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A Randomized, Placebo-Controlled, Crossover Trial of Cannabis Cigarettes in Neuropathic Pain
Open accessAbstract
Unlabelled The Food and Drug Administration (FDA), Substance Abuse and Mental Health Services Administration (SAMHSA), and the National Institute for Drug Abuse (NIDA) report that no sound scientific studies support the medicinal use of cannabis. Despite this lack of scientific validation, many patients routinely use "medical marijuana," and in many cases this use is for pain related to nerve injury. We conducted a double-blinded, placebo-controlled, crossover study evaluating the analgesic efficacy of smoking cannabis for neuropathic pain. Thirty-eight patients with central and peripheral neuropathic pain underwent a standardized procedure for smoking either high-dose (7%), low-dose (3.5%), or placebo cannabis. In addition to the primary outcome of pain intensity, secondary outcome measures included evoked pain using heat-pain threshold, sensitivity to light touch, psychoactive side effects, and neuropsychological performance. A mixed linear model demonstrated an analgesic response to smoking cannabis. No effect on evoked pain was seen. Psychoactive effects were minimal and well-tolerated, with some acute cognitive effects, particularly with memory, at higher doses.Perspective This study adds to a growing body of evidence that cannabis may be effective at ameliorating neuropathic pain, and may be an alternative for patients who do not respond to, or cannot tolerate, other drugs. However, the use of marijuana as medicine may be limited by its method of administration (smoking) and modest acute cognitive effects, particularly at higher doses.
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“Seven studies assessed CBM use on appetite in participants experiencing chronic pain, including two RCTs,59,63 two cross-sectional studies,79,88 two case series,91,92 and one pre-post study.70”
From Clinical Practice Guidelines for Cannabis and Cannabinoid-Based Medicines in the Management of Chronic Pain and Co-Occurring Conditions (2024) · cites this paper as [63]
In the citing paper
“This study reported that cannabinoids compounded the decreased neurocognitive performance of patients that was present at baseline.”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [155]
In the citing paper
“Smoking cannabis cigarettes also improved spontaneous pain relief and pain unpleasantness VAS ratings in patients suffering from mixed forms of neuropathic pain, but failed to alter stimulus-evoked pain.155”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [155]
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The prevalence and incidence of medicinal cannabis on prescription in The Netherlands
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“in the form of Marinol®, while preparations containing THC and/or CBD were shown to be clinically effective for several pain indications, including severe chronic noncancer pain [23], various neuropathic pains [24], postoperative pain [25] and MS [26].”
Bar‐Sela, G., Vorobeichik, M., Drawsheh, S., Omer, A., Goldberg, V., & Muller, E. (2013) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2013/510392 · Cited by 80
Cannabis and the Health and Performance of the Elite Athlete
Ware, M. A., Jensen, D., Barrette, A., Vernec, A. R., & Derman, W. E. (2018) · Clinical Journal of Sport Medicine · doi:10.1097/jsm.0000000000000650 · Cited by 84
Eisenberg, E., Ogintz, M., & Almog, S. (2014) · Journal of Pain & Palliative Care Pharmacotherapy · doi:10.3109/15360288.2014.941130 · Cited by 79
Prescribing cannabis for harm reduction
Collen, M. R. (2012) · Harm Reduction Journal · doi:10.1186/1477-7517-9-1 · Cited by 80
“A closer look at the four RCTs which evaluated smoked cannabis for neuropathic pain [45-48] reveals some common and contrasting elements (Table 1).”
InfluentialBell, A. D., MacCallum, C., Margolese, S., Walsh, Z., Wright, P., Daeninck, P. J., Mandarino, E., Lacasse, G., Kaur Deol, J., de Freitas, L., et al. (2024) · Cannabis & Cannabinoid Research · doi:10.1089/can.2021.0156 · Cited by 78
Medical marijuana users in substance abuse treatment
Swartz, R. (2010) · Harm Reduction Journal · doi:10.1186/1477-7517-7-3 · Cited by 74
“Institute of Medicine [7], the American College of Physicians [8], and other sources [9-12] in relation to psychosis, bipolar disorder, anxiety, pain, anorexia, nausea, and muscle spasticity, including randomized, placebo-controlled, crossover trials [13].”
Cannabis and cannabinoids for symptomatic treatment for people with multiple sclerosis
Filippini, G., Minozzi, S., Borrelli, F., Cinquini, M., & Dwan, K. (2022) · Cochrane Database Systematic Reviews · doi:10.1002/14651858.cd013444.pub2 · Cited by 75
Medicinal Uses of Marijuana and Cannabinoids
Grotenhermen, F., & Müller‐Vahl, K. (2016) · Critical Reviews in Plant Sciences · doi:10.1080/07352689.2016.1265360 · Cited by 72
Aggarwal, S. K., Carter, G. T., Sullivan, M. D., ZumBrunnen, C., Morrill, R. L., & Mayer, J. D. (2018) · Journal of Opioid Management · doi:10.5055/jom.2009.0028 · Cited by 72
Schröder, S., Beckmann, K. H., Franconi, G., Meyer‐Hamme, G., Friedemann, T., Greten, H. J., Rostock, M., & Efferth, T. (2013) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2013/423713 · Cited by 72
“While CIPN has multiple mechanisms of neuronal degeneration, a combination of herbs or substances might deal with multiple targets for the aim of neuroprotection or neuroregeneration in CIPN.”
Cannabinoids: Current and Future Options to Treat Chronic and Chemotherapy-Induced Neuropathic Pain
Blanton, H. L., Brelsfoard, J., Deturk, N., Pruitt, K., Narasimhan, M., Morgan, D. J., & Guindon, J. (2019) · Drugs · doi:10.1007/s40265-019-01132-x · Cited by 71
Cannabis and pain: a scoping review
Pantoja‐Ruiz, C., Restrepo-Jiménez, P., Castañeda‐Cardona, C., Ferreirós, A., & Rosselli, D. (2021) · Brazilian Journal of Anesthesiology (English Edition) · doi:10.1016/j.bjane.2021.06.018 · Cited by 77
Pharmacy Students’ Knowledge and Attitudes Regarding Medical Marijuana
Moeller, K. E., & Woods, B. A. (2015) · American Journal of Pharmaceutical Education · doi:10.5688/ajpe79685 · Cited by 69
Effects of cannabinoid administration for pain: A meta-analysis and meta-regression.
Yanes, J. A., McKinnell, Z. E., Reid, M. A., Busler, J. N., Michel, J. S., Pangelinan, M. M., Sutherland, M. T., Younger, J., González, R., & Robinson, J. L. (2019) · Experimental and Clinical Psychopharmacology · doi:10.1037/pha0000281 · Cited by 68
“Although baseline and end-point pain severity scores were necessary for inclusion, several records omitted associated variance estimates (Abrams et al., 2007; Blake, Robson, Ho, Jubb, & McCabe, 2006; Buggy et al., 2003; Chou et al., 2009; Corey-Bloom et al., 2012; Johnson et al., 2010; Karst et al., 2003; Langford et…”
Cannabinoid Receptor Type 1 and Its Role as an Analgesic: An Opioid Alternative?
Milligan, A. L., Szabo-Pardi, T. A., & Burton, M. D. (2019) · Journal of Dual Diagnosis · doi:10.1080/15504263.2019.1668100 · Cited by 70
“These doses were generally well tolerated by patients who reported a feeling of high but with a “good drug effect” (Wilsey et al., 2008).”
The intersection between cannabis and cancer in the United States
Bowles, D. W., O’Bryant, C. L., Camidge, D. R., & Jimeno, A. (2011) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2011.09.008 · Cited by 66
Carter, G. T., Abood, M. E., Aggarwal, S. K., & Weiss, M. D. (2010) · American Journal of Hospice and Palliative Medicine® · doi:10.1177/1049909110369531 · Cited by 65
“Nonetheless, it is possible, with coordinated effort, to effectively do doubleblind, randomized, placebo-controlled clinical trials with cannabis.(138-141) To properly evaluate both subjective and objective Carter et al 351”
Rabgay, K., Waranuch, N., Chaiyakunapruk, N., Sawangjit, R., Ingkaninan, K., & Dilokthornsakul, P. (2019) · Journal of the American Pharmacists Association · doi:10.1016/j.japh.2019.07.015 · Cited by 69
Shohet, A., Khlebtovsky, A., Roizen, N., Roditi, Y., & Djaldetti, R. (2016) · European Journal of Pain · doi:10.1002/ejp.942 · Cited by 63
“To the best of our knowledge, QST following cannabis treatment has been performed so far only in patients with neuropathic pain (Abrams et al., 2007; Wilsey et al., 2008).”
Aggarwal, S. K. (2013) · The Clinical Journal of Pain · doi:10.1097/ajp.0b013e31824c5e4c · Cited by 62
Salottolo, K., Peck, L., Tanner, A. H., Carrick, M. M., Madayag, R. M., McGuire, E. L., & Bar‐Or, D. (2018) · Patient Safety in Surgery · doi:10.1186/s13037-018-0163-3 · Cited by 63
“Marijuana’s medicinal effects are largely antinociceptive, suggesting a role in treating chronic pain [8–11] and neuropathic pain [12, 13].”
Crowley, D., Collins, C., Delargy, Í., Laird, E. J., & Hout, M. C. V. (2017) · Harm Reduction Journal · doi:10.1186/s12954-016-0129-7 · Cited by 61
Therapeutic benefits of cannabis: a patient survey.
Webb, C. W., & Webb, S. M. (2014) · Europe PMC (PubMed Central) · Cited by 61
Role of Cannabinoids in Pain Management
Russo, E. B., & Hohmann, A. G. (2012) · Springer eBooks · doi:10.1007/978-1-4614-1560-2_18 · Cited by 62
Sainsbury, B., Bloxham, J., Pour, M. H., Padilla, M., & Enciso, R. (2021) · Journal of Dental Anesthesia and Pain Medicine · doi:10.17245/jdapm.2021.21.6.479 · Cited by 61
“2008 [53] (1) Patients with CRPS type I, spinal cord injury, peripheral neuropathy, or nerve injury.”
InfluentialExamining the roles of cannabinoids in pain and other therapeutic indications: a review
Turcotte, D., Dorze, J.-A. L., Esfahani, F., Frost, E. E., Gomori, A. J., & Namaka, M. (2009) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656560903413534 · Cited by 59
Metadata
- Authors
- Wilsey, B., Marcotte, T., Tsodikov, A., Millman, J., Bentley, H., Gouaux, B., & Fishman, S.
- Affiliations
- VA Northern California Health Care System (US)
- University of California San Diego (US)
- University of California Davis Medical Center (US)
- Corresponding author
- Wilsey, Barth
- Venue
- The Journal of Pain
- Publisher
- Elsevier BV
- Published
- 2008-06
- Volume
- 9
- Issue
- 6
- Pages
- 506-521
- ISSN
- 1526-5900 (ISSN-L)
- PMC
- PMC4968043
- OpenAlex
- W2133895281
- Cited by
- 327
- References
- 84
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 13 · 2023: 11 · 2022: 19 · 2021: 20 · 2020: 25 · 2019: 30 · 2018: 34 · 2017: 23 · 2016: 20 · 2015: 27 · 2014: 22 · 2013: 19 · 2012: 12
- FWCI
- 8.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Pain (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UL1TR000002)
- National Institute on Drug Abuse
- National Center for Research Resources (UL1RR024146)
- National Center for Advancing Translational Sciences
- Center for Medicinal Cannabis Research, University of California, San Diego
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Opioid Use
- Keywords
- cannabis, neuropathic pain, medical cannabis, analgesic efficacy, pain intensity, evoked pain, psychoactive effects, cognitive effects, memory, dose-response relationship, central pain, peripheral neuropathic pain
- MeSH terms
- Adult, Affect, Aged, Cannabinoids, Dose-Response Relationship, Drug, Double-Blind Method, Humans, Marijuana Smoking, Middle Aged, Neuralgia, Neuropsychological Tests, Pain Measurement, Time Factors, Linear Models, Cross-Over Studies
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