Lysergic Acid Diethylamide Produces Anxiogenic Effects in the Rat Light/Dark Test and Elevated Plus Maze
Catherine N. Conway, Lisa E Baker
Psi Chi Journal of Psychological Research 2022 DOI: 10.24839/2325-7342.jn27.3.197 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 48 |
| Population | Adult male Sprague-Dawley rats |
| Intervention | LSD |
| Dose | 0.00, 0.02, 0.04, 0.08 mg/kg |
| Duration | 15 minutes after first injection for acute effects; five additional injections once every 48 hours, then tested 48 or 72 hours after last injection for subchronic effects |
| Topics | LSD |
| Citations | 6 |
| Key findings | Acute and subchronic LSD treatment produce transient anxiogenic effects in rats, as shown by decreased exploration of brightly lit areas and increased time in closed arms of an elevated plus maze. |
Abstract
Recent clinical trials indicate favorable therapeutic outcomes of psychedelic-assisted psychotherapy for anxiety and treatment-resistant depression. Whereas the neurobiological systems underlying these effects are not well understood, animal behavioral models can serve to investigate these mechanisms. For the current study, we implemented 2 rodent models predictive of anxiolytic drug effects, a light/dark test and an elevated plus maze (EPM), to investigate the acute and subchronic effects of LSD, respectively. Forty-eight, adult male Sprague-Dawley rats were randomly assigned to receive LSD (0.00, 0.02, 0.04, 0.08 mg/kg) and assessed in the light/dark test 15 min after the first injection. Five additional injections were given, once every 48 hours, after which rats were assessed in the EPM either 48 (n = 24) or 72 hours (n = 24) after the last injection. A dose-dependent and statistically significant decrease was observed in number of entries into, F(3, 44) = 12.79, p < .001,η2 = .47, and time spent, F(3, 48) = 14.15, p < .001, ηp2 = .47, in the brightly lit compartment. In the EPM, closed arm entries, F(1, 17) = 28.85, p < .001, ηp2 =.36, and time spent in closed arms, F(1, 17) = 20.14, p < .001, ηp2=.99, were significantly higher compared to entries or time in open arms by rats assessed 48 hours after the last LSD injection, but not by rats tested 72 hours after the last injection. These findings indicate that acute and subchronic LSD treatment produce transient anxiogenic effects. In consideration of positive therapeutic outcomes of psychedelic-assisted psychotherapy, alternative preclinical models may be warranted to discern the mechanisms underlying the putative therapeutic effects of serotonergic hallucinogens.
Comparable studies
Other preclinical and animal studies on LSD, most cited first.
Citations in the library
Cited by 5
- Lysergic Acid Diethylamide (LSD) for the Treatment of Anxiety Disorders: Preclinical and Clinical Evidence. CNS Drugs September 1, 2023
- Clinical Research on Lysergic Acid Diethylamide (LSD) in Psychiatry and Neuroscience. Pharmaceuticals March 29, 2025
- The effect of psychedelic microdosing on animal behavior: A review with recommendations for the field Neuroscience & Biobehavioral Reviews May 9, 2025
- Short- and Long-Acting Psychedelics: Structure-Activity Relationships, Pharmacology, and Implications for Neuropsychiatric Therapeutics. ACS Chemical Neuroscience June 17, 2026
- Does acute stress play a role in the lasting therapeutic effects of psychedelic drugs? Neuropsychopharmacology September 1, 2023