Major Depressive Disorder (MDD) and chronic pain are independently debilitating conditions that frequently co-occur. This comorbidity poses a significant clinical challenge, resulting in greater symptom severity, higher disability, and worse prognosis than either condition alone. Current therapies often address each disorder in isolation, leaving individuals with comorbid MDD and chronic pain...
Serotonergic psychedelics and 3,4-methylendioxtmethamphetamine (MDMA) are promising treatments for mental disorders with a continuously evolving evidence base. We searched Pubmed/Scopus/clinical trial registries up to 08july2025 for double-blind randomized controlled trials (RCTs) testing MDMA or serotonergic psychedelics in patients with mental disorders. Primary outcomes were change in...
Nitrous oxide may possess antidepressant effects; however, limited data exist on repeated administrations and active placebo-controlled studies in treatment-resistant depression (TRD). We aimed to test the feasibility of a randomised controlled trial examining a 4-week course of nitrous oxide or midazolam, an active placebo. In this randomised, active, placebo-controlled pilot trial, 40...
Emerging evidence suggests that 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy may be a promising intervention for chronic pain. We designed the Ecstasy for Alleviating Severe Chronic Neuropathic Pain (EASE-Pain) trial, a randomized controlled trial comparing MDMA with an active placebo (methylphenidate) for pain relief. We sought to conduct a prospective preference assessment...
The PEACE-PAIN trial study design is supported by patient survey responses but may benefit from modifications, namely incorporating thorough discussions of the current evidence for efficacy, safety, tolerability, and approaches to address adverse effects of psilocybin. Additionally, the interest in participation by individuals with prior psychedelic use holds important methodological...
Chronic pain affects approximately 8 million Canadians (~20%), impacting their physical and mental health while burdening the health care system with costs of upwards of US $60 billion a year. Indeed, patients are often trialed on numerous medications over several years without reductions to their symptoms. Therefore, there is an urgent need to identify new therapies for chronic pain to improve...
PLoS One2024Josh Martin, Fatemeh Gholamali Nezhad, Alice Rueda et al.2 citations
Ketamine has recently attracted considerable attention for its rapid effects on patients with major depressive disorder, including treatment-resistant depression (TRD). Despite ketamine's promising results in treating depression, a significant number of patients do not respond to the treatment, and predicting who will benefit remains a challenge. Although its antidepressant effects are known to...
Nitrous oxide has shown potentially as an efficacious intervention for treatment-resistant depression, yet there remains insufficient evidence pertaining to repeated administration of nitrous oxide over time and active placebo-controlled studies with optimal blinding. Thus, we aim to examine the feasibility and preliminary efficacy of a six-week follow up study examining the effects of a 4 week...
Chronic pain is a public health concern that affects approximately 1.5 billion people globally. Conventional therapeutic agents including opioid and non-opioid analgesics have been associated with adverse side effects, issues with addiction, and ineffective analgesia. Novel agents repurposed to treat pain via different mechanisms are needed to fill the therapeutic gap in chronic pain...
To systematically review published research studies and ongoing clinical trials investigating nitrous oxide (N2 O) in psychiatric disorders, providing an up-to-date snapshot of the clinical research landscape. A comprehensive literature search was conducted for studies published until June 2021 using the OVID databases (MEDLINE, Embase, APA PsycInfo) and the clinical trial registries...
Sandra J Drozdz,1 Akash Goel,1â 3 Matthew W McGarr,4 Joel Katz,3,5â 7 Paul Ritvo,5,7 Gabriella F Mattina,1 Venkat Bhat,8â 10 Calvin Diep,3 Karim S Ladha1,3,10 1Department of Anesthesia, St. Michaelâs Hospital, Toronto, ON, Canada; 2Department of Anesthesiology, Pain and Perioperative Medicine, Stanford University, Stanford, CA, USA; 3Department of Anesthesiology and Pain Medicine,...
Preliminary evidence supports the use of psychedelics for major depressive disorder (MDD). However, less attention has been given to the neural mechanisms behind their effects. We conducted a systematic review examining the neuroimaging correlates of antidepressant response following psychedelic interventions for MDD. Through MEDLINE, Embase, and APA PsycINFO, 187 records were identified and 42...
Pain and depression frequently co-occur. Due to its antidepressant and analgesic properties, ketamine has been used for the management of treatment-resistant depression and pain. This systematic review examined the literature on the efficacy of sub-anesthetic doses of ketamine in individuals experiencing comorbid depression and chronic pain (CDCP), as well as comorbid depression and acute pain...