The acute effects of monoamine reuptake inhibitors on the stimulus effects of hallucinogens.
Jerrold C Winter, Scott Helsley, David Fiorella, R A Rabin
Pharmacology, Biochemistry, and Behavior July 1, 1999 DOI: 10.1016/s0091-3057(99)00039-8 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experiment Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | fluoxetine fluvoxamine venlafaxine |
| Topics | 5-MeO-DMT Ibogaine LSD |
| Keywords | Drug interactions Amplify Enhance Augmentation Potentiation Combined effects Drug-drug interaction Antidepressants Fluoxetine Fluvoxamine Venlafaxine Ssris Snris Psychiatric medications Hallucinogens Dom Psychedelics Psychotomimetics Entheogens Subjective experience Psychopharmacology Neuropharmacology Drug effects Psychotropic drugs Drug research |
| Citations | 14 |
| Key findings | Fluoxetine, fluvoxamine, and venlafaxine potentiate the discriminative stimulus effects of LSD, (-)-DOM, and ibogaine, but only fluoxetine potentiates 5-MeO-DMT, and most combinations with (-)-DOM show additivity rather than true potentiation. |
Abstract
In a previous study it was observed that fluoxetine potentiates the stimulus effects of lysergic acid diethylamide (LSD). In the present investigation, stimulus control was established in groups of rats using as training drugs the hallucinogens lysergic acid diethylamide (LSD); 0.1 mg/kg), (-)-2,5-dimethoxy-4-methylamphetamine [(-)-DOM; 0.56 mg/kg], ibogaine (10 mg/kg), and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT; 3 mg/kg). A two-lever, fixed-ratio 10, positively reinforced task with saline controls was employed. The hypotheses tested were that (a) monoamine uptake inhibitors other than fluoxetine potentiate the discriminative effects of LSD, and (b) hallucinogens other than LSD are potentiated by acute pretreatment with monoamine uptake inhibitors. The effects of a range of doses of each of the training drugs were determined both alone and following pretreatment with the monoamine reuptake inhibitors fluoxetine, fluvoxamine, and venlafaxine. In LSD-trained subjects, all three reuptake inhibitors caused a significant increase in LSD-appropriate responding. Similar results were observed in rats trained with (-)-DOM and with ibogaine. In 5-MeO-DMT-trained subjects, only fluoxetine resulted in an enhancement of drug-appropriate responding. The reuptake inhibitors given alone elicited varying degrees of responses appropriate for the respective training drugs. For fluoxetine in rats trained with LSD and ibogaine, for venlafaxine in LSD trained, and for fluvoxamine in (-)-DOM trained, the degree of responding met our criterion for intermediate responding, i.e., significantly different from both training conditions. Subsequent experiments in (-)-DOM-trained subjects examined a range of doses of each of the reuptake inhibitors in combination with a fixed dose of (-)-DOM (0.1 mg/kg), which alone yielded about 50% (-)-DOM-appropriate responding. With the exception of the point obtained with the highest dose of venlafaxine, all data were compatible with additivity of effects rather than true potentiation. In summary, the present data extend our previous observation of the augmentation of the stimulus effects of LSD by fluoxetine to include other hallucinogens. The mechanisms by which these interactions arise and possible differential effects of acute and chronic treatment remain to be established.
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 10
- A narrative synthesis of research with 5-MeO-DMT. Journal of Psychopharmacology March 1, 2022
- Distribution of the hallucinogens N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine in rat brain following intraperitoneal injection: application of a new solid-phase extraction LC-APcI-MS-MS-isotope dilution method. Journal of Chromatography. B, Biomedical Sciences and Applications February 10, 2001
- Ibogaine and Noribogaine: Comparing Parent Compound to Metabolite CNS Drug Reviews September 1, 2000
- Drug discrimination studies with ibogaine. The Alkaloids: Chemistry and Biology 2001
- Behavioral effects of three synthetic tryptamine derivatives in rodents. Journal of Psychopharmacology April 4, 2025
and 5 more in the library
Cites 14
- A preliminary investigation of ibogaine: case reports and recommendations for further study. Journal of Substance Abuse Treatment 1994
- Identification of a primary metabolite of ibogaine that targets serotonin transporters and elevates serotonin. Life Sciences 1995
- The paradox of 5-methoxy-N,N-dimethyltryptamine: an indoleamine hallucinogen that induces stimulus control via 5-HT1A receptors. Pharmacology, Biochemistry, and Behavior 2000
- In vivo metabolism of 5-methoxy-N,N-dimethyltryptamine and N,N-dimethyltryptamine in the rat. Biochemical Pharmacology May 1, 1987
- Serotonin receptor subtype mediation of the interoceptive discriminative stimuli induced by 5-methoxy-N,N-dimethyltryptamine. Psychopharmacology 1987
and 9 more in the library