Psilocybin administered following extinction sessions does not affect subsequent cocaine cue reinstatement in male and female rats and mice.
Veronika Pohořalá, Martin Kuchař, Rainer Spanagel, Rick E Bernardi
Neuroscience November 1, 2024 DOI: 10.1016/j.neuroscience.2024.09.006 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Sample size | 82 |
| Population | Male and female mice and rats |
| Intervention | Psilocybin |
| Dose | 1.0 mg/kg (mice); 1.0 mg/kg or 2.5 mg/kg (rats) |
| Duration | 8-day self-administration and extinction (mice); 15-day self-administration and extinction (rats) |
| Topics | Addiction Psilocybin |
| Keywords | Addiction treatment Psychedelic research Substance abuse Cocaine dependence Animal studies Cocaine self-administration Mice Rats Reinstatement |
| Citations | 3 |
| Key findings | Psilocybin did not attenuate cue-induced reinstatement of cocaine-seeking in either mice or rats. |
Abstract
There are currently no pharmacological treatments for cocaine use disorder. Recently there has been a great deal of interest in the potential of psychedelic drugs such as psilocybin to treat psychiatric disorders. Human studies have indicated that a single administration of psilocybin can have long-lasting effects. Few preclinical studies have examined a role for psilocybin in addiction models. The goal of the current study was to determine whether psilocybin would enhance extinction following cocaine self-administration in male and female mice and rats and thus result in an attenuation of cue-induced drug-seeking. In experiments in mice, 16 female and 19 male mice underwent 8d of cocaine self-administration (0.5 mg/kg/infusion) and extinction training. Immediately following extinction trials, mice were injected with vehicle or 1.0 mg/kg psilocybin. Following the conclusion of extinction training, mice were tested for cue-induced reinstatement. In experiments in rats, 24 female and 23 male rats underwent 15d of cocaine self-administration (0.8 mg/kg/infusion) and extinction training. Immediately following extinction trials, rats were injected with vehicle, 1.0 mg/kg psilocybin, or 2.5 mg/kg psilocybin. Following the conclusion of extinction training, rats were tested for cue-induced reinstatement. Psilocybin administered following extinction trials had no effect, as both female and male mice and rats demonstrated significant cue-induced reinstatement. These data suggest that psilocybin is ineffective at altering cocaine-seeking behavior in the paradigm and doses used in the current study. It remains to be seen whether treatment with psilocybin under different conditions may be useful in the long-standing goal of finding pharmacotherapies to treat CUD.
Comparable studies
Other preclinical and animal studies on psilocybin for addiction, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics reopen the social reward learning critical period Mice | 2023 | Experimental study in mice | |
| Psilocybin targets a common molecular mechanism for cognitive impairment and increased craving in alcoholism | 2021 | Preclinical study | |
| Psilocybin and LSD have no long-lasting effects in an animal model of alcohol relapse Male and female rats | 2020 | Preclinical animal study | |
| Psilocybin-induced default mode network hypoconnectivity is blunted in alcohol-dependent rats Healthy rats and a rat model of alcohol relapse | 2023 | Randomized, placebo-controlled crossover pharmaco-fMRI study | |
| Psilocybin prevents reinstatement of alcohol seeking by disrupting the reconsolidation of alcohol-related memories. Male and female Marchigian Sardinian alcohol-preferring (msP) rats | 2023 | Preclinical experimental study |
Citations in the library
Cited by 3
- Psychedelics as pharmacotherapeutics for substance use disorders: A scoping review on clinical trials and perspectives on underlying neurobiology British Journal of Pharmacology September 2, 2025
- Short- and Long-Acting Psychedelics: Structure-Activity Relationships, Pharmacology, and Implications for Neuropsychiatric Therapeutics. ACS Chemical Neuroscience June 17, 2026
- Psychedelics for the Treatment of Substance Use Disorder Pharmaceutical Science October 13, 2025
Cites 37
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
- Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer Archives of General Psychiatry September 7, 2010
- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine November 3, 2022
and 32 more in the library