Tag Archives: heroin

Ketamine treatment of alcoholism | Heroin Abuse | Cocaine abuse | 703-844-0184 | Ketamine therapy in Fairfax, Va 22304

NOVA Health Recovery  <<< Ketamine Treatment Center Fairfax, Virginia

CAll 703-844-0184 for an immediate appointment to evaluate you for a Ketamine infusion:

Ketaminealexandria.com    703-844-0184 Call for an infusion to treat your depression. PTSD, Anxiety, CRPS, or other pain disorder today.

email@novahealthrecovery.com  << Email for questions to the doctor

Ketamine center in Fairfax, Virginia    << Ketamine infusions

Ketamine – NOVA Ketamine facebook page – ketamine treatment for depression

facebook Ketamine page

NOVA Health Recovery  << Ketamine clinic Fairfax, Va  – Call 703-844-0184 for an appointment – Fairfax, Virginia

Ketamine Consultants Blog

Ketamine is a dissociative anesthetic that acts on the central nervous system by antagonizing the n-methyl-d-aspartate (NMDA) receptors. It is a rapid acting anti-depressant, but there is a lot more attention being paid to it’s efficacy in alcohol and drug abuse treatment.

Ketamine has been shown in some studies to prolong abstinence from alcohol and drug use disorders. It also has been found to reduce cocaine craving and self-administration in untreated patients.

The mechanisms by which this works has been through the disruption of relevant neural networks which blocks reconciliation of drug-related memories, neuroplasticity and neurogenesis, and enhancing psychological therapy.

We know that addiction is a chronic relapsing disorder with cravings, drug seeking, and unpleasant withdrawal symptoms upon cessation of the drug. Relapse rates with current therapies are between 40-80%.

Pre-clinical research on Ketamine has shown effectiveness in alcohol intake in a rat model:

Alcohol-preferring rats could self-administer
0.08% weight/volume saccharin, 10% weight/volume ethanol or
water. After intraperitoneal administration of either ketamine or
memantine, operant responding and motor activity were assessed.
A dose of 20 mg/kg of ketamine reduced ethanol administration
significantly (33.3% less than vehicle-treated rats) without affecting
motor activity and water consumption. Importantly, coadministration
of rapamycin blocked ketamine-mediated reduction
of alcohol intake, but not that of memantine (Sabino et al.,
2013). Similarly, ketamine’s antidepressant effects are suppressed
by rapamycin. mTOR activation is required for the anti-alcohol effect of ketamine, but not memantine, in alcohol-preferring rats

Also:

Both ketamine and NBQX attenuate alcohol drinking in male Wistar rats.

The devastating consequences of alcohol-use disorder (AUD) on the individual and the society are well established. Current treatments of AUD encompass various strategies, all of which have only modest effectiveness. Hence, there is a critical need to develop more efficacious therapies. Recently, specific glutamatergic receptors have been identified as potential novel targets for intervention in AUD. Thus, the current study was designed to evaluate the effects of acute administration of sub-anesthetic doses of ketamine, an NMDA receptor antagonist, as well as NBQX, an AMPA/kainate receptor antagonist on alcohol intake and its possible behavioural consequences. Adult male Wistar rats were trained in drinking in dark paradigm (3 weeks), and following stable alcohol intake, ketamine, NBQX as well as their combination were injected prior to a 90 min drinking session. In addition to alcohol intake, sucrose preference (overnight), and locomotor activity and forced swim test (FST) were also evaluated before and following alcohol intake. Both doses of ketamine (5 and 10 mg/kg) and NBQX (5 and 10 mg/kg) significantly attenuated percent alcohol intake. The combination of the higher dose of ketamine and NBQX, however, did not significantly affect percent alcohol intake. Moreover, animals exposed to alcohol showed decreased sucrose intake (reflective of anhedonia), decreased locomotor activity and swimming in the FST (reflective of helplessness), that were not affected by ketamine and/or NBQX. These results suggest that selective antagonism of the NMDA or AMPA/kainate receptors may be of therapeutic potential in AUD.

Addiction is characterised by disruptions in learning and memory. Addicts develop cue-specific responses to drug-related
cues. One preclinical study examined the effects of ketamine administration on reconsolidation
where memories are rendered more labile following reactivation. After morphine CPP ( conditioned place preference) was induced, rats were intraperitoneally administered 60 mg/kg of ketamine after being reexposed to the conditioned context or while they were in their home cages. After ketamine administration, preference for morphine decreased significantly in the first retest.  This has been interpreted as evidence that ketamine successfully disrupted reconsolidation of the environment-drug memory.

Effects of scopolamine and ketamine on reconsolidation of morphine conditioned place preference in rats

Persistent memory associated with addictive drugs contributes to the relapse of drug abuse. The current study was conducted to examine the effects of scopolamine and ketamine on reconsolidation of morphine-induced conditioned place preference (CPP). In experiment 1, after morphine CPP was acquired, rats were injected with ketamine (60 mg/kg, intraperitoneally) and scopolamine (2 mg/kg, intraperitoneally), respectively, after reexposure to an earlier morphine-paired context or in their home cages. The CPP was reassessed 24 and 48 h after reexposure. An additional group of rats received saline following reexposure to the earlier morphine-paired context. In experiment 2, two groups of rats were only given saline during the CPP training and subsequent administration of ketamine or scopolamine during the reexposure. In experiment 1, rats failed to exhibit morphine CPP when ketamine and scopolamine were administered only after reexposure to a morphine-paired context. CPP was not abolished by ketamine or scopolamine administration in the animals’ home cages. Also, the animals receiving only saline injections showed strong morphine CPP 24 h after a short exposure to the morphine-paired context. In experiment 2, ketamine or scopolamine treatment alone did not induce CPP or aversion. Administration of scopolamine and ketamine, after reexposure to a drug-paired context, resulted in the disruption of morphine CPP, suggesting the potential effects of scopolamine and ketamine in disrupting memory associated with environmental cues and addictive drugs.

The capacity of ketamine to treat addiction was not investigated scientifically until decades later when Krupitsky and
Grinenko (1997), published work that reported the use of ketamineto reduce relapse in recently detoxified alcoholics. These
published results were a review of 10 years of previous research.The procedure that was investigated was referred to as Ketamine Psychedelic Therapy (KPT) and had been applied since the mid-80sin the former Soviet Union, until ketamine was banned in Russia 1998.  Ten Year Study of Ketamine Psychedelic Therapy (KPT) of Alcohol Dependence [

KPT consisted of three stages. The first step was the preparation,during which patients underwent a preliminary psychotherapy session where a psychotherapist discussed with them the content of the psychedelic experience. They were told that under the influence of ketamine, they would view the world symbolically, realise about the negative aspects of alcohol dependence and see the positive sides of sobriety. They were also told that they would become aware of unconscious mental concepts about the negative aspects of their addiction, such as their personal problems and their self-identity. These insights would help them to accept new life values, purposes and meaning of life and in turn e to overcome
their alcoholism. The second stage was the ketamine session in which ketamine was intramuscularly injected and the psychotherapist interacted with the patient. The psychotherapist verbally guided the patient, with the aim of creating new meaning and purpose in life. At moments of highly intense psychedelic experience, the smell of alcohol was introduced to the individuals. The idea was to enhance the negative emotional valence of the thoughts related to alcohol during the session. Finally, group psychotherapy was performed after the session. The aim of this session was to help patients integrate
insights of psychedelic experience into their lives. It is reported that this procedure was used in
over 1000 alcoholics with no reported complications.In Krupitsky and Grinenko, 1997 report, relapse rates in a group
of recently detoxified alcohol dependent patients undergoing KPT (n ¼ 111) were compared with another group of alcohol dependent patients who were treated with treatment as usual (n ¼ 100). Both groups underwent alcohol detoxification before treatment. After these sessions, the KPT group received an intramuscular injection of ketamine (2.5 mg/kg) along with the corresponding preparation. The control group received ‘conventional, standard methods of treatment’ in the same hospital. Only 24% of the control group remained abstinent after a year, whereas 66% of the KPT group did not relapse during the same period (p < .01).

In a further study, 70 detoxified heroin-dependent patients were randomised into two KPT groups, who were injected different doses of ketamine, in a double-blind manner (Krupitsky et al., 2002). One group (n ¼ 35) received 0.2 mg/kg i.m. of ketamine, which was considered an active placebo, whereas the experimental group (n ¼ 35) received 2.0 mg/kg i.m. After two years, the higher dose of ketamine resulted in a greater rate of abstinence (17% vs 2% abstinent subjects, p < .05). Additionally, the experimental group had a larger positive change in nonverbal unconscious emotional attitudes and a greater and longer-lasting reduction in craving for heroin. The authors therefore concluded that effectiveness of ketamine
was dose dependent. Ketamine psychotherapy for heroin addiction: immediate effects and two-year follow-up

In 2007, Krupitsky’s lab compared the impact of a single vs three KPT sessions (dose: 2.0 mg/kg, i.m.) (Krupitsky et al., 2007). Fifty nine detoxified heroin dependent patients first received a KPT session. After this, 6 participants relapsed and abandoned the treatment. The remaining participants were randomised into two groups: one received a further two KPT sessions (n ¼ 26) in monthly intervals, whereas the other underwent two counseling sessions (n ¼ 27) also in monthly intervals. After a year, 50% in the 3-session KPT group remained abstinent compared to 22% in the single KPT (p < .05) (Krupitsky et al., 2007). This clearly demonstrates the superior efficacy of three KPT sessions in comparison to
one KPT session, which indicates that the KPT sessions are beneficial.  Single Versus Repeated Sessions of Ketamine-Assisted Psychotherapy for People with Heroin Dependence 

In a private psychiatric practice in the US, another psychiatrist has successfully conducted KPT since 1994. He has not only treated patients with drug addiction, but also individuals with other types of addictions (e.g. food addiction) and other psychological disorders. His reported anecdotal, clinical findings are positive, having adhered strictly to the original protocol.  Ketamine Enhanced Psychotherapy: Preliminary Clinical Observations on Its Effectiveness in Treating Alcoholism. Kolp, Eli,Friedman, Harris L.,Young, M. Scott,Krupitsky, Evgeny The Humanistic Psychologist, Vol 34(4), 2006, 399-422

Abstract:

Ketamine is a dissociative anesthetic widely used by physicians in the United States and also a psychedelic drug that physicians can legally prescribe off-label within the United States for other therapeutic purposes. It has been used in Russia and elsewhere to successfully treat alcoholism and other psychological or psychiatric problems, but has not been researched for this purpose in the United States. Results of a series of clinical trials using ketamine for treating alcoholism in the United States are retrospectively reported, along with 2 case studies of how psychotherapy facilitated by this substance helped two individuals achieve abstinence through ketamine’s transpersonal effects. Considering the massive problems caused by alcoholism, the need to begin formal research studies on ketamine psychotherapy for alcoholism is emphasized.

In 2014, 8 cocaine dependent males disinterested in treatment received 3 infusions in a double-blind, cross-over design: 0.41 mg/ kg ketamine, 0.71 mg/kg ketamine, and 2 mg lorazepam (an active benzodiazepine control, which induces mild subjective and anxiolytic effects) (Dakwar et al., 2014b). Infusions lasted 52 min and were separated by 48 h. Before and after each infusion, motivation to quit cocaine and cue-induced craving were assessed. Relative to the lorazepam, motivation to quit cocaine was enhanced and cueinduced craving for cocaine was reduced by the 0.4 mg/kg ketamine (both ps ¼ 0.012), and this latter effect was augmented by the 0.71 mg/kg ketamine dose. During the psychedelic experience,
dissociation and mystical-type effects were assessed. As predicted, the higher dose of ketamine led to greater mystical experiences. Strikingly, these mystical-type experiences, but not the dissociative effects, were found to mediate motivation to quit. However, the small non-treatment-seeking sample, the absence of an inactive placebo and the cross-over design, limit the results.Having said that, the participants showed a significant reduction in the frequency and amount of cocaine
consumed in normal life in the 4 weeks following the experiment, compared to baseline. Dakwar, E., Levin, F., Foltin, R.W., Nunes, E.V., Hart, C.L., 2014b. The effects of subanesthetic ketamine infusions on motivation to quit and cue-induced craving in cocaine-dependent research volunteers. Biol. Psychiatry 76, 40e46. https://doi. org/10.1016/j.biopsych.2013.08.009.

Also, more cocaine research from the same group is here:

Cocaine self-administration disrupted by the N-methyl-D-aspartate receptor antagonist ketamine: a randomized, crossover trial E DakwarMolecular Psychiatry volume22pages76–81 (2017) |

Abstract:

Repeated drug consumption may progress to problematic use by triggering neuroplastic adaptations that attenuate sensitivity to natural rewards while increasing reactivity to craving and drug cues. Converging evidence suggests a single sub-anesthetic dose of the N-methyl-D-aspartate receptor antagonist ketamine may work to correct these neuroadaptations and restore motivation for non-drug rewards. Using an established laboratory model aimed at evaluating behavioral shifts in the salience of cocaine now vs money later, we found that ketamine, as compared to the control, significantly decreased cocaine self-administration by 67% relative to baseline at greater than 24 h post-infusion, the most robust reduction observed to date in human cocaine users and the first to involve mechanisms other than stimulant or dopamine agonist effects. These findings signal new directions in medication development for substance use disorders.

Neural plasticity is defined as the cellular and structural reorganisation
of the brain. Synaptogenesis is a crucial mechanism for
plasticity, since for change to happen within brain circuitry new
synapses between neurons must be formed. Surface expression of
AMPARs and upregulation of other synaptic proteins are involved in
the process of synaptogenesis. Diminished glutamatergic synaptic
transmission and reduced plasticity are thought to be associated
with addiction. Existing models suggest that ketamine’s blockade of NMDA receptors
increases synaptogenesis by stimulating protein synthesis
and the insertion of AMPA receptors. Hence, ketamine’s
effects help to reverse the glutamatergic changes associated
with depression and addiction. 

Animal models of addiction, depression and other psychiatric disorders
have been linked to a reduction in adult neurogenesis . It has been suggested that in addiction
the loss of neurogenesis, especially in cortical and hippocampal
regions, may contribute to levels of self-administration and the
vulnerability of relapsing. The reduction of neurogenesis in addiction is supported in
humans by the reduction in BDNF serum levels. In a study, 37
subjects with diagnosis of alcohol dependence showed significantly
reduced BDNF serum levels compared to healthy individuals
. Similarly, cocaine- and heroin-dependentpatients have significantly lower serum BDNF levels and these
seem to recover during withdrawal. Rapid and transient up-regulation of the neuroplasticity marker
BDNF is implicated as a critical component of the antidepressant
mechanism of ketamine . BDNF knock-out mice do not show anti-depressant response to
ketamine in animal models of depression.

Recent research has
demonstrated that ketamine increases peripheral plasma BDNF in
depressed people who respond to treatment but not in treatment
non-responders or patients receiving an active placebo. These BDNF increases in depressed people given ketamine
are robustly correlated with the drug’s antidepressant effects.

It has been found there is a dispersion in normal brain connectivity and the disruption of the usual pattern of communication  in depression and addictions. . The integrity of functional networks decreased, being the
change maximal in functional hubs such as the thalamus, putamen
and high-level association cortices. In particular, connectivity
within the Default Mode Network was reduced between the posterior
cingulate cortex and the mPFC .
The connectivity between the parahippocampal and the retrosplenial
cortex also decreased as well as the segregation between
other major functional networks such as the salience, attention and
different visual networks Infusions of ketamine have shown to decrease connectivity
between and within resting-state consciousness networks.
Connectivity between the mPFC and the rest of the Default
Mode Network (via the posterior cingulate cortex) has been found
to be reduced, along with the integrity and activity of the salience
and visual networks are also affected. Since it is known
that connectivity with the mPFC is elevated in depression , the reduction of connectivity in the Default Mode
Network observed during the psychedelic experience might be a
mechanism that helps treat depressive states, which are very
common in addicts and predictive of relapse.

Given addiction is highly co-morbid with depression   and ketamine’s role within psychiatry changed
dramatically when it was discovered to be an anti-depressant, we
now briefly describe the research concerning ketamine and
depression. In 2000, the first clinical trial hinted at the potential of
ketamine as a treatment for depression. Four subjects diagnosed
with depression were intravenously administered 0.5 mg/kg of
ketamine in a randomised, double-blind design. The results were
compared to the injection of saline solutions in 3 subjects with an
equivalent diagnosis. Comparison on the Hamilton Rating Scale for
Depression (HAM-D) showed moderate evidence for a greater
reduction in scores after ketamine infusion compared to saline
(Berman et al., 2000). The reduction was rapid and outlasted the
subjective effects of ketamine, lasting for 3 days after infusion.
Despite the small sample size and the limited follow-up, this result
and anti-depressant effects observed in animal models of depression
encouraged researchers in the field to perform more studies in humans . Since then, over 30 studies have
examined the antidepressants effects of ketamine in patients with
treatment-resistant major depressive and bipolar disorders.

Ketamine has shown a 65-70% response rate in treating
depression within 24 h, which contrasts with the ~47% response
rate of conventional monoaminergic antidepressants after weeks
or months . Furthermore,
ketamine’s antidepressant actions are almost immediate and last
for approximately a week ,
whereas conventional antidepressive medications take weeks to
have an effect, are given daily and most of them fail to exert long lasting
effects . Furthermore, studies
have consistently shown that after a ketamine infusion there is a
significant reduction in suicidal ideation which also lasts for several
days.Depression and addiction’s co-expression is almost ubiquitous
People with alcohol, opioids, cannabis and
cocaine use disorders show notably higher rates of depression than
the average of the general population. Furthermore, high levels of depression and anxiety
may predispose relapse to: heroin, alcohol, cannabis and cocaine.

Memories and their creation and alteration is felt to be at the heart of cues and triggers and relapse in addiction. Once consolidated, memories are thought to be stored in a
stabilised state after initial acquisition. Shortly after reactivation
(i.e. remembered) of consolidated memories, these are rendered
transiently unstable and labile, before they then re-stabilise. This
process has been named reconsolidation . After reconsolidation,
the memories are stored again, but they may have been slightly
altered or updated. Each time memories are reactivated the latest
version is retrieved and they are again susceptible to change. During reconsolidation memories may be vulnerable to
manipulation and disruption. This was first demonstrated in animals
using fear conditioning. Rodents were trained to associate a
neutral stimulus with a shock such that the neutral stimulus elicited
a fear response. Researchers eliminated this fear response by
pharmacologically disrupting the reconsolidation process . Reward memories can also be disrupted such that a
neutral stimulus that once elicited appetitive behaviour no longer
does so. Therefore, non-pharmacological and drug therapies that
aim at weakening drug-cue memories via manipulation of reconsolidation
are of interest. Preclinical studies have shown that ketamine affects reconsolidation
of drug memories. . A recent review has suggested that ketamine (along with other psychedelics)
may be able to disrupt maladaptive appetitive memories
(Fattore et al., 2017).  Psychedelics and reconsolidation of traumatic and appetitive maladaptive memories: focus on cannabinoids and ketamine

Article ABSTRACT:

Rationale

Clinical data with 3,4-methylenedioxymethamphetamine (MDMA) in post-traumatic stress disorder (PTSD) patients recently stimulated interest on the potential therapeutic use of psychedelics in disorders characterized by maladaptive memories, including substance use disorders (SUD). The rationale for the use of MDMA in PTSD and SUD is being extended to a broader beneficial “psychedelic effect,” which is supporting further clinical investigations, in spite of the lack of mechanistic hypothesis. Considering that the retrieval of emotional memories reactivates specific brain mechanisms vulnerable to inhibition, interference, or strengthening (i.e., the reconsolidation process), it was proposed that the ability to retrieve and change these maladaptive memories might be a novel intervention for PTSD and SUD. The mechanisms underlying MDMA effects indicate memory reconsolidation modulation as a hypothetical process underlying its efficacy.

Objective

Mechanistic and clinical studies with other two classes of psychedelic substances, namely cannabinoids and ketamine, are providing data in support of a potential use in PTSD and SUD based on the modulation of traumatic and appetitive memory reconsolidation, respectively. Here, we review preclinical and clinical data on cannabinoids and ketamine effects on biobehavioral processes related to the reconsolidation of maladaptive memories.

Results

We report the findings supporting (or not) the working hypothesis linking the potential therapeutic effect of these substances to the underlying reconsolidation process. We also proposed possible approaches for testing the use of these two classes of drugs within the current paradigm of reconsolidation memory inhibition.

Furthermore, a meta-analysis of pre-clinical
studies found evidence suggesting that NMDAR antagonists can
be used to target reward memory reconsolidation, and more successfully
than adrenergic antagonists such as propranolol (Das
et al., 2013)  Das, R.K., Freeman, T.P., Kamboj, S.K., 2013. The effects of N-methyl d-aspartate and B-adrenergic receptor antagonists on the reconsolidation of reward memory: a meta-analysis. Neurosci. Biobehav. Rev. 37, 240-255.:

Abstract

Pharmacological memory reconsolidation blockade provides a potential mechanism for ameliorating the maladaptive reward memories underlying relapse in addiction. Two of the most promising classes of drug that interfere with reconsolidation and have translational potential for human use are N-methyl-d-aspartate receptor (NMDAR) and B-Adrenergic receptor (B-AR) antagonists. We used meta-analysis and meta-regression to assess the effects of these drugs on the reconsolidation of reward memory in preclinical models of addiction. Pharmacokinetic, mnemonic and methodological factors were assessed for their moderating impact on effect sizes. An analysis of 52 independent effect sizes (NMDAR = 30, B-AR = 22) found robust effects of both classes of drug on memory reconsolidation, but a far greater overall effect of NMDAR antagonism than B-AR antagonism. Significant moderating effects of drug dose, relapse process and primary reinforcer were found. The findings suggest that reward memory reconsolidation can be robustly targeted by NMDAR antagonists and to a lesser extent, by B-AR antagonists. Implications for future clinical work are discussed.

Highlights

► Meta-analysis of NMDAR and B-adrenergic antagonists in preclinical reward reconsolidation. ► Larger effects of NMDAR (r = .613) than B-adrenergic (r = .24) antagonists were found. ► ‘Relapse process’, trace type, reinforcer and drug dose moderated effect sizes. ► NMDAR antagonists particularly might be of clinical use in treating addiction.

 

.

                                 Mystical experiences and psychedelic effects

Mystical experiences and psychedelic effects provoked by
classic psychedelic drugs have been shown to be psychologically
beneficial in long-term studies.They have not only been linked with positive
outcomes in various treatments, but also to ‘life-changing’,
‘spiritually meaningful’ and ‘eye opening’ events.In the ketamine studies described
above, anecdotal and qualitative reports suggest that the subjective
psychedelic experience seemed to help patients. For example, to
help them: undergo a cathartic process, improve relationships with
the world and other people, maintain positive psychological
changes and enhance self-awareness and personal growth.During KPT, patients reported a feeling of ‘resolution’ and
‘catharsis’ of some psychological problems, mainly those related to
alcohol. Furthermore, the degree of mystical experience was also
linked to the insight and impact of KPT reported by patients
. Interestingly, the intensity of the negative experiences (experiences associated
with negative emotions, fear and horror) during the
ketamine session was associated with longer remission. This was
blindly and quantitatively assessed by analysing patient’s selfreports.
Moreover, spirituality, self-concept, emotional attitudes
to other people and positive changes in life values and purposes
were improved after the ketamine experience.

Notably, ketamine’s mystical experiences, but not dissociative
effects, were found to mediate ketamine’s increase motivation to
quit 24 h after the infusion in cocaine addicts .
Moreover, consistent with previous studies, it was also observed
that mystical experiences were positively dose-dependent. This
study therefore provides evidence that the mystical experience
induced by ketamine is important in its therapeutic mechanism
. Speculatively, mystical experiences may help
to rapidly shift patients’ mindsets towards the integration and
acceptance of a sober lifestyle.

The acute disruptions of the functional networks, especially the
alterations to the default mode network, are related to the psychedelic
experience. In fact, the degree of network dissolution in
LSD and psilocybin is correlated with the intensity of the psychedelic
experience . The disruption to the default mode network may engender a reduction
in rumination and maladaptive repetitive thoughts. Psychological
therapies for addiction often aim to help the patient consider
different ways of life, especially those without the drug, and a
pharmacological agent such as ketamine which expedites that
process may be useful in treating addiction.

Speculatively, ketamine can
provide a unique mental state during and after acute drug effects
that facilitates and enriches therapeutic experiences, which in turn
may improve efficacy and lengthen treatment effects. Furthermore, synaptogenesis
and neurogenesis are putatively critical in learning new
information . The uptake of psychological therapy may
therefore be facilitated after ketamine infusions due increases in
synaptogenesis and neurogenesis, and thus improved learning of
relapse-reducing strategies, such as those used in relapseprevention
based cognitive behavioural therapy (CBT). In fact, the
idea that neurogenesis and synaptogenesis work synergistically
with psychological therapies is becoming recognised as a new
approach in the treatment of mental disorders . Theoretically, the administration of ketamine (which can
produce a ‘psychedelic’ experience) may open people’s minds so
they are more able to embrace what is presented during therapy as
well as enhancing the uptake of new therapeutic content.

The promise of ketamine in the treatment of addiction is supported
by research with large treatment effect sizes, especially in
comparison to existing treatments. In recently detoxified alcoholics,
ketamine treatment increased one-year abstinence rates in
alcoholics from 24% in the control to 66% in the ketamine group
(Krupitsky and Grinenko, 1997) and reduced cocaine self administration
by 67% relative to baseline in non-treatment
seeking cocaine users (Dakwar et al., 2016). These results clearly
demonstrate profound effects of ketamine administration (with
and without therapy) on drug and alcohol use, of an order of
magnitude which is 2 or 3 times more effective than existing
pharmacotherapies.

Ketamine for the treatment of addiction Evidence and potential mechanisms

Area Codes Near NOVA Health Recovery (703-844-0184)::
Maryland (MD): Bethesda 20814 – Bethesda 20816 – Bethesda 20817 – Chevy Chase 20815 – Colesville 20904 – Cabin John 20815 – Glen Echo 20812 – Gaithersburg 20855 – Gaithersburg 20877- Gaithersburg 20878 – Gaithersburg 20879 – Garrett Park 20896 – Kensington 20895 – Montgomery Village 20886 – Olney 20830 – Olney 20832 – Potomac 20854 – Potomac 20859 – Rockville 20850 – Rockville 20852 – Rockville 20853 – Silver Spring 20903 – Silver Spring 20905 – Silver Spring 20906 – Silver Spring 20910 – Takoma Park 20912 – Wheaton 20902 Washington DC: Crestwood 20011- North Capitol Hill 20002 – Cathedral Heights 20016 – American University Park 20016 – Columbia Heights 20010 – Mount Pleasant 20010 – Downtown 20036 – Dupont Circle 20009 – Logan Circle 20005- Adams Morgan 20009 – Chevy Chase 20015 – Georgetown 20007 – Cleveland Park 20008 – Foggy Bottom 20037 – Rock Creek Park – Woodley Park 20008 – Tenleytown 20016 Northern Virginia: McLean 22101- McLean 22102 – McLean 22106 – Great Falls 22066 – Arlington 22201 – Arlington 22202 – Arlington 22203 – Arlington 22205 – Falls Church 22041 – Vienna 22181 – Alexandria 22314 – 22308 -22306 -22305 -22304 Fairfax – 20191 – Reston – 22009 – Springfield – 22152 22015 Lorton 22199 Fairfax, Va 2303 – 22307 – 22306 – 22309 – 22308 22311 – 22310 – 22312 22315 -22003 – 20120 – 22015 – 22027 20121 – 22031 – 20124 22030 – 22033 – 22032 – 22035 – 22039 22041 – 22043 22042 – 22046 – 22044 – 22060 – 22066 20151 – 22079 – 20153 – 22101 22102 – 20171 – 20170 – 22124 – 22151 22150 – 22153 22152 – 20191 – 20190 – 22181- 20192 22180 – 20194 – 22182 Woodbridge – 22191 – 22192 -22193 -22194 – 22195 Springfield – 22150 – 22151 -22152-22153-22154-22155 -22156 – 22157 -22158 -22159 -22160

 

 

 

 

 

 

 

 

 

 

 

 

 

Heroin addiction hotline – in Fairfax, Va call 703-844-0184

CAll 703-844-0184 for an immediate appointment!

Ketaminealexandria.com    703-844-0184 Call for an infusion to treat your depression. PTSD, Anxiety, CRPS, or other pain disorder today.

email@novahealthrecovery.com

Ketamine center in Fairfax, Virginia    << Ketamine infusions

NOVA Health Recovery – KETAMINE SYSTEMS<< Link

NOVA Addiction Specialists website – Suboxone and telemedicine treatment in Alexandria, Virginia 703-844-0184

Dr. Sendi – at NOVA Addiction Specialists can evaluate you to see if Sublocade will work for you.

NOVA Addiction facebook page

Suboxone treatment in Alexandria, Virginia 703-844-0184

Suboxone treatment in Fairfax, Virginia 703-844-0184

http://www.suboxonewoodbridge.com

Suboxone, buprenorphine telemedicine treatment in Alexandria  << Link here

http://addictiondomain.com/ Addiction Blog

https://www.facebook.com/novaddiction – Facebook page

http://www.suboxonealexandria.com

http://www.suboxonecenter.org/ Suboxone treatment – telemedicine also – 703-844-0184 24/7

For a more general link to a heroin recovery hotline link for your area, click the link below:

 

 

https://www.therecoveryvillage.com/heroin-addiction/    <<< Heroin addiction hotline for your area

 

Area codes treated by Dr. Sendi at NOVA Addiction Specialists:

Maryland (MD):
Bethesda 20814 – Bethesda 20816 – Bethesda 20817 – Chevy Chase 20815 – Colesville 20904 – Cabin John 20815 – Glen Echo 20812 – Gaithersburg 20855 – Gaithersburg 20877- Gaithersburg 20878 – Gaithersburg 20879 – Garrett Park 20896 – Kensington 20895 – Montgomery Village 20886 – Olney 20830 – Olney 20832 – Potomac 20854 – Potomac 20859 – Rockville 20850 – Rockville 20852 – Rockville 20853 – Silver Spring 20903 – Silver Spring 20905 – Silver Spring 20906 – Silver Spring 20910 – Takoma Park 20912 – Wheaton 20902

Washington DC:
Crestwood 20011- North Capitol Hill 20002 – Cathedral Heights 20016 – American University Park 20016 – Columbia Heights 20010 – Mount Pleasant 20010 – Downtown 20036 – Dupont Circle 20009 – Logan Circle 20005- Adams Morgan 20009 – Chevy Chase 20015 – Georgetown 20007 – Cleveland Park 20008 – Foggy Bottom 20037 – Rock Creek Park – Woodley Park 20008 – Tenleytown 20016

Northern Virginia:
McLean 22101- McLean 22102 – McLean 22106 – Great Falls 22066 – Arlington 22201 – Arlington 22202 – Arlington 22203 – Arlington 22205 – Falls Church 22041 – Vienna 22181 – Alexandria 22314 – 22308 -22306 -22305 -22304 Fairfax – 20191 – Reston – 22009 – Springfield – 22152 22015 Lorton 22199
Fairfax, Va
2303 – 22307 – 22306 – 22309 – 22308 22311 – 22310 – 22312
22315 -22003 – 20120 – 22015 – 22027 20121 – 22031 – 20124
22030 – 22033 – 22032 – 22035 – 22039 22041 – 22043
22042 – 22046 – 22044 – 22060 – 22066 20151 – 22079 – 20153 – 22101
22102 – 20171 – 20170 – 22124 – 22151 22150 – 22153
22152 – 20191 – 20190 – 22181- 20192 22180 – 20194 – 22182
Woodbridge – 22191 – 22192 -22193 -22194 – 22195
Springfield – 22150 – 22151 -22152-22153-22154-22155 -22156 – 22157 -22158 -22159 -22160 – 22161
Front Royal 22630
Warren County 22610 22630 22642 22649
Fredericksburg Va 22401 22402 – 22403 – 22404 -22405 -22406 -22407 -22408 – 22412

Heroin and Death – more examples – 703-844-0184 Suboxone treatment Alexandria in Fairfax https://www.novaddiction.com/

Fairfax mother of young heroin addict: ‘There were clues. But we had no clue.’     << Link  to article

Suboxone treatment in Fairfax in Alexandria — Opioid abuse and alcohol treatment – telemedicine

<iframe width=’480′ height=’290′ scrolling=’no’ src=’https://www.washingtonpost.com/video/c/embed/ae95a37e-c3eb-11e3-9ee7-02c1e10a03f0′ frameborder=’0′ webkitallowfullscreen mozallowfullscreen allowfullscreen></iframe>

 

A decade into a federal crackdown on the street use of prescription painkillers such as Vicodin, Percocet or OxyContin, many addicts have switched to heroin because it is cheaper and easier to find.

Heroin use spiked 79 percent in the United States from 2007 to 2012. Heroin-related deaths jumped 58 percent in Maryland from 2011 to 2012 — and nearly doubled in Montgomery County, from 11 to 21. In Virginia, heroin-related deaths jumped from 101 to 213 between 2011 and 2013, according to preliminary data, and more than doubled in the District from 2010 to 2013.

Addicts seeking publicly funded treatment in Virginia face an average wait of 18 days, said Mellie Randall of the state’s Department of Behavioral Health and Developmental Services. The number of publicly funded residential treatment beds is shrinking. State funding is locked at the same amount it was in 2009, and federal funding has been essentially flat since 2002.

Patients on Buprenorphine frequently receive opioid prescriptions as well: Washington Post Article 2-24-2017

NOVA Addiction Specialists LLC – serving Northern Virginia in alcohol and opioid addiction treatments, including Suboxone and Probuphine therapies

https://www.facebook.com/novaddiction/

 

Addiction and opioid Prescriptions still alarmingly high – Washington Post Article

I attached the above Washington Post Article from 2-24-2017 regarding prescription opioids and addiction. It was noted in a study that patients on buprenorphine (Suboxone) were filling out other opioid prescriptions 43% of the time. Whether it was used by the patient or diverted is unknown.

The sane study also showed that patients stayed on Suboxone or buprenorphine products for just 55 days on average. You can’y say they were cured during that time, and most dd not migrate to Methadone.

It is common to hear complaints that the treatment is expensive. Th e medication costs ~250$/month as does the physician visit. It sounds like a lot, but think of the cost of opioid abuse and overdose? Street cost for oxycodone may be up to $40 a pill, and heroin habits can cost several hundred dollars a day. In addition, these same people are unable to  work well at their job, They frequently obtain the extra money in unsafe or illegal means.

Databases are allowing easier tracking of these patients.

What is depressing is that there is no defined period of acceptable treatment with Buprenorphine. Studies show relapse in 40-60% of all patients. Research is clear that medication -assisted treatment (Methadone or Suboxone) is the most successful way to combat addiction.

 

Heroin abuse, memory loss, ageing, and disconnected brains

Opioid abuse has many risks involved, some lethal, while others are life-altering. One such possible poor outcome is acute memory loss.  Cases have been surfacing of heroin abusers losing short and long term memory. The first case documented was in France, in which a person became disoriented with poor executive functioning after snorting heroin:

33 yo French man has hippocampal stroke – reulting in memory loss:

(Neurocase. 2013 Aug;19(4):313-5. doi: 10.1080/13554794.2012.667125. Epub 2012 May 25.)

A 33-year-old man presented to our clinic with amnesia 48 hours after his first heroin inhalation. Examination showed lateral tongue biting and anterograde amnesia demonstrated by impaired performance on verbal and visual Wechsler Memory Scale-Revised tests carried out 10 days after onset, suggesting hippocampal involvement. Magnetic resonance imaging (MRI) of the brain was performed 48 hours after heroin snorting and evoked cortical laminar necrosis (CLN) of the left hippocampus without vascular abnormality. This is the first description of complete hippocampal CLN as a complication subsequent to acute intranasal heroine abuse. While the pathogenic mechanism remains uncertain, our case provides a very specific MRI lesion pattern and highlights the risk of intranasal heroin uptake-induced neurological complication.

Mysterious cluster of amnesia cases, possibly tied to opioids, alarms health officials

 

The report of clusters of amnesia initiated with MMWR as below:

Cluster of an Unusual Amnestic Syndrome — Massachusetts, 2012–2016 _ MMWR  See below for abstracts:

Summary

What is already known about this topic?

Acute, complete, and bilateral ischemia of the hippocampus is a rare cause of memory loss (associated with toxic exposure, among other etiologies) that has been reported rarely and in isolation. A single 2013 case of complete unilateral hippocampal ischemia has been linked to heroin inhalation.

What is added by this report?

A unique cluster of 14 cases of sudden onset amnesia with acute, complete, and bilateral ischemia of the hippocampus was identified in Massachusetts during 2012–2016. No clear etiology exists, but at time of initial evaluation, 13 of 14 tested positive for opioids or had opioid use recorded in their medical history.

What are the implications for public health practice?

The apparent temporospatial clustering, relatively young age at onset (19–52 years), and extensive substance use associated with this group of patients suggests broader surveillance is needed to determine whether this represents an emerging syndrome related to substance use or other causes, including introduction of a toxic substance.

The combination of clinical findings described in this report has previously been reported rarely and in isolation, associated with isolated cocaine use, influenza, and carbon monoxide poisoning (26). This cluster of amnestic syndrome associated with bilateral complete hippocampal ischemia is unusual given the absence of a readily identifiable etiology, the temporospatial clustering, relatively young patient age, and extensive substance use among affected persons.

Cardiopulmonary, cerebrovascular, or other mechanisms might serve as plausible explanations underlying certain findings. Hypoxemic injury to the relatively vulnerable hippocampal regions, for example, has been raised as one possibility (10). However, further case identification and reporting are needed to determine whether these combined observations represent an emerging syndrome related to substance use or other causes (e.g., a toxic exposure).

 

Neurobiological underpinnings of sensation seeking in heroin abusers

A long-term effect of heroin use on brain structure includes  a consistent finding  that abstinent heroin users have reduced gray matter volume in the prefrontal cortex , among other brain regions.  At the psychological level, sensation seeking and impulsivity traits are two personality constructs commonly associated with heroin addiction. Resting state functional connectivity studies found abnormal coupling in brain regions associated with reward processing and cognitive control. Animal models of addiction demonstrated that the reward system is critically involved in heroin-seeking behavior. Two personality constructs closely linked with heroin abuse are sensation seeking and impulsivity traits . Sensation seeking refers to need to seek intense sensations and the desire to engage in risky behavior associated with such sensations ). Individuals with heroin addiction scored higher on this trait compared to controls, even after adjusting for group differences in age, education, and intelligence ). Impulsivity refers to the degree of behavioral control over novel or distracting stimuli and is known to underlie impulsive behavior in various forms of addiction.  A relatively recent study revealed that higher impulsivity trait is associated with lower structural volume of the ventromedial prefrontal cortex.  Heroin abuse might be associated with a particular vulnerability in midbrain dopaminergic synthesis.  The atypical midbrain–sensation seeking relationship this study revealed was such that there was an upward slope between midbrain volume and sensation seeking in healthy controls, but the reverse for the high sensation seeking heroin abusers. Findings suggest that heroin users’ pathologically high sensation seeking trait is more closely related to dopamine properties within the midbrain,  Compared to healthy controls, higher sensation seeking in heroin users was correlated with decreased coupling between the midbrain and DLPFC, but increased coupling between the midbrain and VMPFC. A recent observation has been that heroin abuse is associated with acceleration in biological aging. In the context of addiction, it has been suggested that the DLPFC underlies effortful, top-down executive control that guides behavior in the presence of salient stimulation (e. g., drug-related reward signals)  In the context of addiction, it has been suggested that the DLPFC underlies effortful, top-down executive control that guides behavior in the presence of salient stimulation (e. g., drug-related reward signals) Consistently, the acute effect of heroin was found to reduce response at a lateral prefrontal area in relation to stimulus-driven attention . Although also involved in the guidance of behavior, the VMPFC appears to be deeply implicated in impaired utilization of information on expected outcomes, resulting in the intense “drive” for and compulsion towards drug-taking behavior. In a healthy model, intact top-down control suppresses the learned associations in relation to drug cues, but in heroin users, this suppression diminishes due to the failure of the midbrain–DLPFC coupling. Alternatively, it was also possible that for heroin users, hyperconnectivity between the brain systems that subserve reward signals disturbs the healthy topdown control that guides healthy behavior. Past abusers of heroin are associated with atypical relationships between high sensation seeking trait and midbrain structural volume, together with the midbrain’s functional coupling with the PFC. Furthermore, the direction of midbrain’s couplings with the DLPFC and VMPFC are differentially related to the sensation seeking trait, such that there is a weaker midbrain–DLPFC coupling and stronger midbrain–VMPFC coupling in the heroin abusers. 

So, heroin abuse is associated with hippocampal strokes and memory loss, disconnected brain regions leading to loss of interpreting cues of sensation seeking and impulsivity. Finally, evidence shows that heroin use ages people as well:

Heroin abuse accelerates biological aging a novel insight from telomerase and brain imaging interaction

Heroin abuse and natural aging exert common influences on immunological cell functioning. This observation led to a recent and untested idea that aging may be accelerated in abusers of heroin. We examined this claim by testing whether heroin use is associated with premature aging at both cellular and brain system levels. A group of abstinent heroin users (n=33) and matched healthy controls (n=30) were recruited and measured on various biological indicators of aging. These measures included peripheral blood telomerase activity, which reflects cellular aging, and both structural and functional measures of brain magnetic resonance imaging. We found that heroin users were characterized by significantly low telomerase activity (0.21 vs 1.78; 88% reduction; t(61)=6.96, P<0.001; 95% confidence interval=1.12–2.02), which interacted with heroin use to affect the structural integrity of gray and white matter of the prefrontal cortex (PFC; AlphaSim corrected P<0.05), a key brain region implicated in aging. Using the PFC location identified from the structural analyses as a ‘seed’ region, it was further revealed that telomerase activity interacted with heroin use to impact age-sensitive brain functional networks (AlphaSim corrected P<0.05), which correlated with behavioral performance on executive functioning, memory and attentional control (Pearson correlation, all P<0.05). To our knowledge, this study is the first to attempt a direct integration of peripheral molecular, brain system and behavioral measures in the context of substance abuse. The present finding that heroin abuse is associated with accelerated aging at both cellular and brain system levels is novel and forms a unique contribution to our knowledge in how the biological processes of drug abusers may be disrupted.

Four main results emerged: (1) long-term heroin users had significantly lower telomerase activity, which is an index of cellular aging; (2) low telomerase activity in the heroin users was associated with compromised structural integrity of the right DLPFC; (3) low telomerase activity in the heroin users was associated with an altered pattern of functional connectivity between the right DLPFC and brain regions implicated in heroin abuse and aging; and (4) functional brain regions found to interact with heroin abuse and aging correlated with behavioral performance that are consistent with each of the brain regions’ cognitive domain, namely executive functioning, memory and attentional control.

Heroin and telomerase: acceleration in cellular aging

The observation that long-term heroin abuse is associated with significantly lower telomerase activity suggests that cellular aging may be accelerated in heroin users, consistent with a previously established hypothesis.8 It is also consistent with studies that demonstrated a close-knit relationship between telomerase activity and mental states known to impact physical health. Specifically, acute and chronic stress could elevate and alleviate telomerase activity, respectively.14, 15 Studies on psychiatric conditions reported elevated telomerase activity in unmedicated patients with depression16 and alleviated telomerase activity in an animal model of schizophrenia.17 It was also reported that mentally enhancing activities, such as meditation, could elevate telomerase activity.18 Although these studies seemingly disagreed about whether a pathological state increases or decreases activity levels of telomerase, they need not be incompatible with each other. It is possible that decreased telomerase activity reflects both pathological (reduced cell protection) and beneficial (reduced need to protect) processes. Owing to heroin’s deleterious impact on immunologically related biomarkers,2 it is reasonable to assume that the current observation of lowered telomerase activity in heroin users fits into the pathological model in which heroin abuse exacerbates cellular aging.

 

DLPFC structural alteration: aging at brain system level

If lower telomerase activity in heroin users indeed reflects accelerated aging, then heroin abuse and telomerase activity should interact to impact brain systems related to both heroin abuse and aging. Our observation that the heroin users’ low telomerase activity was associated with greater DLPFC atrophy was therefore consistent with this prediction. The PFC is a key brain area implicated in the neuropathology of drug addiction. In particular, DLPFC is the likely region that mediates the link between substance abuse and impaired higher-cognitive processes.55 Previous neuroimaging studies reported both structural and functional deficits of DLPFC in heroin abusers, especially in the context of cognitively demanding tasks.37, 56 In the context of aging, the DLPFC is one of the most consistently reported brain areas to show an age-sensitive decline,20which is related to the deterioration of various cognitive functions.25Furthermore, our finding that the right, but not left, DLPFC is implicated in heroin-associated aging is compatible with the ‘right hemi-aging’ hypothesis, which suggests that the right lateral PFC is most vulnerable to age-related decline.57 Therefore, the finding that heroin abuse and telomerase activity interacted on the right DLPFC provides us with an additional hint that heroin abuse may accelerate biological aging, and such aging may extend from the cellular to the brain system level.

 

Functional connectivity: the executive functioning, memory and attentional control networks

Resting state functional connectivity is a measure of the intrinsic, spontaneous functional organization of brain systems58 and is reflective of neuronal metabolic processes.59 Functional connectivity of five brain regions with the right DLPFC was found to be abnormally associated with heroin abuse and telomerase activity. In line with the observed behavioral correlates of these regions, they could be broadly divided into three networks in conjunction with the DLPFC: the executive functioning network (OFC), the memory network (EC) and the attentional control network (ACC and OP).

Interaction between the DLPFC and the OFC has been implicated in executive functions and decision-making processes.60 One key theory of decision making posits that the DLPFC mediates ‘cold’ cognition, which acts as an executive control over the emotive ‘hot’ cognition of the OFC.61 It has been proposed that the breakdown in the DLPFC-OFC balance underlies the irresistible urge that leads to compulsive drug taking.55 In the context of heroin abuse, we have previously presented evidence that support this neurocognitive disease model. Specifically, it was found that heroin abusers were characterized by deficits in impulse control,62, 63 which forms a vital component of executive functioning.64 A recent study provides additional support for the DLPFC-OFC imbalance proposal by showing reduced resting-state functional connectivity between these brain regions in heroin abusers.65 The present finding indicates that for the heroin users, there was a negative coupling between the DLPFC and the OFC (which correlated with the performance on executive functioning), but such coupling diminished as telomerase activity decreased. This suggests that a greater acceleration of the cellular aging process in the heroin users was associated with more severe atrophy in the DLPFC-OFC functional connectivity. This interpretation is consistent with both the prefrontal theories of drug addiction55 and the aging literature, which has demonstrated that aging can have a detrimental impact on OFC functions, including reward-based decision-making66 and learning reversal.67

The EC, part of the MTL, was also negatively coupled with the DLPFC in the heroin users, and this negative coupling also diminished as telomerase activity decreased. The DLPFC-EC coupling correlated with performance on executive functioning, suggesting that the connection between these regions form part of the executive functioning network. The DLPFC-EC coupling also correlated with two behavioral tasks related to memory: the n-back task (working memory) and the PAL task (learning and memory). This finding supports our view that the abnormal DLPFC-EC functional connectivity in heroin users also mediates a memory network. There seems to be an intricate relationship between memory and addiction processes at both cellular and brain system levels.38, 68, 69 In relation to prefrontal functioning, it has been suggested that the failure in prefrontal control mechanisms prevents successful suppression of drug-related memory, which triggers addiction processes such as relapse.38 The present observation that EC, but not the hippocampus proper, is related to heroin abuse and aging is an interesting finding. Despite prominent atrophy to the hippocampus as a function of increasing age, the EC is relatively resistant to damage from healthy aging.70 Importantly, the EC seems particularly implicated in age-related diseases, such as dementia. It has been shown that the extent of EC atrophy is predictive of future progression from the healthy to disease state.71, 72, 73 The present EC finding therefore suggests that low telomerase activity in heroin users is also involved in triggering mechanisms that prelude age-related diseases, rather than plain acceleration of healthy aging.

Heroin abuse and low telomerase activity was also related to the functional connectivity between the DLPFC and three other brain regions, namely, the superior OP, the ACC and the STG. Two of these brain regions, the OP and the ACC, are part of the several regions implicated in attention and cognitive control processes.74 The observation that both the DLPFC-OP and the DLPFC-ACC couplings correlated with the performance on the flanker task supported our view that these regions mediate an attentional control network. The attentional control system in heroin abusers (and addiction in general) is known to characterize a bias such that an abnormally large attentional focus is put on drug-related stimuli.75 A recent functional connectivity study on cannabis abuse reported converging evidence of an abnormal connectivity pattern between the PFC and the OP in relation to attentional processes.76 Likewise, deficit in attentional control and related neural circuitry is characteristic of aging.77, 78 It is therefore not a surprise that the attentional system was affected by both heroin abuse and low telomerase activity. Last, the DLPFC-STG functional connectivity was not found to relate to any of the behavioral measures included in this study. An explanation for this observation is that the DLPFC-STG coupling denotes a function that was not part of our primary interest (for instance, auditory processing, which is a known key function of the STG).

Limitations and future directions

The present study consists of several limitations that must be taken into consideration. First, the correlative nature of this study prevents an inference on cause and effect. Although the present findings suggest that heroin abuse may accelerate biological aging, prospective studies are needed to establish the causative mechanisms that mediate heroin abuse and biological aging. Second, telomerase activity was measured via peripheral blood rather than directly from the brain where system level measures were derived and examined with telomerase. Despite the existence of telomerase in neural progenitor cells of the brain,79 to measure it in vivo is not yet feasible. For this reason, we used peripheral telomerase activity as a solution for measuring cellular aging. Moreover, future studies should adopt a multi-aging molecular biomarker approach to further elucidate the relationship between heroin abuse and aging. Third, only male participants were recruited as female abusers of heroin are less prevalent to their male counterparts. Finally, it is important to test whether the present findings are specific to heroin use or a general pattern observable in people who abuse other substances. Previously documented effects of heroin on age-related immunological biomarkers led us to investigate heroin addiction in the present study. However, a recent study provides important evidence that cocaine abuse could also accelerate aging at the brain system level.80

Evidence of accelerated ageing in clinical drug addiction from immune, hepatic and metabolic biomarkers.

In the absence of HIV infection chronic antigenic stimulation in addiction can originate from dental, bronchial and cutaneous foci, from chronic hepatic inflammation and viral shedding, from the use of drugs, and the endobronchial absorption and intravascular injection of particulate substances all of which are directly active on immune cells and the injection of particulate impurities including microbial organisms and antigens. Hence the situation in addiction closely parallels that in ageing, as both demonstrate chronic antigenic overload, immune stimulation, immunosuppression and signs of accelerated ageing. Hence the immune system may not only be a spectator in both the ageing process and in addiction, but a major effector of time dependent decay. 

Results: 739 drug addicted (DA) and 5834 general medical (GM) age matched blood samples were compared. Significant elevation of immune parameters was noted in the C-reactive protein, erythrocyte sedimentation rate, total lymphocyte count, serum globulins and the globulin:albumin ratio (P < 0.01). Alanine aminotranferase, creatinine, urea, and insulin like growth factor-1 were also significantly higher (P < 0.01) in the DA group. Albumin, body mass index and dihydroepiandrosterone sulphate were unchanged and cholesterol was lower (all P < 0.05). Conclusion: These data demonstrate for the first time that addiction is associated with an altered profile of common biomarkers of ageing raising the possibility that the ageing process may be altered in this group. Infective and immune processes may be centrally involved. They suggest that addiction forms an interesting model to further examine the contribution of immune suppression and hyperstimulation to the ageing process.

Of course, the epidemic may just be the early phases of the Walking Dead: 🙂

“Zombie” Outbreak Caused by the Synthetic Cannabinoid AMB-FUBINACA in New York

  1. McCarthy L, Wetzel M, Sliker JK, Eisenstein TK, Rogers TJ. Opioids, opioid receptors, and the immune response. Drug Alcohol Depend 2001; 62: 111–123. | Article | PubMed | ISI |
  2. Reece AS. Evidence of accelerated ageing in clinical drug addiction from immune, hepatic and metabolic biomarkers. Immun Ageing 2007; 4: 6. | Article | PubMed | CAS |
  3. Smyth B, Hoffman V, Fan J, Hser YI. Years of potential life lost among heroin addicts 33 years after treatment. Prev Med 2007; 44: 369–374. | Article | PubMed |
  4. Brugal MT, Domingo-Salvany A, Puig R, Barrio G, Garcia de Olalla P, de la Fuente L. Evaluating the impact of methadone maintenance programmes on mortality due to overdose and aids in a cohort of heroin users in Spain. Addiction 2005; 100: 981–989. | Article | PubMed |
  5. Oppenheimer E, Tobutt C, Taylor C, Andrew T. Death and survival in a cohort of heroin addicts from London clinics: a 22-year follow-up study. Addiction 1994; 89: 1299–1308. | Article | PubMed |
  6. Gronbladh L, Ohlund LS, Gunne LM. Mortality in heroin addiction: impact of methadone treatment. Acta Psychiatr Scand 1990; 82: 223–227. | Article | PubMed | CAS |
  7. Gruver AL, Hudson LL, Sempowski GD. Immunosenescence of ageing. J Pathol 2007; 211: 144–156. | Article | PubMed | CAS |
  8. Reece AS. Chronic immune stimulation as a contributing cause of chronic disease in opiate addiction including multi-system ageing. Med Hypotheses 2010; 75: 613–619. | Article | PubMed |
  9. Blasco MA. Telomeres and human disease: ageing, cancer and beyond. Nat Rev Genet 2005; 6: 611–622. | Article | PubMed | ISI | CAS |
  10. Collado M, Blasco MA, Serrano M. Cellular senescence in cancer and aging. Cell 2007; 130: 223–233. | Article | PubMed | ISI | CAS |
  11. Epel ES. Telomeres in a life-span perspective: a new ‘Psychobiomarker’? Curr Dir Psychol Sci 2009; 18: 6–10. | Article |
  12. Bodnar AG, Ouellette M, Frolkis M, Holt SE, Chiu CP, Morin GB et al. Extension of life-span by introduction of telomerase into normal human cells. Science 1998; 279: 349–352. | Article | PubMed | ISI | CAS |
  13. Cawthon RM, Smith KR, O’Brien E, Sivatchenko A, Kerber RA. Association between telomere length in blood and mortality in people aged 60 years or older. Lancet 2003; 361: 393–395. | Article | PubMed | ISI | CAS |
  14. Epel ES, Blackburn EH, Lin J, Dhabhar FS, Adler NE, Morrow JD et al. Accelerated telomere shortening in response to life stress. Proc Natl Acad Sci USA 2004; 101: 17312–17315. | Article | PubMed | CAS |
  15. Epel ES, Lin J, Dhabhar FS, Wolkowitz OM, Puterman E, Karan L et al. Dynamics of telomerase activity in response to acute psychological stress. Brain Behav Immun 2010; 24: 531–539. | Article | PubMed | ISI |
  16. Wolkowitz OM, Mellon SH, Epel ES, Lin J, Reus VI, Rosser R et al. Resting leukocyte telomerase activity is elevated in major depression and predicts treatment response. Mol Psychiatry 2012; 17: 164–172. | Article | PubMed |
  17. Wolf SA, Melnik A, Kempermann G. Physical exercise increases adult neurogenesis and telomerase activity, and improves behavioral deficits in a mouse model of schizophrenia. Brain Behav Immun 2011; 25: 971–980. | Article | PubMed |
  18. Jacobs TL, Epel ES, Lin J, Blackburn EH, Wolkowitz OM, Bridwell DA et al. Intensive meditation training, immune cell telomerase activity, and psychological mediators. Psychoneuroendocrinology 2011; 36: 664–681. | Article | PubMed | CAS |
  19. Burke SN, Barnes CA. Neural plasticity in the ageing brain. Nat Rev Neurosci 2006; 7: 30–40. | Article | PubMed | ISI | CAS |
  20. Dennis NA, Cabeza R. Neuroimaging of healthy cognitive aging. In: Craik FIM, Salthouse TA (eds) The Handbook of Aging and Cognition 3rd edn. Psychology Press: New York, 2008 pp 1–54.
  21. Reuter-Lorenz PA, Lustig C. Brain aging: reorganizing discoveries about the aging mind. Curr Opin Neurobiol 2005; 15: 245–251. | Article | PubMed |
  22. Grady CL, McIntosh AR, Craik FI. Age-related differences in the functional connectivity of the hippocampus during memory encoding. Hippocampus 2003; 13: 572–586. | Article | PubMed |
  23. Raz N, Lindenberger U, Rodrigue KM, Kennedy KM, Head D, Williamson A et al. Regional brain changes in aging healthy adults: general trends, individual differences and modifiers. Cereb Cortex 2005; 15: 1676–1689. | Article | PubMed | ISI |
  24. Salat DH, Buckner RL, Snyder AZ, Greve DN, Desikan RS, Busa E et al. Thinning of the cerebral cortex in aging. Cereb Cortex 2004; 14: 721–730. | Article | PubMed |
  25. Eyler LT, Sherzai A, Kaup AR, Jeste DV. A review of functional brain imaging correlates of successful cognitive aging. Biol Psychiatry 2011; 70: 115–122. | Article | PubMed | ISI |
  26. Barnes CA. Long-term potentiation and the ageing brain. Philos Trans R Soc Lond B Biol Sci 2003; 358: 765–772. | Article | PubMed |
  27. Liu H, Hao Y, Kaneko Y, Ouyang X, Zhang Y, Xu L et al. Frontal and cingulate gray matter volume reduction in heroin dependence: optimized voxel-based morphometry. Psychiatry Clin Neurosci 2009; 63: 563–568. | Article | PubMed |
  28. Lyoo IK, Pollack MH, Silveri MM, Ahn KH, Diaz CI, Hwang J et al. Prefrontal and temporal gray matter density decreases in opiate dependence. Psychopharmacology (Berl) 2006; 184: 139–144. | Article | PubMed |
  29. Yuan Y, Zhu Z, Shi J, Zou Z, Yuan F, Liu Y et al. Gray matter density negatively correlates with duration of heroin use in young lifetime heroin-dependent individuals. Brain Cogn 2009; 71: 223–228. | Article | PubMed |
  30. Yuan K, Qin W, Dong M, Liu J, Sun J, Liu P et al. Gray matter deficits and resting-state abnormalities in abstinent heroin-dependent individuals. Neurosci Lett 2010; 482: 101–105. | Article | PubMed |
  31. Daglish MR, Weinstein A, Malizia AL, Wilson S, Melichar JK, Britten S et al. Changes in regional cerebral blood flow elicited by craving memories in abstinent opiate-dependent subjects. Am J Psychiatry 2001; 158: 1680–1686. | Article | PubMed | ISI | CAS |
  32. Li Q, Wang Y, Zhang Y, Li W, Yang W, Zhu J et al. Craving correlates with mesolimbic responses to heroin-related cues in short-term abstinence from heroin: an event-related fMRI study. Brain Res 2012; 1469: 63–72. | Article | PubMed |
  33. Xiao Z, Lee T, Zhang JX, Wu Q, Wu R, Weng X et al. Thirsty heroin addicts show different fMRI activations when exposed to water-related and drug-related cues. Drug Alcohol Depend 2006; 83: 157–162. | Article | PubMed |
  34. Zijlstra F, Veltman DJ, Booij J, van den Brink W, Franken IH. Neurobiological substrates of cue-elicited craving and anhedonia in recently abstinent opioid-dependent males. Drug Alcohol Depend 2009; 99: 183–192. | Article | PubMed |
  35. Schultz W. Potential vulnerabilities of neuronal reward, risk, and decision mechanisms to addictive drugs. Neuron 2011; 69: 603–617. | Article | PubMed | CAS |
  36. Garavan H, Stout JC. Neurocognitive insights into substance abuse. Trends Cogn Sci 2005; 9: 195–201. | Article | PubMed | ISI |
  37. Lee TM, Zhou WH, Luo XJ, Yuen KS, Ruan XZ, Weng XC. Neural activity associated with cognitive regulation in heroin users: a fMRI study. Neurosci Lett 2005; 382: 211–216. | Article | PubMed | ISI | CAS |
  38. Volkow ND, Fowler JS, Wang GJ, Goldstein RZ. Role of dopamine, the frontal cortex and memory circuits in drug addiction: insight from imaging studies. Neurobiol Learn Mem 2002; 78: 610–624. | Article | PubMed | CAS |
  39. American Psychiatric Society. Diagnostic and Statistical Manual of Mental Disorders DSM-IV-TR 4th edn. American Psychiatric Association Press: Washington, DC, 2000.
  40. Raven JC. Standard Progressive Matrices Plus Version and Mill Hill Vocabulary Scale. Pearson Assessment: London, 2008.
  41. Bjelland I, Dahl AA, Haug TT, Neckelmann D. The validity of the hospital anxiety and depression scale. An updated literature review. J Psychosom Res 2002; 52: 69–77. | Article | PubMed | ISI |
  42. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand 1983; 67: 361–370. | Article | PubMed | ISI | CAS |
  43. Vasa M, Breitschopf K, Zeiher AM, Dimmeler S. Nitric oxide activates telomerase and delays endothelial cell senescence. Circ Res 2000; 87: 540–542. | Article | PubMed | ISI | CAS |
  44. Yang H, Ou CC, Feldman RI, Nicosia SV, Kruk PA, Cheng JQ. Aurora-A kinase regulates telomerase activity through c-Myc in human ovarian and breast epithelial cells. Cancer Res 2004; 64: 463–467. | Article | PubMed | ISI | CAS |
  45. Ashburner J. A fast diffeomorphic image registration algorithm. Neuroimage 2007; 38: 95–113. | Article | PubMed | ISI |
  46. Yassa MA, Stark CE. A quantitative evaluation of cross-participant registration techniques for MRI studies of the medial temporal lobe. Neuroimage 2009; 44: 319–327. | Article | PubMed |
  47. Yan CC, Zang YF. DPARSF: A MATLAB Toolbox for ‘Pipeline’ data analysis of resting-state fMRI. Front Syst Neurosci 2010; 4: 13. | PubMed |
  48. Song XW, Dong ZY, Long XY, Li SF, Zuo XN, Zhu CZ et al. REST: a toolkit for resting-state functional magnetic resonance imaging data processing. PLoS ONE 2011; 6: e25031. | Article | PubMed |
  49. Heaton KH. Wisconsin Card Sorting Test: Computer Version 4 Research Edition. PAR Psychological Assessment Resources, Inc: North Florida, 2003.
  50. Eriksen BA, Eriksen CW. Effects of noise letters upon the identification of a target letter in a nonsearch task. Percept Psychophys 1974; 16: 143–149. | Article | ISI |
  51. Conners CK. Conners’ Continuous Performance Test II V.5. Mutli-Health Systems Inc.: Toronto, 2004.
  52. Owen AM, McMillan KM, Laird AR, Bullmore E. N-back working memory paradigm: a meta-analysis of normative functional neuroimaging studies. Hum Brain Map 2005; 25: 46–59. | Article |
  53. Owen AM, Sahakian BJ, Semple J, Polkey CE, Robbins TW. Visuo-spatial short-term recognition memory and learning after temporal lobe excisions, frontal lobe excisions or amygdalo-hippocampectomy in man. Neuropsychologia 1995; 33: 1–24. | Article | PubMed | ISI | CAS |
  54. Benton AL, Sivan AB, Hamsher KS, Varney NR, Spreen O. Contributions to Neuropsychological Assessment. Oxford University Press: New York, 1994.
  55. Goldstein RZ, Volkow ND. Dysfunction of the prefrontal cortex in addiction: neuroimaging findings and clinical implications. Nat Rev Neurosci 2011; 12: 652–669. | Article | PubMed | CAS |
  56. Ersche KD, Fletcher PC, Lewis SJ, Clark L, Stocks-Gee G, London M et al. Abnormal frontal activations related to decision-making in current and former amphetamine and opiate dependent individuals. Psychopharmacology (Berl) 2005; 180: 612–623. | Article | PubMed |
  57. Rajah MN, D’Esposito M. Region-specific changes in prefrontal function with age: a review of PET and fMRI studies on working and episodic memory. Brain 2005; 128: 1964–1983. | Article | PubMed | ISI |
  58. Fox MD, Raichle ME. Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nat Rev Neurosci 2007; 8: 700–711. | Article | PubMed | ISI | CAS |
  59. Raichle ME, Mintun MA. Brain work and brain imaging. Annu Rev Neurosci 2006; 29: 449–476. | Article | PubMed | ISI | CAS |
  60. Kringelbach ML, Rolls ET. The functional neuroanatomy of the human orbitofrontal cortex: evidence from neuroimaging and neuropsychology. Prog Neurobiol 2004; 72: 341–372. | Article | PubMed | ISI |
  61. Ochsner KN, Gross JJ. The cognitive control of emotion. Trends Cogn Sci 2005; 9: 242–249. | Article | PubMed | ISI |
  62. Lee TM, Pau CW. Impulse control differences between abstinent heroin users and matched controls. Brain Inj 2002; 16: 885–889. | Article | PubMed |
  63. Pau CW, Lee TM, Chan SF. The impact of heroin on frontal executive functions. Arch Clin Neuropsychol 2002; 17: 663–670. | Article | PubMed |
  64. Kim S, Lee D. Prefrontal cortex and impulsive decision making. Biol Psychiatry 2011; 69: 1140–1146. | Article | PubMed | ISI |
  65. Ma N, Liu Y, Li N, Wang CX, Zhang H, Jiang XF et al. Addiction related alteration in resting-state brain connectivity. Neuroimage 2010; 49: 738–744. | Article | PubMed |
  66. Denburg NL, Cole CA, Hernandez M, Yamada TH, Tranel D, Bechara A et al. The orbitofrontal cortex, real-world decision making, and normal aging. Ann N Y Acad Sci 2007; 1121: 480–498. | Article | PubMed |
  67. Lamar M, Resnick SM. Aging and prefrontal functions: dissociating orbitofrontal and dorsolateral abilities. Neurobiol Aging 2004; 25: 553–558. | Article | PubMed |
  68. Nestler EJ. Common molecular and cellular substrates of addiction and memory. Neurobiol Learn Mem 2002; 78: 637–647. | Article | PubMed | ISI | CAS |
  69. Robbins TW, Everitt BJ. Limbic-striatal memory systems and drug addiction. Neurobiol Learn Mem 2002; 78: 625–636. | Article | PubMed | ISI | CAS |
  70. Raz N, Rodrigue KM, Head D, Kennedy KM, Acker JD. Differential aging of the medial temporal lobe: a study of a five-year change. Neurology 2004; 62: 433–438. | Article | PubMed |
  71. Dickerson BC, Goncharova I, Sullivan MP, Forchetti C, Wilson RS, Bennett DA et al. MRI-derived entorhinal and hippocampal atrophy in incipient and very mild Alzheimer’s disease. Neurobiol Aging 2001; 22: 747–754. | Article | PubMed | ISI | CAS |
  72. Killiany RJ, Gomez-Isla T, Moss M, Kikinis R, Sandor T, Jolesz F et al. Use of structural magnetic resonance imaging to predict who will get Alzheimer’s disease. Ann Neurol 2000; 47: 430–439. | Article | PubMed | ISI | CAS |
  73. Pennanen C, Kivipelto M, Tuomainen S, Hartikainen P, Hanninen T, Laakso MP et al. Hippocampus and entorhinal cortex in mild cognitive impairment and early AD. Neurobiol Aging 2004; 25: 303–310. | Article | PubMed |
  74. Corbetta M, Shulman GL. Control of goal-directed and stimulus-driven attention in the brain. Nat Rev Neurosci 2002; 3: 201–215. | Article | PubMed | ISI | CAS |
  75. Field M, Cox WM. Attentional bias in addictive behaviors: a review of its development, causes, and consequences. Drug Alcohol Depend 2008; 97: 1–20. | Article | PubMed | ISI |
  76. Harding IH, Solowij N, Harrison BJ, Takagi M, Lorenzetti V, Lubman DI et al. Functional connectivity in brain networks underlying cognitive control in chronic cannabis users. Neuropsychopharmacology 2012; 37: 1923–1933. | Article | PubMed |
  77. Chao LL, Knight RT. Prefrontal deficits in attention and inhibitory control with aging. Cereb Cortex 1997; 7: 63–69. | Article | PubMed | ISI | CAS |
  78. Tomasi D, Volkow ND. Aging and functional brain networks. Mol Psychiatry 2012; 17, 471 549–558. | Article |
  79. Caporaso GL, Lim DA, Alvarez-Buylla A, Chao MV. Telomerase activity in the subventricular zone of adult mice. Mol Cell Neurosci 2003; 23: 693–702. | Article | PubMed | CAS |
  80. Ersche KD, Jones PS, Williams GB, Robbins TW, Bullmore ET. Cocaine dependence: a fast-track for brain ageing? Mol Psychiatry 2013; 18: 134–135. | Article | PubMed |

—-Amnesia MMWR references:

References

  1. Small JE, Butler PM, Zabar Y, Barash JA. Complete, bilateral hippocampal ischemia: a case series. Neurocase 2016;22:411–5. CrossRef PubMed
  2. Bolouri MR, Small GA. Neuroimaging of hypoxia and cocaine-induced hippocampal stroke. J Neuroimaging 2004;14:290–1. CrossRef PubMed
  3. Morales Vidal SG, Hornik A, Morgan C. Cocaine induced hippocampi infarction. BMJ Case Rep 2012:bcr0320125998. CrossRef PubMed
  4. Connelly KL, Chen X, Kwan PF. Bilateral hippocampal stroke secondary to acute cocaine intoxication. Oxf Med Case Rep 2015:215–7. CrossRef PubMed
  5. Lopez J, Lomen-Hoerth C, Deutsch GK, Kerchner GA, Koshy A. Influenza-associated global amnesia and hippocampal imaging abnormality. Neurocase 2014;20:446–51. CrossRefPubMed
  6. Kim J, Lee KO, Yoon B, Kim YD, Na SJ. Isolated bilateral hippocampal lesions following carbon monoxide poisoning. Eur Neurol 2011;66:64. CrossRef PubMed
  7. Spiers HJ, Maguire EA, Burgess N. Hippocampal amnesia. Neurocase 2001;7:357–82. CrossRef PubMed
  8. Förster A, Griebe M, Gass A, Kern R, Hennerici MG, Szabo K. Diffusion-weighted imaging for the differential diagnosis of disorders affecting the hippocampus. Cerebrovasc Dis 2012;33:104–15. CrossRef PubMed
  9. Benoilid A, Collongues N, de Seze J, Blanc F. Heroin inhalation-induced unilateral complete hippocampal stroke. Neurocase 2013;19:313–5. CrossRef PubMed
  10. Bhattacharyya S, Gholipour T, Colorado RA, Klein JP. Bilateral hippocampal restricted diffusion: same picture many causes. J Neuroimaging 2017; E-pub January 5, 2017. CrossRef

New Psychoactive Substances

New Psychoactive substances (NPS) are creating a nightmare for physicians, law-enforcement, and public safety. A variety of new synthetic agents, many with opioid-drug similarities have been leeching into the public domain, wreaking havoc and death  among naive users who are not even aware of what drug they are taking

Named examples include AH-7921, U-47700, MT-45, Butyrfentanyl, 4F-butyrfentanyl, acetylfentanyl, 4-MeO butyrfentantl, Furanylfentanyl, and acrylfentanyl.  These have been labeled as ‘not for human consumption’ or ‘research chemical’ thereby circumventing legislative control. Even after illegality is established, other countries may still allow their use and even internet trade. Problems with these chemicals include poor quality control, debasement with other chemicals, and unknown or unintended secondary medical consequences from unknown pharmacodynamics. Fatalities have been documented form unintended or intentional use.

The Swedish STRIDA project, initiated in 2010 by the Karolinska Institute and University Laboratory monitors the occurrence and health hazards of NPS in Sweden, and has documented structurally diverse agents, such as MT-45, which have resulted in a number of unintended toxic effects such as hearing loss, cataracts, and sever skin problems due to use of NPS. Of note, many individuals will mix drugs and create even more risk for side effects or death. Even in spite of public knowledge of medical complications of NPS use, including death, the use of NPS has continued to rise quickly in numerous countries.  NPS distribution has largely been driven by the internet, with countries such as China and India playing significant roles in their manufacture. The European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) identified over 650 diff erent websites selling so-called legal highs on the surface web in 2013; European monitoring center for drugs and drug addiction  More recently, “cryptomarkets”, which are anonymous marketplaces operating on the so-called darknet, and accessible only via specially configured browsers, have played an increasing role in NPS distribution. Multiple agents of varying classes are sold, including hallucinogens and amphetamine-type stimulants. For example, the 2C-x class of empathogens (substances in the 2C-x class, despite often being sold as substitutes for MDMA have other hallucinogenic qualities) , the psychedelic tryptamine DMT, and substituted 2C-x variants of the NBOMe class are sold by the highest number of vendors across markets. α-PVP is also available on cryptomarkets and is sold by around 5% of NPS vendors. In these communities, online vendors depend on consumer feedback to maintain trust with the community, and are thus accountable for the products they sell. People using cryptomarkets to obtain drugs report fewer concerns about drug purity, lower levels of exposure to physical violence, and fewer law enforcement consequences compared with obtaining drugs from other sources.

Death from NPS has been documented throughly: For eample, the fentanyl analogue acetylfentanyl, for example, has been associated with multiple cases of life-threatening intoxication and death.  http://www.emcdda.europa.eu/publications/insights/internet-drug-markets

The internet and Drug Markets – PDF

Drugs and the Internet – Australia

DRUGS AND THE INTERNET – Australia 2016 PDF

https://www.cryptocoinsnews.com/%20%20darknet-marketplace-issues-complete-ban-drug/

Hidden wholesale The drug diffusing capacity of online drug cryptomarkets   The cryptomarket: an ‘anonymous open’ drug market that transcends locale

Novel Synthetic Opioids An Opioid Epidemic Within an Opioid Epidemic   Prescriptions for opioid analgesics paralleled an
increase in opioid abuse and fatalities between 2002 and
2010, leveling off from 2011 to 2013.3 However, drug
overdose deaths involving natural and semisynthetic opioids,
including the most commonly prescribed opioid pain
relievers, oxycodone and hydrocodone, increased by 9%
between 2013 and 2014. However, as
the availability of prescription opioids has decreased, the use
and availability of other opioids has increased. Heroin overdose death rates increased 26% from 2013 and 2014 and have more than tripled since 2010. Even more concerning, between 2013 and 2014
the death rates for synthetic opioids, excluding methadone
(eg, fentanyl), increased by 80%, largely because of increased
use and abuse of nonpharmaceutical fentanyl. There have been spikes in overdose deaths related to fentanyl and its analog, acetylfentanyl.  National Heroin Threat Assessment Summary

Heroin Trafficking in the United States 2016

Concepts of illicit drug quality among darknet market users Purity, embodied experience, craft and chemical knowledge

The internet and Drug Markets

Trends in new psychoactive substances from surface and “dark” net monitoring

New psychoactive substances in prisons high and getting higher

Who sells what Country specific differences in substance availability on the Agora cryptomarket

Everything you always wanted to know about drug cryptomarkets

Safer scoring Cryptomarkets, social supply and drug market violence

Going international Risk taking by cryptomarket drug vendors

The transparency paradox. Building trust, resolving disputes and optimising logistics on conventional and online drugs markets

Results of an international drug testing service for cryptomarket users

Drug use harm trajectories before, during and after the emergence of Silk Road§

In addition to nonpharmaceutical fentanyl, there are myriad other novel synthetic opioids that continue to emerge on the illicit drug market.1 Many of these drugs were initially developed in research laboratories as opioid agonists for analgesic use but were never brought to market for use in human beings. As such, most of the novel synthetic opioids do not have any human pharmacokinetic or pharmacodynamic data available. One such example is the W-series research opioids (W1 to W32), specifically, W-18, developed in 1981 at a Canadian university. Although early reports suggest that W-18 has 100 times the potency of fentanyl, true pharmacologic and potency data are lacking. Recently, in Ohio, multiple overdoses and deaths of patients who believed they were purchasing heroin were attributed to the ultrapotent fentanyl derivative carfentanil.  (elephant-sedative-carfentanil-threat) The synthetic opioids MT-45 and AH-7921 were first reported to the National Forensic Laboratory Information System in 2013. Opiates and Related Drugs 2009-2014 NFLS MT-45 has been associated with 28 deaths reported to the European Monitoring Centre for Drugs and Drug Addiction since 2013 and 2 reported deaths in the United States. MT-45 – opioid dataset  The abuse potential of AH-7921 was identified in 2012, when it was isolated in a seized sample purchased on the Internet, and it has been increasingly used in Japan, the United States, and Europe. Lethal poisonings with AH-7921 in combination with other substances [

Abstract 

J Anal Toxicol. 2014 Oct;38(8):599-604. doi: 10.1093/jat/bku057.

Fatal intoxications associated with the designer opioid AH-7921

AH-7921 (3,4-dichloro-N-[(1-dimethylamino)cyclohexylmethyl]benzamide) is a designer opioid with ∼80% of morphine’s µ-agonist activity. Over a 6-month period, we encountered nine deaths where AH-7921 was involved and detected in blood from the deceased. Shortly after the last death, on August 1 2013, AH-7921 was scheduled as a narcotic and largely disappeared from the illicit market in Sweden. AH-7921 was measured by a selective liquid chromatography-MS-MS method and the concentrations of AH-7921 ranged from 0.03 to 0.99 µg/g blood. Six of our cases had other drugs of abuse on board and most had other medications such as benzodiazepines, antidepressants and analgesics. However, the other medicinal drugs encountered were present in postmortem therapeutic concentrations and unlikely to have contributed to death. In addition to the parent compound, we identified six possible metabolites where two N-demethylated dominated and four mono-hydroxylated were found in trace amounts in the blood. In conclusion, deaths with AH-7921 seem to occur both at low and high concentrations, probably a result of different tolerance to the drug. Hence, it is reasonable to assume that no sharp dividing line exists between lethal and non-lethal concentrations. Further, poly-drug use did not seem to be a major contributing factor for the fatal outcome.]

Abuse of AH-7921 has accounted for at least 16 deaths between 2012 and 2013,16 including one in the United States. AH-7921 PDF  and AH-7921 the list of new psychoactive opioids is expanded An isomer of AH-7921, U-47700, is the new compound reported and is now present in the illicit drug marketplace; it already has one recent report of death related to its use. Legislators are seeking to gain control over the spread of this dangerous drug, and recently the Kansas Bureau of Investigation released a public health warning after a number of unintentional drug overdose deaths in Kansas during the past month related to the use of U-47700.  Several states, including Ohio, Wyoming, Georgia, and Kansas, are taking steps to have U-47700 placed under emergency scheduling to make consumption, possession, and distribution illegal. In addition, anecdotally, many medical toxicology program directors from across Canada and the United States have reported presumed cases of U-47700 exposures and deaths; analytical studies are sorely missing. < Of note as of January 2017 the drug is schedule 1::

AH-7921 is a structurally unique synthetic opioid analgesic that has recently entered the drug arena in Europe, the USA, and Japan. Although it was synthesized and patented in the mid-1970s, it was first identified in a seized sample purchased via the Internet in July 2012 and formally brought to the attention of the European Union early warning system in August 2012 by the United Kingdom. Several in vitro experiments and animal model studies established the morphine-like analgesic action of AH-7921 as a l-opioid receptor agonist that has been found to be several times more potent than codeine and at least as potent as morphine. This novel psychoactive substance has already led to eight non-fatal intoxications and 16 deaths in Sweden, the United Kingdom, Norway, and the USA. AH-7921 is a new, structurally atypical synthetic opioid analgesic that appears to be sold as a ‘‘research chemical’’ or ‘‘legal opioid’’ on the Internet since 2012. It was synthesized in the 1970s by Allen and Hanburys Ltd. as a potential analgesic medicine; however, its development was abandoned due to its addictive properties. It has never been marketed as a medicine, nor used as pharmaceutical or medicinal product; it has also no industrial use [6]. There are very few references available on this compound [7]. In vivo studies in animals indicated its l-opioid receptor agonistic activities, although no studies have evaluated its pharmacological and toxicological properties in humans. Its activities are similar to those of morphine and include analgesia, hypothermia, respiratory depression, and addictive behavior [7–9]. The abuse of AH-7921 has been reported in eight member states of the European Union as well as in Norway, leading to severe toxicity (non-fatal) cases and 16 reported deaths within a limited period of time (December 2012–September 2013).

U-47700:

https://psychonautwiki.org/wiki/U-47700

 

U-47700 (3,4-dichloro-N-[2-(dimethylamino)cyclohexyl]- N-methylbenzamide) is a novel compound with opioid properties, developed by Upjohn in the 1970s and derived from the earlier opioid analgesic AH-7921 (3,4-dichloro-N- {[1-(dimethylamino)-cyclohexyl]methyl}benzamide) . U-47700 is a structural isomer of AH-7921. AH-7921, which possesses the same potency as morphine, was first identified in 2012 in a seizure purchased over the internet and recently entered the recreational and illicit drug market as new psychotropic substance in Japan, the USA, and Europe . U-47700 was never studied in humans and is not registered for medical use in humans. Very little, if any, information on it is available in scientific literature. U-47700 is an opioid analgesic drug, considered to have a potency of approximately 7.5 times that of morphine.

Tolerance and addiction potential -psychwiki

As with other opioids, the chronic use of U-47700 can be considered moderately addictive with a high potential for abuse and is capable of causing psychological dependence among certain users. When addiction has developed, cravings and withdrawal symptoms may occur if a person suddenly stops their usage.

Tolerance to many of the effects of U-47700 develops with prolonged and repeated use. The rate at which this occurs develops at different rates for different effects, with tolerance to the constipation-inducing effects developing particularly slowly for instance. This results in users having to administer increasingly large doses to achieve the same effects. After that, it takes about 3 – 7 days for the tolerance to be reduced to half and 1 – 2 weeks to be back at baseline (in the absence of further consumption). U-47700 presents cross-tolerance with all other opioids, meaning that after the consumption of U-47700 all opioids will have a reduced effect.

The risk of fatal opioid overdoses rise sharply after a period of cessation and relapse, largely because of reduced tolerance.[21] To account for this lack of tolerance, it is safer to only dose a fraction of one’s usual dosage if relapsing. It has also been found that the environment one is in can play a role in opioid tolerance. In one scientific study, rats with the same history of heroin administration were significantly more likely to die after receiving their dose in an environment not associated with the drug in contrast to a familiar environment

U-47700 has a high toxicity relative to its dose due to its extreme potency. As with all opioids, long-term effects can vary but can include diminished libido, apathy and memory loss. It is also potentially lethal when mixed with depressants like alcohol or benzodiazepines.

It is worth noting that U-47700 crystals are particularly corrosive and somewhat caustic to mucous membranes. Careless use may deteriorate the chosen routes of administration so it is important to practice routine maintenance such as soaking the sinus cavity with water prior to and following insufflation. It is unwise to vaporise the substance as it can damage the lungs. Sublingual administration is likely to damage the skin in the mouth.

Combined consumption of U-47700 and fentanyl caused one fatality in Belgium.[19] At least 17 opioid overdoses and several deaths in the USA have also been connected with the use of U-47700.[20]

It is strongly recommended that one use harm reduction practices, and take extreme caution when using this substance.

Erowid links for U47700

Why relapse ends in death

Comparing fatal cases involving U-47700

Fentanyl and a Novel Synthetic Opioid U-47700 masquerading as street Norco in Central California

A case of acute intoxication due to combined use of fentanyl and U-47700

Use of synthetic opioid “U-47700” poses risk to Kansas citizens

Ocfentanil overdose fatality in the recreational drug scene

The hidden web and the fentanyl problem Detection of ocfentanil as an adulterant in heroin

The interest in eight new psychoactive substances before and after scheduling

Next generation of novel psychoactive substances on the horizon – A complex problem to face

The introduction of novel synthetic compounds poses several issues, including limited analytical methods for detecting and monitoring these substances. As shown in the related case report,2 suspicion for the presence of a novel drug is often initiated by experienced recreational drug users who concede that their drug experience was somehow different from normal. Additionally, a significant increase in opioid overdoses, particularly in patients with routine urine drug screens that are negative for opioids, suggests that fentanyl or another novel synthetic opioid is present. Unique toxicities have indeed been reported, including alveolar hemorrhage with butyrfentanyl and ototoxicity with MT-45.  Opioid intoxications involving butyrfentanyl, 4-fluorobutyrfentanyl, and fentanyl from the Swedish STRIDA project b

Tightrope or SlacklineThe Neuroscience of Psychoactive Substances

25B-NBOMe

Case series toxicity from 25B-NBOMe – a cluster of N-bomb cases

SYNTHETIC CANNABINOIDS

A systematic review of adverse events arising from the use of synthetic cannabinoids and their associated treatment

How toxic is ibogaine

METHOXETAMINE

A polydrug intoxication involving methoxetamine in a drugs and driving case.

Methoxetamine (MXE) – A Phenomenological Study of Experiences Induced by a Legal High from the Internet

Acute toxicity associated with the recreational use of the ketamine derivative methoxetamine

MDPV  BATH SALTS

Intoxications involving MDPV in Sweden during 2010–2014

Death following recreational use of designer drug bath salts containing 3,4-Methylenedioxypyrovalerone (MDPV)

NATURE: The Psychoactive Designer Drug and Bath Salt Constituent MDPV Causes Widespread Disruption of Brain Functional Connectivity.

PCP derivatives

Phencyclidine analog use in Sweden—intoxication cases involving 3-MeO-PCP and 4-MeO-PCP from the STRIDA project

FENTANYL-LIKE drugs

Opioid intoxications involving butyrfentanyl, 4-fluorobutyrfentanyl, and fentanyl from the Swedish STRIDA project

Death following intentional ingestion of e-liquid

I like the old stuff better than the new stuff – Subjective experiences of new psychoactive substances

Flubromazolam – A new life-threatening designer benzodiazepine

TRYPTAMINES

Recreational use, analysis and toxicity of tryptamines.

There are many categories of NPS, such as synthetic cannabinoids, synthetic cathinones, phenylethylamines, piperazines, ketamine derivatives and tryptamines. Tryptamines are naturally occurring compounds, which can derive from the amino acid tryptophan by several biosynthetic pathways: their structure is a combination of a benzene ring and a pyrrole ring, with the addition of a 2-carbon side chain. Tryptamines include serotonin and melatonin as well as other compounds known for their hallucinogenic properties, such as psilocybin in ‘Magic mushrooms’ and dimethyltryptamine (DMT) in Ayahuasca brews.

Neuropharmacology of New Psychoactive Substances (NPS) Focus on the Rewarding and Reinforcing Properties of Cannabimimetics and Amphetamine-Like Stimulants.

http://www.fsijournal.org/article/S0379-0738(14)00157-1/pdf::

Abstract

Following the initial popularity of mephedrone (4-methylmethcathinone) there has been a stream of new “recreational drugs” entering the global market. The lack of clinical studies on the effects and toxicity of these drugs has made interpretation of toxicological findings difficult. In an attempt to assist in a better understanding of the extent of their use and the fatalities that have been linked to these compounds we present our collated findings in post-mortem and criminal casework where these have been detected and/or implicated. Between January 2010 and December 2012 we have detected new psychoactive substances (NPS) in 203 cases, with 120 cases in 2012 alone. The drugs detected in in life or post-mortem blood and urine are, in order of decreasing frequency; mephedrone, 4-methylethcathinone, BZP, MDPV, TFMPP, methoxetamine, 4-fluoromethcathinone, 4-methylamphetamine, PMA, methylone, PMMA, naphyrone, alpha-methyltryptamine, butylone, MDAI, desoxypipradrol, D2PM, MPA, synthetic cannabinoids, 2-AI, 5-IAI, 5-MeODALT, MDPBP, 5/6-APB, pentedrone and pentylone. Other drugs or alcohol were detected in 84% of the cases including other NPS and in fatalities it should be noted that alternative causes of death (including mechanical suicide, accidental death and non-psychoactive drug overdose) accounted for the majority. Related to this was that of all fatalities involving cathinones, 41% of these were hangings or other mechanical suicides, this was a higher proportion than seen with other drugs found in such cases. The presence of multiple NPS and/or other stimulants was a particular feature in various cases, however, of the drug deaths only 7% solely involved NPS. Across all case types and including some cases investigated in 2013, NPS concentrations showed a wide range but these and selected cases are presented to assist toxicological interpretation in future cases.

Trifluoromethylphenylpiperazine (TFMPP) is a recreational drug of the piperazine chemical class. Usually in combination with its analogue benzylpiperazine (BZP), it is sold as an alternative to the illicit drug MDMA (“Ecstasy”) under the name “Legal X

α-Methyltryptamine (abbreviated as αMT, AMT) is a psychedelic, stimulant, and entactogen drug of the tryptamine class.[2][3] It was originally developed as an antidepressant by workers at Upjohn in the 1960s,[4] and was used briefly as an antidepressant in Russia under the trade name Indopan before being discontinued

https://psychonautwiki.org/wiki/5-MeO-DALT   << Psychonaut WIKI

5-MeO-DALT, or N,N-diallyl-5-methoxytryptamine, is a psychedelic tryptamine first synthesized by Alexander Shulgin. It is chemically related to the compounds 5-MeO-DPT and DALT. It is described as having rapid, intense and short-acting entheogenic effects.

Alexander Shulgin sent the first material regarding the synthesis and effects of 5-MeO-DALT to a researcher in May 2004; afterwards, it soon circulated online. In June 2004, it became available through the use of online research chemical vendors. In August 2004, the synthesis and effects of 5-MeO-DALT were published by Erowid.

Ephenidine_ A new psychoactive agent with ketamine-like NMDA receptor antagonist properties

Legal Highs– novel and emerging psychoactive drugs a chemical overview for the toxicologist

Spice Kryptonite Black Mamba An Overview of Brand Names and Marketing Strategies of Novel Psychoactive Substances on the Web

An Internet Study of User s Experiences of the Synthetic Cathinone 4 Methylethcathinone 4 MEC

Investigation of Bath Salts Use Patterns Within an Online Sample of Users in the United States

Exploring the Attractiveness of New Psychoactive Substances NPS among Experienced Drug Users

New psychoactive substances and British drug policy A view from the cyber psychonauts

 

https://psychonautwiki.org/wiki/Main_Page

Self-Reported Use of Novel Psychoactive Substances in a US survey

Psychinfo

Web of KNowledge

Who database

Lilacs database

https://health.ebsco.com/products/the-cinahl-database

In chronic fentanyl users, such as those patients who use fentanyl therapeutically for their chronic pain, a ratio of postmortem blood fentanyl to norfentanyl concentrations of less than 2.5 probably indicate chronic fentanyl usage rather than acute fentanyl toxicity, while that of greater than 8 is consistent with acute fentanyl toxicity

Heroin overdoses affect even seemingly successful people

Novaddiction facebook page

http://addictiondomain.com/

Alexandria, Virginia Drug and Alcohol treatment – Suboxone and Naltrexone therapies

Preventable deaths – this is the purpose of Addiction treatment. Even the most successful people can die from heroin overdoses.

 

Link to example of successful person who died from heroin overdose

Ketamine Treatment Center | 703-844-0184 | Ketamine Doctor | IV Vitamin Therapy | Vitamin Drip | Vitamin Doctor | IV NAD Therapy | Intranasal Ketamine | Ketamine for Depression Pain PTSD | IV Ketamine | Addiction Treatment Center |Suboxone | Sublocade |Vivitrol | Alcohol Treatment Center | Fairfax, Va | Addiction doctors| CBD Doctor | CBD Treatment Center | Neograft | Hair Transplantation | Hair Restoration Center | Optifast | Weight Loss Center | Medical Weight Loss | Alexandria | Springfield, Va | 22306 | 22314 | 22030 | 22304 | 22036 | 22037 | 22038 | 20598 | Low Dose Naltrexone | LDN