Are psychedelics the answer to chronic pain: A review of current literature

Kooijman, Nina; Willegers, Tim; Reuser, Anke; Mulleners, Wim M.; Kramers, Cornelis; Vissers, Kris; Wal, Selina E I van der

doi:10.1111/papr.13203

Cited by 12 publications

(10 citation statements)

References 79 publications

(208 reference statements)

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“…Recent studies, albeit limited, have reignited interest in the analgesic potential of LSD. 69 In 2021, a randomized, placebo-controlled, crossover human laboratory study administered low doses of LSD (5, 10, and 20 μg) and showed an increase in pain tolerance and reduction in pain unpleasantness, using the Cold Pressor Test (CPT), a well-established laboratory model of pain. 67 This study provided evidence that sub-hallucinogenic doses of LSD may produce analgesia in humans.…”

Section: Lysergic Acid Diethylamide (Lsd)mentioning

confidence: 99%

From Taboo to Treatment: The Emergence of Psychedelics in the Management of Pain and Opioid Use Disorder

Weleff,

Nunes,

Costa

et al. 2023

Preprint

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The rise of psychedelics in contemporary medicine has sparked interest in their potential therapeutic applications. While traditionally associated with countercultural movements and recreational use, recent research has shed light on the potential benefits of psychedelics in various mental health conditions. In this review, we explore the emerging role of psychedelics in the management of chronic pain and opioid use disorder (OUD), two critical areas in need of innovative treatment options. Pain control remains a significant clinical challenge, particularly for individuals with OUD and those who receive long-term opioid therapy (LTOT) who develop marked tolerance to opioid-induced analgesia. Despite the magnitude of this problem, there is a scarcity of controlled studies investigating pain management alternatives for these populations. Drawing from preclinical and human evidence, we highlight the potential of psychedelics to act on shared neurobiological substrates of chronic pain and opioid use disorder, potentially reversing pain- and opioid-induced neuroadaptations, such as central sensitization. We elaborate on the multifaceted dimensions of the pain experience (sensory, affective, and cognitive) and their intersections that overlap with opioid-related phenomena (opioid craving and withdrawal), hypothesizing how these processes can be modulated by psychedelics. After summarizing the available clinical research, we propose mechanistic insights and methodological considerations for the design of future translational studies and clinical trials, building on a shared clinical and neurobiological understanding of chronic pain and OUD. Our intention is to provide timely perspectives that accelerate the development and exploration of novel therapeutics for chronic pain and OUD amidst the escalating opioid crisis.

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Section: Lysergic Acid Diethylamide (Lsd)mentioning

confidence: 99%

From Taboo to Treatment: The Emergence of Psychedelics in the Management of Pain and Opioid Use Disorder

Weleff,

Nunes,

Costa

et al. 2023

Preprint

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“…[10][11][12][13][14][15][16][17][18][19][20][21] Though the mechanism is not entirely understood, psychedelics, focusing primarily on the classic hallucinogens lysergic acid diethylamide (LSD) and psilocybin, function by activation of the serotonin-2A (5-HT 2A ) receptor as antagonism of the receptor blocks the psychedelic effects. 22,23 Furthermore, 5-HT 2A is involved in both centrally and peripherally mediated pain as sensory nerve fibers transmitting nociceptive signals project onto the dorsal horn. 23 Activation of 5-HT 2A via injection of serotonin (5-HT) into the spinal cord results in antinociceptive effects by potentially interfering with pain signaling.…”

Section: Introductionmentioning

confidence: 99%

“…22,23 Furthermore, 5-HT 2A is involved in both centrally and peripherally mediated pain as sensory nerve fibers transmitting nociceptive signals project onto the dorsal horn. 23 Activation of 5-HT 2A via injection of serotonin (5-HT) into the spinal cord results in antinociceptive effects by potentially interfering with pain signaling. [23][24][25] Additionally, the effect of psychedelics on pain is based on the chronicity of pain.…”

Section: Introductionmentioning

confidence: 99%

“…23 Activation of 5-HT 2A via injection of serotonin (5-HT) into the spinal cord results in antinociceptive effects by potentially interfering with pain signaling. [23][24][25] Additionally, the effect of psychedelics on pain is based on the chronicity of pain. 23 For chronic pain, early data suggest that descending 5-HT pathways have an antinociceptive effect which can be increased with activation.…”

Section: Introductionmentioning

confidence: 99%

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Scoping Review: The Role of Psychedelics in the Management of Chronic Pain

Robinson,

Fonseca,

Diejomaoh

et al. 2024

JPR

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Introduction: Amid a lack of effective chronic pain treatments, psychedelics have gained attention as a potential solution, although their Schedule 1 classification poses challenges. Psychedelics, such as lysergic acid diethylamide (LSD) and psilocybin, have gained popularity as alternatives and adjuncts for chronic pain treatment. Studies suggest that they may modulate pain processing through agonism primarily at the serotonin receptor, 5-HT 2A . One of the first of its nature, we present an artificial intelligence (AI)-powered scoping review primarily focusing on evaluating psychedelics for chronic pain conditions such as cluster headache, phantom limb pain, and fibromyalgia. Methods: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, we used an AI-powered comprehensive search strategy utilizing the ChatGPT4.0 Bing chat to search Medline, Embase, Cochrane, and Google Scholar for articles addressing chronic pain. The query was performed on June 1, 2023, focusing on psychedelics for chronic, non-cancer pain including headache disorders. Inclusion criteria were English-only, peer-reviewed articles involving human participants >18 years, focusing on chronic pain conditions (eg, phantom limb pain and cluster headache), using LSD, 2.5-dimethoxy-4-bromophenethylamine (2C-B), N, N-dimethyltryptamine (DMT), psilocybin, or mescaline. Exclusion criteria were reviews, editorials, and opinion articles and studies focusing on tetrahydrocannabinol/cannabis and/or ketamine. Results: A total of 186 unique database entries were retrieved, of which nine studies were included in the scoping review. These included four case reports/series, an open-label study, a cohort study, two online surveys, and a randomized, double-blind, placebocontrolled trial. They comprised three studies addressing phantom limb pain, four addressing cluster headaches, and two addressing fibromyalgia, spinal cord injury, complex regional pain syndrome, and lumbar radiculopathy. Conclusion: Psychedelics may have potential in alleviating pain symptoms secondary to a multitude of chronic pain conditions. However, further randomized, double-blind, placebo-controlled trials are needed to further explore and evaluate the role of psychedelics in chronic, non-cancer pain.

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“…A study by Kooijman et al 1 discussed the available evidence of the use of psychedelics in treating chronic pain with a specific focus on lysergic acid diethylamide (LSD) and psilocybin.…”

mentioning

confidence: 99%