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

This open-label study investigated the effects of low-dose ibogaine 20mg on subjective mood states and a range of cognitive functions. There was no effect on subjective mood states or cognitive performance related to basic visuomotor function, inhibitory function, memory function, task switching, or selective attention. Future studies would require a wider dose range, placebo-controls, and larger sample sizes to determine whether ibogaine affects these faculties.

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.”

Authors: Bridget Forsyth, Liana Machado, Tim Jowett, Hannah Jakobi, Kira Garbe, Helen Winter & Paul Glue

Summary

Ibogaine is an indole alkaloids present in the root bark of the West African rainforest shrub Tabernanthe iboga. It has been reported to ameliorate opioid withdrawal symptoms and opioid cravings. In light of recent ECG findings, low doses of ibogaine may be more clinically relevant than high doses. We recently published pharmacokinetic and pharmacodynamic data pertaining to pupil diameter and mood state in a study investigating the role of the cytochrome P450 enzyme 2D6 on conversion of single low doses of ibogaine into its active metabolite noribogaine.

In this 15 day study, 21 healthy male volunteers received paroxetine or placebo and were randomized to receive 10mg on days 2-3 and 20mg on days 415. Paroxetine was administered to influence CYP2D6 activity and ibogaine levels were measured on days 2-15. On Day 8, 20 mg of ibogaine was administered to all subjects. Blood samples were collected pre-dose and at 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144 and 168h post-dose. LC-MS/MS analysis of ibogaine and noribogaine in human plasma was performed at 2 and 4 hours on Day 8.

The study used double-blind capsules containing either paroxetine or placebo from Days 2-15, and open-label ibogaine on Day 8 at 8am. Psychological testing occurred on 6 occasions: two familiarization sessions separated by 2 hours on Day 1, baseline testing on Day 7, and testing on Day 15. Simon assessed the ability to ignore irrelevant spatial information, Pro assessed basic visuomotor performance, Anti assessed inhibitory control, and Pro/Anti assessed switching abilities.

Flanker assessed the ability to ignore irrelevant identity-based information by having subjects indicate the identity of the central consonant by pressing the assigned key. Forward Spatial assessed short-term memory capacity by having the subject click on boxes in a predetermined random sequence and if they responded correctly, the program increased the length of the sequence by one box. The battery of tests included a Forward Spatial, Backward Spatial, Pro, Anti, Pro/Anti, Simon, Flanker, and 2-back test. They were designed to assess subjective mood state and a range of cognitive functions that might be sensitive to ibogaine.

We analysed 21 test subjects’ psychological test scores in response to an increase in AM using 8 linear and polynomial regression models. The increase in AM was calculated as the change in each psychological test score from time point T3 to time point T4. The analyses were carried out using R software. The results show that the concentrations of AM increased from 49.9 nM in the placebo group to 121.0 nM in the paroxetine group, and that the psychological test scores decreased from baseline to 2 hours post-ibogaine dosing.

The majority of psychological response variables exhibited a linear trend, with the addition of a quadratic effect improving the fit in some cases, but the quadratic effects were weak. The only response variable with a statistically significant association with AM was Simon Congruent Median RT. Subjects with lower AM concentrations at T4 showed a negative change in RT from T3 to T4, whereas subjects with higher AM concentrations at T4 showed a positive change in RT.

Ibogaine has complex pharmacological activities, interacting with serotonergic, glutamatergic, opioid and cholinergic systems. We could not confirm that ibogaine has stimulant properties in the present study, and the only positive finding in psychological testing was evidence of an association between AM concentrations and the ability to selectively ignore distracting spatial information. This study has some limitations, such as a small sample size and no control group. Further studies should include a placebo arm and a range of ibogaine doses to investigate the potential effects of ibogaine on psychological variables.

In conclusion, a single 20mg dose of ibogaine had no effect on a number of psychological tests or mood ratings, and had no evidence of stimulant properties. The only positive finding was a relationship between AM concentrations and performance in a measure of selective attention. Alper, Lotsof, Kaplan, Antonio, Childers, Rothman, Dersch, King, C., Kuehne, Bornmann, Eshleman, Janowsky, Simon, Reith, Alper, 2013, Antonio, Cameron, Lucas, Machado, 2015.

Studies have shown that oxycodone has cognitive and subjective side effects in healthy middle-aged and older adults, that serotonergic modulation of response inhibition and re-engagement? occurs in healthy human volunteers, and that noribogaine has pharmacokinetics, pharmacodynamics, safety, and tolerability.

The authors of this text have cited several sources that provide more information about ibogaine, including Goutarel, Gollnhofer, Sillans, 2015, Guiney, Lucas, Cotter, J.D., Machado, 2000, Kessels, R.P., van Zandvoort, M.J., Postma, Kappelle, L., de Haan E.H., 2013.