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.
Annals of the New York Academy of Sciences
May 1, 1998
Deborah C. Mash, Craig A. Kovera, Billy E Buck et al.
111 citations
Ibogaine, an indole alkaloid from the rain forest shrub Tabernanthe iboga, has been used by indigenous peoples in equatorial Africa to combat fatigue and hunger and as a religious sacrament. Anecdotal reports from addict self-help groups claim a single dose eliminates withdrawal symptoms and reduces drug cravings for extended periods, but these purported antiaddictive properties require rigorous validation. A rising tolerance study with single administration has been initiated to assess ibogaine's safety for treating cocaine dependency, with primary objectives to determine safety, pharmacokinetics, dose effects, and relevant efficacy parameters. Pharmacokinetic and pharmacodynamic characteristics are assessed via concentration-time data from the Phase I trial and in vitro experiments on metabolism.
Frontiers in Pharmacology
January 1, 2018
Deborah C. Mash, Linda Duque, Bryan Page et al.
109 citations
A single oral dose of ibogaine, administered under medical supervision, diminishes opioid withdrawal symptoms and reduces drug cravings in people seeking to detoxify from opioids or cocaine. In an open-label case series of 191 human volunteers, no significant adverse events occurred at doses effective for blocking withdrawal. Pharmacokinetic measures from whole blood assays tracked ibogaine's metabolism and clearance. Multi-dimensional craving questionnaires showed reduced heroin and cocaine cravings during inpatient detoxification. One-month follow-up data suggested some persistence of craving reduction outside the inpatient setting. The results support developing ibogaine as a treatment for opioid withdrawal during medically supervised detoxification to transition individuals toward abstinence.
Journal of Pharmacology and Experimental Therapeutics
May 1, 2001
Michael H. Baumann, Richard B Rothman, John Pablo et al.
69 citations
Ibogaine, a compound with potential anti-addiction properties, is rapidly converted in the body to noribogaine. In rats, intravenous ibogaine caused dose-related tremors, while noribogaine did not. Both compounds raised stress hormones (corticosterone and prolactin), but ibogaine was more potent for corticosterone. Neither altered dopamine levels in the nucleus accumbens, but both increased extracellular serotonin, with noribogaine being about 10 times more potent as an indirect serotonin agonist. In vitro tests showed both inhibit serotonin uptake. Noribogaine appears biologically active and less likely to cause adverse effects, suggesting it may be a safer alternative for medication development.
Neuropharmacology
December 1, 2015
Émeline L. Maillet, Nicolas Milon, Mari D. Heghinian et al.
59 citations
Noribogaine, the main human metabolite of the anti-addictive substance ibogaine, reaches brain concentrations up to 20 μM after a therapeutic dose. Binding experiments and computational simulations indicate it may bind to the orthosteric morphinan site of opioid receptors. Noribogaine is a weak mu opioid receptor antagonist (Ke=20 μM at both G-protein and β-arrestin pathways) but a G-protein biased kappa opioid receptor agonist: 75% as efficacious as dynorphin A at stimulating GDP-GTP exchange (EC50=9 μM) yet only 12% as efficacious at recruiting β-arrestin. It also functionally inhibits dynorphin-induced kappa β-arrestin recruitment (IC50=1 μM), more potent than its G-protein agonism.
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.
The American Journal of Drug and Alcohol Abuse
January 2, 2018
Deborah C. Mash
29 citations
Ibogaine, an indole alkaloid from the West African shrub Tabernanthe iboga, has a long history of use in spiritual ceremonies, coming-of-age rituals, and healing practices. The abstract introduces the compound but does not present a specific finding or argument.
Journal of psychopharmacology (Oxford, England)
July 1, 2016
Deborah C. Mash, Barbara Ameer, Delphine Prou et al.
29 citations
Oral noribogaine dose dependently reduced naloxone-precipitated morphine withdrawal signs in mice by up to 88% with an ED50 of 13 mg/kg. Noribogaine showed high brain penetration with a brain/blood ratio of 7±1 across all doses tested. In rats, noribogaine up to 100 mg/kg did not produce conditioned place preference, indicating it is not perceived as a hedonic stimulus. Retrospective review of ibogaine studies suggests that differences in route of administration and testing time explain literature discrepancies. Noribogaine, not ibogaine, likely mediates withdrawal-blocking effects and may offer a non-addictive alternative to opiate replacement therapies.
Journal of psychopharmacology (Oxford, England)
June 1, 2015
Qing Chang, Taleen Hanania, Deborah C. Mash et al.
26 citations
Noribogaine, a drug that acts on opioid receptors, nicotinic receptors, and serotonin transporters, was tested for its ability to reduce nicotine self-administration in adult male rats. After training to self-administer nicotine intravenously, rats received oral doses of noribogaine (12.5, 25, or 50 mg/kg), vehicle, varenicline, or saline. Noribogaine dose-dependently decreased nicotine self-administration by up to 64% compared to saline-treated levels, matching the effectiveness of 1.7 mg/kg varenicline. At the highest dose, noribogaine reduced food pellet self-administration by only 23%, indicating greater specificity for nicotine. The findings suggest noribogaine may be a promising treatment for nicotine dependence.
Bioorganic & medicinal chemistry
March 20, 2003
Daniele Passarella, Raffaele Favia, Alessandra Giardini et al.
23 citations
A method to synthesize 7-heteroaryl-2-azabicyclo[2.2.2]oct-7-enes using cycloaddition followed by cross-coupling is described. The binding affinity of these new compounds to the receptor targets characteristic of ibogaine is reported.
Frontiers in Cellular Neuroscience
January 1, 2022
Charles Sutton, Erin Q Williams, Hoomam Homsi et al.
13 citations
Mutations in the dopamine transporter gene cause Dopamine Transporter Deficiency Syndrome (DTDS), a fatal infantile parkinsonism-dystonia with no current treatment. Pharmacological chaperones can rescue some disease-causing variants. This study examined structure-activity relationships for two known chaperones, bupropion and ibogaine. The isoquinuclidine substituent of ibogaine and its analogs is important for chaperone efficacy. For bupropion, the secondary amine group is essential. Additional analogs with varying chemical modifications showed variable chaperone efficacies, contributing to the design of improved dopamine transporter pharmacological chaperones.
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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