OPEN Foundation

OPEN Foundation

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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Salvia divinorum: A Psychopharmacological Riddle and a Mind-Body Prospect

Abstract

The multidisciplinary research on Salvia divinorum and its chemical principles is analyzed concerning whether the ethnobotany, phytochemistry, mental effects, and neuropharmacology of this sacred psychoactive plant and main principle clarify its experienced effects and divinatory uses. The scientific pursuit spans from the traditional practices, continues with the botanical identification, isolation of active molecules, characterization of mental and neural effects, possible therapeutic applications, and impinges upon the mind-body problem. The departure point is ethnopharmacology and therefore the traditional beliefs, ritual uses, and mental effects of this Mazatec sacred mint recorded during a 1973-1983 field research project are described. A water potion of crushed leaves produced short-lasting light-headedness, dysphoria, tactile and proprioceptive sensations, a sense of depersonalization, amplified sound perception, and an increase visual and auditory imagery, but not actual hallucinations. Similar effects were described using questionnaires and are attributable to salvinorin A, but cannot be explained solely by its specific and potent brain kappa-opioid receptor agonist activity. Some requirements for a feasible classification and mechanism of action of consciousness-altering products are proposed and include the activation of neural networks comprising several neurochemical systems. Top-down analyses should be undertaken in order to characterize such neural networks and eventually allowing to explore the differential ethnic effects. As is the case for other consciousness-altering preparations, a careful and encompassing research on this plant and principle can be consequential to endeavors ranging from the mind-body problem, a better understanding of shamanic ecstasy, to the potential generation of analgesic, antidepressant, and drug-abuse attenuating products.

Diaz, J-L (2013) Salvia divinorum: A Psychopharmacological Riddle and a Mind-Body Prospect. Current Drug Abuse Reviews, 6(1), 43-53.
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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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Safety and Side Effects of Ayahuasca in Humans—An Overview Focusing on Developmental Toxicology

Abstract

Despite being relatively well studied from a botanical, chemical, and (acute) pharmacological perspective, little is known about the possible toxic effects of ayahuasca (an hallucinogenic brew used for magico-ritual purposes) in pregnant women and in their children, and the potential toxicity of long-term ayahuasca consumption. It is the main objective of the present text to do an overview of the risks and possible toxic effects of ayahuasca in humans, reviewing studies on the acute ayahuasca administration to humans, on the possible risks associated with long-term consumption by adults and adolescents, and on the possible toxic effects on pregnant animals and in their offspring. Acute ayahuasca administration, as well as long-term consumption of this beverage, does not seem to be seriously toxic to humans. Although some nonhuman developmental studies suggested possible toxic effects of ayahuasca or of some of its alkaloids, the limited human literature on adolescents exposed to ayahuasca as early as in the uterus reports no serious toxic effects of the ritual consumption of the brew. Researchers must take caution when extrapolating nonhuman data to humans and more data are needed in basic and human research before a definite opinion can be made regarding the possible toxic effects of ayahuasca in pregnant women and in their children.

dos Santos, R. G. (2013). Safety and Side Effects of Ayahuasca in Humans— An Overview Focusing on Developmental Toxicology. Journal of Psychoactive Drugs, 45(1), 68-78. http://dx.doi.org/10.1080/02791072.2013.763564
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Role of the 5-HT2A receptor in the locomotor hyperactivity produced by phenylalkylamine hallucinogens in mice

Abstract

The 5-HT2A receptor mediates the effects of serotonergic hallucinogens and may play a role in the pathophysiology of certain psychiatric disorders, including schizophrenia. Given these findings, there is a need for animal models to assess the behavioral effects of 5-HT2A receptor activation. Our previous studies demonstrated that the phenylalkylamine hallucinogen and 5-HT2A/2C agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) produces dose-dependent effects on locomotor activity in C57BL/6J mice, increasing activity at low to moderate doses and reducing activity at high doses. DOI did not increase locomotor activity in 5-HT2A knockout mice, indicating the effect is a consequence of 5-HT2A receptor activation. Here, we tested a series of phenylalkylamine hallucinogens in C57BL/6J mice using the Behavioral Pattern Monitor (BPM) to determine whether these compounds increase locomotor activity by activating the 5-HT2A receptor. Low doses of mescaline, 2,5-dimethoxy-4-ethylamphetamine (DOET), 2,5-dimethoxy-4-propylamphetamine (DOPR), 2,4,5-trimethoxyamphetamine (TMA-2), and the conformationally restricted phenethylamine (4-bromo-3,6-dimethoxybenzocyclobuten-1-yl)methylamine (TCB-2) increased locomotor activity. By contrast, the non-hallucinogenic phenylalkylamine 2,5-dimethoxy-4-tert-butylamphetamine (DOTB) did not alter locomotor activity at any dose tested (0.1–10 mg/kg i.p.). The selective 5-HT2A antagonist M100907 blocked the locomotor hyperactivity induced by mescaline and TCB-2. Similarly, mescaline and TCB-2 did not increase locomotor activity in 5-HT2A knockout mice. These results confirm that phenylalkylamine hallucinogens increase locomotor activity in mice and demonstrate that this effect is mediated by 5-HT2A receptor activation. Thus, locomotor hyperactivity in mice can be used to assess phenylalkylamines for 5-HT2A agonist activity and hallucinogen-like behavioral effects. These studies provide additional support for the link between 5-HT2A activation and hallucinogenesis.

Halberstadt, A. L., Powell, S. B., & Geyer, M. A. (2013). Role of the 5-HT 2A receptor in the locomotor hyperactivity produced by phenylalkylamine hallucinogens in mice. Neuropharmacology, 70, 218-227. 10.1016/j.neuropharm.2013.01.014
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Psilocybin Biases Facial Recognition, Goal-Directed Behavior, and Mood State Toward Positive Relative to Negative Emotions Through Different Serotonergic Subreceptors

Abstract

Background
Serotonin (5-HT) 1A and 2A receptors have been associated with dysfunctional emotional processing biases in mood disorders. These receptors further predominantly mediate the subjective and behavioral effects of psilocybin and might be important for its recently suggested antidepressive effects. However, the effect of psilocybin on emotional processing biases and the specific contribution of 5-HT2A receptors across different emotional domains is unknown.

Methods
In a randomized, double-blind study, 17 healthy human subjects received on 4 separate days placebo, psilocybin (215 g/kg), the preferential 5-HT2A antagonist ketanserin (50 mg), or psilocybin plus ketanserin. Mood states were assessed by self-report ratings, and behavioral and event-related potential measurements were used to quantify facial emotional recognition and goal-directed behavior toward emotional cues.

Results
Psilocybin enhanced positive mood and attenuated recognition of negative facial expression. Furthermore, psilocybin increased goal-directed behavior toward positive compared with negative cues, facilitated positive but inhibited negative sequential emotional effects, and valence-dependently attenuated the P300 component. Ketanserin alone had no effects but blocked the psilocybin-induced mood enhancement and decreased recognition of negative facial expression.

Conclusions
This study shows that psilocybin shifts the emotional bias across various psychological domains and that activation of 5-HT2A receptors is central in mood regulation and emotional face recognition in healthy subjects. These findings may not only have implications for the pathophysiology of dysfunctional emotional biases but may also provide a framework to delineate the mechanisms underlying psylocybin’s putative antidepressant effects.

Kometer, M., Schmidt, A., Bachmann, R., Studerus, E., Seifritz, E., & Vollenweider, F. X. (2012). Psilocybin Biases Facial Recognition, Goal-Directed Behavior, and Mood State Toward Positive Relative to Negative Emotions Through Different Serotonergic Subreceptors. Biological Psychiatry, 72(11), 898-906. http://dx.doi.org/10.1016/j.biopsych.2012.04.005
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Labyrint: Geestverruimende Therapie

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Paddo’s gebruiken om depressieve klachten te bestrijden? Of LSD-therapie om van je rookverslaving af te komen? Op 19 december 2012 zond Labyrint TV een aflevering uit over grensverleggend onderzoek naar het gebruik van psychedelica in de behandelkamer van de psychiater. Gefilmd tijdens Stichting OPEN’s Interdisciplinary Conference on Psychedelic Research in 2012.

Voor het eerst uitgezonden op 19 december 2012.[/fusion_builder_column][/fusion_builder_row][/fusion_builder_container]

Labyrint: Mindblowing Therapy?

Will we be using Magic Mushrooms to fight depression? Or get an LSD treatment to cure your smoking addiction? On December 19 2012 Dutch Labyrint TV screened an episode about groundbreaking research using psychedelics in psychiatric treatment. Interviews with the scientists were filmed at OPEN’s Interdisciplinary Conference on Psychedelic Research in 2012.

First broadcast on the 19th of December, 2012 (English subtitles)

Labyrint TV special over therapieën met psychedelica

psionderzoek

Komende week op Wetenschap24 rapporteert Labyrint TV over grensverleggend onderzoek naar het gebruik van psychedelica in de behandelkamer van de psychiater.

De aflevering is gefilmd op het door OPEN georganiseerde Interdisciplinary Conference on Psychedelic Research 2012 en neemt je mee vanaf het eerste wetenschappelijk onderzoek naar psychedelica in de jaren ’50, het recreatieve gebruik en het verbod op deze middelen, naar het recente onderzoek naar psychedelica als potentiële hulpmiddelen bij psychotherapie. Onder andere de Britse psychofarmacoloog Robin Carhart-Harris en psychofarmacoloog Matthew Johnson, beiden sprekers op ICPR 2012, zullen in de uitzending zijn te zien, waar ze uitgebreid zullen vertellen over hun onderzoek en de potentiële toepassingen van psilocybine.

Vergeet dus vooral niet te kijken aankomende woensdag 19 december, om 20u50 op Nederland 2.

Meer informatie vind je op de Labyrint TV website.

interested in becoming a trained psychedelic-assisted therapist?

Indigenous Talk: Fulni-ô Culture & Jurema - Online Event - Dec 12th