Psilocybin sex-dependently reduces alcohol consumption in C57BL/6J mice
Kenneth Alper, Janelle Cange, Ria Sah, Deanna Schreiber-Gregory, Henry Sershen, Vinod Kumar
Frontiers in Pharmacology January 4, 2023 DOI: 10.3389/fphar.2022.1074633 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Adult male and female C57BL/6J mice |
| Intervention | Psilocybin |
| Dose | 0.1, 0.5, 1.0 or 2.0 mg/kg |
| Duration | Single dose, ethanol provided continuously for 3 days immediately following administration, then withheld for 2 days, then provided for 2 additional days |
| Topics | Psilocybin |
| Keywords | Hallucinogen Ethanol Dose Pharmacology Anesthesia Alcohol consumption |
| Citations | 39 |
| Key findings | Psilocybin reduces voluntary ethanol consumption in male but not female mice in a dose-dependent manner during the three days immediately following administration. |
Abstract
The classical psychedelic psilocybin is of interest as a treatment for alcohol use disorder (AUD). This study investigated the effects of psilocybin on voluntary ethanol consumption in adult male and female C57BL/6J mice administered saline or psilocybin intraperitoneally as a single dose of 0.1, 0.5, 1.0 or 2.0 mg/kg and provided 20% ethanol utilizing a two-bottle choice alcohol drinking paradigm. Ethanol was provided continuously for 3 days immediately following the administration of psilocybin, then withheld for 2 days, and then provided continuously for two subsequent additional days. A multilevel model (MLM) for repeated measures was used to compare ethanol consumption and preference in psilocybin-treated groups versus controls. Ethanol consumption and preference were reduced in male mice during the 3-day interval that immediately followed psilocybin administration. The effect of psilocybin on ethanol consumption was dose-related and was consistent across the 3-day interval at dosages of 0.5 mg/kg or greater. Psilocybin had no effect on consumption or preference when ethanol was subsequently reintroduced after 2 days of withdrawal. In contrast to males, psilocybin had no significant effect on ethanol consumption or preference in female mice at any dosage or time point. The lack of an effect of psilocybin on quinine preference, and its limited interaction with locomotor activity indicated that the observed reduction in voluntary ethanol consumption was not attributable to altered taste perception or motor effects. Total fluid consumption was increased in males at some time points and psilocybin dosages and unchanged in females, and the absence of any decrease in either group at any time point indicated that the observed reduction in ethanol consumption was not mediated by nonspecific effects on consummatory behavior. The finding of a sex-dependent effect of psilocybin on ethanol consumption suggests that the C57BL/6J mouse may provide a useful experimental approach to modeling sex differences in vulnerability to AUD in addition to investigation of the neurobiological basis of the effect of classical psychedelics on alcohol drinking behavior.
Comparable studies
Other preclinical and animal studies on psilocybin, 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 | |
| Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice Mice | 2021 | Experimental study | |
| Psychedelics reopen the social reward learning critical period Mice | 2023 | Experimental study in mice | |
| Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. C57BL/6J mice | 2020 | Experimental study with dose-response experiments | |
| Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Mice | 2013 | Experimental study |
Citations in the library
Cited by 34
- Beyond the 5-HT2A Receptor: Classic and Nonclassic Targets in Psychedelic Drug Action. Journal of Neuroscience November 8, 2023
- Therapeutic mechanisms of psychedelics and entactogens. Neuropsychopharmacology July 24, 2023
- Mechanisms and molecular targets surrounding the potential therapeutic effects of psychedelics. Molecular Psychiatry September 1, 2023
- Potential Differences in Psychedelic Actions Based on Biological Sex. Endocrinology July 1, 2024
- Psilocybin for the treatment of Alzheimer’s disease Frontiers in Neuroscience July 10, 2024
and 29 more in the library
Cites 26
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Psychopharmacology July 7, 2006
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Psilocybin-assisted treatment for alcohol dependence: A proof-of-concept study Journal of Psychopharmacology January 13, 2015
- Long-term follow-up of psilocybin-facilitated smoking cessation The American Journal of Drug and Alcohol Abuse July 21, 2016
and 21 more in the library