Development of tolerance to repeated administration of 5-methoxy-N,N-dimethyltryptamine in rats.
Michael E. Trulson, G F Keltch
European Journal of Pharmacology January 15, 1985 DOI: 10.1016/0014-2999(85)90280-8 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Intervention | 5-MeODMT |
| Dose | 2 mg/kg i.p., every 30 min for 4 h |
| Duration | 4-hour treatment period, with follow-up up to 4 hours after termination |
| Topics | 5-MeO-DMT DMT |
| Citations | 18 |
| Key findings | Repeated administration of 5-MeODMT produced rapid and reversible tolerance in rats, apparently due to decreased binding to serotonin receptors, contrary to earlier studies. |
Abstract
Chronic administration of 5-methoxy-N,N-dimethyltryptamine (5-MeODMT, 2 mg/kg i.p., every 30 min for 4 h) produced a dramatic tolerance to the behavioral effects of the drug in rats. The ED50 for the syndrome-inducing effects of the drug was increased from 1.3 to 2.4 mg/kg, and the mean duration of the syndrome was decreased from 14.9 to 1.2 min after this treatment. This tolerance effect totally disappeared within 4 h following termination of drug treatment. This effect was not due to changes in the uptake of 5MeODMT into the brain, but rather appears to be due to a decrease in the binding of the drug to serotonin receptors in the central nervous system. These studies are in contrast to previous results which reported no development of tolerance to 5-MeODMT.
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 8
- Differential tolerance to biological and subjective effects of four closely spaced doses of N,N-dimethyltryptamine in humans Biological Psychiatry May 1, 1996
- A narrative synthesis of research with 5-MeO-DMT. Journal of Psychopharmacology March 1, 2022
- Benefits and Challenges of Ultra-Fast, Short-Acting Psychedelics in the Treatment of Depression American Journal of Psychiatry 2025
- The effects of monoamine oxidase inhibitors on the ejaculatory response induced by 5-methoxy-N,N-dimethyltryptamine in the rat. British Journal of Pharmacology August 1, 1986
- Subsensitivity of serotonin and substance P receptors involved in nociception after repeated administration of a serotonin receptor agonist. Journal of Neural Transmission 1989
and 3 more in the library
Cites 2
- Inhibitory effect of chlorpromazine on the syndrome of hyperactivity produced by l‐tryptophan or 5‐methoxy‐N,N‐dimethyltryptamine in rats treated with a monoamine oxidase inhibitor British Journal of Pharmacology December 1, 1971
- Behavioral effects of 5-methoxy-N:N-dimethyltryptamine, other tryptamines, and LSD American Journal of Physiology-Legacy Content July 1, 1962