Preadministration of Lorazepam Reduces Efficacy and Longevity of Antidepressant-Like Effect from a Psychedelic.
Meghan Hibicke, Gerald Billac, Charles D. Nichols
Psychedelic Medicine March 1, 2024 DOI: 10.1089/psymed.2023.0037 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experiment Peer reviewed |
|---|---|
| Population | Male Wistar-Kyoto rats |
| Interventions | Psilocin Lorazepam |
| Duration | 14-week follow-up |
| Topics | Depression Psychedelic-assisted therapy |
| Keywords | Antidepressant efficacy Lorazepam Anxiety medication Drug interactions Depression treatment Mental health |
| Citations | 2 |
| Key findings | Intravenous psilocin persistently reduced immobility in the forced swim test, but preadministration of lorazepam diminished this antidepressant-like effect and shortened its duration. |
Abstract
Psychedelics such as psilocybin have been shown to have persistent antidepressant effects, but with considerable individual variability in optimal dosing. Intravenous (IV) dosing is rapid onset and quickly titrated, possibly preceded by an anxiolytic for patient comfort. We explored the viability of IV psilocin with and without preadministration of lorazepam for possible future inpatient therapeutic utility. Male Wistar-Kyoto rats were given saline (S), psilocin (P), or psilocin and lorazepam (P+L). Saline was given intraperitoneally (IP), psilocin was given IV to a second group, and lorazepam was given IP, then psilocin was given IV 30 min later to a final group. Rats were tested in the forced swim test (FST) 3 and 14 weeks after injection. P rats were more active than S rats at both time points. P + L rats were more active in the FST than S rats at 3, but not 14, weeks. P + L rats were less active than P rats at 14 weeks, and less active than themselves at 3 weeks. S rats' behavior was not different at 3 and 14 weeks. Similarly, P rats behaved the same at both time points. IV psilocin persistently decreased immobility in the FST, but lorazepam reduced psilocin's antidepressant-like efficacy and longevity.
Comparable studies
Other preclinical and animal studies on psychedelic-assisted therapy, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| 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 | |
| A Proposal to Study the Safety and Efficacy of Psilocybe cubensis in Preclinical and Clinical Studies as a Therapeutic Alternative for Major Depressive Disorder Healthy adults and patients with major depressive disorder | 2023 | Research project design with preclinical and clinical experimental components | |
| Application of microarray patches for the transdermal administration of psychedelic drugs in micro-doses. Excised neonatal porcine skin and rats | 2025 | Experimental study | |
| Synergistic behavioral and neuroplastic effects of psilocybin-NMDAR modulator administration ICR male mice | 2025 | Observational study | |
| Efficient Acyloxymethylation of Psilocin and Other Tryptamines Yielding ACOM Prodrugs for Psychedelic-Assisted Therapy. | 2025 | In vitro study |
Citations in the library
Cited by 2
Cites 10
- 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
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Scientific Reports October 13, 2017
- Psychedelics, but Not Ketamine, Produce Persistent Antidepressant-like Effects in a Rodent Experimental System for the Study of Depression ACS Chemical Neuroscience March 5, 2020
- Effects of N,N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression ACS Chemical Neuroscience April 17, 2018
and 5 more in the library