Psilocybin prevents reinstatement of alcohol seeking by disrupting the reconsolidation of alcohol-related memories.
Federica Benvenuti, D Colombo, Laura Soverchia, Nazzareno Cannella, Esi Domi, Roberto Ciccocioppo
Psychopharmacology July 1, 2023 DOI: 10.1007/s00213-023-06384-w (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Male and female Marchigian Sardinian alcohol-preferring (msP) rats |
| Intervention | Psilocybin |
| Topics | Addiction Psychedelic-assisted therapy Psilocybin |
| Keywords | Alcoholism Psychedelics Reward Addiction treatment Neuroscience research Substance dependence Memory reconsolidation |
| Citations | 14 |
| Key findings | Psilocybin did not reduce alcohol consumption or relapse but markedly attenuated resumption of alcohol seeking when given during a memory retrieval-reconsolidation paradigm. |
Abstract
For most psychiatric conditions, including alcohol use disorder (AUD), FDA-approved pharmacological treatments are limited and their efficacy is restricted to only certain subgroups of patients. Scientific interest in the potential of psychedelic drugs has dramatically increased because of clinical preliminary evidence of efficacy in treating various psychiatric disorders. One of the most promising compounds belonging to this class of molecules is psilocybin. Here, to elucidate the therapeutic potential and treatment modalities of this drug, we investigated the effect of psilocybin on alcohol drinking and seeking in genetically selected Marchigian Sardinian alcohol-preferring (msP) rats, a well validated animal model of AUD characterized by excessive drinking and seeking. Using male and female msP rats, we tested the effect of psilocybin on home cage voluntary alcohol consumption. We also tested the effect of the drug on the alcohol deprivation effect (ADE) model of relapse and on cue-induced reinstatement of alcohol seeking after a period of abstinence. Finally, we evaluated if psilocybin may disrupt the reconsolidation process of alcohol-related memory. Psilocybin did not reduce alcohol consumption, nor it prevented increased alcohol drinking after a period of forced abstinence and cue-induced reinstatement of alcohol-seeking. Noteworthy, in a memory retrieval-reconsolidation paradigm, psilocybin markedly attenuated resumption of alcohol seeking. Altogether these data suggest that, despite psilocybin does not affect alcohol drinking and relapse, it may be highly effective if used to block the reconsolidation process of alcohol-related memories. This opens to the possibility of using this psychedelic drug in clinical settings in which AUD patients undergo procedures to recall the memory of alcohol and are then treated with psilocybin during the memory reconsolidation phase.
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 | |
| Sex-specific role of the 5-HT2A receptor in psilocybin-induced extinction of opioid reward. Male and female mice | 2025 | Experimental study |
Citations in the library
Cited by 14
- Psilocybin as a lead candidate molecule in preclinical therapeutic studies of psychiatric disorders: A systematic review Journal of Neurochemistry November 29, 2023
- Psychedelics and autobiographical memory - six open questions. Psychopharmacology March 17, 2025
- Epigenetic drugs and psychedelics as emerging therapies for alcohol use disorder: insights from preclinical studies. Journal of Neural Transmission May 1, 2024
- The Effect of Psilocybe cubensis on Spatial Memory and BDNF Expression in Male Rats Exposed to Chronic Unpredictable Mild Stress Journal of Psychoactive Drugs November 13, 2024
- Ayahuasca for the treatment of alcohol use disorder. International review of neurobiology 2024
and 9 more in the library
Cites 27
- Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer Archives of General Psychiatry September 7, 2010
- Human hallucinogen research: guidelines for safety. Journal of Psychopharmacology July 1, 2008
- Psilocybin-assisted treatment for alcohol dependence: A proof-of-concept study Journal of Psychopharmacology January 13, 2015
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction Journal of Psychopharmacology September 11, 2014
and 22 more in the library