Psilocybin and chronic neuropathic pain: a systematic review.

BACKGROUND/IMPORTANCE: Chronic pain affects many people globally, requiring alternative management strategies. Psilocybin is gaining attention for its potential in chronic pain management despite being classified as Schedule I. OBJECTIVE: This systematic review critically evaluates the evidence for psilocybin, a Schedule I substance, in the treatment of chronic pain. The exact purpose of the review is to assess the impact of psilocybin on chronic pain relief, focusing on dosing protocols, treated conditions, and patient outcomes. EVIDENCE REVIEW: A comprehensive review of PubMed, CINAHL, Web of Science, Cochrane Library, and EMBASE was conducted up to January 2024. Eligibility criteria included studies evaluating psilocybin for chronic pain management. The risk of bias was assessed using the MASTER (MethodologicAl STandards for Epidemiological Research) scale, and the strength of evidence was graded using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation). FINDINGS: The review identified 28 relevant studies focusing on dosing, treated conditions, and outcomes. The majority of the included studies (76.2%) were of low or very low quality. Several studies with moderate-to-low-quality evidence utilized a 0.14 mg/kg dosing protocol. The findings suggest promise for the use of psilocybin in chronic pain relief, though the quality of evidence is generally low. CONCLUSIONS: The current research shows potential for psilocybin as a treatment option for chronic pain relief. However, methodological issues and a lack of high-quality evidence underscore the need for further investigations with standardized protocols. Despite these limitations, the potential for psilocybin in chronic pain management is encouraging. PROSPERO REGISTRATION NUMBER: CRD42023493823.

Peripheral Nerve Stimulation for Chronic Pain and Migraine: A Review.

Interventional pain procedures offer treatments for chronic pain conditions refractory to conservative measures. Neuromodulation, including peripheral nerve stimulation (PNS), applies electrical stimuli to neural structures to treat pain. Here we review the literature on PNS for various chronic pain conditions including neuropathic pain, postamputation pain, musculoskeletal pain, migraine, and pelvic pain.

Widespread Pressure Delivered by a Weighted Blanket Reduces Chronic Pain: A Randomized Controlled Trial.

Pleasant sensation is an underexplored avenue for modulation of chronic pain. Deeper pressure is perceived as pleasant and calming, and can improve sleep. Although pressure can reduce acute pain, its effect on chronic pain is poorly characterized. The current remote, double-blind, randomized controlled trial tested the hypothesis that wearing a heavy weighted blanket - providing widespread pressure to the body - relative to a light weighted blanket would reduce ratings of chronic pain, mediated by improvements in anxiety and sleep. Ninety-four adults with chronic pain were randomized to wear a 15-lb. (heavy) or 5-lb. (light) weighted blanket during a brief trial and overnight for one week. Measures of anxiety and chronic pain were collected pre- and post-intervention, and ratings of pain intensity, anxiety, and sleep were collected daily. After controlling for expectations and trait anxiety, the heavy weighted blanket produced significantly greater reductions in broad perceptions of chronic pain than the light weighted blanket (Cohen's f = .19, CI [-1.97, -.91]). This effect was stronger in individuals with high trait anxiety (P = .02). However, weighted blankets did not alter pain intensity ratings. Pain reductions were not mediated by anxiety or sleep. Given that the heavy weighted blanket was associated with greater modulation of affective versus sensory aspects of chronic pain, we propose that the observed reductions are due to interoceptive and social/affective effects of deeper pressure. Overall, we demonstrate that widespread pressure from a weighted blanket can reduce the severity of chronic pain, offering an accessible, home-based tool for chronic pain. The study purpose, targeted condition, study design, and primary and secondary outcomes were pre-registered in ClinicalTrials.gov (NCT04447885: "Weighted Blankets and Chronic Pain"). PERSPECTIVE: This randomized-controlled trial showed that a 15-lb weighted blanket produced significantly greater reductions in broad perceptions of chronic pain relative to a 5-lb weighted blanket, particularly in highly anxious individuals. These findings are relevant to patients and providers seeking home-based, nondrug therapies for chronic pain relief.

Chronic pain and psychedelics: a review and proposed mechanism of action.

The development of chronic pain is a complex mechanism that is still not fully understood. Multiple somatic and visceral afferent pain signals, when experienced over time, cause a strengthening of certain neural circuitry through peripheral and central sensitization, resulting in the physical and emotional perceptual chronic pain experience. The mind-altering qualities of psychedelics have been attributed, through serotonin 2A (5-HT2A) receptor agonism, to 'reset' areas of functional connectivity (FC) in the brain that play prominent roles in many central neuropathic states. Psychedelic substances have a generally favorable safety profile, especially when compared with opioid analgesics. Clinical evidence to date for their use for chronic pain is limited; however, several studies and reports over the past 50 years have shown potential analgesic benefit in cancer pain, phantom limb pain and cluster headache. While the mechanisms by which the classic psychedelics may provide analgesia are not clear, several possibilities exist given the similarity between 5-HT2A activation pathways of psychedelics and the nociceptive modulation pathways in humans. Additionally, the alterations in FC seen with psychedelic use suggest a way that these agents could help reverse the changes in neural connections seen in chronic pain states. Given the current state of the opioid epidemic and limited efficacy of non-opioid analgesics, it is time to consider further research on psychedelics as analgesics in order to improve the lives of patients with chronic pain conditions.