OPEN Foundation

Substance Use Disorder

Why MDMA therapy for alcohol use disorder? And why now?

Abstract

Alcohol use disorder represents a serious clinical, social and personal burden on its sufferers and a significant financial strain on society. Current treatments, both psychological and pharmacological are poor, with high rates of relapse after medical detoxification and dedicated treatment programs. The earliest historical roots of psychedelic drug-assisted psychotherapy in the 1950s were associated with Lysergic acid diethylamide (LSD)-assisted psychotherapy to treat what was then called, alcoholism. But results were varied and psychedelic therapy with LSD and other ‘classical’ psychedelics fell out of favour in the wake of socio-political pressures and cultural changes. A current revisiting of psychedelic clinical research is now targeting substance use disorders – and particularly alcohol use disorder – again. 3,4-Methylenedioxymethamphetamine (MDMA)-assisted psychotherapy has never been formally explored as a treatment for any form of substance use disorder. But in recent years MDMA has risen in prominence as an agent to treat posttraumatic stress disorder (PTSD). With its unique receptor profile and a relatively well-tolerated subjective experience of drug effects when used clinically, MDMA Therapy is ideally suited to allow a patient to explore and address painful memories without being overwhelmed by negative affect. Given that alcohol use disorder is so often associated with early traumatic experiences, the author is proposing in a current on-going UK-based study that patients with alcohol use disorder who have undergone a medical detoxification from alcohol might benefit from a course of MDMA-assisted psychotherapy.

Sessa, B. (2017). Why MDMA therapy for alcohol use disorder? And why now?. Neuropharmacology. 10.1016/j.neuropharm.2017.11.004
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Subjective effectiveness of ibogaine treatment for problematic opioid consumption: Short- and long-term outcomes and current psychological functioning

Abstract

Background and aims

Very few studies have reported the effectiveness of ibogaine as a treatment for chronic opioid use. Therefore, this study evaluated the acute subjective effects of ibogaine, outcomes on problematic opioid consumption, and the long-term associations with psychological functioning.

Methods

Using online data collection, 88 patients who received ibogaine treatment in Mexico between 2012 and 2015 completed our survey.

Results

Most participants (72%) had used opioids for at least 4 years and 69% reported daily use. Most (80%) indicated that ibogaine eliminated or drastically reduced withdrawal symptoms. Fifty percent reported that ibogaine reduced opioid craving, some (25%) reporting a reduction in craving lasting at least 3 months. Thirty percent of participants reported never using opioids again following ibogaine treatment. And over one half (54%) of these abstainers had been abstinent for at least 1 year, with 31% abstinent for at least 2 years. At the time of survey, 41% of all participants reported sustained abstinence (>6 months). Although 70% of the total sample reported a relapse following treatment, 48% reported decreased use from pretreatment levels and an additional 11% eventually achieved abstinence. Treatment responders had the lowest rates of depressive and anxious symptoms, the highest levels of subjective well-being and rated their ibogaine treatment as more spiritually meaningful compared with treatment non-responders.

Conclusion

The results suggest that ibogaine is associated with reductions in opioid use, including complete abstinence, and has long-term positive psychological outcomes. Future research should investigate the efficacy of ibogaine treatment using rigorous longitudinal and controlled designs.

Davis, A. K., Barsuglia, J. P., Windham-Herman, A. M., Lynch, M., & Polanco, M. (2017). Subjective effectiveness of ibogaine treatment for problematic opioid consumption: Short-and long-term outcomes and current psychological functioning. Journal of Psychedelic Studies, (0), 1-9. 10.1556/2054.01.2017.009
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Psychedelic Drugs in Biomedicine

Abstract

Psychedelic drugs, such as lysergic acid diethylamide (LSD), mescaline, and psilocybin, exert profound effects on brain and behavior. After decades of difficulties in studying these compounds, psychedelics are again being tested as potential treatments for intractable biomedical disorders. Preclinical research of psychedelics complements human neuroimaging studies and pilot clinical trials, suggesting these compounds as promising treatments for addiction, depression, anxiety, and other conditions. However, many questions regarding the mechanisms of action, safety, and efficacy of psychedelics remain. Here, we summarize recent preclinical and clinical data in this field, discuss their pharmacological mechanisms of action, and outline critical areas for future studies of psychedelic drugs, with the goal of maximizing the potential benefits of translational psychedelic biomedicine to patients.
Kyzar, E. J., Nichols, C. D., Gainetdinov, R. R., Nichols, D. E., & Kalueff, A. V. (2017). Psychedelic Drugs in Biomedicine. Trends in Pharmacological Sciences. 10.1016/j.tips.2017.08.003
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Does psychedelic drug use reduce risk of suicidality? Evidence from a longitudinal community-based cohort of marginalised women in a Canadian setting

Abstract

OBJECTIVE:
This study aimed to longitudinally investigate whether ever having used a psychedelic drug can have a protective effect on incidence of suicidality among marginalised women.
DESIGN:
Longitudinal community-based cohort study.
SETTING:
Data were drawn from a prospective, community-based cohort of marginalised women in Metro Vancouver, Canada.
PARTICIPANTS:
766 women completed the baseline questionnaire between January 2010 and August 2014. Participants who did not report suicidality at baseline and who completed at least one follow-up visit were included.
MAIN OUTCOME MEASURE:
Extended Cox regression was used to model predictors of new suicidality (suicide ideation or attempts) over 54-month follow-up.
RESULTS:
Nearly half (46%; n=355) of participants reported prior suicidality and were thus excluded from the present analyses. Of 290 women eligible at baseline, 11% (n=31) reported recent suicidality during follow-up, with an incidence density of 4.42 per 100 person-years (95% CI 3.10 to 6.30). In multivariable analysis, reported lifetime psychedelic drug use was associated with a 60% reduced hazard for suicidality (adjusted HR (AHR) 0.40; 95% CI 0.17 to 0.94). Crystal methamphetamine use (AHR 3.25; 95% CI 1.47 to 7.21) and childhood abuse (AHR 3.54; 95% CI 1.49 to 8.40) remained independent predictors of suicidality.
CONCLUSION:
The high rate of suicidality identified in this study is of major concern. Alongside emerging evidence on the potential of psychedelic-assisted therapy to treat some mental illness and addiction issues, our findings demonstrate that naturalistic psychedelic drug use is independently associated with reduced suicidality, while other illicit drug use and childhood trauma predispose women to suicidality. While observational, this study supports calls for further investigation of the therapeutic utility of psychedelic drugs in treating poor mental health and promoting mental wellness.
Argento, E., Strathdee, S. A., Tupper, K., Braschel, M., Wood, E., & Shannon, K. (2017). Does psychedelic drug use reduce risk of suicidality? Evidence from a longitudinal community-based cohort of marginalised women in a Canadian setting. BMJ open7(9), e016025. 10.1136/bmjopen-2017-016025
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A phenomenological analysis of the subjective experience elicited by ibogaine in the context of a drug dependence treatment

Abstract

Objective

This report documents the phenomenology of the subjective experiences of 22 patients with substance-related disorders who were involved in a treatment combining cognitive–behavioral therapy and hospital sessions with ibogaine in Brazil.

Methods

Participants underwent a one-to-one semi-structured interview exploring the subjective effects of ibogaine. We employed interpretative phenomenological analysis to identify relevant phenomenological categories, including physical sensations, perceptual (visual, auditory, and olfactory), emotional, cognitive, and spiritual. Participants also compared ibogaine with other drugs used in life, including psychedelics like ayahuasca, psilocybin mushrooms, and lysergic acid diethylamide.

Results

The findings reveal that the subjective experience with ibogaine has similarities with other psychedelic substances, but also important differences. These include very strong and unpleasant physical effects as well as, at least in this patient population, a very difficult and challenging experience.

Conclusions

Overall, the descriptions involve heightened memory retrieval, specially related to drug abuse and the perception of one’s own future with or without drug use. Strong perceptual phenomena, especially dreamlike visions, were commonly reported. Based on Revonsuo’s evolutionary hypothesis for the function of dreams and of previous suggestions that ibogaine has oneiric properties, we suggest the subjective experience of drug-dependent patients elicited by ibogaine may be framed as simulations of threat and danger.

Schenberg, E. E., de Castro Comis, M. A., Alexandre, J. F. M., Tófoli, L. F., Chaves, B. D. R., & da Silveira, D. X. (2017). A phenomenological analysis of the subjective experience elicited by ibogaine in the context of a drug dependence treatment. Journal of Psychedelic Studies, (0), 1-10. 10.1556/2054.01.2017.007
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Psychotherapy with Adjuvant use of Serotonergic Psychoactive Substances: Possibilities and Challenges

Abstract

Background Recently, scientific interest in the therapeutic potential of serotonergic and psilocybin hallucinogens (psychedelics) such as lysergic acid diethylamide (LSD) and entactogens like 3,4-methylendioxymethamphetamine (MDMA) within the framework of psychotherapy has resumed. The present article provides an overview on the current evidence on substance-assisted psychotherapy with these substances.
Method A selective search was carried out in the PubMed and Cochrane Library including studies investigating the clinical use of serotonergic psychoactive substances since 2000.
Results Studies were found investigating the following indications: alcohol (LSD and psilocybin) and tobacco addiction (psilocybin), anxiety and depression in patients suffering from life-threatening somatic illness (LSD and psilocybin), obsessive-compulsive disorder (OCD) (psilocybin), treatment-resistant major depression (psilocybin), and posttraumatic stress disorder (PTSD) (MDMA).
Discussion Substance use disorders, PTSD and anxiety and depression in patients suffering from life-threatening somatic illness belong to the indications with the best evidence for substance-assisted psychotherapy with serotonergic psychoactive agents. To date, studies indicate efficacy and relatively good tolerability. Further studies are needed to determine whether these substances may represent suitable and effective treatment options for some treatment-resistant psychiatric disorders in the future.
Majić, T., Jungaberle, H., Schmidt, T. T., Zeuch, A., Hermle, L., & Gallinat, J. (2017). Psychotherapy with Adjuvant use of Serotonergic Psychoactive Substances: Possibilities and Challenges. Fortschritte der Neurologie-Psychiatrie85(7), 383. 10.1055/s-0043-103085
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The 2017 Ayahuasca Technical Report

ICEERS has just released the 2017 edition of the Ayahuasca Technical Report. Signed by ten of the world’s leading ayahuasca researchers, this report is an important document that summarizes the most relevant scientific findings from the past few decades, as well as key information about the history, legality, pharmacology, and potential therapeutic or adverse effects of ayahuasca. Our intention with this report is to provide objective and up-to-date information to policy makers, judges, lawyers and other officials in charge of developing policies, programs, legislation or involved in legal cases relating to ayahuasca.
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Ayahuasca: what mental health professionals need to know

Abstract

Background

Ayahuasca is a psychoactive ethnobotanical concoction that has been used for decades by indigenous groups of the Northwestern Amazon and by syncretic religious organizations for ritual and therapeutic purposes. In the last two decades, it is being used worldwide in evolving practices. Ayahuasca seem to therapeutic effects, but controlled studies are lacking. Moreover, its safety and toxicity are not completely understood.

Objectives

To present an overview of the effects of ayahuasca based on the most recent human studies.

Methods

Narrative review.

Results

Ayahuasca administration in controlled settings appears to be safe from a subjective and physiological perspective, with few adverse reactions being reported. More frequent adverse reactions occur in non-controlled settings. Prolonged psychotic reactions are rare and seem to occur especially in susceptible individuals. Ayahuasca showed antidepressive, anxiolytic, and antiaddictive effects in animal models, observational studies, and in open-label and controlled studies.

Discussion

Ayahuasca administration in controlled settings appear to be safe. Moreover, ayahuasca seem to have therapeutic effects for treatment-resistant psychiatric disorders that should be further investigated in randomized controlled clinical trials. However, medical complications and cases of prolonged psychotic reactions have been reported, and people with personal or family history of psychotic disorders should avoid ayahuasca intake.

Santos, R. G. D., Bouso, J. C., & Hallak, J. E. C. (2017). Ayahuasca: what mental health professionals need to know. Archives of Clinical Psychiatry (São Paulo)44(4), 103-109. 10.1590/0101-60830000000130
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Treatment of opioid use disorder with ibogaine: detoxification and drug use outcomes

Abstract

BACKGROUND:
Ibogaine is a monoterpene indole alkaloid used in medical and nonmedical settings for the treatment of opioid use disorder. Its mechanism of action is apparently novel. There are no published prospective studies of drug use outcomes with ibogaine.
OBJECTIVES:
To study outcomes following opioid detoxification with ibogaine.
METHODS:
In this observational study, 30 subjects with DSM-IV Opioid Dependence (25 males, 5 females) received a mean total dose of 1,540 ± 920 mg ibogaine HCl. Subjects used oxycodone (n = 21; 70%) and/or heroin (n = 18; 60%) in respective amounts of 250 ± 180 mg/day and 1.3 ± 0.94 g/day, and averaged 3.1 ± 2.6 previous episodes of treatment for opioid dependence. Detoxification and follow-up outcomes at 1, 3, 6, 9, and 12 months were evaluated utilizing the Subjective Opioid Withdrawal Scale (SOWS) and Addiction Severity Index Composite (ASIC) scores, respectively.
RESULTS:
SOWS scores decreased from 31.0 ± 11.6 pretreatment to 14.0 ± 9.8 at 76.5 ± 30 hours posttreatment (t = 7.07, df = 26, p < 0.001). At 1-month posttreatment follow-up, 15 subjects (50%) reported no opioid use during the previous 30 days. ASIC Drug Use and Legal and Family/Social Status scores were improved relative to pretreatment baseline at all posttreatment time points (p < .001). Improvement in Drug Use scores was maximal at 1 month, and subsequently sustained from 3 to 12 months at levels that did not reach equivalence to the effect at 1 month.
CONCLUSION:
Ibogaine was associated with substantive effects on opioid withdrawal symptoms and drug use in subjects for whom other treatments had been unsuccessful, and may provide a useful prototype for discovery and development of innovative pharmacotherapy of addiction.
Brown, T. K., & Alper, K. (2017). Treatment of opioid use disorder with ibogaine: detoxification and drug use outcomes. The American Journal of Drug and Alcohol Abuse, 1-13. 10.1080/00952990.2017.1320802
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Therapeutic Applications of Classic Hallucinogens

Abstract

This chapter reviews what is known about the therapeutic uses of the serotonergic or classic hallucinogens, i.e., psychoactive drugs such as LSD and psilocybin that exert their effects primarily through agonist activity at serotonin 2A (5HT2A) receptors. Following a review of the history of human use and scientific study of these drugs, the data from clinical research are summarized, including extensive work on the use of classic hallucinogens in the treatment of alcoholism and other addictions, studies of the use of LSD and psilocybin to relieve distress concerning death, particularly in patients with advanced or terminal cancer, and more limited data concerning the use of classic hallucinogens to treat mood and anxiety disorders. A survey of possible mechanisms of clinically relevant effects is provided. The well-established safety of classic hallucinogens is reviewed. To provide a clinical perspective, case summaries are provided of two individuals who received treatment in recent controlled trials of psilocybin: one being treated for alcoholism, the other suffering from anxiety and depression related to fear of death due to a cancer diagnosis. Although promising early phase research conducted from the 1950s through the early 1970s was discontinued before firm conclusions could be reached concerning the efficacy of any of the classic hallucinogens for any clinical condition, the research that was conducted in that era strongly suggests that classic hallucinogens have clinically relevant effects, particularly in the case of LSD treatment of alcoholism. In the past decade, clinical trials have resumed investigating the effects of classic hallucinogens in the treatment of existential distress in the face of cancer, and in the treatment of addictions including alcoholism and nicotine addiction. The studies that have been completed to date are not sufficient to establish efficacy, but the outcomes have been very encouraging, and larger trials, up to and including phase 3, are now underway or being planned. Although research has elucidated many of the acute neurobiological and psychological effects of classic hallucinogens on humans, animals, and in vitro systems, the mechanisms of clinically relevant persisting effects remain poorly understood.
Bogenschutz, M. P., & Ross, S. (2016). Therapeutic applications of classic hallucinogens. 10.1007/7854_2016_464
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