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Behavioral effects of three synthetic tryptamine derivatives in rodents.

Rebecca D Hill, Ritu A Shetty, Nathalie Sumien, Jeanne Priddy, Michael J Forster, Michael B Gatch

Journal of psychopharmacology (Oxford, England) April 4, 2025 DOI: 10.1177/02698811251330737 via PubMed

Summary

AI-generated from the abstract

Three new synthetic tryptamines—5-MeO-DBT, 5-Cl-DMT, and 4-OH-MiPT—were tested in mice and rats for their effects on movement and their ability to mimic the hallucinogen DOM. All three produced depressant phases similar to DOM but were less potent. In rats trained to discriminate DOM, only 4-OH-MiPT fully substituted for DOM, suggesting it shares DOM's abuse potential, while 5-MeO-DBT and 5-Cl-DMT did not fully substitute and decreased response rates.

Study at a glance

Characteristics Preclinical study Peer reviewed
Population Swiss Webster mice and male Sprague-Dawley rats
Interventions 5-MeO-DBT 5-Cl-DMT 4-OH-MiPT DOM
Dose DOM 0.5 mg/kg
Topics Serotonin
Keywords Drug discrimination Hallucinogens psychedelics Entheogens Drug research pharmacology
Key finding Only 4-OH-MiPT fully substituted for DOM in a drug discrimination assay, indicating it may have abuse liability similar to DOM, whereas 5-MeO-DBT and 5-Cl-DMT did not.

Abstract

New synthetic tryptamine derivatives have emerged in the underground market. They act on serotonin receptors mimicking the effects of hallucinogenic drugs such as DOM. The DEA has identified three tryptamine derivatives of concern, 5-MeO-DBT, 5-Cl-DMT, and 4-OH-MiPT. Swiss Webster mice were tested for locomotor activity. Discriminative stimulus effects were tested in male Sprague-Dawley rats trained to discriminate DOM (0.5 mg/kg, 30-min pretreatment) from vehicle (0.9% saline). In the locomotor activity tests, DOM (ED50 = 4.8 mg/kg) produced a 40-100-min depressant phase. 5-MeO-DBT (ID50 = 16.5 mg/kg; ED50 = 0.074 mg/kg) had a 50-min depressant phase and a 100-min stimulant phase. 5-Cl-DMT (ID50 = 12.3 mg/kg; ED50 = 6.1 mg/kg) produced a 20-40-min depressant phase and a 30-min stimulant phase. 4-OH-MiPT (ID50 = 5.8 mg/kg; ED50 = 0.6 mg/kg) had a 30-130-min depressant phase and a 50-minute stimulant phase. In the drug discrimination assay, 4-OH-MIPT (ED50 = 0.77 mg/kg) was fully substituted, whereas 5-Cl-DMT partially substituted for the discriminative stimulus effects produced by DOM (ED50 = 0.23 mg/kg). 5-MeO-DBT failed to substitute for the discriminative stimulus of DOM. 5-CL-DMT and 5-MeO-DBT decreased response rate. The locomotor depressant effects of the three synthetic tryptamine derivatives were similar to DOM, but not as potent. In the drug discrimination assay, only 4-OH-MIPT was substituted fully for DOM. These results support the possibility that 4-OH-MIPT has abuse liability similar to DOM, whereas 5-MeO-DBT and 5-Cl-DMT may not.

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