Striking long-term beneficial effects of single dose psilocybin and psychedelic mushroom extract in the SAPAP3 rodent model of OCD-like excessive self-grooming
Molecular Psychiatry – October 11, 2024
Source: OpenAlex
Summary
A single dose of the hallucinogen psilocybin dramatically reduced symptoms resembling Obsessive-Compulsive Spectrum Disorders. In a trial with 50 mice, a placebo-like vehicle increased self-grooming by 118.71% over 21 days. Psilocybin decreased it by 14.60%, and a psychedelic mushroom extract by 19.20%. Concomitant anxiety and other behaviors also improved. This impactful finding in Psychology highlights psilocybin's potential in Medicine, offering new avenues for Psychedelics and Drug Studies, including those addressing Body Image and Dysmorphia.
Abstract
Abstract Obsessive compulsive disorder (OCD) is a highly prevalent disorder that causes serious disability. Available treatments leave 40% or more of people with OCD significantly symptomatic. There is an urgent need for novel therapeutic approaches. Mice that carry a homozygous deletion of the SAPAP3 gene (SAPAP3 KO) manifest a phenotype of excessive self-grooming, tic-like head-body twitches and anxiety. These behaviors closely resemble pathological self-grooming behaviors observed in humans in conditions that overlap with OCD. Following a preliminary report that the tryptaminergic psychedelic, psilocybin, may reduce symptoms in patients with OCD, we undertook a randomized controlled trial of psilocybin in 50 SAPAP3 KO mice (28 male, 22 female). Mice that fulfilled inclusion criteria were randomly assigned to a single intraperitoneal injection of psilocybin (4.4 mg/kg), psychedelic mushroom extract (encompassing the same psilocybin dose) or vehicle control and were evaluated after 2, 12, and 21 days by a rater blind to treatment allocation for grooming characteristics, head-body twitches, anxiety, and other behavioral features. Mice treated with vehicle (n = 18) manifested a 118.71 ± 95.96% increase in total self-grooming (the primary outcome measure) over the 21-day observation period. In contrast, total self-grooming decreased by 14.60 ± 17.90% in mice treated with psilocybin (n = 16) and by 19.20 ± 20.05% in mice treated with psychedelic mushroom extract (n = 16) (p = 0.001 for effect of time; p = 0.0001 for time × treatment interaction). Five mice were dropped from the vehicle group because they developed skin lesions; 4 from the psilocybin group and none from the psychedelic mushroom extract group. Secondary outcome measures such as head-body twitches and anxiety all showed a significant improvement over 21 days. Notably, in mice that responded to psilocybin (n = 12) and psychedelic mushroom extract (n = 13), the beneficial effect of a single treatment persisted up to 7 weeks. Mice initially treated with vehicle and non-responsive, showed a clear and lasting therapeutic response when treated with a single dose of psilocybin or psychedelic mushroom extract and followed for a further 3 weeks. While equivalent to psilocybin in overall effect on self-grooming, psychedelic mushroom extract showed superior effects in alleviating head-body twitches and anxiety. These findings strongly justify clinical trials of psilocybin in the treatment of OCD and further studies aimed at elucidating mechanisms that underlie the long-term effects to alleviate excessive self-grooming observed in this study.