Influence of CYP2D6 activity on the pharmacokinetics and pharmacodynamics of a single 20 mg dose of ibogaine in healthy volunteers.
Paul Glue, Helen Winter, Kira Garbe, Hannah Jakobi, Alexander Lyudin, Zoe Lenagh-Glue, Cheung-Tak Hung
The Journal of Clinical Pharmacology June 1, 2015 DOI: 10.1002/jcph.471 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 21 |
| Population | Healthy subjects |
| Interventions | Ibogaine Paroxetine |
| Dose | 20 mg |
| Duration | 168 hours |
| Topics | Ibogaine |
| Keywords | Paroxetine Pharmacodynamics Ibogaine pharmacokinetics Cyp2d6 enzyme activity Drug safety optimization |
| Citations | 39 |
| Key findings | Inhibiting CYP2D6 with paroxetine approximately doubled exposure to the active moiety of ibogaine, suggesting dose reduction is prudent for CYP2D6 poor metabolizers. |
Abstract
Conversion of ibogaine to its active metabolite noribogaine appears to be mediated primarily by CYP2D6. We compared 168 hours 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 hours. Compared with placebo-pretreated subjects, paroxetine-pretreated subjects had rapid (Tmax = 1.5 hours) and substantial absorption of ibogaine, with detectable levels out to 72 hours, and an elimination half-life of 10.2 hours. In this group, ibogaine was also rapidly converted to noribogaine with a median Tmax of 3 hours. 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.
Comparable studies
Other randomized controlled trials on ibogaine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Ascending Single-Dose, Double-Blind, Placebo-Controlled Safety Study of Noribogaine in Opioid-Dependent Patients. Patients on methadone opioid substitution therapy seeking to discontinue methadone | 2016 | Randomized controlled trial | n = 27 |
| Ascending-dose study of noribogaine in healthy volunteers: pharmacokinetics, pharmacodynamics, safety, and tolerability. Healthy drug-free male volunteers | 2015 | Randomized controlled trial | n = 36 |
Citations in the library
Cited by 37
- Ibogaine treatment outcomes for opioid dependence from a twelve-month follow-up observational study. The American Journal of Drug and Alcohol Abuse 2018
- The emerging science of microdosing: A systematic review of research on low dose psychedelics (1955–2021) and recommendations for the field Neuroscience & Biobehavioral Reviews May 21, 2022
- Ibogaine Detoxification Transitions Opioid and Cocaine Abusers Between Dependence and Abstinence: Clinical Observations and Treatment Outcomes. Frontiers in Pharmacology 2018
- How toxic is ibogaine? Clinical Toxicology 2016
- A systematic literature review of clinical trials and therapeutic applications of ibogaine. Journal of Substance Abuse Treatment July 1, 2022
and 32 more in the library
Cites 8
- Treatment of acute opioid withdrawal with ibogaine. American Journal on Addictions 1999
- The ibogaine medical subculture. Journal of Ethnopharmacology January 4, 2008
- Ibogaine: complex pharmacokinetics, concerns for safety, and preliminary efficacy measures. Annals of the New York Academy of Sciences September 1, 2000
- Ibogaine, an anti-addictive drug: pharmacology and time to go further in development. A narrative review. Human & Experimental Toxicology March 1, 2008
- Ascending-dose study of noribogaine in healthy volunteers: pharmacokinetics, pharmacodynamics, safety, and tolerability. The Journal of Clinical Pharmacology February 1, 2015
and 3 more in the library