Chronic Stress
January 1, 2022
Sarah Kuburi, Anne-Marie Di Passa, Vanessa K. Tassone et al.
14 citations
A systematic review of neuroimaging studies on psychedelics for major depressive disorder found that psilocybin, ayahuasca, and LSD alter brain activity and connectivity in ways linked to antidepressant response. Key changes include amygdala activity and functional connectivity alterations, shifts in medial and ventromedial prefrontal cortex connectivity, and decreased global brain network modularity. One ayahuasca study reported increased limbic activity. The evidence, based on only four datasets, suggests the default mode and limbic networks may be important targets for future research, but more data are needed to confirm these preliminary findings.
Canadian Journal of Pain
November 8, 2024
Jiwon Lee, Kaylyssa Philip, Hance Clarke et al.
3 citations
A proposed clinical trial design for psilocybin as a treatment for neuropathic pain, called the PEACE-PAIN trial, is supported by patient survey responses but could be improved by adding detailed discussions of the existing evidence on efficacy, safety, tolerability, and management of adverse effects. The finding that individuals with prior psychedelic use are interested in participating has important implications for the trial's inclusion and exclusion criteria.
Journal of Pain Research
June 1, 2022
Sandra J Drozdz, Akash Goel, Matthew W Mcgarr et al.
2 citations
Ketamine-assisted psychotherapy (KAP) can, in specific circumstances, initiate and prolong clinically significant reductions in pain, anxiety, and depressive symptoms, while encouraging rapport and treatment engagement, and promoting abstinence in patients addicted to other substances. A systematic review of seventeen articles including 603 participants found that combining ketamine with psychotherapy, provided before, during, and after ketamine sessions, can maximize and prolong benefits despite much variance in how KAP is applied. Additional large-scale randomized controlled trials are warranted to understand better the mutually influential relationships between psychotherapy and ketamine in optimizing responsiveness and sustaining long-term benefits in patients with chronic pain.
Pharmacology research & perspectives
April 1, 2026
Jordana Kazdan, Karim S. Ladha, M. Ishrat Husain
Major Depressive Disorder and chronic pain often co-occur, worsening symptoms and prognosis, yet treatments typically address each condition separately. Serotonergic psychedelics like psilocybin, DMT, and LSD show promise for both depression and pain. This narrative review examines mechanisms—including 5-HT2A receptor modulation, anti-inflammatory effects, neuroplasticity, altered brain network dynamics, and psychological influences—that could target both conditions simultaneously. The authors argue that existing evidence supports psychedelics as a unified therapeutic approach for comorbid MDD and chronic pain, providing a rationale for future clinical trials.