OPEN Foundation

Substance Use Disorder

Ibogaine Detoxification Transitions Opioid and Cocaine Abusers Between Dependence and Abstinence: Clinical Observations and Treatment Outcomes

Abstract

Ibogaine may be effective for transitioning opioid and cocaine dependent individuals to sobriety. American and European self-help groups provided public testimonials that ibogaine alleviated drug craving and opioid withdrawal symptoms after only a single dose administration. Preclinical studies in animal models of addiction have provided proof-of-concept evidence in support of these claims. However, the purported therapeutic benefits of ibogaine are based on anecdotal reports from a small series of case reports that used retrospective recruitment procedures. We reviewed clinical results from an open label case series (N = 191) of human volunteers seeking to detoxify from opioids or cocaine with medical monitoring during inpatient treatment. Whole blood was assayed to obtain pharmacokinetic measures to determine the metabolism and clearance of ibogaine. Clinical safety data and adverse events (AEs) were studied in male and female subjects. There were no significant adverse events following administration of ibogaine in a dose range that was shown to be effective for blocking opioid withdrawal symptoms in this study. We used multi-dimensional craving questionnaires during inpatient detoxification to test if ibogaine was effective in diminishing heroin and cocaine cravings. Participants also completed standardized questionnaires about their health and mood before and after ibogaine treatment, and at program discharge. One-month follow-up data were reviewed where available to determine if ibogaine’s effects on drug craving would persist outside of an inpatient setting. We report here that ibogaine therapy administered in a safe dose range diminishes opioid withdrawal symptoms and reduces drug cravings. Pharmacological treatments for opioid dependence include detoxification, narcotic antagonists and long-term opioid maintenance therapy. Our results support product development of single oral dose administration of ibogaine for the treatment of opioid withdrawal during medically supervised detoxification to transition drug dependent individuals to abstinence.
Mash, D. C., Duque, L., Page, B., & Allen-Ferdinand, K. (2018). Ibogaine Detoxification Transitions Opioid and Cocaine Abusers Between Dependence and Abstinence: Clinical Observations and Treatment Outcomes. Frontiers in Pharmacology9. 10.3389/fphar.2018.00529
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Psychedelic therapy as a complementary treatment approach for alcohol use disorders

Abstract

Background

Traditional treatment interventions for alcohol use disorders (AUD) have produced mixed outcomes and the global increase in AUDs demands novel and innovative approaches to addiction treatment. Psychedelic substances have been reintroduced into the Western medical community as a potential intervention to complement the treatment of AUDs.

Objectives

This paper will discuss the implications of using psychedelic substances as a complementary approach within the treatment of AUDs.

Methods

A thorough review of pertinent research focused on the use of psychedelics in relation to the affective, cognitive, social, legal, and spiritual issues commonly associated with AUDs.

Results

Research suggests the clinical efficacy and safety of psychedelic therapy as a complementary treatment for AUDs.

Conclusion

Future directions and implications to AUD treatment are provided.

Eischens, P., & Atherton, W. L. (2018). Psychedelic therapy as a complementary treatment approach for alcohol use disorders. Journal of Psychedelic Studies, 1-9. 10.1556/2054.2018.005
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Ayahuasca and Its DMT- and β-carbolines – Containing Ingredients Block the Expression of Ethanol-Induced Conditioned Place Preference in Mice: Role of the Treatment Environment

Abstract

Ayahuasca is a hallucinogenic beverage produced from the decoction of Banisteriopsis caapi (Bc) and Psychotria viridis (Pv), β-carboline- and N,N-dimethyltryptamine(DMT)-containing plants, respectively. Accumulating evidence suggests that ayahuasca may have therapeutic effects on ethanol abuse. It is not known, however, whether its effects are dependent on the presence of DMT or if non-DMT-containing components would have therapeutic effects. The aim of the present study was to investigate the rewarding properties of ayahuasca (30, 100, and 300 mg/kg, orally), Bc (132, 440, and 1320 mg/kg, orally) and Pv (3.75, 12.5 and 37.5 mg/kg, i.p.) extracts and their effects on ethanol (1.8 g/kg, i.p.) reward using the conditioned place preference (CPP) paradigm in male mice. Animals were conditioned with ayahuasca, Bc or Pv extracts during 8 sessions. An intermediate, but not a high, dose of ayahuasca induced CPP in mice. Bc and Pv did not induce CPP. Subsequently, the effects of those extracts were tested on the development of ethanol-induced CPP. Ayahuasca, Bc or Pv were administered before ethanol injections during conditioning sessions. While Bc and Pv exerted no effects on ethanol-induced CPP, pretreatment with ayahuasca blocked the development of CPP to ethanol. Finally, the effects of a post-ethanol-conditioning treatment with ayahuasca, Bc or Pv on the expression of ethanol-induced CPP were tested. Animals were conditioned with ethanol, and subsequently treated with either ayahuasca, Bc or Pv in the CPP environment previously associated with saline or ethanol for 6 days. Animals were then reexposed to ethanol and ethanol-induced CPP was quantified on the following day. Treatment with all compounds in the ethanol-paired environment blocked the expression of ethanol-induced CPP. Administration of an intermediate, but not a high, dose of ayahuasca and Bc, as well as Pv administration, in the saline-paired compartment blocked the expression of ethanol-induced CPP. The present study sheds light into the components underlying the therapeutic effects of ayahuasca on ethanol abuse, indicating that ayahuasca and its plant components can decrease ethanol reward at doses that do not exert abuse liability. Importantly, the treatment environment seems to influence the therapeutic effects of ayahuasca and Bc, providing important insights into clinical practice.
Cata-Preta, E. G., Serra, Y. A., Moreira-Junior, E. D. C., Reis, H. S., Kisaki, N. D., Libarino-Santos, M., … & Costa, J. L. (2018). Ayahuasca and Its DMT-and β-carbolines–Containing Ingredients Block the Expression of Ethanol-Induced Conditioned Place Preference in Mice: Role of the Treatment Environment. Frontiers in pharmacology9. 10.3389/fphar.2018.00561
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The epidemiology of 5-methoxy- N,N-dimethyltryptamine (5-MeO-DMT) use: Benefits, consequences, patterns of use, subjective effects, and reasons for consumption

Abstract

BACKGROUND/AIM:
5-Methoxy- N,N-dimethyltryptamine (5-MeO-DMT) is a psychoactive compound found in several plants and in high concentrations in Bufo alvarius toad venom. Synthetic, toad, and plant-sourced 5-MeO-DMT are used for spiritual and recreational purposes and may have psychotherapeutic effects. However, the use of 5-MeO-DMT is not well understood. Therefore, we examined patterns of use, motivations for consumption, subjective effects, and potential benefits and consequences associated with 5-MeO-DMT use.
METHODS:
Using internet-based advertisements, 515 respondents ( Mage=35.4. SD=11.7; male=79%; White/Caucasian=86%; United States resident=42%) completed a web-based survey.
RESULTS:
Most respondents consumed 5-MeO-DMT infrequently (<once/year), for spiritual exploration, and had used less than four times in their lifetime. The majority (average of 90%) reported moderate-to-strong mystical-type experiences ( Mintensity=3.64, SD=1.11; range 0-5; e.g., ineffability, timelessness, awe/amazement, experience of pure being/awareness), and relatively fewer (average of 37%) experienced very slight challenging experiences ( Mintensity=0.95, SD=0.91; range 0-5; e.g., anxiousness, fear). Less than half (39%) reported repeated consumption during the same session, and very few reported drug craving/desire (8%), or legal (1%), medical (1%), or psychiatric (1%) problems related to use. Furthermore, of those who reported being diagnosed with psychiatric disorders, the majority reported improvements in symptoms following 5-MeO-DMT use, including improvements related to post-traumatic stress disorder (79%), depression (77%), anxiety (69%), and alcoholism (66%) or drug use disorder (60%).
CONCLUSION:
Findings suggest that 5-MeO-DMT is used infrequently, predominantly for spiritual exploration, has low potential for addiction, and might have psychotherapeutic effects. Future research should examine the safety and pharmacokinetics of 5-MeO-DMT administration in humans using rigorous experimental designs.
Davis, A. K., Barsuglia, J. P., Lancelotta, R., Grant, R. M., & Renn, E. (2018). The epidemiology of 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) use: Benefits, consequences, patterns of use, subjective effects, and reasons for consumption. Journal of Psychopharmacology, 0269881118769063. 10.1177/0269881118769063
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Assessment of Alcohol and Tobacco Use Disorders Among Religious Users of Ayahuasca.

Abstract

The aims of this study were to assess the impact of ceremonial use of ayahuasca-a psychedelic brew containing N,N-dimethyltryptamine (DMT) and β-carboline -and attendance at União do Vegetal (UDV) meetings on substance abuse; here we report the findings related to alcohol and tobacco use disorder. A total of 1,947 members of UDV 18+ years old were evaluated in terms of years of membership and ceremonial attendance during the previous 12 months. Participants were recruited from 10 states from all major regions of Brazil. Alcohol and tobacco use was evaluated through questionnaires first developed by the World Health Organization and the Substance Abuse and Mental Health Services Administration. Analyses compared levels of alcohol and tobacco use disorder between the UDV and a national normative sample (n = 7,939). Binomial tests for proportions indicated that lifetime use of alcohol and tobacco was higher in UDV sample compared to the Brazilian norms for age ranges of 25-34 and over 34 years old, but not for the age range of 18-24 years old. However, current use disorders for alcohol and tobacco were significantly lower in the UDV sample than the Brazilian norms. Regression analyses revealed a significant impact of attendance at ayahuasca ceremonies during the previous 12 months and years of UDV membership on the reduction of alcohol and tobacco use disorder.
Ribeiro Barbosa, P. C., Tofoli, L. F., Bogenschutz, M. P., Hoy, R., Berro, L. F., Marinho, E. A., … & Winkelman, M. J. (2018). Assessment of alcohol and tobacco use disorders among religious users of ayahuasca. Frontiers in psychiatry9, 136., 10.3389/fpsyt.2018.00136
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Changes in Withdrawal and Craving Scores in Participants Undergoing Opioid Detoxification Utilizing Ibogaine

Abstract

Opioid use disorder (OUD) is currently an epidemic in the United States (US) and ibogaine is reported to have the ability to interrupt opioid addiction by simultaneously mitigating withdrawal and craving symptoms. This study examined opioid withdrawal and drug craving scores in 50 participants with OUD undergoing a week-long detoxification treatment protocol with ibogaine. The Addiction Severity Index (ASI) was used for baseline characterization of participants’ OUD. Clinical Opioid Withdrawal Scale (COWS), Subjective Opioid Withdrawal Scale (SOWS), and Brief Substance Craving Scale (BSCS) scores were collected at 48 and 24 hours prior to ibogaine administration, as well as 24 and 48 hours after ibogaine administration. At 48 hours following ibogaine administration, withdrawal and craving scores were significantly lowered in comparison to baseline: 78% of patients did not exhibit objective clinical signs of opioid withdrawal, 79% reported minimal cravings for opioids, and 68% reported subjective withdrawal symptoms in the mild range. Ibogaine appears to facilitate opioid detoxification by reducing opioid withdrawal and craving in participants with OUD. These results warrant further research using rigorous controlled trials.
Malcolm, B. J., Polanco, M., & Barsuglia, J. P. (2018). Changes in Withdrawal and Craving Scores in Participants Undergoing Opioid Detoxification Utilizing Ibogaine. Journal of psychoactive drugs, 1-10. 10.1080/02791072.2018.1447175
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Ceremonial ‘Plant Medicine’ use and its relationship to recreational drug use: an exploratory study

Background: The ceremonial use of psychoactive/hallucinogenic plant based drugs, such as ayahuasca, psilocybin and others, is a growing trend in the United States (US) and globally. To date, there has been little research documenting how many people are using psychoactive substances in this context, who the users are, what benefits/risks exist in the use of these drugs and the relationship between ceremonial drug use and recreational drug use.
In this paper we describe a cohort of plant medicine facilitators in the US and explore how they differentiate plant medicine use from recreational drug use.
Methods: Using modified ethnography, individual interviews were conducted in 2016 with 15 participants who are currently facilitating plant medicine ceremonies in the US. Descriptive content analysis was performed to discover themes and to inform a larger mixed-method study.
Results: Ceremonial drug use was seen by participants as a natural healing and treatment modality used in the context of community and ritual. Three main themes were identified relating to participants’ differentiation between ceremonial plant medicine use and recreational drug use: (1) participants see a clear delineation between plant medicine use and recreational drug use; (2) plant medicine is seen as a potential treatment for addiction, but concerns exist regarding potential interference with recovery; and (3) plant medicine use may influence recreational use.
Conclusions: More research is needed on who is using plant medicine, motivators for use, perceived and real risks and benefits of plant medicine use and harm reduction techniques regarding safe ingestion.
Dorsen, C., Palamar, J., & Shedlin, M. G. (2018). Ceremonial ‘Plant Medicine’use and its relationship to recreational drug use: an exploratory study. Addiction Research & Theory, 1-8. 10.1080/16066359.2018.1455187
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Sex differences in sub-anesthetic ketamine’s antidepressant effects and abuse liability.

Abstract

Sub-anesthetic ketamine produces rapid antidepressant effects in patients with bipolar and unipolar major depression where conventional monoaminergic-based antidepressant drugs have been ineffective or ridden with side effects. A single ketamine infusion can produce antidepressant effects lasting up to two weeks, and multiple ketamine infusions prolong this effect. Pre-clinical studies are underway to uncover ketamine’s mechanisms of action, but there are still many questions unanswered regarding the safety of its long-term use. Abuse liability is one area of concern, as recreational ketamine use is an ongoing issue in many parts of the world. Another understudied area is sex differences in responsivity to ketamine. Women are twice as likely as men to be diagnosed with depression, and they progress through stages of drug addiction more rapidly than their male counterparts. Despite this, preclinical studies in ketamine’s antidepressant and addictive-like behaviors in females are limited. These intersecting factors in recent clinical and pre-clinical studies are reviewed to characterize ketamine’s therapeutic potential, its limitations, and its potential mechanisms of action.
Wright, K. N., & Kabbaj, M. (2018). Sex differences in sub-anesthetic ketamine’s antidepressant effects and abuse liability. Current opinion in behavioral sciences23, 36-41., 10.1016/j.cobeha.2018.02.001
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Sex differences in sub-anesthetic ketamine's antidepressant effects and abuse liability.

Abstract

Sub-anesthetic ketamine produces rapid antidepressant effects in patients with bipolar and unipolar major depression where conventional monoaminergic-based antidepressant drugs have been ineffective or ridden with side effects. A single ketamine infusion can produce antidepressant effects lasting up to two weeks, and multiple ketamine infusions prolong this effect. Pre-clinical studies are underway to uncover ketamine’s mechanisms of action, but there are still many questions unanswered regarding the safety of its long-term use. Abuse liability is one area of concern, as recreational ketamine use is an ongoing issue in many parts of the world. Another understudied area is sex differences in responsivity to ketamine. Women are twice as likely as men to be diagnosed with depression, and they progress through stages of drug addiction more rapidly than their male counterparts. Despite this, preclinical studies in ketamine’s antidepressant and addictive-like behaviors in females are limited. These intersecting factors in recent clinical and pre-clinical studies are reviewed to characterize ketamine’s therapeutic potential, its limitations, and its potential mechanisms of action.
Wright, K. N., & Kabbaj, M. (2018). Sex differences in sub-anesthetic ketamine’s antidepressant effects and abuse liability. Current opinion in behavioral sciences23, 36-41., 10.1016/j.cobeha.2018.02.001
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The Psychedelic Debriefing in Alcohol Dependence Treatment: Illustrating Key Change Phenomena through Qualitative Content Analysis of Clinical Sessions

Abstract

Research on the clinical applications of psychedelic-assisted psychotherapy has demonstrated promising early results for treatment of alcohol dependence. Detailed description of the content and methods of psychedelic-assisted psychotherapy, as it is conducted in clinical settings, is scarce.

Methods: An open-label pilot (proof-of-concept) study of psilocybin-assisted treatment of alcohol dependence (NCT01534494) was conducted to generate data for a phase 2 RCT (NCT02061293) of a similar treatment in a larger population. The present paper presents a qualitative content analysis of the 17 debriefing sessions conducted in the pilot study, which occurred the day after corresponding psilocybin medication sessions.

Results: Participants articulated a series of key phenomena related to change in drinking outcomes and acute subjective effects of psilocybin.

Discussion: The data illuminate change processes in patients’ own words during clinical sessions, shedding light on potential therapeutic mechanisms of change and how participants express effects of psilocybin. This study is unique in analyzing actual clinical sessions, as opposed to interviews of patients conducted separately from treatment.

Nielson, E. M., May, D. G., Forcehimes, A. A., & Bogenschutz, M. P. (2018). The Psychedelic Debriefing in Alcohol Dependence Treatment: Illustrating Key Change Phenomena through Qualitative Content Analysis of Clinical Sessions. Frontiers in Pharmacology9, 132. 10.3389/fphar.2018.00132
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