Psychedelic-like effects induced by 2,5-dimethoxy-4-iodoamphetamine, lysergic acid diethylamide, and psilocybin in male and female C57BL/6J mice.
Shelby A. McGriff, Jacquelin C Hecker, Alexander D. Maitland, John S. Partilla, Michael H. Baumann, Grant C. Glatfelter
Psychopharmacology May 17, 2025 DOI: 10.1007/s00213-025-06795-x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Male and female C57BL/6J mice |
| Interventions | DOI LSD psilocybin |
| Dose | DOI 0.03-10 mg/kg, LSD 0.003-1 mg/kg, psilocybin 0.03-10 mg/kg |
| Duration | Acute effects |
| Topics | LSD Psilocybin |
| Keywords | 5-ht2a Head twitch response Mice Psychedelics hallucinogens Entheogens Psychoactive drugs Sexual dimorphism Neuroscience brain research Neurobiology Neural activity |
| Citations | 12 |
| Key findings | No substantial sex differences in potency to induce head twitch responses were found for DOI, LSD, and psilocybin in C57BL/6J mice, but females uniformly displayed more HTRs at high doses. |
Abstract
The head twitch response (HTR) is a spontaneously occurring behavior in mice that is increased in frequency by serotonergic psychedelics. The mouse HTR is often used as a proxy for psychedelic-like drug effects, but limited information is available about sex differences in HTRs evoked by various classes of psychedelics (i.e., phenethylamines, lysergamides, tryptamines). To examine potential sex differences in responsiveness to structurally-distinct psychedelics, acute effects of subcutaneous 2,5-dimethoxy-4-iodo-amphetamine (DOI, 0.03-10 mg/kg), lysergic acid diethylamide (LSD, 0.003-1 mg/kg), and 4-phosphoryloxy-N,N-dimethyltryptamine (psilocybin, 0.03-10 mg/kg) on HTRs were compared in male and female C57BL/6J mice. For comparison, effects of the drugs on locomotor activity and body temperature were also determined. Drug potencies for inducing HTRs were similar in males and females for all drugs, with only LSD exhibiting detectable differences due to increased maximal counts in females. Importantly, the maximum number of HTRs observed for all drugs was higher in females, with significant differences between sexes for DOI and LSD. Dose x sex interactions for the dose-response data were statistically significant for psilocybin and LSD, with females displaying more HTRs after the highest or peak doses of all drugs. The acute effects of drugs on locomotion and temperature varied by drug, but were similar in both sexes. The present results overall show no substantial sex differences in the potencies to induce HTRs for DOI, LSD, and psilocybin in C57BL/6J mice. However, females uniformly displayed more HTRs at high doses administered across chemotypes. The results further suggest that commonly used doses of psychedelics induce comparable psychedelic-like effects in male and female C57BL/6J mice, but modest differences may emerge at high doses.
Comparable studies
Other preclinical and animal studies on LSD, most cited first.
Citations in the library
Cited by 13
- Sex-dependent developmental changes in behavior, brain structure, functional connectivity, and sensory perception following exposure to psilocybin during adolescence Neuropsychopharmacology February 18, 2026
- Differential effects of psilocybin and lisuride on serotonin and dopamine neuronal activity and behavior Progress in Neuro-Psychopharmacology and Biological Psychiatry October 1, 2025
- Dual Modulation of 5-HT2A Receptors and SERT by α-Ethyltryptamine and Its Optical Isomers. ACS Chemical Neuroscience December 17, 2025
- Rapid, open-source, and automated quantification of the head twitch response in C57BL/6J mice using DeepLabCut and Simple Behavioral Analysis bioRxiv Preprint Server April 28, 2025
- Synthesis and Biological Evaluation of 4-Bromo- N,N- dimethyltryptamine (4-Br-DMT): A Synthetic Building Block for Future Analog Development ACS Omega June 23, 2026
and 8 more in the library
Cites 52
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Neuroreport December 1, 1998
- Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens. European Neuropsychopharmacology May 20, 2016
- Activation of Serotonin 2A Receptors Underlies the Psilocybin-Induced Effects on Oscillations, N170 Visual-Evoked Potentials, and Visual Hallucinations Journal of Neuroscience June 19, 2013
- The neural basis of psychedelic action. Nature Neuroscience October 24, 2022
- Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. Neuropharmacology May 1, 2020
and 47 more in the library