Sex differences in ibogaine antagonism of morphine-induced locomotor activity and in ibogaine brain levels and metabolism.
S M Pearl, L B Hough, D L Boyd, Stanley D Glick
Pharmacology, Biochemistry, and Behavior August 1, 1997 DOI: 10.1016/s0091-3057(96)00383-8 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled experiment Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | Ibogaine Noribogaine |
| Dose | 40 mg/kg, i.p.; 10-60 mg/kg, i.p.; 5-40 mg/kg, i.p. |
| Topics | Ibogaine |
| Citations | 58 |
| Key findings | Female rats show greater ibogaine-induced antagonism of morphine's locomotor effects than males, corresponding to higher brain and plasma ibogaine levels. |
Abstract
The present study demonstrates that the putative antiaddictive agent ibogaine produces more robust behavioral effects in female than in male rats and that these behavioral differences correlate with higher levels of ibogaine in the brain and plasma of female rats. There were no differences in basal locomotor activity between the sexes, and the response of rats to ibogaine differed between the sexes even in the absence of morphine. Five h after receiving ibogaine (40 mg/kg, i.p.). antagonism of morphine-induced locomotor activity was evident in female but not in male rats. Either 19 h after administration of ibogaine (10-60 mg/kg, i.p.), or one h after administration of noribogaine (5-40 mg/kg, i.p.), a suspected metabolite, antagonism of morphine was significantly greater in female than in male rats. Brain and plasma levels of ibogaine (1 h) and noribogaine (5 h), measured by gas chromatography-mass spectrometry, were greater in females as compared with males receiving the same dose of ibogaine. Levels of both ibogaine and noribogaine were substantially lower at 19 h than at earlier times after ibogaine administration, contrary to a previous study in humans. For both sexes, subcutaneous administration of ibogaine (40 mg/kg, i.p., 19 h) produced greater antagonism of morphine-induced locomotor activity than did a comparable intraperitoneal injection, consistent with previous studies from this laboratory demonstrating that the former route of administration produces higher levels of ibogaine in the brain. These data show that there are sex differences in the effects of ibogaine and that this may be due to decreased bioavailability of ibogaine in males as compared to females.
Comparable studies
Other preclinical and animal studies on ibogaine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Noncompetitive Functional Inhibition at Diverse, Human Nicotinic Acetylcholine Receptor Subtypes by Bupropion, Phencyclidine, and Ibogaine TE671/RD cells (human muscle-type nAChR) and SH-SY5Y neuroblastoma cells (human... | 1999 | In vitro study | |
| Degeneration of Purkinje cells in parasagittal zones of the cerebellar vermis after treatment with ibogaine or harmaline. Ibogaine- or harmaline-treated rats | 1993 | Experimental animal study | |
| Effects and aftereffects of ibogaine on morphine self-administration in rats. Rats | 1991 | Preclinical experimental study | |
| Effects of iboga alkaloids on morphine and cocaine self-administration in rats: relationship to tremorigenic effects and to effects on dopamine release in nucleus accumbens and striatum. Rats | 1994 | Experimental study | |
| Glial Cell Line-Derived Neurotrophic Factor Mediates the Desirable Actions of the Anti-Addiction Drug Ibogaine against Alcohol Consumption Rats | 2005 | Experimental study |
Citations in the library
Cited by 42
- Clinical applications of hallucinogens: A review. Experimental and Clinical Psychopharmacology August 1, 2016
- Treatment of opioid use disorder with ibogaine: detoxification and drug use outcomes. The American Journal of Drug and Alcohol Abuse 2018
- Anti-addictive actions of an iboga alkaloid congener: a novel mechanism for a novel treatment. Pharmacology, Biochemistry, and Behavior June 1, 2003
- Ibogaine in the treatment of substance dependence. Current Drug Abuse Reviews March 1, 2013
- Ibogaine, an anti-addictive drug: pharmacology and time to go further in development. A narrative review. Human & Experimental Toxicology March 1, 2008
and 37 more in the library
Cites 17
- Effects and aftereffects of ibogaine on morphine self-administration in rats. European Journal of Pharmacology April 3, 1991
- Effects of iboga alkaloids on morphine and cocaine self-administration in rats: relationship to tremorigenic effects and to effects on dopamine release in nucleus accumbens and striatum. Brain Research September 19, 1994
- Inhibitory effects of ibogaine on cocaine self-administration in rats. European Journal of Pharmacology September 14, 1993
- Mechanisms of action of ibogaine and harmaline congeners based on radioligand binding studies. Brain Research February 7, 1992
- Interactions between ibogaine, a potential anti-addictive agent, and morphine: an in vivo microdialysis study. European Journal of Pharmacology June 18, 1991
and 12 more in the library