDN or had unbearable withdrawal, even after a prolonged use. Based on what I understand now, this “dependence” on LDN does not look like dependence to opioids or benzodiazepines (Xanax®, Ativan®, Valium®, etc.). It looks more like dependence to coffee. Some people who drink coffee every day and stop abruptly also complain of withdrawals – they have no energy, no concentration, they start having headaches, etc. These symptoms, however, are more of a nuisance than a tragedy. As a rule, they subside in a few days. Based on what I know now and what I read, I would not stop LDN because of the fear of dependence.

…I do not know a case when a patient could not stop LDN or had unbearable withdrawal, even after a prolonged use.

Have you seen any side effects from LDN?

The patients I treat are probably more vulnerable to vivid dreams and their dreams might become unpleasant. Additionally, after a couple of surprises, I do not forget to tell my female patients to be more careful about pregnancy precautions, because they might become unexpectedly more fertile.What kind of research on LDN for sexual dysfunction are you interested in?

There is a tight connection between autoimmune conditions and hormone imbalance; there is even an opinion that autoimmune conditions are caused by hormone imbalance. Sexual dysfunctions (not only disorders of performance, but also disorders of desire and satisfaction) are only a small part of the consequences of the hormone imbalance. My most recent project is focusing on post-coital dysphoria or “post-sex blues”. Basically, it describes a phenomenon when people become dysphoric (tearful, depressed, or, possibly, argumentative) after they have an orgasm, even though they had satisfying sex with a person they loved. The phenomenon is most likely related to the skyrocketing and then sudden dropping of the dopamine level. The mechanism is somewhat similar to the crash following cocaine use. A few years ago, I came up with the idea of using LDN prior to sex to normalize this dopamine/endorphin response. In essence, taking LDN prior to sex can fix the problem, and the only question left is the timing and the amount of LDN.

In essence, taking LDN prior to sex can fix the problem, and the only question left is the timing and the amount of LDN.

What dose and timing do you recommend for this kind of sexual dysfunction condition?

In practice, I recommend LDN as a part of a stimulant-vitamin-drug combination. At this point, I need a little more data to announce the magic combination, dose and timing. I would like to invite the readers, whether you are on LDN currently or not, openly or anonymously, to share your experience about using LDN for this condition.

LDN can → ↑ BDNF as well as: exercise caloric restriction glutamate, cucurmin

To boost endorphins, use LDN with: ● high-protein food ● vitamins: B, C, Omega-3 with vit D, E, Zink; ● avoiding sugar, flour, coffee – (“exorphins”) ● exercise, massage, acupuncture, sunlight ● guided imagery, music, romance, nature

BDNF – norbuprenorphine, kratom, cannabidiol (Epidiolex), THC (Marinol) – inhibited by trazodone, buprenorphine

Naltrexone Alcoholism Medication

Naltrexone is a medication that can be used for the treatment of opioid violations and alcohol addiction. The research that was conducted in order to study the action of this drug showed that naltrexone can also be taken within the patients suffering from severe depression.

As a result of the research, it was found that taking the drug naltrexone can help to reduce depression. The patients participating in the research were people, who had depression and took antidepressants. It was set up that the severity of depression was reduced within the patients taking naltrexone. The results of the research were published in the Journal of Affective Disorders in January 2017.

The author of this study was David Mischoulon, a medical specialist of the Massachusetts Hospital and one of the specialists of the Harvard Medical School. He was the leader of the group that studied a variety of ways to treat severe depression. The group studied the action mechanism and the effect of antidepressant medications, as well as the mechanisms that contribute to the development of depression. Initially, the LDN drug was patented as the drug indicated for the treatment of restless legs syndrome (RLS), but during the treatment of patients with RLS taking LDN, it was found that LDN also positively affects suppression of depression.

One of the mechanisms of the low dose naltrexone medication is dopamine. It is a neurotransmitter, which is associated with the regulation of human mood and helps to reduce depression.

The studies, connected with LDN, have also shown that if a patient suffers from depression and takes antidepressants that work with dopaminergic mechanisms, the additional use of LDN in combination with the antidepressant drugs can help to cope with depression in a shorter period of time.

There was also a disadvantage of the research. It is connected with the fact that there were just 12 patients who participated in the study. This number of the participants is too small to make exact conclusions, concerning the LDN action mechanisms and taking it in order to treat depression. To be sure about the action of this drug during treating depression, more studies should be done, involving larger groups of participants. In the study described above, the patients used just the antidepressants, acting through dopaminergic mechanisms. This fact does not give any confidence that LDN will act positively in combination with other antidepressants, for example, with serotonergic and noradrenergic antidepressants.

Moreover, it would be useful to conduct an optimal LDN study, as the LDN medication includes a number of different dosages and they are all defined as low doses. Such a study has not previously been conducted. Therefore, some medical specialists who prescribe LDN should inform their patients about this drug and warn the patients that the therapy associated with LDN while treating depression is experimental. The patients should be aware of the potential risks before taking this medication, as the drug is not accepted in medicine, regarding the treatment of depression.

LDN can’t be bought at most pharmacies, although it can be obtained by prescription from a licensed doctor. The commercially available forms of naltrexone come in much higher doses. To get LDN, you need to bring a prescription from your doctor to the pharmacy and there the appropriate dosage form will be prepared for you. In general, LDN is available for the majority of people.

Ketamine has rapid and robust antidepressant effects. However, there are concerns about the abuse liability of ketamine.1This concern was heightened recently owing to a preliminary report suggesting that antidepressant effects of ketamine might be dependent on opiate receptor stimulation.2 Below, we present pilot data that indicate that the antidepressant effects of ketamine are not attenuated by naltrexone pretreatment. As a result, the combination of opiate receptor antagonism with ketamine might be a strategy to reduce addiction risk among patients with depression at risk for substance abuse.Methods

We recruited and obtained written informed consent from 5 patients with current major depressive disorder and alcohol use disorder. In this 8-week open-label pilot study, which recieved institutional review board approval by the VA Connecticut Healthcare System Human Subjects Subcommittee, patients received injectable naltrexone (380 mg once 2-6 days prior to the first ketamine infusion) and repeated intravenous ketamine treatment (0.5 mg/kg once a week for 4 weeks; a total of 4 ketamine infusions). The study had 2 phases: (1) a 4-week ketamine treatment phase and (2) a 4-week follow-up phase. All patients were abstinent from alcohol for 5 days or longer prior to the first ketamine infusion. The primary outcome measure was clinical response defined as a 50% or higher improvement from baseline in the Montgomery-Åsberg Depression Rating Scale scores at 4 hours postinfusion.Results

The combination of naltrexone and ketamine was associated with reduced depressive symptoms. The Figure shows that 60% (3 of 5) of patients met response criteria after their initial ketamine dose and 100% (5 of 5) met response criteria by their fourth dose, although 1 patient left the trial after receiving 2 ketamine infusions. The Table shows that depressive symptoms improved about 57% to 92%. Also, 80% (4 of 5) of patients reported improvement in alcohol craving and consumption as measured by the Obsessive Compulsive Drinking Scale. The combination treatment was safe and well tolerated in all participants. No serious adverse effects were reported in the trial.Discussion

Our pilot data suggest that naltrexone pretreatment did not interfere with the antidepressant effects of ketamine and might enhance the treatment of comorbid alcohol use disorder. This result conflicts with that reported by Williams et al2 in which pretreatment with 50 mg of naltrexone reduced the rate of clinical response to ketamine from 71% (5 of 7 individuals) to 0% (0 of 7 individuals). Their data and an editorial by George,3 although preliminary, make a case for a central role for opiate agonism in the antidepressant effects of ketamine. Although our pilot data were collected under somewhat different conditions than those of Williams et al2 (eg, different primary outcome time of 4 hours vs 1 day postinfusion, presence vs absence of alcohol use disorder, injectable vs oral naltrexone), they do not support the hypothesis that opiate receptor stimulation mediates the antidepressant effects of ketamine. Since Williams et al2 did not provide depression ratings over a 4-hour period postinfusion, we cannot examine whether 50 mg of oral naltrexone blunted ketamine response in this early 4-hour period. Our findings are consistent with an earlier study in healthy individuals showing that the behavioral effects of an antidepressant dose of ketamine were not altered by pretreatment with 25 mg of naltrexone,4 and some preclinical evidence that ketamine isomers may be weak partial agonists at μ opiate receptors.5

The initial report by Williams et al2 and our preliminary data should be interpreted with great caution. Larger randomized clinical trials are needed to better understand whether opiate receptor stimulation contributes to the antidepressant effects of ketamine. If so, then preclinical research will be needed to help us to understand this role for opiates and its implications for future rapid-acting antidepressant treatments.

Unique Drug Combo Promising for Severe, Intractable Pain

 Low doses of the hormone oxytocin along with the anestheticketamine may provide a unique and effective therapeutic approach to some patients with severe, intractable pain

This therapeutic approach is “incredibly unique” and is safe and effective in some patients with intractable pain. “If you put these two together, you could replace any short-acting opiate,” Caron Pedersen, FNP-C, DC, BSN, BS-PT, a nurse practitioner, chiropractor, and physical therapist specializing in patients with spinal pain, told Medscape Medical News.

Dr Caron Pedersen

Dr Pedersen has been working with pain management expert, Forest Tennant, MD, DPH, Veract Intractable Pain Clinic, West Covina, California, to find better ways to treat patients with very severe pain.

Such patients, said Dr Pedersen, “are pretty much opioid-dependent and have been for long time, and are not getting relief.”

Dr Pedersen presented some of her research here at the Academy of Integrative Pain Management (AIPM) 28th Annual Meeting.

Alternative to Opioids?

A variety of antiseizure, antidepressant, and anti-inflammatory agents, as well as muscle relaxants and adrenergic blocking agents, provide mild to moderate pain relief. But these approaches are not always a substitute for opioids in patients with severe pain.

Both oxytocin and ketamine provide analgesia by mechanisms other than stimulating opioid receptors.

Produced in the hypothalamus, oxytocin is a potent natural pain reliever. The hormone is released in pregnant women during labor and also in other painful conditions or stressful events.

It has been reported to relieve pain in patients with headache, chronic back pain, and fibromyalgia, and there is “a mountain of research” on oxytocin’s complex production, release, and receptor system, said Dr Pedersen.

Dr Tennant explained that some of the hormone is released into the peripheral circulation via the posterior pituitary and some into the central nervous system, including the spinal fluid.

Oxytocin receptors are found at multiple sites in the brain and throughout the spinal cord, said Dr Tennant. In addition to activating its own receptors and decreasing pain signals, oxytocin binds to opioid receptors and stimulates endogenous opioid release in the brain.

In addition to relieving pain, oxytocin lowers serum cortisol and can produce a calming effect and improve mood.

“It has the effect of making people happy, making them feel a little less anxious,” said Dr Pedersen. “It changes the central nervous system; it makes the hypothalamus pump out chemicals that are telling the body it’s okay, calm down.”

Oxytocin can block “anticipatory pain,” added Dr Pedersen. Patients with intractable pain are constantly waiting for “the next burse of pain” so are “in constant stress,” she said.

However, when they take oxytocin, “they may actually get a lot of relief based on the fact that they are no longer having that anticipation.”

Pain Free, No Side Effects

The investigators are working to determine optimal doses and routes of administration for oxytocin. They have experimented with combining oxytocin with low-dose naltrexone, benzodiazepines, neuropathic agents, opioids, and now ketamine, an N-methyl-D-aspartic acid receptor antagonist.

There has been a resurgence of interest in ketamine as a possible therapy for chronic pain conditions, including neuropathic pain, complex regional pain syndrome, fibromyalgia, postherpetic neuralgia, migraines, and spinal cord injury

At relatively high doses, ketamine has significant psychomimetic and euphoric properties that have led to abuse. Oral ketamine, sometimes called Special K, has become a popular nightclub drug.

Dr Tennant and Dr Pedersen have been experimenting with low-dose ketamine added to oxytocin in patients with the most severe intractable pain.

The study they presented at the AIPM meeting included five such patients (mean age, about 40 years) who had used oxycodonemorphinehydrocodone, or hydromorphone for over a year.

Patients had not taken their short-acting opiate for several hours when they received 0.5 mL (2 mg — half of a syringe, or 20 units) of liquid oxytocin sublingually. Within 10 minutes, all five patients reported varying degrees of pain relief.

About 15 minutes after receiving the oxytocin, patients then received 0.25 to 0.50 mL (12.5 to 25 mg) of liquid ketamine, also sublingually.

The ketamine enhanced the pain relief. With the combination, two patients became completely pain free. These patients would “positively not” have been pain free with opioids, said Dr Pedersen.

The pain relief lasted about 4 hours with no side effects.

The Worst of the Worst

Dr Pedersen said the study patients were “the very worst” of pain patients. In her clinic, many patients suffer intractable pain — pain that never completely goes away with surgery or with drugs. “Some have had, say, seven or eight back surgeries and they have so much inflammation in their spine.”

Some are battling an autoimmune disease, such as lupus. Others have arachnoiditis, an incurable inflammatory condition of the arachnoid mater, the middle layer of the meninges.

Because oxytocin is a hormone, its pain-relieving ability varies from patient to patient and its effectiveness is related, among other things, to blood levels, pain severity, and sex. 

In her experience, Dr Pedersen has found that men tend to have a better response to the combination of oxytocin and ketamine than women.

But women also respond “fabulously,” she said. She described one 38-year-old female patient in her practice with a disc herniation who had been taking opioids, which were not helping her much. “She stopped taking them when she started using this combination therapy.”

Other patients have been able to cut back on opioids “significantly enough that if they had to stop taking them, they would be okay,” said Dr Pedersen.

The combination therapy may also address the issue of addiction, said Dr Pedersen. Some of her patients had become addicted to opioids, but after using the oxytocin-ketamine regimen, they’re not craving or abusing opioids.

The liquid form taken sublingually provides “the best delivery system” and is much more effective than pills, said Dr Pedersen.

Although liquid oxytocin typically has a shelf life of only about 10 days, Dr Pedersen has found pharmacies that put the hormone in a suspension that lasts for 3 months.

Intriguing Results

Commenting on the research for Medscape Medical News, Charles E. Argoff, MD, professor of neurology, and director, Comprehensive Pain Center, Albany Medical College, New York, said it “provides intriguing results.”

However, he said, a single-center open-label study of only five patients “is insufficient to draw any conclusions.”

While the use of oxytocin as an analgesic is supported by basic science, “this study does not add significantly to the human studies already completed, given its size and design,” said Dr Argoff.

Adding ketamine “dampens enthusiasm” for this therapeutic approach because of concerns about dependency and side effects, said Dr Argoff.

Adverse effects of ketamine can include nausea, headaches, fatigue, and dysphoria.

The authors have disclosed no relevant financial relationships.

Academy of Integrative Pain Management (AIPM) 28th Annual Meeting. Abstract 24. Presented October 21, 2017. 

Pain Sand Diego

Web Blog Pain management Link


Metformin & Pain

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A diabetes drug used for many who have no diabetes. Recent discussion on metformin here and here.

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Metformin “can lead to a long-lasting reversal of pain hypersensitivity even long after treatment cessation, indicative of disease modification.” [ref below]

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References:

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A successful case of pain management using metformin in a patient with adiposis dolorosa.

International Journal of Clinical Pharmacology and Therapeutics [2013], from Medical University of Silesia, Katowice, Poland

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This is a very rare condition that has no known treatment.

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Abstract:

In this case report, we describe a patient with Dercum’s disease who was successfully managed with metformin. The administration of metformin reduced pain intensity from 9/10 to 3/10 and favorably affected the profile of inflammatory cytokines (i.e., TNF a, IL-1β, IL-6, and IL-10), adipokines (i.e., adiponectin, leptin, and resistin), and β-endorphin. Because each variable was affected moderately by the drug, in the range of 20 – 30%, it follows that these effects are additive, i.e., they act independently of each other. However, taking into account advances in the pharmacology of metformin, it seems that other phenomena, such as modulation of synaptic plasticity, activation of microglia, and autophagy of the afferents supplying painful lipomas should be taken into consideration. Nonetheless, metformin deserves further exploration in the biology of pain.

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The use of metformin is associated with decreased lumbar radiculopathy pain

Journal of pain [2013], from University of Arizona Tucson, Ted Price’s lab, and USC

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Abstract:

Lumbar radiculopathy pain represents a major public health problem, with few effective long-term treatments. Preclinical neuropathic and postsurgical pain studies implicate the kinase adenosine monophosphate activated kinase (AMPK) as a potential pharmacological target for the treatment of chronic pain conditions. Metformin, which acts via AMPK, is a safe and clinically available drug used in the treatment of diabetes. Despite the strong preclinical rationale, the utility of metformin as a potential pain therapeutic has not yet been studied in humans. Our objective was to assess whether metformin is associated with decreased lumbar radiculopathy pain, in a retrospective chart review. We completed a retrospective chart review of patients who sought care from a university pain specialist for lumbar radiculopathy between 2008 and 2011. Patients on metformin at the time of visit to a university pain specialist were compared with patients who were not on metformin. We compared the pain outcomes in 46 patients on metformin and 94 patients not taking metformin therapy. The major finding was that metformin use was associated with a decrease in the mean of “pain now,” by −1.85 (confidence interval: −3.6 to −0.08) on a 0–10 visual analog scale, using a matched propensity scoring analysis and confirmed using a Bayesian analysis, with a significant mean decrease of −1.36 (credible interval: −2.6 to −0.03). Additionally, patients on metformin showed a non-statistically significant trend toward decreased pain on a variety of other pain descriptors. Our proof-of-concept findings suggest that metformin use is associated with a decrease in lumbar radiculopathy pain, providing a rational for larger retrospective trials in different pain populations and for prospective trials, to test the effectiveness of metformin in reducing neuropathic pain.

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The anti-diabetic drug metformin protects against chemotherapy-induced peripheral neuropathy in a mouse model.

PLoS One [2014] from MD Anderson Cancer Center

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Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) characterized by loss of sensory sensitivity and pain in hands and feet is the major dose-limiting toxicity of many chemotherapeutics. At present, there are no FDA-approved treatments for CIPN. The anti-diabetic drug metformin is the most widely used prescription drug in the world and improves glycemic control in diabetes patients. There is some evidence that metformin enhances the efficacy of cancer treatment. The aim of this study was to test the hypothesis that metforminprotects against chemotherapy-induced neuropathic pain and sensory deficits. Mice were treated with cisplatin together with metformin or saline. Cisplatin induced increased sensitivity to mechanical stimulation (mechanical allodynia) as measured using the von Frey test. Co-administration of metformin almost completely prevented the cisplatin-induced mechanical allodynia. Co-administration of metformin also prevented paclitaxel-induced mechanical allodynia. The capacity of the mice to detect an adhesive patch on their hind paw was used as a novel indicator of chemotherapy-induced sensory deficits. Co-administration of metformin prevented the cisplatin-induced increase in latency to detect the adhesive patch indicating that metformin prevents sensory deficits as well. Moreover, metformin prevented the reduction in density of intra-epidermal nerve fibers (IENFs) in the paw that develops as a result of cisplatin treatment. We conclude that metformin protects against pain and loss of tactile function in a mouse model of CIPN. The finding that metformin reduces loss of peripheral nerve endings indicates that mechanism underlying the beneficial effects of metformin includes a neuroprotective activity. Because metformin is widely used for treatment of type II diabetes, has a broad safety profile, and is currently being tested as an adjuvant drug in cancer treatment, clinical translation of these findings could be rapidly achieved.

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Proteomic and functional annotation analysis of injured peripheral nerves reveals ApoE as a protein upregulated by injury that is modulated by metformin treatment

from Mol Pain [2013], from University of Arizona

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Abstract

BACKGROUND:

Peripheral nerve injury (PNI) results in a fundamental reorganization of the translational machinery in the injured peripheral nerve such that protein synthesis is increased in a manner linked to enhanced mTOR and ERK activity. We have shown that metformin treatment, which activates adenosine monophosphate-activated protein kinase (AMPK), reverses tactile allodynia and enhanced translation following PNI. To gain a better understanding of how PNI changes the proteome of the sciatic nerve and ascertain how metformin treatment may cause further change, we conducted a range of unbiased proteomic studies followed by biochemical experiments to confirm key results.

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CONCLUSIONS:

These proteomic findings support the hypothesis that PNI leads to a fundamental reorganization of gene expression within the injured nerve. Our data identify a key association of ApoE with PNI that is regulated by metformin treatment. We conclude from the known functions of ApoE in the nervous system that ApoE may be an intrinsic factor linked to nerve regeneration after PNI, an effect that is further enhanced by metformin treatment.

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Targeting AMPK for the Alleviation of Pathological Pain

Volume 107 of the series Experientia Supplementum [2016] from University of Texas Dallas

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Abstract:

Chronic pain is a major clinical problem that is poorly treated with available therapeutics. Adenosine monophosphate-activated protein kinase (AMPK) has recently emerged as a novel target for the treatment of pain with the exciting potential for disease modification. AMPK activators inhibit signaling pathways that are known to promote changes in the function and phenotype of peripheral nociceptive neurons and promote chronic pain. AMPK activators also reduce the excitability of these cells suggesting that AMPK activators may be efficacious for the treatment of chronic pain disorders, like neuropathic pain, where changes in the excitability of nociceptors is thought to be an underlying cause. In agreement with this, AMPK activators have now been shown to alleviate pain in a broad variety of preclinical pain models indicating that this mechanism might be engaged for the treatment of many types of pain in the clinic. A key feature of the effect of AMPK activators in these models is that they can lead to a long-lasting reversal of pain hypersensitivity even long after treatment cessation, indicative of disease modification. Here, we review the evidence supporting AMPK as a novel pain target pointing out opportunities for further discovery that are likely to have an impact on drug discovery efforts centered around potent and specific allosteric activators of AMPK for chronic pain treatment.

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Targeting adenosine monophosphate-activated protein kinase (AMPK) in preclinical models reveals a potential mechanism for the treatment of neuropathic pain.

Mol Pain [2011] from University of Arizona

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Abstract

Neuropathic pain is a debilitating clinical condition with few efficacious treatments, warranting development of novel therapeutics. We hypothesized that dysregulated translation regulation pathways may underlie neuropathic pain. Peripheral nerve injury induced reorganization of translation machinery in the peripheral nervous system of rats and mice, including enhanced mTOR and ERK activity, increased phosphorylation of mTOR and ERK downstream targets, augmented eIF4F complex formation and enhanced nascent protein synthesis. The AMP activated protein kinase (AMPK) activators, metformin and A769662, inhibited translation regulation signaling pathways, eIF4F complex formation, nascent protein synthesis in injured nerves and sodium channel-dependent excitability of sensory neurons resulting in a resolution of neuropathic allodynia. Therefore, injury-induced dysregulation of translation control underlies pathology leading to neuropathic pain and reveals AMPK as a novel therapeutic target for the potential treatment of neuropathic pain.

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Contrasting effects of chronic, systemic treatment with mTOR inhibitors rapamycin and metformin on adult neural progenitors in mice.

Age [20124, from University of Arizona

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Abstract:

The chronic and systemic administration of rapamycin extends life span in mammals. Rapamycin is a pharmacological inhibitor of mTOR. Metformin also inhibits mTOR signaling but by activating the upstream kinase AMPK. Here we report the effects of chronic and systemic administration of the two mTOR inhibitors, rapamycin and metformin, on adult neural stem cells of the subventricular region and the dendate gyrus of the mouse hippocampus. While rapamycin decreased the number of neural progenitors, metformin-mediated inhibition of mTOR had no such effect. Adult-born neurons are considered important for cognitive and behavioral health, and may contribute to improved health span. Our results demonstrate that distinct approaches of inhibiting mTOR signaling can have significantly different effects on organ function. These results underscore the importance of screening individual mTOR inhibitors on different organs and physiological processes for potential adverse effects that may compromise health span.

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Two Weeks of Metformin Treatment Enhances Mitochondrial Respiration in Skeletal Muscle of AMPK Kinase Dead but Not Wild Type Mice

.PLoS One from University of Copenhagen [2013].

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Abstract:

Metformin is used as an anti-diabetic drug. Metformin ameliorates insulin resistance by improving insulin sensitivity in liver and skeletal muscle. Reduced mitochondrial content has been reported in type 2 diabetic muscles and it may contribute to decreased insulin sensitivity characteristic for diabetic muscles. The molecular mechanism behind the effect of metformin is not fully clarified but inhibition of complex I in the mitochondria and also activation of the 5′AMP activated protein kinase (AMPK) has been reported in muscle. Furthermore, both AMPK activation and metformin treatment have been associated with stimulation of mitochondrial function and biogenesis. However, a causal relationship in skeletal muscle has not been investigated. We hypothesized that potential effects of in vivo metformin treatment on mitochondrial function and protein expressions in skeletal muscle are dependent upon AMPK signaling. We investigated this by two weeks of oral metformin treatment of muscle specific kinase dead α2 (KD) AMPK mice and wild type (WT) littermates. We measured mitochondrial respiration and protein activity and expressions of key enzymes involved in mitochondrial carbohydrate and fat metabolism and oxidative phosphorylation. Mitochondrial respiration, HAD and CS activity, PDH and complex I-V and cytochrome c protein expression were all reduced in AMPK KD compared to WT tibialis anterior muscles. Surprisingly, metformin treatment only enhanced respiration in AMPK KD mice and thereby rescued the respiration defect compared to the WT mice. Metformin did not influence protein activities or expressions in either WT or AMPK KD mice.

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We conclude that two weeks of in vivo metformin treatment enhances mitochondrial respiration in the mitochondrial deficient AMPK KD but not WT mice. The improvement seems to be unrelated to AMPK, and does not involve changes in key mitochondrial proteins.

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Effects of metformin on microvascular function and exercise tolerance in women with angina and normal coronary arteries

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Journal of the American College of Cardiology [2006], from University of Glasgow Cardiovascular Research Centre
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Abstract:

We conducted an 8-week double-blind, randomized, placebo-controlled study of metformin 500 mg twice a day in 33 women with a prior history of normal coronary angiography but 2 consecutive positive (ST-segment depression ≥1 mm) exercise tolerance tests.Women randomized to metformin (n = 16) showed significant improvements in endothelium-dependent microvascular function (p < 0.0001) and maximal ST-segment depression (p = 0.013), and a trend (p = 0.056) toward reductions in chest pain incidence relative to placebo recipients. Hence, metformin may improve vascular function and decrease myocardial ischemia in nondiabetic women with chest pain and angiographically normal coronary arteries. Larger controlled trials of longer duration are warranted.

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The material on this site is for informational purposes only.

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It is not legal for me to provide medical advice without an examination.

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It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

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This site is not for email and not for appointments.

If you wish an appointment, please telephone the office to schedule.

~~~~~

For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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Please IGNORE THE ADS BELOW. They are not from me.

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Posted in AMPK agonistAngina in WomenAnti-iinflammatoryChemotherapy induced neuropathyChronic PainMetforminMicrovascularMitochondrial respirationmTORNeuropathySciaticaUncategorized. Tags: AMPK agonistAngina in WomenAnti-inflammatoryChemotherapy induced neuropathyChronic PainMetforminMicrovascularMitochondrial respirationmTORPeripheral NeuropathySciaticaLeave a Comment »

Metformin Targets Aging – no lactic acidosis, no significant hypoglycemia in 18,000 patients-years of follow-up

03/15/2017 — Nancy Sajben MD      Rate This

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Metformin targets multiple pathways affected by aging (pdf)

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Authors Nir Barzilai, Jill P. Crandall, Stephen B. Kritchevsky, and Mark A. Espeland from aging research centers at Albert Einstein Medical School and Wake Forest Medical School, Cell Metabolism June 2016

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….in 2012, when over 18,000 patients-years of follow-up had accrued, and by which time 20% of the cohort was age 70 or older (mean age 64). There were no cases of lactic acidosis or significant hypoglycemia (Diabetes Prevention Pro- gram Research Group, 2012). Mild anemia occurred in 12% of metformin-treated participants versus 8% in the placebo group (p = 0.04). Vitamin B12 deficiency occurred in 7% of metformin group versus 5% in placebo group after 13 years; risk of B12 deficiency increases with duration of use but was not greater in older compared with younger subjects in DPPOS (Lalau et al., 1990). Further, the risk of lactic acidosis appears to be related to renal function, not age per se, and is currently considered to be very low (Aroda et al., 2016).

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B12 deficiency is related to MTHFR. I prescribe the doses of B vitamins to take daily, as published by University of Oxford for seniors. Their work shows it prevents 90% of brain atrophy in those areas that are known to involve Alzheimers Disease [avoid toxic B6 doses that damage brain].

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When time permits, I will be adding more on metformin.

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If low blood sugar (hypoglycemia) occurs, juice works quickly but rapidly disappears and then blood sugar is low again in minutes. Use good diet practices, and use plenty of small protein snacks if needed. Protein lasts longer and does not trigger sugar spikes like juice.

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Common side effects, if present at all, are mostly GI such as diarrhea, nausea, gas, distension of the belly with discomfort, indigestion, anorexia, headache, asthenia. If present, stop the drug, wait till all resolve, and very slowly, increase only as tolerated. This is not a speed test.

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Lactic Acidosis potential rare side effect

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The potentially serious side effect of concern is lactic acidosis. I advise patients to review its list of potential side effects.

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http://www.medsafe.govt.nz/profs/PUarticles/5.htm

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https://www.healthgrades.com/conditions/lactic-acidosis–symptoms

Introduction

Symptoms

Causes

Treatments

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What are the symptoms of lactic acidosis?

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Symptoms of lactic acidosis may include nausea and vomiting, abdominal pain, weakness, rapid breathing, rapid heart rate or irregular heart rhythm, and mental status changes.

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Common symptoms of lactic acidosis

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If you experience lactic acidosis, it may be accompanied by symptoms that include:

Abdominal pain

Anxiety

Fatigue

Irregular heart rate (arrhythmia)

Lethargy

Nausea with or without vomiting

Rapid breathing (tachypnea)

Rapid heart rate (tachycardia)

Shortness of breath

Weakness

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Serious symptoms that might indicate a life-threatening condition

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In some cases, lactic acidosis can be life threatening.

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Seek immediate medical care (call 911) if you, or someone you are with, have any of these life-threatening symptoms including:

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Bluish coloration of the lips or fingernails

Change in level of consciousness or alertness, such as passing out or unresponsiveness

Chest pain, chest tightness, chest pressure, palpitations

High fever (higher than 101 degrees Fahrenheit)

Not producing any urine, or an infant who does not produce the usual amount of wet diapers

Rapid heart rate (tachycardia)

Respiratory or breathing problems, such as shortness of breath, difficulty breathing, labored breathing, rapid breathing, or not breathing

Severe abdominal pain

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…….

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The material on this site is for informational purposes only.

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It is not legal for me to provide medical advice without an examination.

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It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

~~

This site is not for email and not for appointments.

If you wish an appointment, please telephone the office to schedule.

~~~~~

For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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Posted in AgingAnti-iinflammatoryMetabolomeMetforminSide Effects. Tags: AgingAlzheimer’sAnti-inflammatoryMetforminSide EffectsLeave a Comment »

METFORMIN for Nerve Pain

03/06/2017 — Nancy Sajben MD      2 Votes

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Is metformin the new wonder pill or snake oil? Based on one man’s response to metformin and recent exciting research on the drug, I am looking forward to finding out how it works clinically for my patients with intractable pain (and possibly treatment resistant depression). Hopefully most will confirm it is well tolerated. I am just beginning to trial it after learning this one man’s amazing story:

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50% relief of nerve pain &

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musculoskeletal pain

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after 2nd week on metformin

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One Man’s Story

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A few days ago I spoke with a man, not my patient, who had 50% relief of pain after the second week on metformin. He’s taken it for 3 months now, but the big change came dramatically after the second week when he had been on the 2,000 mg dose a full week. In 2013, he was on the side of the freeway median lane, and had crawled into the engine of his disabled Ford F350 reaching in with his left hand when his vehicle was hit by a Lexus SUV going 70 mph and he was thrown. He doesn’t talk about his pain. Ever. He needs total knee replacement in the next few weeks, and has had four surgeries on his left wrist, mangled in that engine, now with a long steel plate in the wrist. He broke the titanium plate and it wasn’t healing. Since metformin, the skin and surgical scar is healing. He’s one of these quiet guys who don’t ever talk about pain. His wife simply said these days he’s sleeping since on metformin.

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But no one had asked him about pain since on metformin or for years either. It took 30 minutes to get one little bit of information from him on pain, like pulling teeth: Since metformin, he’s had 50% relief including the nerve pain at his wrist.

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She said he used to sit up all night in pain for years and was very irritable. Irritability is what happens with no sleep; pain is worse with no sleep. I could not get him to rate his pain. Stoic. Bright man, stoic. Devilish sense of humor. Severe pain for so many years he would never talk about. His surgeon had him stop the Vicodin 5/325 weeks before his last surgery “to help it heal.”

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Some of his relief may have also been influenced by blood sugar dropping from 170 to 90, no more excessive thirst and urination keeping him awake, but the neuropathic pain at his wrist had been nasty a few years. Pain had kept him up for months. He had no side effects.

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Metformin

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Metformin is a medication approved in Canada in 1972 and in the United States by the FDA in 1994 for type 2 diabetes. It is well tolerated when prescribed for people who do not have diabetes but who have other conditions such as PCOS (polycystic ovary syndrome), infertility; and it is the focus of intense activity being studied for its

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(1) anti-aging (PDF from Wake Forest University or the Albert Einstein Medical School Longevity study clinicaltrials.gov), 

(2) anti-cancer (it “has become the focus of intense research as a potential anticancer agent” per Cancer Treat. Res. publication 2014) and now recently being studied for

(3) anti-inflammatory analgesic effects.

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“Metformin increases the number of oxygen molecules released into a cell, which appears to boost robustness and longevity. It works by suppressing glucose production in the liver and increasing insulin sensitivity, therefore benefiting patients with type 2 diabetes.”

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I am very interested by all the new research being done on an old drug, metformin, that has suddenly turned heads in just the last few months as we learn its mechanisms involving the pain matrix. Is this metformin some miracle drug, another hot trendy bandwagon people jump on in medicine? It’s an old drug already FDA approved, now repurposed, with excellent safety, and four months ago a publication shows it to be a glial modulator and anti-inflammatory, centrally active. Best of all, it was dramatically potent in the setting of this man’s intractable nerve and musculoskeletal pain.

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But how do we get from 1994 to 2017, through the Decade of Pain, seeing patients who have astonishing pain relief without asking a single patient, millions of patients if it helped pain? A recent past president of the American Endocrine Society said: “No good data on metformin to treat pain. Everything else, but not pain.” He also said, “Safe. We do it all the time for people with PCOS, infertility, cancer, etc. The anti-aging people use it all the time. No risk of hypoglycemia. Just be sure their GFR is above 40.” So ask your doctor who may not know it’s hot research right now.

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When was it first mentioned for pain?

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Less than one year ago, a report on metformin’s use for pain was a 2016 poster presentation at the annual meeting of the American Pain Society from Ted Price’s lab at University Texas Dallas. “The AMPK activator metformin has been shown by our lab to reverse the effects of chronic neuropathic pain in various short term studies….The treatment successfully decreased the hypersensitivity and cold allodynia associated with neuropathic pain, and showed persistent relief for several weeks post-injection. Metformin also decreased the activation of microglia in the spinal cord.”

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I have cautiously held back prescribing it for pain until I heard this man’s story a few days ago, and days later I am still astonished at the relief he had. I immediately suspected metformin must be a strong glial modulator and that mechanism was confirmed in a publication four months ago, in animal (discussed at end).

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O

 SIDE EFFECTS

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If some develop side effects, stop the medication until all side effects are zero. Then at your own body’s rate, as slowly as needed, increase if needed to 1000 mg twice daily.

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If you again have side effects, again stop til all are zero. Maybe your top dose with no side effects is less than 2,000 mg/day.

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More information on potential side effects  are on the next metformin post – almost none in 18,000 patient years, and not a single case of lactic acidosis.

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STUDIES NEEDED

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It would be extremely helpful to see a study on metformin’s use for pain in a major cancer center, including the range of all underlying diagnoses of those patients who may not be in best of health.  What are % of side effects?

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INFLAMMATION

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Metformin helps inflammation. Inflammation is the cause of 90% mortality. Almost all disease in the body begins with inflammation including atherosclerosis that leads to plaque, heart attacks, stroke. And the same risk factors for heart disease are same for Alzheimers. Inflammation manifests differently in each of us, but to relieve pain, major depression, bipolar disease, PTSD, it can be very dynamic to see response in a few hours once you have the right dose and combination of glial modulators. If this one can relieve 50% of severe chronic pain in two weeks, with few or no side effects, then millions can benefit now. It is an old generic drug repurposed for pain, that is anti-inflammatory. Best of all anti-inflammatory up there in the brain where the inflammatory cytokines produced by glia make you feel like you have the flu:  difficulty thinking, fatigue, drowsy, achey, irritable, needing sleep. That is inflammation. The innate immune system going into gear to attack a virus or…..damage.

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Studies reported about 2001, NIMH showed brain atrophy and memory loss in chronic depression, and about 2009 others showed the same in chronic low back pain.

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My focus for years has been on inflammation in the CNS (brain, spinal cord) because NSAIDs like ibuprofen, Aleve, do not reach the CNS and do not interact on the cells of interest: glia, the cells of the innate immune system that produce a balance of anti-inflammatory and pro-inflammatory chemicals called cytokines. BALANCE.

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Tolerance is a big issue in treating pain or major depression. I strongly recommend reading yesterday’s post on tolerance, i.e. when the body stops responding to ketamine or morphine or an antidepressant after several days or weeks or years. Inflammation may be one cause.

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A publication four months ago shows metformin has both immune and glial suppressive effects that can relieve tolerance to morphine.  It’s a centrally acting analgesic because that’s where chronic pain or major depression is, in the CNS.

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MECHANISM of PAIN RELIEF

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It has both immune and glial suppressive effects: J Neuroinflammation. 2016 Nov 17;13(1):294.

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Metformin reduces morphine tolerance by inhibiting microglial-mediated neuroinflammation.

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ABSTRACT

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BACKGROUND:

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Tolerance [see post on this subject yesterday] seriously impedes the application of morphine in clinical medicine. Thus, it is necessary to investigate the exact mechanisms and efficient treatment. Microglial activation and neuroinflammation in the spinal cord are thought to play pivotal roles on the genesis and maintaining of morphine tolerance. Activation of adenosine monophosphate-activated kinase (AMPK) has been associated with the inhibition of inflammatory nociception. Metformin, a biguanide class of antidiabetic drugs and activator of AMPK, has a potential anti-inflammatory effect. The present study evaluated the effects and potential mechanisms of metformin in inhibiting microglial activation and alleviating the antinociceptive tolerance of morphine.

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RESULTS:

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We found that morphine-activated BV-2 cells, including the upregulation of p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation, pro-inflammatory cytokines, and Toll-like receptor-4 (TLR-4) mRNA expression, which was inhibited by metformin.Metformin suppressed morphine-induced BV-2 cells activation through increasing AMPK phosphorylation, which was reversed by the AMPK inhibitor compound C. Additionally, in BV-2 cells, morphine did not affect the cell viability and the mRNA expression of anti-inflammatory cytokines. In bEnd3 cells, morphine did not affect the mRNA expression of interleukin-1β (IL-1β), but increased IL-6 and tumor necrosis factor-α (TNF-α) mRNA expression; the effect was inhibited by metformin. Morphine also did not affect the mRNA expression of TLR-4 and chemokine ligand 2 (CCL2). Furthermore,systemic administration of metformin significantly blocked morphine-induced microglial activation in the spinal cord and then attenuated the development of chronic morphine tolerance in mice.

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CONCLUSIONS:

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Metformin significantly attenuated morphine antinociceptive tolerance by suppressing morphine-induced microglial activation through increasing AMPK phosphorylation.

BACKGROUND:

Tolerance seriously impedes the application of morphine in clinical medicine. Thus, it is necessary to investigate the exact mechanisms and efficient treatment. Microglial activation and neuroinflammation in the spinal cord are thought to play pivotal roles on the genesis and maintaining of morphine tolerance. Activation of adenosine monophosphate-activated kinase (AMPK) has been associated with the inhibition of inflammatory nociception. Metformin, a biguanide class of antidiabetic drugs and activator of AMPK, has a potential anti-inflammatory effect. The present study evaluated the effects and potential mechanisms of metformin in inhibiting microglial activation and alleviating the antinociceptive tolerance of morphine.

METHODS:

The microglial cell line BV-2 cells and mouse brain-derived endothelial cell line bEnd3 cells were used. Cytokine expression was measured using quantitative polymerase chain reaction. Cell signaling was assayed by western blot and immunohistochemistry. The antinociception and morphine tolerance were assessed in CD-1 mice using tail-flick tests.

RESULTS:

We found that morphine-activated BV-2 cells, including the upregulation of p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation, pro-inflammatory cytokines, and Toll-like receptor-4 (TLR-4) mRNA expression, which was inhibited by metformin. Metformin suppressed morphine-induced BV-2 cells activation through increasing AMPK phosphorylation, which was reversed by the AMPK inhibitor compound C. Additionally, in BV-2 cells, morphine did not affect the cell viability and the mRNA expression of anti-inflammatory cytokines. In bEnd3 cells, morphine did not affect the mRNA expression of interleukin-1β (IL-1β), but increased IL-6 and tumor necrosis factor-α (TNF-α) mRNA expression; the effect was inhibited by metformin. Morphine also did not affect the mRNA expression of TLR-4 and chemokine ligand 2 (CCL2). Furthermore, systemic administration of metformin significantly blocked morphine-induced microglial activation in the spinal cord and then attenuated the development of chronic morphine tolerance in mice.

CONCLUSIONS:

Metformin significantly attenuated morphine antinociceptive tolerance by suppressing morphine-induced microglial activation through increasing AMPK phosphorylation.

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NOVA Health Recovery | Alexandria, Va 22306 | Call for esketamine and nasal ketamine as well as IV Ketamine for depression, PTSD, anxiety  703-844-0184 < Link

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Ketamine Infusion Combined With Magnesium as a Therapy for Intractable Chronic Cluster Headache: Report of Two Cases

Chronic cluster headache (CH) is a rare, highly disabling primary headache condition. As NMDA receptors are possibly overactive in CH, NMDA receptor antagonists, such as ketamine, could be of interest in patients with intractable CH.

Ketamine Infusion Combined With Magnesium as a Therapy for Intractable Chronic Cluster Headache: Report of Two Cases

September 1, 2017 by CHSG Admin

Authors: Xavier Moisset MD, PhD, Pierre Clavelou MD, PhD, Michel Lauxerois MD, Radhouane Dallel DDS, PhD, Pascale Picard MD
Source: Headache, Vol. 57, Issue 8, September 2017: 1261–1264. 

Abstract

Background

Chronic cluster headache (CH) is a rare, highly disabling primary headache condition. As NMDA receptors are possibly overactive in CH, NMDA receptor antagonists, such as ketamine, could be of interest in patients with intractable CH.

Case reports

Two Caucasian males, 28 and 45 years-old, with chronic intractable CH, received a single ketamine infusion (0.5 mg/kg over 2 h) combined with magnesium sulfate (3000 mg over 30 min) in an outpatient setting. This treatment led to a complete relief from symptoms (attack frequency and pain intensity) for one patient and partial relief (50%) for the other patient, for 6 weeks in both cases.

Conclusion

The NMDA receptor is a potential target for the treatment of chronic CH. Randomized, placebo-controlled studies are warranted to establish both safety and efficacy of such treatment.

Ketamine Infusions for Treatment Refractory Headache

December 27, 2016

Management of chronic migraine (CM) or new daily persistent headache (NDPH) in those who require aggressive outpatient and inpatient treatment is challenging. Ketamine has been suggested as a new treatment for this intractable population.

Ketamine Infusions for Treatment Refractory Headache

December 27, 2016 by CHSG Admin

Authors: Jared L. Pomeroy MD, MPH, Michael J. Marmura MD, Stephanie J. Nahas MD, MSEd, Eugene R. Viscusi MD
Source: Headache, Dec. 27, 2016

Abstract

Background

Management of chronic migraine (CM) or new daily persistent headache (NDPH) in those who require aggressive outpatient and inpatient treatment is challenging. Ketamine has been suggested as a new treatment for this intractablepopulation.

Methods

This is a retrospective review of 77 patients who underwent administration of intravenous, subanesthetic ketamine for CM or NDPH. All patients had previously failed aggressive outpatient and inpatient treatments. Records were reviewed for patients treated between January 2006 and December 2014.

Results

The mean headache pain rating using a 0-10 pain scale was an average of 7.1 at admission and 3.8 on discharge (P < .0001). The majority (55/77, 71.4%) of patients were classified as acute responders defined as at least 2-point improvement in headache pain at discharge. Some (15/77, 27.3%) acute responders maintained this benefit at their follow-up office visit but sustained response did not achieve statistical significance. The mean length of infusion was 4.8 days. Most patients tolerated ketamine well. A number of adverse events were observed, but very few were serious.

Conclusions

Subanesthetic ketamine infusions may be beneficial in individuals with CM or NDPH who have failed other aggressive treatments. Controlled trials may confirm this, and further studies may be useful in elucidating more robust benefit in a less refractory patient population.

Ketamine i. v. for the treatment of cluster headaches: An observational study

April 11, 2016

Cluster headaches have an incidence of 1–3 per 10,000 with a 2.5:1 male-to-female gender ratio. Although not life threatening, the impact of the attacks on the individual patient can result in tremendous pain and disability. The pathophysiology of the disease is unclear, but it is known that the hypothalamus, the brainstem, and genetic factors, such as the G1246A polymorphism, play a role. A distinction is made between episodic and chronic cluster headaches. In a controlled setting, we treated 29 patients with cluster headaches (13 with chronic cluster and 16 with the episodic form), who had been refractory to conventional treatments, with a low dose of ketamine (an NMDA receptor antagonist) i.v. over 40 min to one hour every 2 weeks or sooner for up to four times. It was observed that the attacks were completely aborted in 100 % of patients with episodic headaches and in 54 % of patients with chronic cluster headaches for a period of 3–18 months. We postulated neuroplastic brain repair and remodulation as possible mechanisms.

Safety and Efficacy of Prolonged Outpatient Ketamine Infusions for Neuropathic Pain

July 1, 2006

Ketamine has demonstrated usefulness as an analgesic to treat nonresponsive neuropathic pain; however, it is not widely administered to outpatients due to fear of such side effects as hallucinations and other cognitive disturbances. This retrospective chart review is the first research to study the safety and efficacy of prolonged low-dose, continuous intravenous (IV) or subcutaneous ketamine infusions in noncancer outpatients.

Ketamine has demonstrated usefulness as an analgesic to treat nonresponsive neuropathic pain; however, it is not widely administered to outpatients due to fear of such side effects as hallucinations and other cognitive disturbances. This retrospective chart review is the first research to study the safety and efficacy of prolonged low-dose, continuous intravenous (IV) or subcutaneous ketamine infusions in noncancer outpatients. Thirteen outpatients with neuropathic pain were administered low-dose IV or subcutaneous ketamine infusions for up to 8 weeks under close supervision by home health care personnel. Using the 10-point verbal analog score (VAS), 11 of 13 patients (85%) reported a decrease in pain from the start of infusion treatment to the end. Side effects were minimal and not severe enough to deter treatment. Prolonged analgesic doses of ketamine infusions were safe for the small sample studied. The results demonstrate that ketamine may provide a reasonable alternative treatment for nonresponsive neuropathic pain in ambulatory outpatients.

Intranasal Ketamine for the Relief of Cluster Headache

Ketamine’s Mechanism of Action

Ketamine (2-chlorophenyl)-2-(methylamino)-cyclohexanone hydrochloride), a human and veterinary anesthetic agent, has an extremely varied set of pharmacologic actions depending on the dosage used.1 A selective uncompetitive N-Methyl-D-aspartic acid (NMDA) glutamate receptor antagonist, the drug has been in legitimate clinical use since 1963.

When administered as an appropriate pharmacologic agent, ketamine has been shown to serve as a safe anesthetic agent. At sub-anesthetic doses, ketamine acts as an uncompetitive antagonist at ionotropic NMDA-type glutamate receptors, binding to a site on the receptor while it is open. Ionotropic glutamate receptors (iGluRs) mediate the majority of excitatory neurotransmission throughout the mammalian brain. Based on their pharmacology, there are three main classes of glutamate-activated channels:

  • α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs)
  • kainate receptors
  • N-methyl-d-aspartate receptors (NMDAR).

Among ion-gated receptor subtypes (iGluRs), NMDAR are exceptional in their high unitary conductance, high Ca2+ permeability, and remarkably slow gating kinetics.

Ketamine has relatively specific effects on other glutamate subtypes. Several families of these receptors also include AMPA-type and kainate receptors, and the metabotropic family of receptors, of which many exist. NMDARs, in particular, are glutamate-gated ion channels primarily for calcium ions and are crucial for neuronal communication. NMDARs form tetrameric complexes that consist of several subunits. The subunit composition of NMDARs is subject to many changes, resulting in large numbers of receptor subtypes. Each subtype has distinct pharmacological and signaling properties.1 Interest and research is growing and abounds in defining specific functions of subtypes of the glutamate receptor system in both normal and pathological conditions in the central nervous system.

Clinical use of ketamine has led to reports of psychedelic side effects, such as hallucinations, memory defects, panic attacks, as well as nausea/vomiting, somnolence, cardiovascular stimulation and, in a minority of patients, hepatoxicity.In the author’s clinical experience, patients may feel a temporary sense of calm or fogginess after ketamine infusion.

Use in Migraine, Cluster Headache, and Neuropathic Pain Disorders

In more recent years, a very small number of clinicians, including the author, have used ketamine intravenously (IV), and in some cases, via intramuscular injection, to treat migraine, cluster headache, and various other chronic pain disorders, including mixed headache and neuropathic pain clinical syndromes.3-21 In the author’s clinic specifically, ketamine has been used via IV administration for more than 20 years to treat nearly 1,000 patients with various headache and pain disorders. These include: migraine and cluster headache flare-ups; headaches associated with orofacial pain disorders, such as trigeminal neuralgia (TN); atypical face pain; temporomandibular joint disorder (TMD); and neck pain.

Clinical use of ketamine has led to reports of psychedelic side effects, such as hallucinations, memory defects, panic attacks, as well as nausea/vomiting, somnolence, cardiovascular stimulation and, in a minority of patients, hepatoxicity. In the author’s clinical experience, patients may feel a temporary sense of calm or fogginess after a ketamine infusion.

The focus of this paper is to provide a summary of specific retrospective cases in which intranasal ketamine was used for the rescue of cluster headache in patients who had previously experienced a positive outcome from IV ketamine in the author’s outpatient clinic. Cluster headache was successfully eradicated in several patients [n = 17], prompting a mini anecdotal-based trial of rescue intranasal ketamine for continuing or new cluster headache flare-ups to be used by these patients at their home. Table I outlines the outpatient clinic’s treatment of various migraine and headache types. As shown, cluster headache was successfully eradicated in several patients [n = 17], prompting a mini anecdotal-based trial of rescue intranasal ketamine for continuing or new cluster headache flare-ups to be used by these patients at their home.

Retrospective Case Summaries

The dose of intranasal ketamine prescribed to patients ranged between 7.5 mg and 15 mg per 0.1 cc nasal spray (75 and 150 mg of ketamine per cc compounded in normal saline by a pharmacy). Patients were instructed to use one spray in the nostril of the affected side and wait 10 to 15 minutes to feel any effects, including side effects. They were to use the spray when they felt a cluster attack coming on. Patients were asked to use another spray of ketamine in the same nostril at 10- to 15-minute intervals until a sufficient degree of relief (at least 60 to 75%) was obtained for that cluster attack. If the attack still came on after about one hour, the instructions were for the patient to repeat the procedure. All patients were instructed not to drive after taking the medication and signed off on this agreement. Patients were also instructed to keep the nasal spray refrigerated when not in use; no efficacy loss was reported. Of the 17 patients who trialed the nasal spray, 11 elected not to have the intranasal ketamine compounded, or were lost to follow-up, leaving six case scenarios which are summarized herein.

Case 1

A 38-year-old male, with a 16-year history of cluster headache, including a family history of the same, had tried a number of acute and prophylactic agents with, at best, a shortening of the cluster episode. His attacks tended to flare in the spring and lasted up to three months at a time with 4 to 6 episodes per day. The attacks prevented him from working and he came to the outpatient clinic for IV treatment with ketamine, which resulted in a complete cessation after three days, with resolution of allodynia on the right side as well. He elected to try intranasal ketamine (15 mg) at the first onset of his next cluster episode. He reported pain relief and a feeling of calm after 2 to 3 sprays, with no adverse effects. Sometimes, he had to repeat the dosing regimen the next day.

Case 2

A 25-year-old woman was thrown from a horse during a competition and fractured her cervical spine, requiring surgery. The injury included syringomyelia between C3 and C7-T1 and left her with left-sided dystonia of the upper and lower body, abdomen, and chest wall, together with left-sided migraines, which she reported as new. Several times a year, she would awaken every night with left-sided cluster headache episodes, with facial allodynia, tearing, eyelid drooping, and increased dystonia and neck spasm; these occurred primarily in the winter season, with several up to six episodes in per night for a period of three to six weeks.

IV ketamine relieved most of her dystonic, cluster headache, and migraine symptoms, when complemented by IV and oral baclofen and tizanidine, as well as rescue opioids. Nasal spray ketamine was compounded, as well as buccal troches; both allowed her to continue working full-time in her hair salon. She reported no side effects while using the nasal spray ketamine. Liver function tests conducted every three to six months were unremarkable.

Cluster headache is characterized by excruciating, debilitating pain lasting from 15 to 180 minutes, or occasionally longer. The pain is typically located around or through one eye or on the temple. (Source: 123RF)

Case 3

A 55-year-old woman with episodic cluster headache and migraine (3 to 4 attacks per week) also experienced chronic neck pain and had diagnosed TN on the right side. Her cluster headache attacks started at age 27, with tearing, allodynia, and facial numbness. On occasion, her migraine would evolve into a cluster episode that came on during sleep and was seasonal as well, lasting about 2 months on average. She was not a smoker and had no family history of cluster headache but did have a family history of migraine.

She was treated successfully for migraine, right TN, and neck pain with botulinum toxin-A injections (Botox) every 3 to 5 months, supplemented by prophylactic neuropathically active medications, but no opioids. The Botox did not affect her cluster headache, except when they evolved from a migraine, and only to a slight extent (15 to 20%). Multiple acute and prophylactic therapies were attempted to resolve the cluster headache episodes to no significant avail.

IV ketamine was tried on one occasion over a period of 4 days during a cluster headache episode. As a result, the attacks were reduced from 5 per day to 1 per day, and only 1 cluster attack the following week, which was resolved with additional oral oxcarbazepine (600 mg).

The patient agreed to trial nasal spray ketamine which was compounded at 10 mg per 0.1 cc spray with the suggestion that she spray the right nostril every 10 to 15 minutes upon attack to give the medicine time to absorb from the nasal mucosa and to repeat the process until at least 75% relief was obtained. She reported being happy with this approach as it gave her control of her hardest-to-treat symptom. She also reported that her cluster episodes became less frequent over about 1 year and that her migraine and TN also improved; her Botox injection intervals grew longer over time.

Case 4

A 70-old-male, with a 40-plus year history of right-sided cluster attacks with eyelid drooping, tearing, allodynia, neck pain, and other symptoms was treated for these symptoms for many years. Opioids provided him with partial relief, at best. He had a chronic cluster headache that typically awoke him from a sound sleep at 1 or 2 am. These episodes were especially bad in the winter and during weather changes. He had a history of facial and other traumas before the headaches started, including a car accident, but no family history of cluster headache. He also had occasional migraine, about three per month, as well as chronic neck and back pain. He was treated with IV medications, including ketamine, up to 200 mg over 5 hours, with relief of his symptoms in the clinic.

He agreed to trial a compounded nasal spray of ketamine [12.5 mg per 0.1 cc] to use at each bedtime. Two sprays were indicated before each bedtime and at the first onset of any cluster headache at night. Sprays were repeated every 10 minutes until 50 to 65% relief was achieved. He took tizanidine before bedtime for neck spasm and sleep. The patient would, on occasion, repeat one or two ketamine sprays in the morning or during the day if he felt the next cluster attack coming on. As he was on frequent IV and nasal spray ketamine, his liver functions tests were routinely monitored over the course of several years; there was no observed impact.

Case 5

A 34-year-old male who worked in construction began having episodic cluster headache episodes at age 22. He had a family history of migraine and cluster headache. His attacks were season-specific, occurring mostly in the early summer of each or every other year. He described the attacks as very disabling and often awoke from a sound sleep for several weeks at a time as a result of them. He had tried several oral medications, including opioids, for suppression of symptoms without any real benefit and many side effects. When he first presented to the clinic, he trialed IV lidocaine, IV valproate sodium, and IV magnesium sulfate with only partial success in shutting down the episode.

IV ketamine was also offered at the beginning of one of his episodes, and it proved to work more effectively than other treatments. Specifically, the patient’s cluster episode duration was reduced by more than two-thirds (6 to 7 weeks to 7 to 10 days). Based on this result, he was prescribed compounded nasal spray ketamine (7.5 mg per 0.1cc spray) and instructed to use the spray once at bedtime, with additional sprays in one nostril (the affected side of the cluster headache) every 10 minutes until relief was obtained to at least 75%. The patient was also instructed to use the same approach during the day if the cluster headache returned. He used nasal spray ketamine for several years and his overall pattern became easier to treat successfully. His episodes grew further apart and he has reported only one short cluster headache episode in the past four years.

She got extinction of the cluster episode or at least 75% reductions in the cluster headache severity with up to 4-5 nasal sprays of ketamine at the dose described above, and has also noticed a shortening and diminution of the cluster headache episodes as time has gone by.

Case 6

A 51-year-old male, with a family history of cluster headache began having episodic attacks at age 18 with strong occurrences in the spring. He was a smoker. He had tried a calcium channel blocker, lithium, and other medications to little or no avail over the years. He found that triptans taken early in the course of a cluster attack, at several doses, would sometimes abort or lighten the burden of that particular cluster series.

A 3-day course of IV ketamine at the onset of one of his episodes nearly eradicated the episode, and since he lived a great distance (6 hours each way) from the clinic, he wanted to try the nasal spray form of ketamine for at-home application. He reported that a daily dose of 1500 mg of Depakote-ER often softened the arrival of his next cluster headache episode, as did prescribed triptans. However, he did not experience an end to the attack until IV ketamine had been administered.

15 mg per 0.1cc of nasal spray ketamine were compounded for this patient. He reported some nasal burning with the nasal ketamine formulation, so was advised by his pharmacist to use one drop of 2% lidocaine and orange oil as part of the prescription. This addition alleviated the side effect. The patient has successfully used this approach for many years to date. He requires 5 to 6 nasal sprays of ketamine per day, and his episodic cluster headache pattern has markedly softened and shortened in the past few years. He has reduced his dosage of Depakote-ER to 1 or 2 per day as well and attempted to stop smoking several times.

Discussion and Recommendation

The specificity of the ketamine speaks to a unique mechanism of action primarily through the blockade of the NMDA-glutamate and other close-related receptors. This treatment approach may provide insight into the distinctive involvement of this receptor family in the generation and maintenance of this and perhaps other, more rare trigeminal autonomic cephalalgias, or TACs.21

Based on this anecdotal evidence, observed retrospectively in the author’s outpatient clinic over a period of 20 years, intranasal ketamine seems to offer a legitimate, safe pharmacologic treatment for cluster headache rescue. The medication adds a new dimension to managing out-of-control cluster headache and mixed headache/pain disorders in an outpatient setting with no monitoring. Double-blind, placebo-controlled studies are needed to confirm these primarily open-label observations. It should be noted that a small number of patients (5) were given sham nasal treatment and their cluster headache did not respond.

The author found sub-anesthetic doses of intranasal ketamine to be very useful in the control of episodic and chronic cluster headache attacks, as well as in managing certain trigeminal neuralgia symptoms. On a 0 to 10 visual analog scale, pain scores were below 60 to 65% from initial baseline pain score after the use of the intranasal ketamine spray. Efficacy, as well as safety, and tolerability, of low dose IV ketamine were seen consistently in the outpatient clinic, without significant adverse effects. In the author’s opinion, therefore, ketamine may be considered when treating this clinically disabling condition. When used under controlled conditions, ketamine in a nasal spray form may offer a safe and more effective option to patients than emergency room visits and may also serve as a substitute for more standard IV-based rescue cluster headache medications.

About Cluster Headache:Cluster headache is characterized by excruciating, debilitating pain lasting from 15 to 180 minutes, or occasionally longer. The pain is typically located around or through one eye or on the temple. A series of cluster headaches can take place over several weeks to months, and may occur once or twice per year. Several of the following related symptoms may occur: lacrimation, nasal congestion, rhinorrhea, conjunctival injection, ptosis, miosis of the pupil, or forehead and facial sweating. Nausea, bradycardia and general perspiration may present as well. Attacks usually recur on the same side of the head. Cluster headaches afflict males more than females by a 2.5 to 1 ratio and have an overall prevalence of 0.4%. Onset of clusters is usually between ages 20 and 45. There is often no family history of cluster headache.

  1. Robert K, Simon C. Pharmacology and Physiology in Anesthetic Practice. 4th ed. Baltimore, MD: Lippincott, Williams & Wilkins; 2005
  2. Niesters M, Martini C, Dahan A. Ketamine for chronic pain: risks and benefits. Br J Clin Phamacol. 2014;77(2):357–367.
  3. Virginia Scott-Krusz, Jeanne Belanger, RN, Jane Cagle, LVN, Krusz, JC, Effectiveness of IV therapy in the headache clinic for refractory migraine, poster at 9th EFNS meeting Athens, Greece. 2005.
  4. Krusz, JC. Intravenous treatment of chronic daily headaches in the outpatient headache clinic. Curr Pain Headache Rep. 2006;10(1):47-53.
  5. Krusz JC, Cagle J, Belanger J, Scott-Krusz, V. Effectiveness of IV therapy for pain in the clinic, Poster P183 presented at 2nd International Congress on Neuropathic Pain Berlin, Germany. 2007
  6. Krusz JC, Cagle J, Hall S. Efficacy of IV ketamine to treat pain disorders in the pain clinic, (poster 216). J Pain. 27th Annual Scientific. American Pain Society, 2008.
  7. Krusz JC, Cagle J, Hall S. Efficacy of IV ketamine in treating refractory migraines in the clinic (poster 218). J Pain. 27th Annual Scientific. American Pain Society, 2008.
  8. Krusz JC, Cagle J, Hall S. Intramuscular (IM) ketamine for treating headache and pain flare-ups in the clinic (poster 219). J Pain. 27th Annual Scientific. American Pain Society, 2008.
  9. Krusz JC. IV ketamine in the clinic to treat Cluster Headache (poster abstract). American Academy of Neurology. Neurol. 2009;72(11):A89-90.
  10. Krusz JC, Cagle J, Scott-Krusz VB. Ketamine for treating multiple types of headaches (poster). 14th Congress International Headache Society. Cephalalgia. 2009;29(Suppl 1)163.
  11. Krusz JC. Difficult Migraine Patient. Pract Pain Manage. 2011;11(4):16.
  12. Krusz JC, Cagle J. IV Ketamine: Rapid Treatment for All TAC Subtypes in the Clinic, Abstract Poster #72, 15th Congress of the International Headache Society, Berlin, Germany, 2011.
  13. Krusz JC, Cagle J. IM ketamine for intractable headaches and migraines (poster abstract). American Headache Society Annual Meeting, Los Angeles, CA, 2012.
  14. Krusz JC. Traumatic Brain Injury: Treatment of Post-traumatic Headaches. Pract Pain Manage. 2013;13(5):57-68.
  15. Krusz JC, Cagle J, Belanger J, Scott-Krusz V. Effectiveness of IV therapy for pain in the clinic, Poster P183. European J Pain:11, Suppl 1, pS80, presented at 2nd Int’l Congress on Neuropathic Pain, Berlin, Germany. 2007.
  16. Krusz JC, Cagle J, Hall S. Efficacy of IV ketamine to treat pain disorders in the pain clinic, (poster 216). J Pain, 9: Suppl 2, P30, 27th Annual Scientific. American Pain Society. 2008.
  17. Krusz JC. Ketamine IV in an outpatient setting: effective treatment for neuropathic pain syndromes (poster #378). 32nd Annual Scientific Meeting, American Pain Society, New Orleans, 2013.
  18. Krusz JC. Ketamine IV – for CRPS, TN/TMD and other neuropathic pain in the outpatient clinic (poster #524). 4th International Congress on Neuropathic Pain, Toronto, Ontario, 2013.
  19. Krusz JC. The IV ketamine experience: treatment of migraines, headaches and TAC. JAMA Neurol. 2018
  20. Matharu MS, Goadsby PJ. Trigeminal Autonomic Cephalalgias: Diagnosis and Management. In: Silberstein SD, Lipton RB, Dodick DW, eds. Wolff’s Headache and Other Head Pain. 8th ed. New York, NY: Oxford Univ Press; 2008:379-430.
  21. Johnson JW, Glasgow NG, Povysheva NV. Recent insights into the mode of action of memantine and ketamine. Curr Opin Pharmacol. 2015 ;20:54-63. 

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Fast-Acting Depression Drug, Newly Approved, Could Help Millions

A nasal spray version of the drug ketamine has shown promise as an antidepressant, even if its properties still aren’t well understood.

Of the 16 million American adults who live with depression, as many as one-quarter gain little or no benefit from available treatments, whether drugs or talk therapy. They represent perhaps the greatest unmet need in psychiatry. On Tuesday, the Food and Drug Administration approved a prescription treatment intended to help them, a fast-acting drug derived from an old and widely used anesthetic, ketamine.

The move heralds a shift from the Prozac era of antidepressant drugs. The newly approved treatment, called esketamine, is a nasal spray developed by Janssen Pharmaceuticals Inc., a branch of Johnson & Johnson, that will be marketed under the name Spravato. It contains an active portion of the ketamine molecule, whose antidepressant properties are not well understood yet.

“Thank goodness we now have something with a different mechanism of action than previous antidepressants,” said Dr. Erick Turner, a former F.D.A. reviewer and an associate professor of psychiatry at Oregon Health & Science University. “But I’m skeptical of the hype, because in this world it’s like Lucy holding the football for Charlie Brown: Each time we get our hopes up, the football gets pulled away.”

The generic anesthetic is already increasingly available for depression, at hundreds of clinics around the country that provide a course of intravenous treatments, and studies suggest it can help treatment-resistant people. It often causes out-of-body and hallucinogenic sensations when administered; in the 1980s and 1990s it was popular as a club drug, Special K.

The cost for these treatments typically is out of pocket, as the generic anesthetic is not approved by the F.D.A. for depression. In contrast, esketamine likely would be covered under many insurance plans, and its side effects, though similar to those of generic ketamine, are thought to be less dramatic.

The recommended course of the newly approved drug is twice a week, for four weeks, with boosters as needed, along with one of the commonly used oral antidepressants. F.D.A. approval requires that doses be taken in a doctor’s office or clinic, with patients monitored for at least two hours, and their experience entered in a registry; patients should not drive on the day of treatment.

Esketamine, like ketamine, has the potential for abuse, and both drugs can induce psychotic episodes in people who are at high risk for them. The safety monitoring will require doctors to find space for treated patients, which could present a logistical challenge, some psychiatrists said.

The cost for a one-month course of treatment will be between $4,720 and $6,785, said Janssen, and experts said it will give the company a foothold in the $12 billion global antidepressant market, where most drugs now are generic.[L

The approval of esketamine marks a new approach to treating serious mood problems, experts said. Prozac and similar drugs enhance the activity of brain messengers such as serotonin; they are mildly effective, but they take weeks or months for their effects to be felt, and for many patients they provide little or no relief from depression. In contrast, the ketamine-based compounds — several others are being developed — work within hours or days, and are effective in some people who are considered “treatment resistant,” meaning they have not benefited from other antidepressants.

“These are exciting times, for sure,” said Dr. Todd Gould, an associate professor of psychiatry in the University of Maryland School of Medicine. “We have drugs that work rapidly to treat a very severe illness.” Dr. Gould was not involved in the Janssen study but has identified a metabolite, or ketamine breakdown product, that could be developed into another drug.

Experts with long experience in treating depression were encouraged by the news, but also chary. The effectiveness of the previous class of antidepressants such as Prozac and Paxil was vastly exaggerated when they came on the market. And the results of esketamine trials, which were paid for and carried out by Janssen, were mixed.

In each trial submitted, all patients were started on a new antidepressant drug, and given a course of esketamine treatment or a placebo. In one monthlong study, those on esketamine performed better statistically than those on placebo, reducing scores on a standard, 60-point depression scale by 21 points, compared to 17 points for placebo. But in two others trials, the drug did not statistically outperform placebo treatment. Historically, the F.D.A. has required that a drug succeed in two short-term trials before it is approved; the agency loosened its criteria for esketamine, opting instead to study relapse in people who did well on the drug.

In that trial, Janssen reported that only about one-quarter of subjects relapsed, compared to 45 percent of subjects who received the placebo spray. All the subjects had been given a diagnosis of treatment-resistant depression, or T.R.D., having previously failed multiple courses of drug treatment.

“We’ve had nothing new in 30 years,” said Steven Hollon, a professor of psychiatry and behavior sciences at Vanderbilt University. “So if this drug is an effective way to get a more rapid response in people who are treatment resistant, and we can use it safely, then it could be a godsend.”

One question that will need to be answered is how well esketamine performs in comparison to intravenous ketamine.

Theresa, 57, an adjunct professor of English in New York, who asked that her last name be omitted to protect her privacy, has lived much of her life with deep depression. She tried a course of I.V. generic ketamine last summer, at a local clinic, which typically entails a half-dozen infusions, given over a couple of weeks, for about $500 apiece, with follow-up “booster” treatments as needed.

“I remember floating, I was really high,” she said. “I was tripping on sounds, textures and shapes, that was very much a part of it.”

The first infusion provided no relief, she said. But after the third or fourth, she noticed a satisfying “shift” in her underlying mood. “It’s a hard thing to describe. I was still anxious, but I felt somehow more solid, like something gelled within me, and my husband has noticed it, too.”

Dr. Glen Brooks, the founder and medical director of NY Ketamine Infusions, a clinic in downtown Manhattan, said he has treated some 2,300 people, of all ages, with intravenous ketamine, the generic anesthetic. His clients had received a variety of diagnoses, including post-traumatic stress, anxiety, and obsessive-compulsive disorder, as well as depression.

“What they all have in common is that other medications have failed,” Dr. Brooks, an anesthesiologist, said. “They’re hopeless, and they think, ‘Nothing else has worked, why should this?’” He said that, in his experience, the infusions quickly reduced symptoms for teenagers and young adults, but seemed to be less effective for people over 50.

The data that Janssen presented to the F.D.A. likewise suggested that esketamine was less effective in people aged 65 and older, barely better than placebo treatment.

Ketamine was developed more than five decades ago as a safer alternative to the anesthetic phencyclidine, or PCP, and is used worldwide, in operating rooms, on the battlefield and in pediatric clinics. The World Health Organization has listed ketamine as one of its essential medicines since 1985.

By the 1990s, interest turned to the drug’s potential to combat depression, when a government scientist named Phil Skolnick argued that targeting glutamate pathways — the primary “excitatory,” or neuroactivating, brain processes — could produce antidepressant effects. In 2000, a team of researchers at Yale University and the Connecticut Mental Health Center, led by Dr. Robert M. Berman, reported that doses of ketamine provided quick relief to seven people with depression.

The field took off in 2006, when a team at the National Institute of Mental Health led by Dr. Carlos Zarate Jr. reported that 18 treatment-resistant people who received the drug intravenously reported that their despair lifted within hours.

“What seems remarkable is that the drug also seems to help domains other than depression, like anxiety, suicidal thinking, and anhedonia” — the inability to feel pleasure — said Dr. Zarate, chief of the N.I.M.H.’s experimental therapeutics and pathophysiology branch. “It seems to have more broad effects, on many areas of mood.”

The apparent ability of ketamine to blunt suicidal thinking is particularly compelling, and Janssen is pursuing this indication for esketamine. In jails and psychiatry wards, suicide is an acute risk for people in crisis, and a fast-acting drug could save many lives, doctors said.

For now, no one knows whether esketamine, or any of the other ketamine-based compounds being studied, are any more effective than the generic anesthetic itself — or, for that matter, whether the out-of-body and hallucinatory “side effects” are in fact integral to its antidepressant properties.

“For that, we will need head-to-head studies,” Dr. Zarate said. “And we don’t have those yet.”





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FDA approves ketamine-like nasal spray for depression

The US Food and Drug Administration approved Janssen Pharmaceuticals Inc.’s esketamine on Tuesday for treatment-resistant depression; the drug is the chemical cousin of ketamine, the powerful anesthetic that has been used illegally as the club drug Special K.It will be sold as Spravato. More specifically, it’s for patients who have tried at least two other medications without success, and it should be taken with an oral antidepressant.”There has been a longstanding need for additional effective treatments for treatment-resistant depression, a serious and life-threatening condition,” Dr. Tiffany Farchione, acting director of the Division of Psychiatry Products at the FDA’s Center for Drug Evaluation and Research, said in a news release announcing the approval.Spravato is a nasal spray administered by an approved health care provider in a doctor’s office or a medical clinic. It may also be self-administered but only under the supervision of a care provider and cannot be taken home.  “Because of [safety] concerns, the drug will only be available through a restricted distribution system and it must be administered in a certified medical office where the health care provider can monitor the patient,” Farchione said.Depending on the severity of the patient’s depression, it is given either once a week or once every other week.

Esketamine is an option for patients with treatment-resistant depression.

 Esketamine is an option for patients with treatment-resistant depression.The drug is rapidly acting, so it starts working faster than other antidepressants, according to Janssen. It works by restoring brain cells in patients with treatment-resistant depression.Currently available treatments for major depression are ineffective in 30% to 40% of patients. According to the FDA, there is one other approved medication for treatment-resistant depression, Symbyax, which was approved in 2009.Side effects of Spravato include dizziness, nausea, vertigo, anxiety, lethargy, increased blood pressure, vomiting, feeling drunk, decreased sensitivity, sedation and dissociation, a feeling of being temporarily “disconnected” from your body and your mind.The drug label will contain a “boxed warning” to alert patients to the risk of “sedation, and difficulty with attention, judgment and thinking (dissociation), abuse and misuse, and suicidal thoughts and behaviors after administration of the drug,” the agency said in its announcement.Because of these risks, patients must be monitored for at least two hours after being given the drug.Get CNN Health’s weekly newsletterIn clinical trials, six patients who were taking the drug died, three from suicide, but FDA background materials reviewed by the advisory committee that recommended approval last monthsaid, “It is difficult to consider these deaths as drug-related.”Because of the drug’s close relationship to ketamine, experts have raised concerns about its potential for misuse and abuse, but clinical trials found those risks to be unfounded.Concerns have also been raised about a lack of long-term data on possible health effects, most notably cognitive ones.The drug was designated as a breakthrough therapy in 2013, a status intended to “expedite the development and review of drugs for serious or life-threatening conditions,” the FDA said at the time.Greg Panico, a spokesman for Janssen, a division of Johnson & Johnson, did not say when Spravato will be available. He wrote in an email, “We are working quickly to educate and certify treatment centers on the unique administration requirements of SPRAVATO™ to ensure patients can access this important medicine.”As for the cost, it will be “generally comparable with other specialty mental health drugs,” Panico said: about $590 to $885 per treatment session, based on the dosage and not accounting for mandatory discounts or negotiated rebates.

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Ketamine Seems to Ease Depression. We’ll Soon See What Else It Does.

Clinical trials are not enough to prove any drug is safe and effective – especially one that could be as widely used as Johnson & Johnson’s depression drug esketamine, a slightly altered form of the street drug ketamine. The FDA approval process is a balancing act, weighing safety and efficacy testing against the need to get potentially life-saving drugs out as soon as possible.

An advisory panel to the FDA decided this month that the benefits outweigh the risks, and approval is expected soon. But scientists who study depression say there’s a lot more to learn about esketamine’s long-term effects.

While best known as a recreational drug, ketamine has been used since the 1970s as an anesthetic, in doses much higher than what’s likely to be given to depression patients. The trials so far seem to show that the drug is not highly addictive, according to a story in the medical website STAT. But time will tell.

The most promising clinical trials followed people whose depression had been resistant to conventional therapy. Fifty percent of patients improved when given conventional therapy plus a placebo, as compared to 70 percent who got conventional therapy and esketamine.

Taking the drug will be a lot more complicated than taking Prozac. It’s been formulated so that it can be delivered as a nasal spray, but people have to get the drug at a doctor’s office, and they won’t be allowed to drive for at least 24 hours, said Gerard Sanacora, a Yale University psychiatrist who has been involved in the clinical trials.

He said he believes there’s potential for benefit, because the drug works for some people who get no relief from conventional treatments and because works faster, which might even prevent suicide. But there’s a lot more to learn about the drug’s potential long-term consequences. So far it looks like people will get two treatments a week to start, then one for maintenance. But scientists don’t know whether it can be tapered down further, or discontinued, and whether there’s a risk for relapse, he said.

Sanacora said that ketamine is based on a very different model of how depression works. Standard therapy is based on the principle that depression is a chemical imbalance involving the transmitting chemical serotonin. But an alternative view started to take shape in the 1990s that depression was more of a problem with the connections between neurons, triggered by chronic stress and mediated by something called the glutaminergic system.

Because ketamine interacts with this system, researchers started testing it as a depression drug. Although it seems effective, there’s still no agreement on how depression actually works – and there is some concern that it might work very differently in different patients.

Ketamine can affect cardiovascular health, and in the short term can cause patients to lose their sense of their bodies’ position in space – the sense of proprioception. They sometimes feel their arms are floating.

That hasn’t stopped people from flocking to clinics to get treated with IV ketamine infusions for depression and other problems. This is legal because the drug is approved for anesthesia, and prescribers can use it off-label for other purposes. An investigation by the medical website STAT raised concerns that clinic staff didn’t have the necessary expertise, and there was considerable marketing hype in many cases. The infusions cost between $350 and $1,000 each, and can go on for five or six treatments.

Another red flag popped up last week when the Boston Globe ran a storyabout three women who claim to have been sexually abused by psychiatrist Keith Ablow – a frequent commentator for Fox News. The Globe reported that Ablow was treating the women with ketamine, and one expert cited in the lawsuits said a patient had become “very dependent on this medication and dependent on Dr. Ablow to supply it.”

Ablow’s Twitter feed is full of positive stories about ketamine in places such as Reader’s Digest, followed by a phone number to call for a “free ketamine screening.” The allegations illustration that it’s not just patients that will need to be tracked for abuse, but the doctors as well.

On the positive side, FDA approval would give patients who want the drug a standardized treatment that would be covered by many insurance plans. Approval also creates an opportunity to collect data on longer-term use. (An earlier column exploring the promise of big data in medicine points out that clinical trials are often not long-running enough or big enough to catch even deadly side effects.)

Yale’s Sanacora thinks of the next series of trials as Phase 4. Sanacora also brought up what he poignantly called the “Flowers for Algernon” effect, referring to the short story in which the main character, Charlie Gordon, is treated for an intellectual disability. The treatment works, but eventually wears off, leaving Charlie back where he started. The disappointment makes for a tragic tale. An arc like this would be the last thing depression patients need – though if no other treatment is helping, it might be a risk worth taking.

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Ketamine-like depression treatment on track for FDA approval

 

Ketamine offers lifeline for people with severe depression, suicidal thoughtsThe drug is a close relative of ketamine, a powerful medication used in hospitals primarily as an anesthetic; recent scientific studies have also shown its potential with treatment-resistant depression and suicidal ideation. Ketamine is also used recreationally — and illegally — as a club drug known as Special K. It generates an intense high and dissociative effects.Esketamine, which is not FDA-approved for any conditions, targets a different brain pathway than approved antidepressants, many of which have been around for decades. It is expected to be used in combination with antidepressants, but the latter can take a month or two to take effect. Esketamine, on the other hand, might have an effect within hours or days, according to an FDA briefing document.The drug was designated as a breakthrough therapy in 2013, intending to “expedite the development and review of drugs for serious or life-threatening conditions,” the FDA says. First-line treatments don’t work for roughly 30% to 40% of patients with major depressive disorder, according to the briefing document.The FDA does not have to follow the recommendation of advisory committees, though it often does.

ERs 'flooded' with mentally ill patients with no place else to turn

ERs ‘flooded’ with mentally ill patients with no place else to turnHowever, the research behind esketamine has come under some criticism, with two of five key studies failing to meet their primary endpoints. Only one of these studies is a positive short-term trial, whereas most FDA-approved antidepressants are backed by at least two, according to the briefing document. But Janssen has maintained that the overall picture is positive.Adverse events tended to occur in the first two hours patients received the drug, including sedation, blood pressure increases and dissociation. For this reason, patients wouldn’t be able to pick it up at a local pharmacy; it would be given under the supervision of health care professionals who can keep an eye on the person during those first two hours.Because of the drug’s close relationship to ketamine, experts have also raised concerns about its potential for misuse and abuse. The clinical trials have not seen evidence of this risk, according to presentations made during the meeting.Advisory panelists also expressed concern that not enough long-term data was available to characterize the drug’s cognitive effects and other health impacts down the line.Get CNN Health’s weekly newsletter

There were six deaths of patients taking esketamine in trials, including three suicides, but FDA materials concluded “it is difficult to consider these deaths as drug-related.”The only current FDA-approved medication for treatment-resistant depression combines two other drugs already on the market. Other non-pharmaceutical treatments exist, such as electroconvulsive therapy.Janssen spokesman Greg Panico said no information about pricing would be available at this time. An FDA decision is expected in early March, he added.

 

CNN)A ketamine-like drug for treatment-resistant depression was backed by a US Food and Drug Administration advisory committee on Tuesday. If it is then approved by the FDA, the drug — called esketamine — may provide a new option for patients with major depressive disorder who have tried at least two other antidepressants without success.A panel of experts voted to endorse the drug, which is made in nasal spray form by the pharmaceutical company Janssen, a division of Johnson & Johnson. Fourteen members voted that the benefits outweighed the risk, with two opposed and one abstaining.

Ketamine offers lifeline for people with severe depression, suicidal thoughts
703-844-0184 | NOVA Health Recovery | Alexandria, Va 22306

Ketamine offers lifeline for people with severe depression, suicidal thoughtsThe drug is a close relative of ketamine, a powerful medication used in hospitals primarily as an anesthetic; recent scientific studies have also shown its potential with treatment-resistant depression and suicidal ideation. Ketamine is also used recreationally — and illegally — as a club drug known as Special K. It generates an intense high and dissociative effects.Esketamine, which is not FDA-approved for any conditions, targets a different brain pathway than approved antidepressants, many of which have been around for decades. It is expected to be used in combination with antidepressants, but the latter can take a month or two to take effect. Esketamine, on the other hand, might have an effect within hours or days, according to an FDA briefing document.The drug was designated as a breakthrough therapy in 2013, intending to “expedite the development and review of drugs for serious or life-threatening conditions,” the FDA says. First-line treatments don’t work for roughly 30% to 40% of patients with major depressive disorder, according to the briefing document.The FDA does not have to follow the recommendation of advisory committees, though it often does.

ERs 'flooded' with mentally ill patients with no place else to turn

ERs ‘flooded’ with mentally ill patients with no place else to turnHowever, the research behind esketamine has come under some criticism, with two of five key studies failing to meet their primary endpoints. Only one of these studies is a positive short-term trial, whereas most FDA-approved antidepressants are backed by at least two, according to the briefing document. But Janssen has maintained that the overall picture is positive.Adverse events tended to occur in the first two hours patients received the drug, including sedation, blood pressure increases and dissociation. For this reason, patients wouldn’t be able to pick it up at a local pharmacy; it would be given under the supervision of health care professionals who can keep an eye on the person during those first two hours.Because of the drug’s close relationship to ketamine, experts have also raised concerns about its potential for misuse and abuse. The clinical trials have not seen evidence of this risk, according to presentations made during the meeting.Advisory panelists also expressed concern that not enough long-term data was available to characterize the drug’s cognitive effects and other health impacts down the line.Get CNN Health’s weekly newsletter

There were six deaths of patients taking esketamine in trials, including three suicides, but FDA materials concluded “it is difficult to consider these deaths as drug-related.”The only current FDA-approved medication for treatment-resistant depression combines two other drugs already on the market. Other non-pharmaceutical treatments exist, such as electroconvulsive therapy.Janssen spokesman Greg Panico said no information about pricing would be available at this time. An FDA decision is expected in early March, he added.

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Depression Therapy With Party-Drug Roots Faces FDA Panel Review

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Potential for abuse and strategies for containing any risks from an experimental depression treatment from Johnson & Johnson will be in focus at an Food and Drug Administration panel next week.

J&J’s nasal spray, esketamine, a close cousin of the party drug ketamine, will be considered by an FDA advisory panel on Feb. 12. While agency staff seemed satisfied that the likelihood of abuse is low, they raised questions about safety issues connected to a dreamlike sensation the medication can create in some users.

“Ketamine abuse is relatively uncommon in the general population,” agency staff said in a report ahead of next week’s meeting. Just 1.3 percent of people over age 12 abuse the drug, lower than abuse rates for other hallucinogens like ecstasy and LSD.

At the same time, reviewers worried that patients could get into accidents or otherwise be harmed if they leave a doctor’s office while still experiencing disassociation, a known side effect of ketamine — and a sought-after experience for casual users who have dubbed the spacey feeling the “K-hole.”

It takes roughly 90 minutes for disassociation symptoms from esketamine to resolve, according to the report. FDA staff also cited elevated blood pressure as a safety concern.

Esketamine is a key part of J&J’s pharmaceutical pipeline, as the company faces flagging sales this year weighed down by drug pricing scrutiny and looming generic competition. Its shares, which rose 2.3 percent this year through Thursday’s close, were were little changed in early trading on Friday.

In addition to weighing in on the drug’s safety and a proposed risk-evaluation and mitigation strategy, FDA staff will ask advisers to vote on whether esketamine effectively treated the depression of patients who weren’t helped by other therapies. They’ll also discuss whether additional studies are needed before or after the drug is potentially approved.

The staff report noted there were six deaths among patients taking the J&J drug, of which three were suicide in the esketamine depression program, but they didn’t see a clear link to the drug itself.

“Given the small number of cases, the severity of the patients’ underlying illness, and the lack of a consistent pattern among these cases, it is difficult to consider these deaths as drug related,” staff reviewers noted.

A decision on whether to allow the drug on the market is expected by March 4. Esketamine has the FDA’s breakthrough-therapy designation in treatment-resistant depression as well as for depressed people at risk of suicide. Results from a study in suicidal patients are expected this year. Allergan is also testing a fast-acting antidepressant, rapastinel, which is about a year behind esketamine in testing.

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CBD Gummies for Anxiety and Depression :
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CBD become one of the most sought-after medicines on the market today. Not only is it able to treat a wide range of ailments ranging from cancer to arthritis, CBD is known to be effective without causing any obvious side effects. It can be used safely in the long-term without causing addiction and dependence.

NOVA Heath Recovery Ketamine Treatment Center | Call 703–844-0184 for a Ketamine Treatment | Alexandria, Va 22306 | 7 days a week and evening appointments as well! We also evaluate depression, ADHD, PTSD. Intranasal Ketamine available.   The email is EMAIL@novahealthrecovery.com

There are tons of ways to use CBD, and one of the most popular is to use CBD gummies. These products provide patients with a tasty and fun way to medicate themselves. In this article, we’re going to talk about the use of CBD gummies for helping to fight off anxiety and depression.

What is CBD?

CBD, also known as cannabidiol, is one of the main cannabinoids found in the cannabis and hemp plants. CBD is known to treat a number of illnesses, both mental and physical. Some of the things that CBD is most commonly used to treat include:

  • Arthritis and other inflammatory conditions
  • Anxiety, depression, and other mental health problems
  • Cancer
  • Various diseases of the intestinal tract like IBS and Crohn’s disease
  • Various forms of pain, both chronic and acute

These are just a few of the things that CBD can be useful for treating. CBD works by affecting the body’s endocannabinoid system, a system of neurotransmitters that affects a huge number of our bodily processes. We’ll touch on that later in the neurochemistry section.

CBD is attractive to a number of people because it presents a holistic alternative to a lot of pharmaceutical medications. Many people find that their pharmaceuticals may be effective for treating a problem on the surface, but the side effects often compete with the benefits and in the long-run the illness is rarely treated.

CBD gummies, on the other hand, can help people manage the symptoms of their illnesses without actually becoming dependent on a drug or overwhelmed by side effects. This provides a unique opportunity to actually heal the root of the problem.

CBD vs THC

Many people are hesitant to use CBD because they know that it comes from the same plant as THC. THC, or tetrahydrocannabinol, is another cannabinoid. This one is largely responsible for many of the psychoactive effects that a person can experience when smoking marijuana.

Marijuana is quite a powerful drug and it’s understandable that some people would want to ensure that they’re not going to get high when using CBD. Rest assured, CBD and THC have vastly different effects, and CBD is not psychoactive at all.

This is interesting because structurally, CBD and THC are almost identical. Their molecules have the same number and same type of atoms; they are simply arranged differently. This contributes to the vast differences in experiences when using these two compounds.

CBD Effects

The interesting thing about CBD is that it will not have many effects if you are not treating an actual problem. That is to say, CBD works by helping to restore balance and function to the endocannabinoid system (ECS), as mentioned earlier. If your endocannabinoid system is in perfect health, then taking CBD won’t do much for you.

Unfortunately, the reality is that most of us have at least some imbalance in our ECS. These imbalances can come from a number of things that we’re exposed to on a daily basis: pollution, stress, unhealthy food, etc.

For these people, CBD is known for providing a number of positive benefits:

  • Reduced inflammation, improving pain and swelling for people with problems like arthritis
  • Increased relaxation and ability to fall asleep
  • Reduced anxiety and depression
  • Improved sociability
  • Improved concentration
  • Improved digestion

All of these benefits can work together to help ward off various illnesses and diseases.

Does CBD Get You High?

CBD does not get you high. As mentioned earlier, the CBD molecule is nearly identical to the THC molecule. However, because of the arrangement of these molecules, the two compounds act entirely different inside the body.

THC directly affects the body whereas CBD indirectly affects the body. This is why THC is much more apparent when ingested than CBD.

CBD Gummies

CBD Products

There are a huge number of different products containing CBD available. The variety in products allows for patients to choose from a number of ways of consuming CBD. The different methods of taking CBD will provide differences in the effects and duration of the substance.

  • CBD oil and tinctures are among the most popular CBD products. These oils and tinctures are so popular that we have dedicated a section to them below.
  • CBD capsules. Capsules are great for oral use but they can also be broken apart and taken sublingually or under-the-tongue. Capsules tend to come on slower than the other methods of using CBD but they also last for a bit longer.
  • Smokeables and vape products are useful for people who have acute problems like pain or panic attacks. These products can be inhaled and the effects felt almost immediately, though they tend to wear off much quicker.
  • Topical products. There are a number of products made with CBD that can be applied directly to the skin. These products are great because the active ingredient can be absorbed into the skin and there won’t be any effects on a person’s mental or physical site except where they apply it.

CBD Oil

CBD oil is one of the most popular forms of using CBD. This is because the oil provides you with a concentrated form of the active extract that can be consumed in a number of ways

The most effective way to use CBD oil is to take it sublingually. This involves holding the oil under your tongue for about 5 minutes so the CBD can be absorbed into the blood vessels there. This causes it to hit you faster and you’ll end up using less of it this way, thus saving money.

CBD oil is also used in the making of a number of other CBD products, like edibles.

CBD Edibles

CBD edibles are one of the most popular ways to consume CBD. People have had great success using CBD oil to make snacks and treats filled with CBD that people can eat. Ranging from CBD gummies to CBD peanut butter, edibles are a great way to medicate yourself.

One of the best things about edibles is that they are more slowly metabolized than the other forms of CBD. This means that the active effects may come on a bit slower but they will linger for much longer.

CBD and Anxiety

One of the most popular uses for CBD gummies and other forms of CBD is for helping people manage anxiety.

Many people were baffled by the implications of this, particularly because THC is well-known for causing anxiety in many people. Folks were wondering how a cannabinoid – especially one so similar to THC – could be used for fighting anxiety.

We’ll discuss the reasoning a bit more in the neurochemistry section below. For now, the simple fact of the matter is that CBD helps to manage anxiety by relaxing the mind and body, as well as balancing out the endocannabinoid system.

CBD has been shown to be useful for fighting all sorts of anxiety, ranging from generalized anxiety to panic disorder. Many have found success using a vape pen to help them manage acute panic attacks. CBD has even been shown to help fight anxiety associated with serious conditions like post-traumatic stress disorder.

CBD and Depression

CBD has proven to be a very exciting alternative for helping people manage depression.

Many traditional antidepressants are known for causing a huge number of side effects. These drugs often take a long time to work – many people have to use them for up to three weeks before these drugs work – and they often have drastic effects on a person’s physical and mental health.

CBD might not be as potent as some of these antidepressants, but it targets the problem in a much more holistic manner. Instead of blunting your emotions or inhibiting your ability to feel depressed by overloading your brain with neurotransmitters, CBD helps you overcome acute symptoms of depression so you’re actually able to identify and heal the root of the problem.

CBD gummies and other forms of CBD are a great tool for helping some people get the treatment that they need to actually eliminate their depression. After this, they can stop using CBD. This is in stark contrast to traditional antidepressants which many people find themselves using for the rest of their lives.

Neurochemistry and CBD

We have touched on the subject of CBD and neurochemistry in this article, but only briefly. In this section we will give a bit more information about the way CBD affects our brain and nervous system.

As mentioned, CBD affects the ECS. This massive system of neurotransmitters and receptors is responsible for governing many facets of our brains and bodies. It helps to regulate our immune system, manage our digestion, regulate our mental health, and generally help to ensure that we function properly.

Unfortunately, many of us have an imbalance in the ECS. CBD works by helping to restore balance to this vast system by indirectly influencing it.

This is one of the reasons that CBD has such vastly different effects than THC. THC directly binds to what are known as cannabinoid receptors. By binding to these receptors, THC can have a direct, immediate, and profound effect on this entire system.

CBD, on the other hand, works indirectly. Not only does it not bind to the receptors, but it actually makes it more difficult for substances like THC to bind to them. Instead, CBD works ‘behind the scenes’ to have a positive and regulatory effect on certain neurotransmitters like dopamine, serotonin, and our own naturally produced cannabinoids.

CBD Dosage

The dosage that one requires when they are using CBD depends on their condition and how serious it is. Dosages vary greatly between people and since CBD hasn’t been approved by federal organizations there is no standard dosage.

However, there are certainly some standards that one could expect to use.

  • People with anxiety may need anywhere from 10 to 50 mg of CBD. 10 mg doses of capsules or oils can be useful for helping to treat mild-to-moderate social anxiety and general anxiety. Higher doses can stave off a panic attack in its tracks.
  • People with pain or inflammation often require slightly higher doses. 20 mg can be effective for mild-to-moderate inflammation, but doses of anywhere from 50-100 mg are quite common.
  • People with depression often take higher doses, beginning at around 50 mg. However, people with melancholy or mild depression caused by situations or events can find some improvement using around 20 mg.

Keep in mind the way that you consume your CBD also has an impact on how much you need. Consuming CBD gummies or tinctures orally causes some of the drug to be destroyed by the liver before it’s absorbed into the bloodstream. Taking it sublingually helps to prevent this and reduces the amount required by about 40 percent.

CBD Side Effects

The vast majority of people won’t experience any side effects from CBD. Aside from the fact that higher doses might make you sleepy and unfit to drive a motor vehicle, CBD won’t cause any serious side effects unless you are allergic to cannabinoids.

That said, some people are extremely sensitive to the compound. These people may experience symptoms like dry mouth, diarrhea, and nausea. However, this may indicate that the medicine was not prepared properly or was produced in a facility with low safety and health standards.

One thing to be noted is that people using THC for recreational purposes might find the effects diminished if they use CBD. However, people who are using THC for medicinal purposes often find that the benefits are enhanced when they are using CBD in addition to THC.

Hopefully, this article has helped you to better understand CBD and the powerful benefits that it can provide for you and those that you love. Good luck healing yourself with this fantastic medicine.

What is Depression?

Depression is a mental health disorder associated with significant morbidity and mortality, being a major risk factor for suicide, substance abuse, poor outcomes of medical conditions, and impaired functionality. It is characterized by flattening of mood, loss of emotional expression, and retardation of thought and movements. Individuals who have depression usually have a depressed mood, loss of interest in activities they were usually interested in, sleep disturbance, loss of energy, and reduced ability to thick or focus.

The American Psychiatric Association’s Diagnostic Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) categorizes depressive disorders into major depressive disorder, persistent depressive disorder, premenstrual dysphoric disorder, disruptive mood dysregulation disorder, and depressive disorder due to a medical condition. However, all these classes of depression are characterized by the presence of a sad or irritable mood with associated difficulty in thinking, concentrating, and carrying out normal physical tasks, impairing the individual’s daily functioning.

Stats about Depression

Between 2009 and 2012, approximately 7.6% of Americans aged 12 and above were diagnosed with depression and it was more common among females and persons aged 40 and 59. In 2015, about 16.1 million adults aged 18 and over had a minimum of one depressive episode in the previous year.

Depression has been found to occur in children at an incidence rate of 0.9% in preschool-aged children, 1.9% in school-aged children, and approximately 4.7% in adolescents. In prepubertal children, depression occurs in boys and girls at an equal rate. Generally, depression in men and women has the highest rates in those aged between 25 to 44 years and the incidence of severe depression increases with age.

What are the Traditional Treatments for Depression?

There is a wide range of treatments for depression which have proven effective in improving symptoms. A combination of medications and psychotherapy is effective in reducing the symptoms of depression, and therapy with either form alone is often ineffective. Combination therapy has been found to increase quality of life and improve treatment compliance in patients with depression.

Advanced treatment techniques used for the treatment of depression include electroconvulsive therapy which uses high-energy electric stimulation, and bright-light therapy involving exposure of an individual with depression to bright light at an intensity of 10,000 lux for a period of one hour in the morning.

Therapy for Depression

Psychotherapy is often combined with medications in the treatment of depression. There are different types of therapy for depression and these can be grouped based on their efficacies. A therapy is considered “efficacious and specific” if studies in at least two settings (hospital, home therapy, rehab center etc.) have proven it more effective than medications. A therapy is considered “efficacious” if it has been proven from at least two settings that it is superior to no treatment at all, and it is “possibly efficacious” if it has been proven effective in at least one study in a single setting.

Examples of efficacious and specific therapies include cognitive behavioral therapy, problem-solving therapy, and interpersonal therapy which help the individual modify their behaviors and interpersonal relationships. An example of an efficacious therapy includes mindfulness-based cognitive therapy to prevent a recurrence or relapse, and an example of possibly efficacious therapy is continuation cognitive therapy to prevent recurrence by helping the individual develop positive thinking and behavioral patterns.

Medications for Depression

Medications used for treating depression are of different classes, each with a different mechanism of action, characteristics, and side effects. Some of these drugs include Fluoxetine (Prozac), Citalopram, Amitriptyline, Imipramine, and Nortriptyline. These drugs generally increase the concentration of stimulant substances in the brain to improve the depressive symptoms.

Home Remedies for Depression

Patients with depression could benefit from a number of home remedies which could help to improve their symptoms, in addition to antidepressants and therapy:

  • St. John’s wort – This plant, although not approved for treatment of depression by the FDA, has been linked with increased amounts of serotonin in the body correlating to improvement of depressive symptoms.
  • Omega-3 fatty acids – Omega-3 fatty acids are commonly found in fish such as salmon, sardines, and trout, and this substance has been linked to improvement in depressive symptoms.
  • SAM-e – S-adenosylmethionine (SAM-e) is artificially designed to function like chemicals in the brain which elevate mood. It is considered a supplement useful in improving symptoms of depression.
  • Folate – Folic acid which is found in a number of foods such as beans, lentils, dark leafy greens, and fortified cereals have been found to improve the effectiveness of medications used in treating the disorder.

What is CBD?

Cannabidiol (CBD) is a naturally occurring chemical compound found in the hemp plant. It is one of the numerous unique compounds called cannabinoids which naturally occur in hemp. Generally, cannabinoids can be produced in the body (these are known as endocannabinoids) or found in the hemp plant as phytocannabinoids. CBD is industrially extracted from the cannabis plant and separated from the other cannabinoids, representing about 40% of cannabis extracts.

CBD is a phytocannabinoid which helps to stimulate the regulation of the central nervous system. CBD, therefore, helps supplement the effects of endocannabinoids in regulating appetite, mood, functions of the immune system, sensation, and keeping our bodies working normally. CBD oil is made from hemp plants and can be purchased legally in the United States. CBD is available in different forms such as tinctures, concentrates, capsules, sprays, tapes, and topicals.

CBD vs. THC

Most times, people interchange CBD for tetrahydrocannabinol (THC), another cannabinoid found in the hemp plant. Both of them represent the commonest compounds found in the plant. However, they have numerous differences.

THC, unlike CBD, is intoxicating causing a high and euphoria. It is responsible for the “high” felt by marijuana users. CBD, on the other hand, is not a psychoactive substance as it does not act via the same biological pathways in the body as THC.

CBD Oil Effects

Although, CBD oil has not been approved by the FDA for the treatment of any condition, there have been several studies demonstrating some of its health benefits:

  • CBD has been shown to have anti-oxidant properties which means that it is capable of mopping up toxic substances obtained from food or generated in the body. These substances are often at the center of inflammatory conditions such as myocardial infarction, inflammatory bowel disease, and stroke.
  • Oxidative stress caused by the release of these toxic substances causes age-related diseases such as Alzheimer’s disease and Parkinson’s disease and CBD has been found to protect against these degenerative diseases of the brain and reduce their clinical progression in patients suffering from them. CBD may also help in the clinical improvement of some autoimmune disease such as lupus and rheumatoid arthritis.
  • Clinical trials have shown that CBD oils are effective in the treatment of epilepsy and other seizure disorders.
  • Studies have shown that CBD may have therapeutic benefits for brain disorders such as psychosis, depression, and multiple sclerosis.
  • Other benefits of CBD are currently being investigated, including its effects on anxiety and depression, as well as on social anxiety disorder and post-traumatic stress disorder.

Does CBD Get You High?

CBD is a non-psychoactive form of cannabinoid which has been found not to interfere with the cognitive functions of the brain. It does not get you “high,” in contrast to THC, which alters the cognitive functions of the brain.

Is CBD Addictive?

According to a recent report by the World Health Organization (WHO), CBD is not addictive and it has no potential for abuse or dependence. This is mainly because CBD does not contain any addictive substances, in contrast to THC and some cannabinoids which contain such and are, therefore, capable of being addictive.

Is CBD Safe?

There have been extensive reviews on the toxic potentials of CBD and reports have revealed that CBD has a relatively low toxicity. It has been found to be safe with little potential for adverse effects. CBD was found to have no effect on fetal development and other bodily functions. Generally, CBD does not produce the adverse effects seen with THC and other psychoactive cannabinoids. However, reports demonstrate that some reactions may occur as a result of its interactions with other drugs co-administered with it.

How Could CBD Help with Depression?

CBD has been found to be effective in the treatment of depression. While CBD does not cure the condition, it has been linked to improvement of the symptoms.

The cannabinoids produced in our bodies (endocannabinoids) help to regulate several functions of the body such as mood, pain sensation, sleep, and appetite. These substances exert their actions by binding to specific points of brain cells called the receptors through which they potentiate the actions of a substance called serotonin which acts to improve mood and reduce stress levels. Serotonin also acts by binding to its receptors in brain cells. When these chemical substances bind to their respective receptors, they trigger a series of events within each brain cell stimulating processes that improve mood and stress control.

CBD has been found to help improve depressive symptoms by modulating the actions of the endocannabinoids and also potentiating the effects of serotonin by enhancing the activity of the receptors unto which serotonin binds.

CBD oil helps to significantly improve depressive symptoms and the individual’s quality of life.

CBD Oil Dosage

CBD oil is available in several forms including tinctures, capsules, concentrates, and topical forms. However, it is most commonly administered orally. It is important to note that CBD is most effective when used regularly in maintenance doses, though it may be used for treating acute flare-ups.

In the management of depression, CBD oil may be taken in the tincture and capsule forms. Individuals with depression can begin with a dose of 5 to 10mg daily until the desired results are achieved. Gel capsules of CBD are available as 25mg per pill and it is safe to begin at this dosage as CBD has a good safety profile. The effects of CBD lasts several hours after a dose is ingested and most persons report feeling better for up to 24 hours. However, you will only begin to notice these improvements after 90 minutes of ingestion of CBD oil.

For managing acute flare-ups, it is best to vaporize CBD isolate for fast relief of symptoms. However, the maintenance dose should not be discontinued. Although you may also use the ingestible forms of CBD in treating acute flare-ups, these, generally, have a relatively longer onset of action.

Generally, it is recommended that you consult with your physician before starting CBD oils to prevent drug interactions and exacerbations of any medical conditions you may have. Do not, also, discontinue or start any drug while using CBD without consulting your physician.

For information on where to obtain CBD Oil, go here.

CBD Oil Side Effects

CBD oil is generally safe to use with minimal risk of adverse effects. Side effects may be seen when high doses are taken. Some studies have revealed that if taken at high doses, it may cause a weakening of your immune system. However, the main concern with the use of CBD is the risk of drug interactions, therefore, it is recommended that you consult your physician before using CBD oil.

Bottom Line: Can CBD Help You?

CBD is one of the naturally occurring chemical substances found in the cannabis plant and though the stigma associated with the psychoactive counterpart, THC, has rubbed off on it, it has been shown to have immense health benefits in treating conditions such as anxiety, depression, mood disorders, and inflammatory diseases. CBD oil helps to significantly improve depressive symptoms and the individual’s quality of life. However, it should be noted that CBD does not provide a cure for the disorder, but leads to a better quality of life for the patient.

Resources

https://emedicine.medscape.com/article/286759-overview#a4

https://www.webmd.com/depression/features/natural-treatments#1

https://www.healthline.com/health/depression/herbs-supplements

https://ministryofhemp.com/wp-content/uploads/2016/10/The-Complete-CBD-Resource.pdf

https://www.royalqueenseeds.com/blog-new-who-report-shows-cbd-is-not-addictive-nor-dangerous-n771

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3648779/

https://keytocannabis.com/blogs/cannabis/cbd-for-depression

https://www.ncbi.nlm.nih.gov/pubmed/24923339

https://www.ncbi.nlm.nih.gov/pubmed/22729452

https://www.ncbi.nlm.nih.gov/pubmed/20002102

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NOVA Heath Recovery Ketamine Treatment Center | Call 703–844-0184 for a Ketamine Treatment | Alexandria, Va 22306 | 7 days a week and evening appointments as well! We also evaluate depression, ADHD, PTSD. Intranasal Ketamine available.   The email is EMAIL@novahealthrecovery.com

Ketamine for Depression: Does it work?

What is Ketamine?

Ketamine, also known as Ketalar, Ketaset, and Ketanest, is a medication that’s currently FDA approved only as an anesthetic but it’s showing great potential as a treatment for severe depression. In fact, numerous Ketamine Clinics have begun to appear throughout the United States to solve this problem. Depressed patients with stubborn symptoms get relief within hours rather than weeks with conventional anti-depressants. Doctors can only prescribe ketamine for depression off-label because studies are relatively new, but experts are saying that ketamine is one of the biggest breakthroughs in severe depression treatment to come along in decades [1].

Ketamine is a powerful pain reliever and a relaxant, but at higher doses it can also induce unconsciousness and disturbances in how a person experiences sight and sound. In high doses, it can produce hallucinations and delusions and its ability to create strong dissociative experiences have made it popular in the club scene where it’s known as “Special K”. An overdose of ketamine can be fatal and it can be addictive if patients don’t follow their doctor’s prescription guidelines. Currently, ketamine is scheduled as a class III drug and it’s created a lot of controversy among experts who disagree about whether it’s safe for doctors to prescribe it as a treatment for chronic depression. Despite the intrigue and the need for additional research to establish its safety and efficacy, ketamine clinics are now offering infusion treatments to patients all over the United States [1][2][8][9].

Effects of Ketamine

As a street drug, ketamine creates a sense of dissociation and can change a person’s sense of hearing and sight, but for patients with severe depression, ketamine relieves mood problems within hours or sometimes moments for about 85% of those treated. While conventional anti-depressants can take several weeks to take effect, studies have shown that ketamine often improves depression symptoms almost immediately. Patients typically feel better within hours [1][2].

Doctors, dentists, and psychiatrists prescribe ketamine to help their patients achieve a variety of different health goals. Doctors often use ketamine in FDA approved situations such as procedures involving cardiac catheterization, orthopedics, skin grafting, or diagnostics involving the eye, ear, nose, and throat. Surgical dentists may also use ketamine as an anesthesia during tooth extractions. After other treatment options have been attempted and failed, doctors may use ketamine to treat certain types of seizures in patients with status epilepticus [2].

Researchers demonstrated in 2014 that ketamine reduced symptoms of post-traumatic stress disorder in 41 patients and there are other exciting possibilities on the horizon in terms of PTSD treatment. Treatment-resistant depression and substance use disorders could both be treated with this drug, though many medical professionals view ketamine treatment for these mental health issues as controversial [2].

Ketamine for Pain Management (CRPS)

Central Sensitization is a process the central nervous system goes through which causes Complex Regional Pain Syndrome (CRPS/RSD) and other types of chronic pain. In central sensitization the number of NMDA receptors increases which amplifies a patients’ experience of pain. Ketamine interferes with NMDA receptors which puts a damper on pain signaling, providing pain relief and a desensitization to pain for patients affected by CRPS [8].

At low doses, ketamine can relieve chronic pain and potentiate the effects of sedatives. Researchers believe that ketamine could provide an alternative to more addictive painkillers like morphine if the FDA approves it for this use [1][8].

Ketamine for Anesthesia

In the 1960’s doctors used ketamine as an anesthetic on the battlefields in Vietnam because administration lends itself well to use in disaster zones; doctors don’t need electricity, an oxygen supply, or even highly trained staff to give patients ketamine. Since that time, the FDA has only approved ketamine for use as an anesthetic in hospitals and medical settings. As an anesthetic, ketamine doesn’t lower the patient’s breathing rate or blood pressure, which makes it safer than other anesthesia options. It’s for this reason that veterinarians use ketamine more than any other type of anesthetic for surgery on animals [1][2].

Ketamine for Depression

Depression is a major issue in the United States and though there are many anti-depressants on the market, about one-third of patients don’t experience any relief from their symptoms using the drugs that are currently available. Ketamine acts on depression by rebalancing a different set of neurotransmitters and receptors (the NMDA/glutamate receptors and GABA receptors) than the old-school Selective Serotonin Reuptake Inhibitors (which function by blocking reabsorption of serotonin). By blocking glutamate receptors in the brain, the majority of patients with ‘Treatment Resistant Depression’ are able to experience relief from their symptoms using ketamine [1].

Even though ketamine has yet to be approved by the FDA for use in treating depression, patients are flocking to ketamine clinics to receive the treatment off-label. It provides fast relief, which is vitally important in cases where patients feel suicidal and for depressed patients who have tried all of the other anti-depressants available with no luck, ketamine offers new hope. Infusion treatments take about 1 hour at a clinic, but the results are long-lasting with most patients returning only once every one to two weeks over a specified period of time. The treatment is expensive, but the results are promising enough that patients are willing to pay out-of-pocket for it [5][8][9].

The FDA hasn’t yet approved ketamine for use as an anti-depressant, but both Esketamine and Rapastinel (developed by Johnson & Johnson and Allergan respectively) have been fast-tracked as breakthrough drugs. The demand for these two medications is projected to grow rapidly in the coming years.  Still, doctors can only prescribe ketamine for depression off-label since ketamine has been FDA approved for use as an anesthetic, not as an anti-depressant. Researchers have cautioned doctors to avoid over-prescribing this drug because the long-term health and well-being of patients could be at risk. Ketamine has a high potential for abuse, after all and experts claim that the evidence does not exist to prove that this drug is safe [1][2][6].

Ketamine as Drugs of Abuse

Ketamine is abused as a recreational drug and it has effects that are similar to Phenylcyclidine (PCP), LSD, dextromethorphan (DXM) and nitrous oxide (laughing gas). Ketamine is a dissociative anesthetic that can alter one’s sense of sight and sound and also produce profound relaxation, hallucinations, and delusions for about an hour. The effects of the drug come on almost immediately. It has been used as a rape drug that can render women unable to speak or to move [1][2].

People who abuse ketamine have developed serious bladder and kidney problems such as ulcerative cystitis, stomach issues, and memory loss. In fact, street users even risk developing depression as a result of addiction and dependence on the drug [2].

How is Ketamine used for depression?

Doctors may prescribe ketamine by itself or in tandem with other anti-depressants [3]. Many experts on depression recommend that ketamine only be used as a short-term depression treatment option while other anti-depressants are taking effect. Though there are convenient ketamine nasal sprays in research and development by Johnson & Johnson, the high-potential for abuse of this drug has made many doctors and psychiatrists wary of using this drug to treat depression long-term. Further, some medical organizations are concerned that the long-term effects of chronic ketamine use is not well-understood. According to these organizations, more research is needed to establish the safety of this drug [1][2][6].

Promising Remedy for ‘Treatment Resistant Depressions’

Thomas Insel, the director of the National Institute of Mental Health says, “Recent data suggest that ketamine, given intravenously might be the most important breakthrough anti-depressant in decades.” Conventional anti-depressants aren’t able to help about one-third of patients with major depression, but new ketamine drugs such as esketamine (in development by Johnson and Johnson) may offer new hope. Infusion therapies available through ketamine clinics across the United States report a high success rate of 60% to 70% treating Treatment Resistant Depression as well as Major Depression with risk of suicide [1][3][5][6].

Fast-Tracked by FDA

Two drugs, Johnson & Johnson’s Esketamine and Allergan’s Rapastinel, were both upgraded to ‘fast-track’ status by the FDA in 2016 due to their importance and promise in treating treatment resistant depression.

Depression is the leading cause of disability in the world and currently, 12% of Americans (about 29 million people) are taking anti-depressant medications. The suicide rate is higher now than it has been in over 30 years. And about one-third of depressed Americans don’t experience relief taking conventional anti-depressants. In the interest of capitalizing on the market value of depression, which is projected to almost double by the year 2024, the FDA will review the use of these new ketamine-based depression drugs in 2018 and 2019, allowing Johnson & Johnson and Allergan to go through an abbreviated version of the normally lengthy FDA approval process for new drug therapies [5][6].

Experimental Trials

Drug trials have shown that 60% to 70% of patients with Treatment-Resistant Depression have been responsive to ketamine. Esketamine, a nasal spray developed by Johnson & Johnson, is in Phase III clinical trials right now. They are expected to receive FDA approval later in 2018, and once that happens, it will open doors for administering ketamine outside a clinic setting.

Rapastinel, which was developed by Allergan, is out of Phase III and awaiting FDA approval. The drug can be administered within 30 seconds intravenously and Allergan is working to develop an oral version of the drug as well [2][3][5].

How Ketamine Therapy Works

Ketamine therapy is usually performed at a ketamine clinic. Patients receive an intravenous infusion of the drug with relief from depression symptoms that can last for several weeks.

Ketamine Infusion or Intravenous Therapy (Infusion Process)

Ketamine can be injected directly into muscle tissue or it can be given intravenously. Researchers for Johnson & Johnson have also recently developed new treatment protocol called Esketamine that’s awaiting FDA approval. Using Esketamine, patients will be able to self-administer the drug as a nasal mist [2][3].

Patients must receive a referral from a doctor to go to a ketamine clinic. There, patients can receive an intravenous infusion of ketamine. On the first visit, a doctor will assess the patient before hooking the patient up to a ketamine IV. Patients then experience a variety of sensations during the infusion and for up to 2 hours following the infusion. Many patients report feeling a sense of deep relaxation and the ability to reflect on past traumas and anxieties calmly [7][9].

How does it work?

Researchers have demonstrated that a deficiency in certain vital connections between certain neurons in the brain may cause depression. Ketamine works as an NMDA receptor antagonist (NMDA is a glutamate receptor also known as N-methyl-d-aspartate) and an AMPA receptor stimulator. As such, ketamine stimulates the development of new receptors and synapses in the brain which helps patients regulate their mood, sleep better, and experience better focus [2][8].

Ketamine works by interfering with and rebalancing the glutamatergic system (glutamate and GABA) to stimulate new synaptic connections, better memory, and brain plasticity [8]. During ketamine infusions, patients may feel capable of exploring traumatic memories more calmly to reframe the past or they may feel a pleasant sensation of relaxation or floating [7]. Effects from an infusion can last for up to a week or two.

Intranasal ketamine formulas work by binding to a receptor called N-methyl-d-aspartate. In the brain, ketamine blocks the neurotransmitter glutamate which causes communication between the conscious mind and other parts of the mind (such as mood centers) to be blocked. In low doses, it relieves depression, but in higher doses, it can cause patients to feel an uncomfortable sense of dissociation from the body similar to a near death experience [2][3][4].

While most anti-depressant medications must build up in the body over the course of several weeks in order to have an effect, ketamine’s mood-altering benefits happen as the drug leaves the body. Researchers don’t know why this is the case, or even exactly how the drug achieves its strong anti-depressant effects but the fact is, ketamine works quickly to relieve depression symptoms in 85% of patients who are resistant to other forms of therapy [1]. Standard anti-depressants target the neurotransmitters serotonin, norepinephrine, and dopamine, but ketamine is different. Ketamine blocks glutamate and stimulates synaptic plasticity or the ability of the brain to change and grow [5].

Doctors don’t fully understand how ketamine works or the potential effects that patients may experience from taking tiny doses of this drug over and over again. What is known is that recreational users can suffer ulcerative cystitis or cognitive issues as a result of prolonged use [5].

Ketamine Infusion Dose/Dosage

Researchers are working to find the perfect ketamine dose for depression patients. The risk of overdosing on this drug is high for the recreational user because there is only a slight difference between a dosage that leads to desirable effects and one that can cause a lethal overdose. The goal for researchers is to find an exact dosage that’s high enough to get rid of symptoms of depression but low enough to prevent patients from experiencing hearing and sight disturbances as well as the other negative effects from the drug [1][2][9]. Ketamine produces only temporary effects on severe depression. Patients must continue to return to the clinic for infusions every few weeks to keep their depression symptoms in check [5].

Ketamine therapy cost? Is ketamine therapy covered by insurance?

Ketamine therapy is rarely covered by insurance and it’s pricey. Patients typically pay between $400 and $800 per infusion in many centers.

Ketamine Infusion Side-Effects

Ketamine use can cause a variety of side effects including:

  • Extreme fatigue or exhaustion
  • Nervousness or restlessness
  • Sweating
  • Amnesia
  • Puffy or swollen eyelids, lips, or tongue
  • Hives, itching, or rash
  • Delusions
  • Difficulty thinking or learning
  • Loss of appetite
  • Nausea
  • Fast heartbeat, slow heartbeat, irregular heartbeat
  • Dizziness, fainting
  • Difficulty swallowing
  • Confusion
  • Convulsions
  • Difficulty breathing
  • Chest pain or discomfort
  • Blurry vision
  • Inability to control eye movement
  • Slurred speech
  • Difficulty urinating, frequent urination, cloudy or bloody urine
  • Paleness, bluish lips, skin, or fingernails
  • Increased pressure in the brain and the eyes [1][2]

Where can you get ketamine therapy? | NOVA Health Recovery Ketamine Treatment Center | Alexandria, Va 22306 | 703-844-0184

Off-label ketamine infusion therapy is an unregulated business that has gotten the attention of both clinicians and medical organizations. There are currently ketamine clinics in a number of cities throughout the United States [10].

s ketamine therapy addictive?

Patients who use ketamine long-term may develop a tolerance and addiction to the drug over time. In medical settings, ketamine is safe to use because the dosage is carefully calibrated and monitored, but there is a high potential for abuse when patients use ketamine recreationally as  a street drug. If patients don’t follow their doctor’s prescription for ketamine it can have extremely negative mental and physical effects particularly on the brain and bladder [2].

Ketamine-Based Drugs in Late Stage Trials

Both Rapastinel and Esketamine are ketamine-based drugs that have been ‘fast-tracked’ by the FDA because the FDA has identified them as “breakthrough drugs” [5].

Rapastinel

Allergan developed Rapastinel, a ketamine drug that can be administered in 30 seconds intravenously. It works on the same receptors as ketamine, but it doesn’t produce hallucinations. An oral version of Rapastinel is also in development. The FDA considers Rapastinel to be a “breakthrough drug” which means that Allergan can speed through the lengthy drug approval process and get the drug to market by 2019 [5].

Esketamine

The FDA has designated Esketamine a “breakthrough therapy”, which means that the drug developers, a subsidiary of Johnson & Johnson, can speed through the lengthy drug approval process to get the drug on the market more quickly. Esketamine can be administered like a nasal decongestant, which would make it more convenient than intravenous therapy for depression patients. Experts feel that Esketemine would be most appropriately used as an adjunct therapy in combination with other anti-depressant medications, not as a standalone treatment for depression [5][6].

According to one recent study, when administered in combination with other oral antidepressants, Esketamine reduced patients’ depression symptoms more than oral anti-depressants alone. The anti-depressant effects of using a conventional anti-depressant in conjunction with Esketamine occurred within only about 1 week. When used alone, Esketamine effects seem to last 1 to 7 days in most patients. Esketamine is in Phase 3 testing with the FDA for use as a drug for ‘Treatment Resistant Depression’ and Major Depression with risk of suicide. Johnson & Johnson will file for FDA approval for this drug as a depression treatment in 2018 [3][6].

Risks of Ketamine Abuse

Ketamine abuse is a serious problem. It is possible to become addicted to ketamine. Patients may begin to need higher doses of the drug in order to experience the positive effects. An overdose of ketamine can be deadly. The effects of using ketamine chronically over a long period of time have not been established, but recreational drug users who have used ketamine long-term have developed ulcerative cystitis as well as cognitive issues [1][2].

The Ketamine Controversy

While ketamine can literally save lives by relieving the symptoms of major, Treatment Resistant Depression, including the risk of suicide, research still has not established the safety of ketamine for long-term use. The lethal dose of ketamine is only slightly higher than the therapeutic dose and its addictive properties mean that it could cause depressed patients more problems than it solves. Ketamine clinics have popped up all over the country to cash in on the high demand for a depression treatment that really works, but the research hasn’t demonstrated that this drug is safe for chronic use. So this is an instance where the buyer needs to beware. The FDA has fast-tracked these drugs because it’s constituents see market potential, but important research still needs to be done on this drug to demonstrate it’s safety and long-term efficacy.

Resources:

[1] Collins, S. (2005-2018). What you need to know about ketamine’s effects. Retrieved April 3, 2018 from https://www.webmd.com/depression/features/what-does-ketamine-do-your-brain#1

[2] Davis, K. (2017). What are the uses of ketamine? Retrieved April 3, 2018 from https://www.medicalnewstoday.com/articles/302663.php

[3] Pagliarulo, N. (2018). J& J builds case for ketamine-based depression drug. Retrieved April 3, 2018 from https://www.biopharmadive.com/news/jj-builds-case-for-ketamine-based-depression-drug/513866/

[4] No Author (2007-2018). Special K and X. Retrieved April 3, 2018 from http://goaskalice.columbia.edu/answered-questions/special-k-and-x

[5] Oaklander, M. (2017). New Hope for Depression. Retrieved April 3, 2018 from http://time.com/4876098/new-hope-for-depression/

[6] Oberhaus, D. (2017). Ketamine Nasal Spray Will Totally Change the Market for Antidepressant Drugs. Retrieved April 3, 2018 from https://tonic.vice.com/en_us/article/wjxd9b/ketamine-nasal-spray-will-totally-change-the-market-for-antidepressant-drugs

[7] Ketamine Advocacy Network (2015). The Infusion Experience. Retrieved April 3, 2018 from http://www.ketamineadvocacynetwork.org/the-infusion-experience/

[8] Ketamine Clinics of Los Angeles (2018). How does ketamine infusion therapy work? Retrieved April 3, 2018 from https://www.ketamineclinics.com/about-ketamine/how-it-works/

[10] Ault, A. (2017). US Ketamine Clinics Continue to Mushroom With No Regulation. Retrieved April 3, 2018 from https://www.medscape.com/viewarticle/886750

Ketamine Doctor | 703-844-0184 | Arlington, Va 22201 | The history of Ketamine | CBD Doctor | CBD Center | IV Vitamin Therapy | Ketamine for Alcohol and drug addiction | Ketamine for depression | Alexandria, Va 22304 | Ketamine intranasal Center | Ketamine Psychotherapy

Psychedelic Medicine 101: The curious case of ketamine



Psychedelic Medicine 101: The curious case of ketamine

Vials of Ketamine
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The urban myth of ketamine as a horse tranquilizer became prominent as the drug moved into...

Ketamine is known for generating a profoundly dissociative out-of-body experience
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John Lilly and his infamous isolation tank

John Lilly and his infamous isolation tank

A psychedelic renaissance is underway in medical research as certain taboo drugs return to the hands of doctors and researchers after decades in the wilderness. Once considered illicit, with no medical value, these psychedelic compounds are now being legitimately evaluated by scientists and revolutionizing how we practice medicine.

Psychedelic medicine 101 is a series that will investigate the past, present and future medical uses of these formerly taboo substances. Our first feature examined the story of psilocybin and magic mushrooms, while this new episode documents the curious story of ketamine, initially developed to be an anesthetic before researchers and psychonauts discovered its unique and unusual effects on the brain.

The curious case of ketamine

In 1956, a chemist at pharmaceutical company Parke Davis in Detroit, Michigan was experimenting with synthesizing new compounds in an attempt to find a better anesthetic. A compound called phencyclidine was initially created, and in early animal studies it demonstrated defiantly unusual effects. Some animals exhibited a drunk-like state when administered with it, while others entered states of delirium.

Human tests quickly ruled out the compound as clinically useful with some patients exhibiting major delirious and dissociative states for prolonged periods of time. This was despite the fact the it did seem to function remarkably well as an anesthetic. In later years, phencyclidine hit the streets as a recreational drug, becoming infamous due it its violent side effects. Its street name was PCP, or angel dust.

In the early 1960s, Parke Davis researchers began searching for a phencyclidine derivative that could limit the compounds unmanageable side effects. It was here that ketamine was born and after successful animal tests it was administered to the first human subject in 1964, demonstrating remarkable anesthetic effects.

Initially approved for veterinary uses, ketamine quickly found a place as an effective short-acting anesthetic, officially passed by the FDA in 1970 for human uses. One of its first major human uses was as a battlefield anesthetic in Vietnam. It has been suggested that this initial use in the early 1970s was what led to it moving into recreational circles as veterans returned to the United States and continued using the drug.

Non-medical uses continued throughout the 1970s, culminating in several high profile publications “outing” the drug. Perhaps the most infamous of these accounts came in scientist and psychonaut John C. Lilly’s 1978 autobiography The Scientist: A Novel Autobiography.

John Lilly and his infamous isolation tank

Ketamine, sensory deprivation and alien communication

John C. Lilly is perhaps best known for his work blending LSD, isolation tanks and human-animal communications. After developing the first isolation tank in 1954, Lilly began experimenting with LSD in the tanks in the early 1960s. His extreme work sat at the boundary of conventional science, and the extraordinary 1980 psychedelic film Altered States was significantly inspired by his experiences.

It was the early 1970s, however, when Lilly first crossed paths with ketamine. Lilly had long suffered extreme migraines, almost daily, for much of his life. During an attack, a physician friend suggested ketamine may be helpful. So Lilly jumped into an isolation tank, was injected with a small dose of ketamine, and his migraine disappeared … for 20 minutes. When it roared back his physician friend gave him another injection, this time double the dose. For about half an hour the migraine disappeared, but then it stormed back, so finally the physician again doubled the dose and sent Lilly back into the tank.

After an hour Lilly got out of the tank and his migraine had gone. A month later, with his migraine still yet to return, Lilly became convinced ketamine had somehow reprogrammed his brain in ways that his earlier massive LSD experiences couldn’t. For the next few years Lilly’s personal ketamine experiments became more and more extreme.

Lilly became convinced he could communicate with a network of extraterrestrial entities he dubbed ECCO, or the Earth Coincidence Control Office. ECCO guided Lilly’s research but as he began to consume more and more ketamine he came across another, more malevolent entity called SSI, Solid State Intelligence.

SSI was a massive cosmic supercomputer, with evil intent. At one point, in the midst of an epic nearly month-long physical experiment with ketamine, consisting of injections nearly every hour, Lilly tried to contact President Gerald Ford to warn the world of a potential doomsday scenario. One of the president’s aides intervened before Lilly could reach Ford.

These stories, and others, recounted in the late 1970s, slowly added to the infamy surrounding ketamine, but they also started to pique the attention of the authorities. The peripheral clinical uses of the substance were still pervasive enough for it to not be completely regulated until the United States government moved to make it a Schedule III controlled drug in 1999. This added a degree of regulatory oversight as to how the drug was dispensed but still allowed it to be utilized for clinical purposes.

William Hurt in Altered States, a film loosely based on the experiences of John Lilly

The Russian research

In 1985, two Russian researchers hypothesized that ketamine could be a good drug to utilize in a psychotherapeutic context. It was short-acting, controllable, relatively accessible and known to induce psychedelic experiences. For the next decade, Evgeny Krupitsky and his team at the Leningrad Regional Center for Alcoholism and Drug Addiction Therapy pioneered what they called Ketamine Psychedelic Therapy.

Over the next decade, ketamine was used to treat more than 1,000 patients for an assortment of drug dependencies, primarily alcoholism. In a systemic study of the work, published in 1997, the researchers reported that the KPT process they developed resulted in zero major side effects, such as protracted psy­choses, flashbacks, agitation, or ketamine abuse. It also proved to be extremely effective in helping patients, with total abstinence rates for more than one year in KPT-treated alcoholic patients hitting around 65 percent compared to conventional treatment which was only successful in 24 percent of patients after one year.

For an extended period of time across the 1980s and early 1990s, this Russian team were extraordinarily the only researchers in the world investigating the therapeutic outcomes of ketamine. Krupitsky suggested this could be because Russia was not suffering from a culture of recreational psychedelic usage, which helped allow his work to continue for so long with no authoritative challenge.

“It seems to be an especially powerful tool in Russia, where there was no psychedelic revolution in the 1960’s and almost nobody knows what “psychedelic” means or can even imagine that this drug can be used for recre­ation,” the researchers concluded in their ten-year report.

Ketamine is known for generating a profoundly dissociative out-of-body experience

The 21st century resurgence

In the early 2000s, ketamine began to reemerge in Western research circles as a potential therapeutic agent, initially for depression. A very small studypublished in 2000 highlighted the drug’s impressive antidepressant qualities, but it was a 2006 study that really turned the tide.

The study, from the National Institute of Mental Health (NIMH), highlighted the remarkably rapid anti-depressant effects of ketamine. It was a small but strong piece of research involving a cohort of patients diagnosed with major, treatment-resistant depression. Two small doses of ketamine were administered, one week apart, and by the end of the first day 71 percent of subjects in the ketamine group reported a nearly 50 percent decline in their symptoms. Even more remarkable, after a week nearly a third of the ketamine group reported complete remission of their depressive symptoms.

This kind of rapid and immense effect was unheard of and the study hit the mainstream media, propelling ketamine into the news for something other than an illicit street use for the first time in years.

The rapid anti-depressant effect of ketamine has been a fundamental and exciting area of research in recent years with scientists slowly homing in on the extraordinarily unique qualities of how the drug operates on the brain. A 2017 study from Columbia University Medical Center revealed impressive results when examining patients suffering from acute suicidal thoughts.

The study, composed of 80 patients with clinically significant suicidal thoughts, displayed a major reduction in reducing such thoughts within 24 hours of a single low-dose infusion. A six-week follow up also found the effects impressively held for an extended duration, especially when compared to a control-group that were administered a sedative called midazolam.

A model of the ketamine molecule

But how does it work?

How the drug actually works to achieve its rapid anti-depressant effects is a hot area of research. While it has been known for several decades that ketamine blocks a protein receptor in the brain called N-methyl-D-aspartate (NMDA), it hasn’t been understood exactly where in the brain this mechanism could be operating.

A recent study from Zhejiang University in China excitingly revealed that this mechanism could be concentrated in the lateral habenula, an area of the brain often referred to as our “anti-reward center.” Overactivity in the lateral habenula has been strongly related to depression and the new study revealed that ketamine directly reduces neuronal activity in that region.

Ketamine’s broad use as a pain- and depression-relieving agent is finding burgeoning uses in treating other conditions peripherally connected to those symptoms. A growing body of anecdotal patient-driven evidence is suggesting the drug could be effective in treating fibromyalgia and chronic fatigue syndrome, two chronic conditions that are somewhat linked by widespread feelings of pain and fatigue.

In regards to fibromyalgia, some small studies have found ketamine to be incredibly effective in reducing acute pain related to the condition. The effects were frustratingly short-lived, unfortunately, but some patients have reported single infusions dulling pain for up to three weeks.

The use of ketamine to treat chronic fatigue syndrome is still in the nascent research stages, but a 2016 study revealed a fascinating insight into the drug as an anti-fatigue compound. While fatigue and depression are profoundly interlinked, the broader NMDA-blocking effects of ketamine are convincingly hypothesized to potentially improve the symptoms of patients suffering from chronic fatigue.

The 2016 study was small, and limited to patients being treated with ketamine for bipolar disorder during an episode of acute depression. It found that ketamine significantly improved symptoms of fatigue when compared to patients in the placebo group, with the anti-fatigue effects most prominent 48 hours after the initial infusion event. The study concludes by suggesting ketamine’s NMDA receptor inhibition could be a novel target for anti-fatigue interventions in a variety of conditions, including chronic fatigue syndrome.

The urban myth of ketamine as a horse tranquilizer became prominent as the drug moved into...

The rise of the ketamine clinic

Unlike other more restricted drugs, ketamine is still available for medical uses. This has led to the recent upsurge of ketamine clinics in the United States. Ketamine is legally approved for use as an anesthetic, but its off-label use for other conditions is not illegal.

Since around 2015, it is estimated that well over 100 ketamine clinics have opened up in the US. These clinics target patients looking for an alternate way to treat their depression. For up to US$1,000 a dose, patients can receive an infusion of ketamine either weekly or monthly. Different clinics have different treatment processes, from specific 10-week programs to more casual dose-by-dose appointments.

It’s the wild west of medical treatments out there, with no clear science on how long these treatments last, or how safe long-term ketamine use like this actually is. The CEO of Actify Neurotherapies, a chain of 10 treatment centers, said recently “It scares the hell out of me that this is still unregulated.”

Actify Neurotherapies is actively resisting the term “ketamine clinic,” recently rebranding itself as a mental health clinic that happens to also provide off-label ketamine treatments. While Actify is positioning itself at the more credible end of the off-label ketamine provider spectrum, it is still part of a troubling, unregulated industry with the science yet to offer real clarity on the best way this drug should be delivered.

Well over 100 ketamine clinics are operating in the United States

A little less psychedelic?

The giant hurdle facing most ketamine research is trying to find a way to overcome the often unpleasant dissociative psychedelic effects of the drug. While NMDA-receptor antagonism is looking like an exciting new pathway to treat a whole host of conditions, the side effects of ketamine are proving tricky to manage when implemented into broader clinical applications.

A recent Australian trial into a ketamine nasal spray for treating depression had to be aborted after several participants started to experience psychotic-like side effects. One of the researchers suggested the dose problems stemmed from inconsistencies in the nasal-delivery method.

“We saw a range of tolerance levels and we think it’s because one person’s blood vessels in the nose can be so different to the next person’s, and when you spray, it crosses the thin lining, gets taken into the blood and straight to the brain. Some people got huge hits.”

Several researchers are now racing to develop compounds chemically similar to ketamine that still act on NMDA receptors but can reduce the psychoactive side effects. One of the most promising new alternatives is called esketamine, and it is currently at the tail end of Phase III clinical trials.

Esketamine is an isomer of ketamine, and reportedly has slightly less dissociative characteristics compared to its sibling. It is thought to be twice as potent as ketamine, which means it is suggested that lower doses could have similar NMDA-inhibiting effects to ketamine without the equivalent hallucinogenic result.

Despite the FDA offering esketamine a breakthrough designation in 2016, suggesting the compound is highly effective and will be rapidly pushed through the trial process, results have been decidedly mixed over the past few years. Most recently, some of the early Phase III results suggest the compound is only mildly effective, and in some cases barely better than the placebo control.

Ketamine + therapy = success?

Of course, some researchers are finding ways to work with the compound’s extremely hallucinogenic properties. An exciting new trial currently underway at the University of Exeter and University College London is directly inspired by Evgeny Krupitsky’s 1980s research in Russia. The trial is called KARE – Ketamine for reduction of Alcoholic Relapse, and it is setting out to examine how well ketamine, in conjunction with psychotherapy, can reduce alcohol dependence and promote abstinence.

The rigorous study, which is double blind and placebo-controlled, involves subjects being administered one dose of ketamine a week for a period of three weeks, alongside seven sessions of cognitive behavioral therapy. The study has a six-month follow-up phase to better understand the long-term effects of this kind of ketamine-assisted psychotherapeutic treatment.

Unlike the attempts to create a less psychoactive compound, this research suggests the holistic effect of ketamine could be vital to its absolute efficacy. The often unwanted hallucinogenic effects may very well be important. And unlike some of the ketamine clinics popping up around the US, this trial offers ketamine within the context of a controlled series of psychotherapy sessions helping patients integrate their experiences into positive outcomes.

The story of ketamine is a curious one, defiantly unlike other psychedelic substances being co-opted for medical uses. Ketamine is essentially legal, prescribable, yet still wholly experimental. It works on the brain in a completely novel way and we are only just understanding its broad potential uses.

With the rise of ketamine clinics, a strange kind of clinical practice has jumped ahead of research, giving rise to a wild west of drug providers administering the compound as a magic bullet for anything and everything in an unregulated landscape. More research undeniably needs to be done before we understand this deeply mysterious and unique drug, but it is looking like it will certainly become a fundamentally important compound in a bright future of psychedelic medicine.