Ibogaine: Complex Pharmacokinetics, Concerns for Safety, and Preliminary Efficacy Measures

Abstract

Ibogaine is an indole alkaloid found in the roots of Tabernanthe Iboga (Apocynaceae family), a rain forest shrub that is native to western Africa. Ibogaine is used by indigenous peoples in low doses to combat fatigue, hunger and thirst, and in higher doses as a sacrament in religious rituals. Members of American and European addict self-help groups have claimed that ibogaine promotes long-term drug abstinence from addictive substances, including psychostimulants and opiates. Anecdotal reports attest that a single dose of ibogaine eliminates opiate withdrawal symptoms and reduces drug craving for extended periods of time. The purported efficacy of ibogaine for the treatment of drug dependence may be due in part to an active metabolite. The majority of ibogaine biotransformation proceeds via CYP2D6, including the O-demethylation of ibogaine to 12-hydroxyibogamine (noribogaine). Blood concentration-time effect profiles of ibogaine and noribogaine obtained for individual subjects after single oral dose administrations demonstrate complex pharmacokinetic profiles. Ibogaine has shown preliminary efficacy for opiate detoxification and for short-term stabilization of drug-dependent persons as they prepare to enter substance abuse treatment. We report here that ibogaine significantly decreased craving for cocaine and heroin during inpatient detoxification. Self-reports of depressive symptoms were also significantly lower after ibogaine treatment and at 30 days after program discharge. Because ibogaine is cleared rapidly from the blood, the beneficial aftereffects of the drug on craving and depressed mood may be related to the effects of noribogaine on the central nervous system.

Glial Cell Line-Derived Neurotrophic Factor Mediates the Desirable Actions of the Anti-Addiction Drug Ibogaine against Alcohol Consumption

“…We found that ethanol intake was increased significantly after 2 weeks of extinction, compared with preextinction baseline levels: ibogaine reduced the enhanced ethanol intake to baseline levels. Interestingly, human anecdotal reports also suggest a decrease in craving and relapse to addictive drugs after ibogaine intake (Mash et al, 2000). Together, these findings indicate that ibogaine reduces ethanol intake, suggesting that the identification of its molecular mechanism of action for this effect may be beneficial.…”

Ibogaine reduces organ colonization in murine systemic and gastrointestinal Candida albicans infections

“…Ibogaine is a naturally occurring compound with antiaddictive properties (Mash et al, 2000). A few investigations in vivo have demonstrated that ibogaine is rapidly transformed to 12-hydroxyibogaine (noribogaine), which persists in the bloodstream for at least 1 day (Baumann et al, 2001a;Mash et al, 1995).…”

Ibogaine labeling with 99mTc-tricarbonyl: Synthesis and transport at the mouse blood–brain barrier

“…Clinical trials have shown that ibogaine facilitates abstinence towards many drugs (morphine, heroin, cocaine, nicotine, alcohol, and psychostimulants) by reducing withdrawal symptoms. [15][16][17] This effect does not seem to be due to its direct interaction with an ibogaine receptor alone, but may well also involve synthesis of the glial cell line-derived neurotrophic factor (GDNF) by dopaminergic neurons. 18,19 Its high lipophilicity (Log P (o/w) 3.6) 20 and rapid, sustained accumulation in the mouse brain 15,21 make ibogaine an attractive candidate as a vector for new g-emitting radiotracers for in vivo imaging of the brains of addicts.…”