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Substance Use Disorder

Clinical interpretations of patient experience in a trial of psilocybin-assisted psychotherapy for alcohol use disorder

February 20, 2018 / Mushrooms / Psilocybin, Papers, Psychology, Publications, Substance Use Disorder / By / , , , , , ,

Abstract

After a hiatus of some 40 years, clinical research has resumed on the use of classic hallucinogens to treat addiction. Following completion of a small open-label feasibility study, we are currently conducting a double-blind placebo-controlled clinical trial of psilocybin-assisted treatment of alcohol use disorder. Although treatment effects cannot be analyzed until the study is complete, descriptive case studies provide a useful window into the therapeutic process of psychedelic-assisted treatment of addiction. Here we describe treatment trajectories of three participants in the ongoing trial to illustrate the range of experiences and persisting effects of psilocybin treatment. Although it is difficult to generalize from a few cases, several qualitative conclusions can be drawn from the data presented here. Although participants often find it difficult to describe much of their psilocybin experience, pivotal moments tend to be individualized, extremely vivid, and memorable. Often, the qualitative content extends beyond the clinical problem that is being addressed. The participants discussed in this paper experienced acute and lasting alterations in their perceptions of self, in the quality of their baseline consciousness, and in their relationship with alcohol and drinking. In these cases, experiences of catharsis, forgiveness, self-compassion, and love were at least as salient as classic mystical content. Finally, feelings of increased “spaciousness” or mindfulness, and increased control over choices and behavior were reported following the drug administration sessions. Ultimately, psilocybin-assisted treatment appears to elicit experiences that are extremely variable, yet seem to meet the particular needs of the individual.

Bogenschutz, M. P., Podrebarac, S. K., Duane, J. H., Amegadzie, S. S., Malone, T. C., Owens, L. T., … & Mennenga, S. E. (2018). Clinical interpretations of patient experience in a trial of psilocybin-assisted psychotherapy for alcohol use disorder. Frontiers in Pharmacology, 9, 100. 10.3389/fphar.2018.00100
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Psychedelics and related drugs: therapeutic possibilities, mechanisms and regulation

February 14, 2018 / Anxiety Disorders / PTSD, Depressive Disorders, Ketamine, LSD, MDMA, Mushrooms / Psilocybin, Papers, Psychology, Publications, Substance Use Disorder / By / , ,

Abstract

The word “psychedelic” derives from the Greek terms for mind—psyche—and “delos” which means “clear, manifest,” so in essence, psychedelic drugs can be seen as the prototype “window on the mind” concept. The term was originally coined in the 1950s to describe lysergic acid diethylamide (LSD), mescaline, and other hallucinogens, drugs that profoundly alter human experience. These have subsequently been shown to act primarily as agonists at the 5-HT2Areceptor in the brain. Research into the therapeutic potential and mechanisms of action of psychedelic and related drugs peaked in the late 1960s but then stagnated for 50 years after the 1971 UN Psychotropics Convention made psychedelic research with humans almost impossible to carry out (Kyzar et al. 2017).

Recently, however, this area is experiencing a renaissance as drugs often associated with recreational use—such as LSD, ketamine, and cannabis/cannabinoids—have been shown to have therapeutic potential in a range of disorders such as treatment-resistant depression, suicidal ideation, and some pediatric epilepsies. Further, recent pilot studies suggest that MDMA as well as the classic psychedelics, LSD, and psilocybin may contribute to the pharmacopeia for post-traumatic stress disorder (PTSD) and other difficult-to-treat psychiatric disorders. Research has also been stimulated by functional neuroimaging studies of single doses of psychedelics showing that they produce widespread changes in brain connectivity as well as profound alterations to perception and cognition. At the same time, as one would expect from a relatively fledgling area, many questions remain about mechanisms of action, safety, and efficacy. These include what type of psychological therapies best combine with which type of psychedelic drug, whether some types of drug have benefits even without psychological treatment, what the optimal doses are, from single dose through to intermittent or repeated dosing. The current renaissance in empirical psychedelic research stimulated this Special Issue of Psychopharmacology. The articles are grouped into three sections: Clinical efficacy and clinical issues; Effects and Mechanisms of action; Regulation and history.

Curran, H. V., Nutt, D., & de Wit, H. (2018). Psychedelics and related drugs: therapeutic possibilities, mechanisms and regulation. 10.1007/s00213-017-4822-3
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The Effects of Ibogaine on Uterine Smooth Muscle Contractions: Relation to the Activity of Antioxidant Enzymes

February 11, 2018 / Iboga / Ibogaine, Neuroscience, Papers, Psychiatry & Medicine, Publications, Substance Use Disorder / By / , , , , , ,

Abstract

Ibogaine is an indole alkaloid originally extracted from the root bark of the African rainforest shrub Tabernanthe iboga. It has been explored as a treatment for substance abuse because it interrupts drug addiction and relieves withdrawal symptoms. However, it has been shown that ibogaine treatment leads to a sharp and transient fall in cellular ATP level followed by an increase of cellular respiration and ROS production. Since contractile tissues are sensitive to changes in the levels of ATP and ROS, here we investigated an ibogaine-mediated link between altered redox homeostasis and uterine contractile activity. We found that low concentrations of ibogaine stimulated contractile activity in spontaneously active uteri, but incremental increase of doses inhibited it. Inhibitory concentrations of ibogaine led to decreased SOD1 and elevated GSH-Px activity, but doses that completely inhibited contractions increased CAT activity. Western blot analyses showed that changes in enzyme activities were not due to elevated enzyme protein concentrations but posttranslational modifications. Changes in antioxidant enzyme activities point to a vast concentration-dependent increase in H2O2 level. Knowing that extracellular ATP stimulates isolated uterus contractility, while H2O2 has an inhibitory effect, this concentration-dependent stimulation/inhibition could be linked to ibogaine-related alterations in ATP level and redox homeostasis.
Oreščanin-Dušić, Z., Tatalović, N., Vidonja-Uzelac, T., Nestorov, J., Nikolić-Kokić, A., Mijušković, A., … & Blagojević, D. (2018). The Effects of Ibogaine on Uterine Smooth Muscle Contractions: Relation to the Activity of Antioxidant Enzymes. Oxidative medicine and cellular longevity, 2018. 10.1155/2018/5969486
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Evaluating the abuse potential of psychedelic drugs for medical use in humans

February 7, 2018 / LSD, MDMA, Mushrooms / Psilocybin, Papers, Psychiatry & Medicine, Psychology, Publications, Salvia / Salvinorin A, Substance Use Disorder / By / , ,

Abstract

Psychedelics comprise drugs come from various pharmacological classes including 5-HT2A agonists, indirect 5-HT agonists, e.g. MDMA, NMDA antagonists and κ-opioid receptor agonists. There is resurgence in developing psychedelics to treat psychiatric disorders with high unmet clinical need. Many, but not all, psychedelics are schedule 1 controlled drugs (CDs), i.e. no approved medical use. For existing psychedelics in development, regulatory approval will require a move from schedule 1 to a CD schedule for drugs with medical use, i.e. schedules 2-5. Although abuse of the psychedelics is well documented, a systematic preclinical and clinical evaluation of the risks they pose in a medical-use setting does not exist. We describe the non-clinical tests required for a regulatory evaluation of abuse/dependence risks, i.e. drug-discrimination, intravenous self-administration and physical dependence liability. A synopsis of the existing data for the various types of psychedelics is provided and we describe our findings with psychedelic drugs in these models. FDA recently issued its guidance on abuse/dependence evaluation of drug-candidates [59]. We critically review the guidance, discuss the impact this document will have on non-clinical abuse/dependence testing, and offer advice on how non-clinical abuse/dependence experiments can be designed to meet not only the expectations of FDA, but also other regulatory agencies. Finally, we offer views on how these non-clinical tests can be refined to provide more meaningful information to aid the assessment of the risks posed by CNS drug-candidates for abuse and physical dependence.
Heal, D. J., Gosden, J., & Smith, S. L. (2018). Evaluating the abuse potential of psychedelic drugs for medical use in humans. Neuropharmacology. 10.1016/j.neuropharm.2018.01.049
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Ayahuasca: Psychological And Physiologic Effects, Pharmacology And Potential Uses In Addiction And Mental Illness

January 24, 2018 / Ayahuasca, Depressive Disorders, Papers, Psychology, Publications, Substance Use Disorder / By / , , ,

Abstract

Ayahuasca, a traditional Amazonian decoction with psychoactive properties, is made from bark of the Banisteriopsis caapi vine (contains beta-carboline alkaloids) and leaves of the Psychotria viridis bush (supply the hallucinogen N,N-dimethyltryptamine (DMT)). Originally used by indigenous shamans for the purposes of spirit communication, magical experiences, healing, and religious rituals, across several South American countries ayahuasca has been incorporated into folk medicine and spiritual healing, and several Brazilian churches use it routinely to foster spiritual experience. More recently it is being used in Europe and North America, not only for religious or healing reasons, but also for recreation.
OBJECTIVE:
To review ayahuasca’s behavioral effects, possible adverse effects, proposed mechanisms of action and potential clinical uses in mental illness.
METHOD:
We searched Medline, in English, using the terms ayahuasca, dimethytryptamine, Banisteriopsis caapi, and Psychotria viridis and reviewed the relevant publications.
RESULTS:
The following aspects of ayahuasca are summarized: Political and legal factors; acute and chronic psychological effects; electrophysiological studies and imaging; physiological effects, safety and adverse effects; pharmacology; potential psychiatric uses.
CONCLUSION:
Many years of shamanic wisdom have indicated potential therapeutic uses for ayahuasca, and many present day studies suggest that it may be useful for treating various psychiatric disorders and addictions. The side effect profile appears to be relatively mild, but more detailed studies need to be done. Several prominent researchers feel that government regulations with regard to ayahuasca should be relaxed so that it could be provided more readily to recognized credible researchers to conduct comprehensive clinical trials.
Hamill, J., Hallak, J., Dursun, S. M., & Baker, G. (2018). Ayahuasca: Psychological And Physiologic Effects, Pharmacology And Potential Uses In Addiction And Mental Illness. Current neuropharmacology. 10.2174/1570159X16666180125095902
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Ketamine for the treatment of addiction: Evidence and potential mechanisms

January 12, 2018 / Ketamine, Papers, Psychology, Publications, Substance Use Disorder / By / , , ,

Abstract

Ketamine is a dissociative anaesthetic drug which acts on the central nervous system chiefly through antagonism of the n-methyl-d-aspartate (NMDA) receptor. Recently, ketamine has attracted attention as a rapid-acting anti-depressant but other studies have also reported its efficacy in reducing problematic alcohol and drug use. This review explores the preclinical and clinical research into ketamine’s ability to treat addiction. Despite methodological limitations and the relative infancy of the field, results thus far are promising. Ketamine has been shown to effectively prolong abstinence from alcohol and heroin in detoxified alcoholics and heroin dependent individuals, respectively. Moreover, ketamine reduced craving for and self-administration of cocaine in non-treatment seeking cocaine users. However, further randomised controlled trials are urgently needed to confirm ketamine’s efficacy. Possible mechanisms by which ketamine may work within addiction include: enhancement of neuroplasticity and neurogenesis, disruption of relevant functional neural networks, treating depressive symptoms, blocking reconsolidation of drug-related memories, provoking mystical experiences and enhancing psychological therapy efficacy. Identifying the mechanisms by which ketamine exerts its therapeutic effects in addiction, from the many possible candidates, is crucial for advancing this treatment and may have broader implications understanding other psychedelic therapies. In conclusion, ketamine shows great promise as a treatment for various addictions, but well-controlled research is urgently needed.
Ezquerra-Romano, I. I., Lawn, W., Krupitsky, E., & Morgan, C. J. A. (2018). Ketamine for the treatment of addiction: Evidence and potential mechanisms. Neuropharmacology. 10.1016/j.neuropharm.2018.01.017
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A sub-set of psychoactive effects may be critical to the behavioral impact of ketamine on cocaine use disorder: Results from a randomized, controlled laboratory study

January 5, 2018 / Ketamine, Papers, Psychology, Publications, Substance Use Disorder / By / , , , , ,

Abstract

Efforts to translate sub-anesthetic ketamine infusions into widespread clinical use have centered around developing medications with comparable neurobiological activity, but with attenuated psychoactive effects so as to minimize the risk of behavioral toxicity and abuse liability. Converging lines of research, however, suggest that some of the psychoactive effects of sub-anesthetic ketamine may have therapeutic potential. Here, we assess whether a subset of these effects – the so-called mystical-type experience – mediates the effect of ketamine on craving and cocaine use in cocaine dependent research volunteers. We found that ketamine leads to significantly greater acute mystical-type effects (by Hood Mysticism Scale: HMS), dissociation (by Clinician Administered Dissociative States Scale: CADSS), and near-death experience phenomena (by the Near-Death Experience Scale: NDES), relative to the active control midazolam. HMS score, but not the CADSS or NDES score, was found to mediate the effect of ketamine on global improvement (decreased cocaine use and craving) over the post-infusion period. This is the first controlled study to show that mystical-type phenomena, long considered to have therapeutic potential, may work to impact decision-making and behavior in a sustained manner. These data suggest that an important direction for medication development is the identification of ketamine-like pharmacotherapy that is selectively psychoactive (as opposed to free of experiential effects entirely), so that mystical-type perspectival shifts are more reliably produced and factors lending to abuse or behavioral impairment are minimized. Future research can further clarify the relationship between medication-occasioned mystical-type effects and clinical benefit for different disorders.
Dakwar, E., Nunes, E. V., Hart, C. L., Hu, M. C., Foltin, R. W., & Levin, F. R. (2018). A sub-set of psychoactive effects may be critical to the behavioral impact of ketamine on cocaine use disorder: Results from a randomized, controlled laboratory study. Neuropharmacology. 10.1016/j.neuropharm.2018.01.005
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Breaking the cycle of opioid use disorder with Ibogaine

December 7, 2017 / Iboga / Ibogaine, Neuroscience, Papers, Psychology, Publications, Substance Use Disorder / By /

Abstract

Ibogaine is an indole alkaloid that comes from the root of the West African shrub Tabernanthe iboga. Ibogaine has been used for centuries in spiritual celebrations, coming of age rituals, and healings among the Babongo and Mitsogo people of West Central Africa. In Africa today, approximately 2–3 million members of the Bwiti religion scattered in groups throughout the countries of the Gabon, Zaire, and the Cameroun take large doses for the “Bwiti initiation ritual”—a powerful “rebirth” ceremony that group members typically undergo before the commencement of their teenage years.
The discovery that ibogaine eliminates the signs and symptoms of opioid withdrawal and diminishes craving for opioids was first made in the 1960s by a group of self-treating individuals with heroin use disorder; a single oral dose administration of ibogaine was associated with a disruption of five addicted individual’s use of opiates for up to 6 months . An underground railroad of individuals in recovery helping others with addictions arose, using ibogaine to help people break their cycle of addiction to heroin, cocaine, and alcohol. Ibogaine is thought to enable individuals with opioid use disorder to transition to abstinence and establish a substance-free recovery through an ibogaine-induced experience that has personal meaning and/or other benefits. Ibogaine’s long-lasting metabolite noribogaine may reset brain circuits to block the intractable cravings and desire to use opioids that set the addiction relapse cycle into motion.
C. Mash, D. (2017). Breaking the cycle of opioid use disorder with Ibogaine. The American Journal of Drug and Alcohol Abuse, 1-3. 10.1080/00952990.2017.1357184
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Psychedelics and reconsolidation of traumatic and appetitive maladaptive memories: focus on cannabinoids and ketamine

November 25, 2017 / Depressive Disorders, Ketamine, MDMA, Papers, Psychology, Publications, Substance Use Disorder / By / , , , ,

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.

Conclusions

Metaplasticity may be the process in common between cannabinoids and ketamine/ketamine-like substance effects on the mediation and potential manipulation of maladaptive memories.

Fattore, L., Piva, A., Zanda, M. T., Fumagalli, G., & Chiamulera, C. (2017). Psychedelics and reconsolidation of traumatic and appetitive maladaptive memories: focus on cannabinoids and ketamine. Psychopharmacology, 1-13. 10.1007/s00213-017-4793-4
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Well-being, problematic alcohol consumption and acute subjective drug effects in past-year ayahuasca users: a large, international, self-selecting online survey

November 9, 2017 / Ayahuasca, Papers, Psychology, Publications, Substance Use Disorder / By / , , , , , ,

Abstract

Ayahuasca is a natural psychedelic brew, which contains dimethyltryptamine (DMT). Its potential as a psychiatric medicine has recently been demonstrated and its non-medical use around the world appears to be growing. We aimed to investigate well-being and problematic alcohol use in ayahuasca users, and ayahuasca’s subjective effects. An online, self-selecting, global survey examining patterns of drug use was conducted in 2015 and 2016 (n = 96,901). Questions were asked about: use of ayahuasca, lysergic acid diethylamide (LSD) and magic mushrooms; demographics, current well-being and past-year problematic alcohol use of past-year ayahuasca users and comparison drug users; and subjective effects of ayahuasca and comparison drugs. Ayahuasca users (n = 527) reported greater well-being than both classic psychedelic users (n = 18,138) and non-psychedelic drug-using respondents (n = 78,236). Ayahuasca users reported less problematic drinking than classic psychedelic users, although both groups reported greater problematic drinking than the other respondents. Ayahuasca’s acute subjective effects usually lasted for six hours and were most strongly felt one hour after consumption. Within our online, self-selecting survey, ayahuasca users reported better well-being than comparison groups and less problematic drinking than classic psychedelic users. Future longitudinal studies of international samples and randomised controlled trials are needed to dissect the effects of ayahuasca on these outcomes.
Lawn, W., Hallak, J. E., Crippa, J. A., Santos, R., Porffy, L., Barratt, M. J., … & Morgan, C. J. (2017). Well-being, problematic alcohol consumption and acute subjective drug effects in past-year ayahuasca users: a large, international, self-selecting online survey. Scientific reports, 7(1), 15201. 10.1038/s41598-017-14700-6
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