Development of tolerance to repeated administration of 5-methoxy-N,N-dimethyltryptamine in rats.
European journal of pharmacology January 15, 1985 DOI: 10.1016/0014-2999(85)90280-8 via PubMed
Summary
AI-generated from the abstractRepeated doses of the psychedelic compound 5-MeODMT in rats rapidly produced tolerance to its behavioral effects, with the effective dose doubling and the duration of the syndrome dropping from about 15 minutes to just over 1 minute. This tolerance completely vanished within 4 hours after stopping treatment. The effect was not caused by changes in how much drug entered the brain, but appeared to result from reduced binding of the drug to serotonin receptors. These findings contradict earlier reports that claimed no tolerance develops to 5-MeODMT.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Intervention | 5-methoxy-N |
| 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 |
| Citations | 18 |
| Key finding | 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.