A systematic review by the Canadian Network for Mood and Anxiety Treatments evaluated evidence for racemic ketamine in treatment-resistant depression. Single intravenous infusions have Level 1 evidence for efficacy in adults, while multiple or maintenance infusions have only Level 3 evidence. Adverse events include dissociative symptoms and hypertension. Non-IV formulations have Level 3 or 4 evidence. Single-dose IV racemic ketamine is a third-line recommendation; repeated use requires careful case-by-case risk-benefit assessment. Oral and other formulations should be limited to specialists with ketamine expertise at tertiary centers due to limited evidence and risk of misuse.
Serotonergic psychedelics are being reconsidered as potential treatments for major depressive disorder. A Canadian task force systematically reviewed clinical trials from 1990 to 2021 and found that only psilocybin and ayahuasca have been tested in contemporary studies. Two pilot studies of single-dose ayahuasca for treatment-resistant depression showed preliminary positive effects (Level 3 evidence). Small randomized controlled trials of psilocybin combined with psychotherapy for major depressive disorder showed superiority to waitlist controls and comparable efficacy and safety to escitalopram with supportive psychotherapy, with additional trials showing efficacy in cancer-related depression (Level 3 evidence).
Obsessive-compulsive disorder (OCD) involves imbalances in serotonin, dopamine, and glutamate. About 40-60% of patients do not respond to first-line treatments and are considered treatment resistant. There is no gold-standard treatment for these patients. This scoping review examined evidence for cannabinoids and psychedelics (psilocybin, LSD, DMT, MDMA) in OCD. Most evidence comes from surveys and case reports, with few controlled trials. The review found a lack of evidence supporting cannabinoids for OCD, but a stronger signal for psilocybin in treatment-resistant OCD. Well-controlled randomized trials are needed.