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ACS Chem Neurosci. 2018 Oct 17;9(10):2475-2483. doi: 10.1021/acschemneuro.8b00294. Epub 2018 Oct 9.

DARK Classics in Chemical Neuroscience: Ibogaine.

Author information

1
Division of Pharmaceutical, Administrative and Social Sciences , Duquesne University School of Pharmacy , 600 Forbes Avenue , Pittsburgh , Pennsylvania 15282 , United States.
2
Arnold & Marie Schwartz College of Pharmacy and Health Sciences , Long Island University-Brooklyn , 75 DeKalb Avenue , Brooklyn , New York 11201 , United States.

Abstract

The West African iboga plant has been used for centuries by the Bwiti and Mbiri tribes to induce hallucinations during religious ceremonies. Ibogaine, the principal alkaloid responsible for iboga's psychedelic properties, was isolated and sold as an antidepressant in France for decades before its adverse effects precipitated its removal from the market. An ibogaine resurgence in the 1960s was driven by U.S. heroin addicts who claimed that ibogaine cured their opiate addictions. Behavioral pharmacologic studies in animal models provided evidence that ibogaine could blunt self-administration of not only opiates but cocaine, amphetamines, and nicotine. Ibogaine displays moderate-to-weak affinities for a wide spectrum of receptor and transporter proteins; recent work suggests that its actions at nicotinic acetylcholine receptor subtypes may underlie its reputed antiopiate effects. At micromolar levels, ibogaine is neurotoxic and cardiotoxic and has been linked to several deaths by cardiac arrest. Structure-activity studies led to the isolation of the ibogaine analog 18-methoxycoronaridine (18-MC), an α3β4 nicotinic receptor modulator that retains ibogaine's anticraving properties with few or no adverse effects. Clinical trials of 18-MC treatment of nicotine addiction are pending. Ibogaine analogs may also hold promise for treating anxiety and depression via the "psychedelic-assisted therapy" approach that employs hallucinogens including psilocybin and methylenedioxymethamphetamine ("ecstasy").

KEYWORDS:

addiction; hallucinogen; iboga; nicotine; opioid; therapeutic

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