Behavioural Effects of High Doses of Psilocybin in Female Rats
Larissa Rocha
November 21, 2024 DOI: 10.26686/wgtn.27872025 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Pre-clinical trial |
|---|---|
| Population | Adult female rats |
| Intervention | Psilocybin |
| Dose | 4, 8, or 16 mg/kg |
| Topics | Anxiety Psilocybin |
| Keywords | Depression economics Open field Elevated plus maze Population Clinical psychology Hallucinogen |
| Key findings | Psilocybin did not produce robust effects on depression- or anxiety-like measures in female rats, but trends and a possible protective effect of the oestrous cycle phase were observed. |
Abstract
Depression and anxiety are two of the most predominant mental disorders and leading causes of disability. The World Health Organization estimated that 3.8% of the world's population suffers from depression, and between 0.4% and 3.6% have an anxiety spectrum diagnosis. Psychedelics, particularly psilocybin, have been extensively studied as new and promising treatments, showing long-lasting positive results when combined with psychotherapy for patients with depression and anxiety, among other disorders. However, pre-clinical trials investigating the precise neurobiological mechanisms underlying these results are still scarce, especially with female subjects. Additionally, emerging evidence suggests that hormonal fluctuations may influence the drug's efficacy, potentially providing a protective effect. This study utilised adult female rats to examine the behavioural effects of high doses of psilocybin on locomotor activity and on depression and anxiety-like measures. Symptomatology was induced using either early maternal separation or a genetic reduction in the serotonin transporter. The open field (OFT) and affective disorders test (ADT) were employed to assess the effects of doses of 4, 8, or 16 mg/kg of psilocybin. Additionally, the effects of the phase of the oestrous cycle when animals were injected were evaluated. Results showed a significant effect of psilocybin on locomotion activity in the OFT 3 hours and 24 hours post-injection but not after 8 days. No robust effects on depression and anxiety-like measures were observed at any of the doses tested. However, trends were observed in both depression and anxiety-like measures with doses of 4 and 8mg/kg. Moreover, a preliminary evaluation in small groups revealed an interaction between treatment and the phase of the oestrous cycle, suggesting that female hormones might have some protective effect against the effects of the drug in depression-like measures.
Comparable studies
Other preclinical and animal studies on psilocybin for anxiety, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics, but Not Ketamine, Produce Persistent Antidepressant-like Effects in a Rodent Experimental System for the Study of Depression Rats | 2020 | Preclinical study | |
| Psilocin and ketamine microdosing: effects of subchronic intermittent microdoses in the elevated plus-maze in male Wistar rats Wistar rats | 2018 | Experimental study | n = 40 |
| Striking long-term beneficial effects of single dose psilocybin and psychedelic mushroom extract in the SAPAP3 rodent model of OCD-like excessive self-grooming SAPAP3 knockout mice | 2024 | Randomized controlled trial | n = 50 |
| Psilocybe cubensis extract potently prevents fear memory recall and freezing behavior in short- but not long-term in a rat model of posttraumatic stress disorder. Male rats | 2024 | Preclinical study | |
| Psilocybin induces acute anxiety and changes in amygdalar phosphopeptides independently from the 5-HT2A receptor Mice | 2024 | Experimental study |