OPEN Foundation

Substance Use Disorder

Ibogaine in the Treatment of Substance Dependence

Abstract

Ibogaine is a psychoactive alkaloid derived from Tabernanthe iboga, a plant used in initiatory rituals in West Central Africa. Largely because of ibogaine’s status as a Schedule I substance in the U.S., the development of ibogaine’s use in the treatment of drug addiction took place outside conventional clinical and medical settings. This article reviews the history of ibogaine’s use in the treatment of drug addiction, and discusses progress made towards, and obstacles blocking, the establishment of controlled clinical trials of ibogaine’s efficacy. Preclinical research has generally supported anecdotal claims that ibogaine attenuates withdrawal symptoms and reduces drug cravings. Concerns about ibogaine’s safety, as well as a dearth of solid data from human studies, have hampered progress in its development as an approved medication. This article outlines major findings from preclinical studies, discusses concerns about ibogaine’s safety, and details previous and ongoing research on ibogaine’s use as an anti-addictive treatment for humans.

Brown, T. K. (2013). Ibogaine in the Treatment of Substance Dependence. Current Drug Abuse Reviews, 6(1), 3-16.
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Ayahuasca-Assisted Therapy for Addiction: Results from a Preliminary Observational Study in Canada

Abstract

Introduction: This paper reports results from a preliminary observational study of ayahuasca-assisted treatment for problematic substance use and stress delivered in a rural First Nations community in British Columbia, Canada.

Methods: The “Working with Addiction and Stress” retreats combined four days of group counselling with two expert-led ayahuasca ceremonies. This study collected pre-treatment and six months follow-up data from 12 participants on several psychological and behavioral factors related to problematic substance use, and qualitative data assessing the personal experiences of the participants six months after the retreat.

Findings: Statistically significant (p < 0.05) improvements were demonstrated for scales assessing hopefulness, empowerment, mindfulness, and quality of life meaning and outlook subscales. Self-reported alcohol, tobacco and cocaine use declined, although cannabis and opiate use did not; reported reductions in problematic cocaine use were statistically significant. All study participants reported positive and lasting changes from participating in the retreats.

Conclusions: This form of ayahuasca-assisted therapy appears to be associated with statistically significant improvements in several factors related to problematic substance use among a rural aboriginal population. These findings suggest participants may have experienced positive psychological and behavioral changes in response to this therapeutic approach, and that more rigorous research of ayahuasca-assisted therapy for problematic substance use is warranted.

Thomas, G., Lucas, P., Capler, N.R., Tupper, K. W., & Martin, G. (2013). Ayahuasca-Assisted Therapy for Addiction: Results from a Preliminary Observational Study in Canada. Current Drug Abuse Reviews, 6(1), 30-42.
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Can MDMA Play a Role in the Treatment of Substance Abuse?

Abstract

A wider array of treatments are needed for people with substance abuse disorders. Some psychedelic compounds have been assessed as potential substance abuse treatments with promising results. MDMA may also help treat substance abuse based on shared features with psychedelic compounds and recent reports indicating that MDMA-assisted psychotherapy can reduce symptoms of PTSD. Narrative reports and data from early investigations found that some people reduced or eliminated their substance use after receiving MDMA, especially in a therapeutic setting. MDMA is a potent monoamine releaser with sympathomimetic effects that may indirectly activate 5-HT2A receptors. It increases interpersonal closeness and prosocial feelings, potentially through oxytocin release. Findings suggest that ecstasy, material represented as containing MDMA, is associated with deleterious long-term effects after heavy lifetime use, including fewer serotonin transporter sites and impaired verbal memory. Animal and human studies demonstrate moderate abuse liability for MDMA, and this effect may be of most concern to those treating substance abuse disorders. However, subjects who received MDMA-assisted psychotherapy in two recent clinical studies were not motivated to seek out ecstasy, and tested negative in random drug tests during follow-up in one study. MDMA could either directly treat neuropharmacological abnormalities associated with addiction, or it could indirectly assist with the therapeutic process or reduce symptoms of comorbid psychiatric conditions, providing a greater opportunity to address problematic substance use. Studies directly testing MDMA-assisted psychotherapy in people with active substance abuse disorder may be warranted.

Jerome, L, Schuster, S., & Yazar-Klosinski, B. B. (2013) Can MDMA Play a Role in the Treatment of Substance Abuse? Current Drug Abuse Reviews, 6(1), 54-62.
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Hypotheses regarding the mechanisms of ayahuasca in the treatment of addictions

Ayahuasca is a medicinal plant mixture utilized by indigenous peoples throughout the Amazon River basin for healing purposes. The “vine of the soul” or “vine of death,” as it is known in South America, contains a combination of monoamine oxidase inhibitors and N,N-dimethyltryptamine (DMT). When ingested together, these medicines produce profound alterations in consciousness. Increasingly, ayahuasca is being utilized to treat addictions. However, the mechanism of action by which ayahuasca treats addictions remains unclear. We offer four hypotheses to explain possible biochemical, physiological, psychological, and transcendent mechanisms by which ayahuasca may exert its anti-addiction effects.

Liester, M. B., & Prickett, J. I. (2012). Hypotheses regarding the mechanisms of ayahuasca in the treatment of addictions. Journal of psychoactive drugs, 44(3), 200-208. 10.1080/02791072.2012.704590
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Serotonergic Hallucinogens and Emerging Targets for Addiction Pharmacotherapies

Abstract

• Converging lines of evidence from pharmacologic, electrophysiologic, and behavioral
research in animals strongly suggest that activation of cortical 5-hydroxytryptamine-2A
receptors is the most critical step in initiating a cascade of biological events that accounts
for serotonergic hallucinogen (SH) psychoactive properties.
• Psilocybin produces hyperfrontality with divergent prefrontal–subcortical activation in such
a way as to increase cognitive and affective processing in the context of reduced gating
and reduced focus on external stimulus processing.
• In contrast to all other drugs of abuse, SHs are not considered to be capable of producing
sufficient reinforcing effects to cause dependence (addiction) syndromes.
• Given that SHs increase extracellular glutamate levels and activity in the prefrontal–
limbic circuitry, it is possible that a normalization in functional connectivity in this
network through a glutamate-dependent neuroplastic adaptation could produce an
anti-addictive effect.

Ross, S. (2012). Serotonergic hallucinogens and emerging targets for addiction pharmacotherapies. Psychiatric Clinics of North America, 35(2), 357-374. http://dx.doi.org/10.1016/j.psc.2012.04.002
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LSD effective in the treatment of alcohol addiction

alcoholismLSD can be effective in the treatment of alcoholism, according to a new study of a Norwegian research team. This study, published in the Journal of Psychopharmacology, shows that administration of LSD in alcoholics can contribute to the success of the treatment.

In this meta-analysis, the results of six randomized clinical trials that were published between 1966 and 1970 were used. In these studies LSD was administered in a total of 325 cases, and a placebo in 211 cases. Of the patients that received LSD 59% percent improved during the treatment, compared to only 38% of the persons receiving a placebo. The researchers conclude that there is evidence for a positive effect of LSD in the treatment of alcoholism.

Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials

Abstract

Assessments of lysergic acid diethylamide (LSD) in the treatment of alcoholism have not been based on quantitative meta-analysis. Hence, we performed a meta-analysis of randomized controlled trials in order to evaluate the clinical efficacy of LSD in the treatment of alcoholism. Two reviewers independently extracted the data, pooling the effects using odds ratios (ORs) by a generic inverse variance, random effects model. We identified six eligible trials, including 536 participants. There was evidence for a beneficial effect of LSD on alcohol misuse (OR, 1.96; 95% CI, 1.36–2.84; p = 0.0003). Between-trial heterogeneity for the treatment effects was negligible (I² = 0%). Secondary outcomes, risk of bias and limitations are discussed. A single dose of LSD, in the context of various alcoholism treatment programs, is associated with a decrease in alcohol misuse.

Krebs, T. S., & Johansen, P. Ø. (2012). Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials. Journal of Psychopharmacology, 26(2), 994-1002. http://dx.doi.org/10.1177/0269881112439253
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Single versus repeated sessions of ketamine-assisted psychotherapy for people with heroin dependence

Abstract

A prior study found that one ketamine-assisted psychotherapy session was significantly more effective than active placebo in promoting abstinence (Krupitsky et al. 2002). In this study of the efficacy of single versus repeated sessions of ketamine-assisted psychotherapy in promoting abstinence in people with heroin dependence, 59 detoxified inpatients with heroin dependence received a ketamine-assisted psychotherapy (KPT) session prior to their discharge from an addiction treatment hospital, and were then randomized into two treatment groups. Participants in the first group received two addiction counseling sessions followed by two KPT sessions, with sessions scheduled on a monthly interval (multiple KPT group). Participants in the second group received two addiction counseling sessions on a monthly interval, but no additional ketamine therapy sessions (single KPT group). At one-year follow-up, survival analysis demonstrated a significantly higher rate of abstinence in the multiple KPT group. Thirteen out of 26 subjects (50%) in the multiple KPT group remained abstinent, compared to 6 out of 27 subjects (22.2%) in the single KPT group (p < 0.05). No differences between groups were found in depression, anxiety, craving for heroin, or their understanding of the meaning of their lives. It was concluded that three sessions of ketamine-assisted psychotherapy are more effective than a single session for the treatment of heroin addiction.

Krupitsky, E. M., Burakov, A. M., Dunaevsky, I. V., Romanova, T. N., Slavina, T. Y., & Grinenko, A. Y. (2007). Single versus repeated sessions of ketamine-assisted psychotherapy for people with heroin dependence. Journal of psychoactive drugs, 39(1), 13-19. https://dx.doi.org/10.1080/02791072.2007.10399860
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Combating substance abuse with ibogaine: pre- and posttreatment recommendations and an example of successive model fitting analyses

Abstract

Ibogaine is an indole alkaloid derived from the root bark of the African shrub Tabernan the iboga and it has been used for many years as a medicinal and ceremonial agent in West Central Africa. Furthermore, both anecdotal observations and recent studies suggest that ibogaine alleviates withdrawal symptoms and reduces drug cravings. Although ibogaine articles typically include information bearing on the duration of drug abstinence following treatment, little if any attention is given to the psychological and environmental factors that might facilitate a positive treatment outcome. Hence, a major purpose of the present review is to suggest a number of theory-driven, pretreatment and posttreatment recommendations that have good potential for enhancing ibogaine’s effectiveness. The second major purpose of this review is to demonstrate, through a reanalysis of previously published results, the utility of conducting successive model fitting analyses on ibogaine treatment data. Such analyses are useful for determining both the strength and form of the association between pre-ibogaine treatment variables and post-ibogaine treatment outcomes. Finally, in order to facilitate future quantitative reviews, the authors recommend that a minimum set of patient- and treatment-related variables be included in all ibogaine publications involving human participants.

Hittner, J. B., & Quello, S. B. (2004). Mechanisms of antiaddictive actions of ibogaine. Journal of Psychoactive Drugs, 36(2), 191-199. http://dx.doi.org/10.1080/02791072.2004.10399729
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Assessment of addiction severity among ritual users of ayahuasca

Abstract

Ayahuasca is a psychoactive beverage used for magico-religious purposes in the Amazon. Recently, Brazilian syncretic churches have helped spread the ritual use of ayahuasca abroad. This trend has raised concerns that regular use of this N,N-dimethyltryptamine-containing tea may lead to the medical and psychosocial problems typically associated with drugs of abuse. Here we assess potential drug abuse-related problems in regular ayahuasca users. Addiction severity was assessed using the Addiction Severity Index (ASI), and history of alcohol and illicit drug use was recorded. In Study 1, jungle-based ayahuasca users (n=56) were compared vs. rural controls (n=56). In Study 2, urban-based ayahuasca users (n=71) were compared vs. urban controls (n=59). Follow-up studies were conducted 1 year later. In both studies, ayahuasca users showed significantly lower scores than controls on the ASI Alcohol Use, and Psychiatric Status subscales. The jungle-based ayahuasca users showed a significantly higher frequency of previous illicit drug use but this had ceased at the time of examination, except for cannabis. At follow-up, abstinence from illicit drug use was maintained in both groups except for cannabis in Study 1. However, differences on ASI scores were still significant in the jungle-based group but not in the urban group. Despite continuing ayahuasca use, a time-dependent worsening was only observed in one subscale (Family/Social relationships) in Study 2. Overall, the ritual use of ayahuasca, as assessed with the ASI in currently active users, does not appear to be associated with the deleterious psychosocial effects typically caused by other drugs of abuse.

Fábregas, J. M., González, D., Fondevila, S., Cutchet, M., Fernández, X., Barbosa, P. C., Riba, J., … Bouso J. C. (2010). Assessment of addiction severity among ritual users of ayahuasca. Drug and Alcohol Dependence,  111(3), 257–261. http://dx.doi.org/10.1016/j.drugalcdep.2010.03.024
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