Anesthesiology
October 1, 2023
Akash Goel, Yeshith Rai, Shayan Sivadas et al.
29 citations
Chronic pain affects about 1.5 billion people worldwide. Current treatments like opioids and non-opioid drugs can cause side effects, addiction, or fail to relieve pain. Psychedelics such as LSD and psilocybin may alter pain perception through serotonin receptor activation, anti-inflammatory effects, and synaptic remodeling. This scoping review identified 21 human studies on psychedelics for pain. Few clinical trials exist, and sample sizes are small, limiting clinical use. Overall, psychedelics show promise for analgesia in certain headache disorders and cancer pain. Future research should examine combining psychotherapy with psychedelics for chronic pain.
PloS one
January 1, 2024
Josh Martin, Fatemeh Gholamali Nezhad, Alice Rueda et al.
2 citations
Ketamine shows rapid antidepressant effects in major depressive disorder, including treatment-resistant depression, but many patients do not respond, and predicting who will benefit is difficult. This study will examine computational mechanisms behind changes in the auditory mismatch negativity response after intravenous ketamine, linking them to neural causes using a hierarchical Bayesian model and a neural mass model. Thirty patients with treatment-resistant depression will undergo EEG recordings during an auditory mismatch negativity task before three of four ketamine infusions, with depression, suicidality, and anxiety assessed throughout. The findings may improve understanding of treatment response and resistance, and model parameters could enable single-patient treatment predictions.
Canadian journal of anaesthesia = Journal canadien d'anesthesie
September 1, 2025
Mindy Lu, Victoria Tucci, Nandana Parakh et al.
Most patients with chronic pain at a Toronto pain clinic were willing to join a clinical trial testing MDMA-assisted therapy for pain relief. Among 42 patients surveyed, 76% expressed willingness to participate in the EASE-Pain trial, which compares MDMA with an active placebo. White/European participants were more likely to be willing than nonwilling. The main motivators were pain relief (62%) and seeking alternatives to ineffective treatments (26%). Common concerns included side effects (43%), impacts on comorbidities (19%), and stigma associated with MDMA (19%). The findings suggest that protocol modifications, such as better patient education on drug effects, may improve trial enrollment and acceptability.
BJPsych open
September 12, 2025
Karim S Ladha, Jiwon Lee, Gabriella F Mattina et al.
A pilot trial tested the feasibility of a four-week course of nitrous oxide compared with midazolam (an active placebo) for treatment-resistant depression. Forty participants were randomly assigned to weekly one-hour inhalations of either 50% nitrous oxide or 50% oxygen plus intravenous midazolam. Recruitment, withdrawal, adherence, and missing data rates met feasibility criteria. Depression severity, measured by the MADRS scale, changed by -20.5% in the nitrous oxide group and -9.0% in the placebo group. Adverse events were mostly mild to moderate and transient. The results support conducting a full-scale trial.
PloS one
January 1, 2024
Karim S Ladha, Jiwon Lee, Gabriella F Mattina et al.
A pilot trial will test whether weekly inhaled nitrous oxide is feasible and preliminarily effective for treatment-resistant depression compared with the active placebo midazolam. Forty participants will receive either nitrous oxide (1 hour at 50% concentration) plus intravenous saline or oxygen (1 hour at 50% concentration) plus intravenous midazolam once per week for 4 weeks, with 6 weeks of follow-up. Feasibility will be assessed by recruitment and withdrawal rates, adherence, missing data, and adverse events. The main exploratory clinical outcome is change in depression scores at day 42. Results will guide a future definitive trial.
Acta psychiatrica Scandinavica
August 1, 2022
Helen Liu, Jaimie Kerzner, Ilya Demchenko et al.
A systematic review of published studies and ongoing clinical trials on nitrous oxide (N2O) for psychiatric disorders identified five published articles, four of which focused on depression. Three randomized controlled trials (RCTs) for treatment-resistant depression and major depressive disorder suggest that N2O has preliminary feasibility with rapid-acting effects on depressive symptoms. Ten ongoing trials are exploring N2O for depression, post-traumatic stress disorder, bipolar disorder, obsessive-compulsive disorder, and suicidal ideation. Typical treatment involves a single session of 50% N2O for 60 minutes, though 25% is also being tested. Larger-scale RCTs with repeated doses and follow-up beyond one month are needed to confirm efficacy and sustainability.