Journal of Analytical Toxicology
October 1, 1996
J. C. Callaway, Lionel P. Raymon, William Lee Hearn et al.
158 citations
After ritual ingestion of ayahuasca, the highest plasma concentrations in 15 healthy male volunteers were 222.3 ng/mL for harmine, 134.5 ng/mL for tetrahydroharmine, and 9.4 ng/mL for harmaline, with N,N-dimethyltryptamine (DMT) also quantitated. Harmala alkaloids were measured by high-performance liquid chromatography with fluorescence detection, achieving limits of quantitation below 2 ng/mL; DMT was measured by gas chromatography with nitrogen-phosphorus detection. Recovery was quantitative for all analytes. These are the first reported measurements of DMT and harmala alkaloids in human plasma following ritual ayahuasca ingestion. The methods may apply to other biological matrices.
European Journal of Neuroscience
November 16, 2007
Susan Schenk, Lincoln S. Hely, Barbara Lake et al.
113 citations
MDMA self-administration was studied in previously drug-naïve rats. Acquisition varied widely, with about 60% of rats learning to self-administer MDMA over 15 days, a lower rate and slower onset than for cocaine. Responding depended on dose, and breakpoints under a progressive ratio schedule increased with dose. Rats that self-administered MDMA showed lower densities of serotonin transporter sites (SERT) across brain regions, comparable to reductions from experimenter-administered MDMA. The findings indicate MDMA has high abuse liability and that long-term self-administration may cause lasting deficits in serotonin neurotransmission.
Pharmacological research
April 1, 2023
Deborah C. Mash
37 citations
Ibogaine is a psychoactive substance that alters perception and mood and can interrupt addictive behaviors. It has a long history of ethnobotanical use in low doses for combating fatigue, hunger, and thirst, and in high doses as a sacrament in African rituals. In the 1960s, self-help groups reported that a single dose alleviated drug craving, opioid withdrawal, and prevented relapse for weeks to years. Ibogaine is rapidly metabolized to noribogaine, and both interact with multiple central nervous system targets, showing predictive validity in animal addiction models. Over ten thousand people have sought unregulated treatment, and open-label pilot studies show positive benefit. Ibogaine has regulatory approval for a Phase 1/2a clinical trial.
Drug Science Policy and Law
September 1, 2025
David Nutt, David Erritzøe, Anne Katrin Schlag et al.
9 citations
The field of psychedelic research lacks standardized terminology for clinical development, dosing, safety monitoring, and regulatory classification. A comprehensive framework is proposed that classifies psychedelics by pharmacology (serotonergic, glutamatergic, kappaergic, GABAergic, and atypical), introduces dose-dependent categories (microdose, minidose, mididose, macrodose), and standardizes terms like “short-acting” with specific pharmacokinetic parameters. Safety considerations include cardiovascular and psychological effects, with risk mitigation protocols for higher-risk compounds like ibogaine. A three-phase treatment model—preparation, dosing, and integration—is recommended as a minimum standard. The lack of comparative research on psychotherapy modalities is identified as a critical gap.
Psychedelics as Psychiatric Medications
March 1, 2023
Deborah C. Mash
1 citation
Ibogaine, derived from the root bark of Tabernanthe iboga, has a century-long history of traditional ceremonial and medicinal use in Western Africa. It acts on multiple neurotransmitter systems including dopamine, serotonin, opioid, nicotinic, and glutamatergic pathways. The UK MHRA has approved a Phase 1/2a clinical trial; Phase 1 assesses safety at escalating doses, and Phase 2 is a randomized, placebo-controlled proof-of-concept study in patients seeking opioid detoxification. Existing clinical reports indicate ibogaine helps manage both physical opioid withdrawal symptoms and behavioral aspects of addiction that drive relapse.
The FASEB Journal
April 1, 2015
Émeline L. Maillet, Nicolas Milon, James A. Fishback et al.
1 citation
Noribogaine, the primary metabolite of the anti-addictive substance ibogaine, modulates opioid receptors in ways that may explain its therapeutic effects. At mu-opioid receptors, noribogaine acts as a moderately potent antagonist of both G-protein and β-arrestin signaling pathways. At kappa-opioid receptors, it is a partial agonist of the G-protein pathway, activating at 75% the maximal efficacy of Dynorphin A with a potency of 9 µM, while poorly activating the β-arrestin pathway. Noribogaine functionally inhibits Dynorphin A-induced β-arrestin recruitment at physiologically relevant concentrations, with an IC50 of 1.45 µM. Computational simulations suggest noribogaine binds to the orthosteric morphinan binding site.
The Oxford Handbook of Opioids and Opioid Use Disorder
December 18, 2023
Deborah C. Mash, Michael Karukin
Ibogaine, a compound from the Tabernanthe iboga plant, has been used anecdotally since the 1960s to block opioid withdrawal and promote drug-free abstinence after a single oral dose, though it has never been tested in human clinical trials. This chapter reviews open-label evidence suggesting ibogaine may help manage opioid withdrawal symptoms and facilitate abstinence, while also discussing its complex mechanism of action related to mu-opioid receptor adaptations. The unregulated use of ibogaine in for-profit clinics raises serious safety concerns. The drug's future as a treatment depends on controlled trials that clarify its benefits, risks, and safety.
The FASEB Journal
April 1, 2015
Émeline L. Maillet, Qing Chang, Nicolas Milon et al.
Noribogaine, a drug that acts on opioid receptors, nicotinic receptors, and serotonin transporters, was tested for its effects on nicotine dependence. It inhibited several types of nicotinic acetylcholine receptors, including α3β4 and α7. In a rat model of nicotine self-administration, noribogaine dose-dependently reduced nicotine intake by up to 64% compared to saline-treated rats, an effect comparable to the approved smoking cessation drug varenicline. These results suggest noribogaine may have potential for treating smoking cessation, substance abuse, and anxiety disorders.
ChemInform
March 23, 1999
Simon M. N. Efange, Deborah C. Mash, Anil B. Khare et al.
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