In rats, five days of ketamine injections induced schizophrenia-like behaviors—increased activity and climbing, reduced exploration, impaired object-recognition memory, and lowered BDNF in the prefrontal cortex. Females showed additional effects: lower pain threshold (hyperalgesia) and less immobility in the forced swim test (an antidepressant-like effect). A single dose of olanzapine after the last ketamine injection reversed most behavioral deficits in both sexes, including memory impairment, and normalized pain threshold and immobility in females. Olanzapine did not affect BDNF levels, suggesting its therapeutic actions in this model do not rely on BDNF upregulation in the prefrontal cortex.
Psilocybin, the active compound in magic mushrooms, shows potential for treating neuropsychiatric disorders including major depressive disorder, posttraumatic stress disorder, anxiety disorders, and obsessive-compulsive disorder (OCD). Evidence for OCD is very limited. This review examined 15 articles from 268 initial search results. All clinical studies—both case reports and clinical trials—reported improvement in OCD symptoms. Preclinical studies using OCD-like models were rare and showed some conflicting results. The review identifies shortcomings in assessing psilocybin's effects on OCD and calls for more detailed preclinical studies and clinical trials with dozens of participants.