OPEN Foundation

H. Winter

Effects of low dose ibogaine on subjective mood state and psychological performance

Abstract

Ethnopharmacological relevance: Root bark from Tabernanthe iboga has been used traditionally in West Africa as a psychoactive substance in religious rituals. In smaller doses it is reported anecdotally to have stimulant properties.

Aim of the study: To evaluate the influence of a single 20 mg ibogaine dose on psychological variables reflecting subjective mood state and a range of cognitive functions.

Materials and methods: 21 healthy male volunteers received single 20 mg doses of ibogaine after 6 days pretreatment with double-blind paroxetine or placebo. We compared responses to a battery of psychometric tests and subjective mood ratings performed before and 2 h after ibogaine dosing, and assessed relationships between changes in test scores and concentrations of active moiety (the sum of molar noribogaine and ibogaine concentrations). Psychological tests were chosen based on responsiveness to opioid and serotonergic ligands.

Results: Ibogaine had minimal influence on psychological tests and mood ratings. The ability to selectively ignore distracting spatial information showed some evidence of modulation; however because this effect was limited to the less challenging condition calls into question the reliability of this result.

Conclusion: We were unable to identify stimulant effects after single 20 mg doses of ibogaine. Future research is needed to confirm whether active moiety concentrations impact selective attention abilities while leaving other cognitive functions and mood state unaffected.

Forsyth, B., Machado, L., Jowett, T., Jakobi, H., Garbe, K., Winter, H., & Glue, P. (2016). Effects of low dose ibogaine on subjective mood state and psychological performance. Journal of Ethnopharmacology. http://dx.doi.org/10.1016/j.jep.2016.05.022

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Influence of CYP2D6 activity on the pharmacokinetics and pharmacodynamics of a single 20 mg dose of ibogaine in healthy volunteers

Abstract

Conversion of ibogaine to its active metabolite noribogaine appears to be mediated primarily by CYP2D6. We compared 168 h pharmacokinetic profiles of both analytes after a single oral 20 mg dose of ibogaine in 21 healthy subjects who had been pretreated for 6 days with placebo or the CYP2D6 inhibitor paroxetine. In placebo-pretreated subjects, ibogaine was rapidly converted to noribogaine. Median peak noribogaine concentrations occurred at 4 h. Compared with placebo-pretreated subjects, paroxetine-pretreated subjects had rapid (Tmax = 1.5 h) and substantial absorption of ibogaine, with detectable levels out to 72 h, and an elimination half-life of 10.2 h. In this group, ibogaine was also rapidly converted to noribogaine with a median Tmax of 3 h. Extent of noribogaine exposure was similar in both groups. CYP2D6 phenotype was robustly correlated with ibogaine AUC0-t (r = 0.82) and Cmax (r = 0.77). Active moiety (ibogaine plus noribogaine) exposure was ∼2-fold higher in paroxetine-pretreated subjects. Single 20 mg ibogaine doses were safe and well tolerated in all subjects. The doubling of exposure to active moiety in subjects with reduced CYP2D6 activity suggests it may be prudent to genotype patients awaiting ibogaine treatment, and to at least halve the intended dose of ibogaine in CYP2D6 poor metabolizers.

Glue, P., Winter, H., Garbe, K., Jakobi, H., Lyudin, A., Lenagh‐Glue, Z., & Hung, C. T. (2015). Influence of CYP2D6 activity on the pharmacokinetics and pharmacodynamics of a single 20 mg dose of ibogaine in healthy volunteers. The Journal of Clinical Pharmacology. https://dx.doi.org/10.1002/jcph.471
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