Behavioral effects of three synthetic tryptamine derivatives in rodents.
Rebecca D. Hill, Ritu A. Shetty, Nathalie Sumien, Jeanne A. Priddy, Michael J Forster, Michael B. Gatch
Journal of Psychopharmacology April 4, 2025 DOI: 10.1177/02698811251330737 (opens in new tab)
Study at a glance
AI-extracted from the abstract| 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 Drug testing Preclinical studies 5-HT Drugs |
| Key points | 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.
Comparable studies
Other preclinical and animal studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
Citations in the library
Cites 15
- Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens. European Neuropsychopharmacology May 20, 2016
- Neuropharmacology of N,N-dimethyltryptamine Brain Research Bulletin April 30, 2016
- Hallucinogen-like actions of 5-methoxy-N,N-diisopropyltryptamine in mice and rats. Pharmacology, Biochemistry, and Behavior 2006
- Effect of Ring Fluorination on the Pharmacology of Hallucinogenic Tryptamines Journal of Medicinal Chemistry October 19, 2000
- Investigation of the Structure–Activity Relationships of Psilocybin Analogues ACS Pharmacology & Translational Science December 14, 2020
and 10 more in the library