JMIR research protocols
April 17, 2024
Akash Goel, Bhavya Kapoor, Hillary Chan et al.
2 citations
Chronic pain affects about 8 million Canadians (20%) and costs the healthcare system over US $60 billion yearly. This paper describes the planned protocol for a pilot randomized controlled trial testing three treatments: intravenous ketamine alone, cognitive behavioral therapy with mindfulness meditation (CBT/MM), or a combination of both. The primary goal is to assess feasibility—recruitment, consent, withdrawal, adherence, missing data, and adverse events—in 30 participants over 20 weeks. Secondary outcomes include changes in pain intensity and pain interference at week 20. Recruitment had not started as of November 2023; the study is expected to complete by December 2025. Results will inform a larger trial.
Canadian Journal of Pain
March 4, 2026
Nandana D. Parakh, Danielle Lessor, Kevin Dang et al.
All participants reported decreased pain with ketamine infusions, though pain experiences varied. To improve ketamine's benefit for chronic neuropathic pain, it is important to address stigma, research ways to extend the duration of its effects, and provide a safe treatment environment. Understanding barriers and facilitators, along with implementing participant suggestions, can inform ketamine programs, improve access to pain management, and guide future research.
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.