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Smoked cannabis for chronic neuropathic pain: a randomized controlled trial
Open accessAbstract
BACKGROUND: Chronic neuropathic pain affects 1%-2% of the adult population and is often refractory to standard pharmacologic treatment. Patients with chronic pain have reported using smoked cannabis to relieve pain, improve sleep and improve mood. METHODS: Adults with post-traumatic or postsurgical neuropathic pain were randomly assigned to receive cannabis at four potencies (0%, 2.5%, 6% and 9.4% tetrahydrocannabinol) over four 14-day periods in a crossover trial. Participants inhaled a single 25-mg dose through a pipe three times daily for the first five days in each cycle, followed by a nine-day washout period. Daily average pain intensity was measured using an 11-point numeric rating scale. We recorded effects on mood, sleep and quality of life, as well as adverse events. RESULTS: We recruited 23 participants (mean age 45.4 [standard deviation 12.3] years, 12 women [52%]), of whom 21 completed the trial. The average daily pain intensity, measured on the 11-point numeric rating scale, was lower on the prespecified primary contrast of 9.4% v. 0% tetrahydrocannabinol (5.4 v. 6.1, respectively; difference = 0.7, 95% confidence interval [CI] 0.02-1.4). Preparations with intermediate potency yielded intermediate but nonsignificant degrees of relief. Participants receiving 9.4% tetrahydrocannabinol reported improved ability to fall asleep (easier, p = 0.001; faster, p < 0.001; more drowsy, p = 0.003) and improved quality of sleep (less wakefulness, p = 0.01) relative to 0% tetrahydrocannabinol. We found no differences in mood or quality of life. The most common drug-related adverse events during the period when participants received 9.4% tetrahydrocannabinol were headache, dry eyes, burning sensation in areas of neuropathic pain, dizziness, numbness and cough. CONCLUSION: A single inhalation of 25 mg of 9.4% tetrahydrocannabinol herbal cannabis three times daily for five days reduced the intensity of pain, improved sleep and was well tolerated. Further long-term safety and efficacy studies are indicated. (International Standard Randomised Controlled Trial Register no. ISRCTN68314063).
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“An RCT of smoked cannabis found that it improved depressive symptoms significantly with a medium-sized effect over placebo.60”
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 [60]
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“Several additional studies found improvements in chronic pain associated with CBM use within samples that included participants concurrently using opioids to treat pain.52,54,60,100,101”
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 [60]
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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
Bell, 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
“60 Three cross-sectional studies also report antidepressant effects of CBM. 82,97,98 Studies involving the use of cannabis extracts are generally less positive regarding the benefits of CBM for treating depression in people with chronic pain.”
BackgroundMedicinal Uses of Marijuana and Cannabinoids
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Opioid and cannabinoid synergy in a mouse neuropathic pain model
Kazantzis, N. P., Casey, S. L., Seow, P. W., Mitchell, V. A., & Vaughan, C. W. (2016) · British Journal of Pharmacology · doi:10.1111/bph.13534 · Cited by 71
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Smoke Gets in Your Eyes: Medical Marijuana Laws and Tobacco Cigarette Use
Choi, A., Dave, D., & Sabia, J. J. (2018) · American Journal of Health Economics · doi:10.1162/ajhe_a_00121 · Cited by 68
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
Chemotherapy-Induced Peripheral Neuropathy: A Recent Update on Pathophysiology and Treatment
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Endocannabinoid System and Exogenous Cannabinoids in Depression and Anxiety: A Review
Hasbi, A., Madras, B. K., & George, S. R. (2023) · Brain Sciences · doi:10.3390/brainsci13020325 · Cited by 69
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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
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
Therapeutic Use of Cannabis and Cannabinoids
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Metadata
- Authors
- Ware, M. A., Wang, T., Shapiro, S., Robinson, A., Ducruet, T., Huynh, T., Gamsa, A., Bennett, G. J., & Collet, J.-P.
- Affiliations
- McGill University (CA)
- University of British Columbia (CA)
- Venue
- Canadian Medical Association Journal
- Publisher
- CMA Impact Inc.
- Published
- 2010-08-30
- Volume
- 182
- Issue
- 14
- Pages
- E694-E701
- ISSN
- 0820-3946 (ISSN-L)
- 1488-2329
- PMC
- PMC2950205
- OpenAlex
- W2120142285
- Semantic Scholar
- 6125159a7712bfe53b79c9d5d0c060fe71bcf8a6
- Cited by
- 450
- References
- 39
- Citations by year
- 2026: 18 · 2025: 24 · 2024: 18 · 2023: 29 · 2022: 36 · 2021: 31 · 2020: 37 · 2019: 31 · 2018: 39 · 2017: 34 · 2016: 33 · 2015: 35 · 2014: 32 · 2013: 16 · 2012: 20
- FWCI
- 12.45
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Canadian Medical Association Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- McGill University
- Louise and Alan Edwards Foundation
- Canadian Institutes of Health Research (JHM-50014)
- 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
- chronic neuropathic pain, cannabis smoking, tetrahydrocannabinol, post-traumatic neuropathic pain, pain intensity, sleep quality, mood, quality of life, adverse events, cannabis potency, cannabinoids, headache, dizziness, dry eye, cough, numbness, burnout, burnout prevention, burnout intervention, burnout symptoms
- MeSH terms
- Adult, Aged, Chronic Disease, Double-Blind Method, Female, Humans, Male, Marijuana Smoking, Middle Aged, Neuralgia, Pain Measurement, Placebos, Quality of Life, Sleep, Dronabinol, Linear Models, Treatment Outcome, Cross-Over Studies
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