The paradox of 5-methoxy-N,N-dimethyltryptamine: an indoleamine hallucinogen that induces stimulus control via 5-HT1A receptors.
Jerrold C Winter, R A Filipink, D Timineri, Scott Helsley, R A Rabin
Pharmacology, Biochemistry, and Behavior 2000 DOI: 10.1016/s0091-3057(99)00178-1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | 5-methoxy-N N-dimethyltryptamine (-)-2 5-dimethoxy-4-methylamphetamine (+/-)-pindolol WAY-100635 pirenperone |
| Dose | 5 mg/kg 5-MeO-DMT, 0.56 mg/kg (-)-DOM |
| Topics | 5-MeO-DMT DMT Serotonin |
| Keywords | Psychoactive compound Hallucinogens Psychedelics Psychoactive drugs Entheogens Serotonin receptors 5-HT Receptors 5-ht1a 5-ht2 Brain receptors Neuroreceptors Mechanism of action Pharmacodynamics Drug action Receptor binding Neuropharmacology |
| Citations | 80 |
| Key points | 5-MeO-DMT-induced stimulus control is mediated primarily by 5-HT1A receptors, but also includes a 5-HT2 receptor component that is not essential for its effects. |
Abstract
Stimulus control was established in rats trained to discriminate either 5-methoxy-N,N-dimethyltryptamine (3 mg/kg) or (-)-2,5-dimethoxy-4-methylamphetamine (0.56 mg/kg) from saline. Tests of antagonism of stimulus control were conducted using the 5-HT1A antagonists (+/-)-pindolol and WAY-100635, and the 5-HT2 receptor antagonist pirenperone. In rats trained with 5-MeO-DMT, pindolol and WAY-100635 both produced a significant degree of antagonism of stimulus control, but pirenperone was much less effective. Likewise, the full generalization of 5-MeO-DMT to the selective 5-HT1A agonist [+/-]-8-hydroxy-dipropylaminotetralin was blocked by WAY-100635, but unaffected by pirenperone. In contrast, the partial generalization of 5-MeO-DMT to the 5-HT2 agonist DOM was completely antagonized by pirenperone, but was unaffected by WAY-100635. Similarly, in rats trained with (-)-DOM, pirenperone completely blocked stimulus control, but WAY-100635 was inactive. The results obtained in rats trained with (-)-DOM and tested with 5-MeO-DMT were more complex. Although the intraperitoneal route had been used for both training drugs, a significant degree of generalization of (-)-DOM to 5-MeO-DMT was seen only when the latter drug was administered subcutaneously. Furthermore, when the previously effective dose of pirenperone was given in combination with 5-MeO-DMT (s.c.), complete suppression of responding resulted. However, the combination of pirenperone and WAY-100635 given prior to 5-MeO-DMT restored responding in (-)-DOM-trained rats, and provided evidence of antagonism of the partial substitution of 5-MeO-DMT for (-)-DOM. The present data indicate that 5-MeO-DMT-induced stimulus control is mediated primarily by interactions with 5-HT1A receptors. In addition, however, the present findings suggest that 5-MeO-DMT induces a compound stimulus that includes an element mediated by interactions with a 5-HT2 receptors. The latter component is not essential for 5-MeO-DMT-induced stimulus control, but is revealed in animals tested or trained with a 5-HT2-selective agonist such as (-)-DOM. Based upon the present data, we conclude that 5-MeO-DMT differs from DOM with respect to the serotonergic element that mediates stimulus control in the rat, but that it shares with DOM a functionally significant interaction with 5-HT2 receptors.
Comparable studies
Other preclinical and animal studies on 5-MeO-DMT, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelic N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine modulate innate and adaptive inflammatory responses through the sigma-1 receptor of human monocyte-derived dendritic cells. Human primary monocyte-derived dendritic cells | 2014 | In vitro study | |
| Effects of N,N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression Adult male Sprague-Dawley rats | 2018 | Experimental study | |
| Hallucinogen-like actions of 5-methoxy-N,N-diisopropyltryptamine in mice and rats. Mice and rats | 2006 | Preclinical study | |
| Agonist Properties of N,N-Dimethyltryptamine at Serotonin 5-HT2A and 5-HT2C Receptors Rats and transfected fibroblasts | 1998 | Experimental study | |
| Subtypes of the 5-HT receptor mediating the behavioural responses to 5-methoxy-N,N-dimethyltryptamine in the rat Intact rats and rats depleted of monoamines with reserpine | 1985 | Experimental study |
Citations in the library
Cited by 66
- Towards an understanding of psychedelic-induced neuroplasticity. Neuropsychopharmacology 2023
- The hallucinogenic world of tryptamines: an updated review. Archives of Toxicology August 1, 2015
- Designer drugs: mechanism of action and adverse effects Archives of Toxicology April 1, 2020
- Differential contributions of serotonin receptors to the behavioral effects of indoleamine hallucinogens in mice Journal of Psychopharmacology December 8, 2010
- Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions. Current Drug Metabolism October 1, 2010
and 61 more in the library
Cites 19
- Evidence for 5-HT2 involvement in the mechanism of action of hallucinogenic agents. Life Sciences December 17, 1984
- Agonist Properties of N,N-Dimethyltryptamine at Serotonin 5-HT2A and 5-HT2C Receptors Pharmacology, Biochemistry, and Behavior November 1, 1998
- Subtypes of the 5-HT receptor mediating the behavioural responses to 5-methoxy-N,N-dimethyltryptamine in the rat European Journal of Pharmacology October 1, 1985
- Differential tolerance to biological and subjective effects of four closely spaced doses of N,N-dimethyltryptamine in humans Biological Psychiatry May 1, 1996
- Serotonin receptor subtype mediation of the interoceptive discriminative stimuli induced by 5-methoxy-N,N-dimethyltryptamine. Psychopharmacology 1987
and 14 more in the library