Chronic pain

First published June 2023, revised and referenced September 2026

Persistent pain can be a manifestation of dozens of different conditions. It is commonly encountered in multiple sclerosis, cancer, HIV, after injury or surgery, in arthritis and other degenerative diseases of the joints and connective tissue, and after burns.¹

Pain is not a disease in itself but a symptom, and one patients often struggle to manage. Everyone experiences it with different intensity, frequency and duration, and pain that has lasted more than three months is classed as chronic.

A problem for a great many of us

In the largest European survey, roughly one adult in five (19%) reported chronic pain of moderate to severe intensity lasting six months or more, and 40% of them said their pain was inadequately managed.² Global estimates are similar, at around 20% of adults, with some studies reporting more than 30%.^3,1

People with chronic pain need to reduce it as far as possible while minimising the side effects of many common painkillers. Untreated chronic pain erodes sleep, mood, relationships and the ability to work, and in the European survey one in five sufferers had been diagnosed with depression because of their pain.² Good symptom control is part of comprehensive care. It complements conventional treatment; it does not replace it.

Different mechanisms and forms

Cannabis-based medicines act on the endocannabinoid system, which is involved in how pain signals are processed in the spinal cord and brain (more on the endocannabinoid system). Used alone or alongside other analgesics they can reduce pain for some patients, and can also ease the nausea that severe pain, or the medicines used to treat it, can cause.^4,5

Route matters. Inhaling vapour gives fast relief, because cannabinoids reach the bloodstream within minutes and the effect peaks within 15 to 30 minutes and fades over two to three hours. Oral forms, such as capsules, drops and extracts, start working after 30 to 90 minutes, peak at two to three hours and last four to twelve hours depending on dose.^6,7 Oral THC can also be less predictable and more intense, because absorption varies and the liver converts part of the dose into an active metabolite, 11-hydroxy-THC.⁷

A complex mixture for a complex problem

The interplay of cannabinoids, terpenes and other substances in the plant is often proposed as the reason whole-plant preparations may behave differently from an isolated cannabinoid. This is called synergy, or the entourage effect.⁸ It is a plausible hypothesis with some laboratory support, but it has not been confirmed in controlled clinical trials and remains debated.⁹

Analgesic and anti-inflammatory effects have been described in laboratory and animal studies for several cannabinoids besides THC and CBD. Cannabichromene (CBC), one of the major cannabinoids and present in appreciable amounts in some varieties, is the best studied of these.^10,11 These are preclinical findings, and no clinical trial has yet tested CBC in patients with pain.

Alongside other painkillers

Cannabis-based medicines are sometimes used for cancer pain that is not controlled by opioids. The picture here is more cautious than it once appeared. A small study in 1975 found that a single oral dose of THC gave mild pain relief comparable to codeine,¹² and a 2010 trial of a THC:CBD extract added to opioids was positive.¹³ But two later phase 3 trials did not meet their primary endpoints, and a 2020 meta-analysis of six randomised trials found that adding cannabinoids to optimised opioid treatment did not reduce cancer pain, while causing more drowsiness and dizziness.^14,15

Animal studies show a strong synergy between cannabinoids and opioids, and in one small clinical study, vaporised cannabis added to a stable opioid dose reduced pain by about a quarter.^4,16 Surveys of patients report large reductions in opioid use, but randomised trials have so far not confirmed an opioid-sparing effect, so the question is open.¹⁷

Conditions where it is used, and what the evidence says

• Nausea and loss of appetite during chemotherapy. Among the best-supported uses; the US National Academies rated the evidence for oral cannabinoids in chemotherapy-induced nausea and vomiting as conclusive.⁵
• Peripheral neuropathic pain, spinal cord injury and central pain. A 2018 Cochrane review of 16 trials found a modest benefit: 30% pain relief in 39% of patients on cannabis-based medicines against 33% on placebo, with more nervous-system and psychiatric side effects.¹⁸
• Painful neuropathy in HIV. Two small randomised trials of smoked cannabis found roughly twice as many patients achieved meaningful relief as on placebo.^19,20
• Chronic pain with poor sleep. Trials of non-inhaled cannabis-based medicines show small improvements in pain and in sleep quality.²¹
• Arthritis. Commonly reported by patients, but not yet established in controlled trials of adequate quality.⁵
• Pain after surgery. The evidence does not support cannabinoids for acute post-operative pain: trials have found no advantage over placebo and no reduction in opioid use.^22,23

Taken together, the major reviews describe a modest average benefit in a minority of patients, mainly with non-inhaled THC-containing products, in short trials, with side effects that are usually transient. Guideline bodies differ: a 2021 BMJ panel gave a weak recommendation to offer a trial of non-inhaled medical cannabis alongside standard care for chronic pain, while the International Association for the Study of Pain declined to endorse cannabinoids for pain until higher-quality research exists.^24,25 Both positions are consistent with cannabis being a treatment to consider for selected patients after other options, under medical supervision, not a first choice.

References

1. Cohen SP, Vase L, Hooten WM. Chronic pain: an update on burden, best practices, and new advances. Lancet 2021;397(10289):2082-2097. doi:10.1016/S0140-6736(21)00393-7
2. Breivik H, Collett B, Ventafridda V, Cohen R, Gallacher D. Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment. European Journal of Pain 2006;10(4):287-333. doi:10.1016/j.ejpain.2005.06.009
3. Goldberg DS, McGee SJ. Pain as a global public health priority. BMC Public Health 2011;11:770. doi:10.1186/1471-2458-11-770
4. Abrams DI, Couey P, Shade SB, Kelly ME, Benowitz NL. Cannabinoid-opioid interaction in chronic pain. Clinical Pharmacology and Therapeutics 2011;90(6):844-851. doi:10.1038/clpt.2011.188
5. National Academies of Sciences, Engineering, and Medicine. The Health Effects of Cannabis and Cannabinoids. Washington, DC: National Academies Press; 2017. doi:10.17226/24625
6. Grotenhermen F. Pharmacokinetics and pharmacodynamics of cannabinoids. Clinical Pharmacokinetics 2003;42(4):327-360. doi:10.2165/00003088-200342040-00003
7. Huestis MA. Human cannabinoid pharmacokinetics. Chemistry and Biodiversity 2007;4(8):1770-1804. doi:10.1002/cbdv.200790152
8. Russo EB. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. British Journal of Pharmacology 2011;163(7):1344-1364. doi:10.1111/j.1476-5381.2011.01238.x
9. Christensen C, Rose M, Cornett C, Allesø M. Decoding the postulated entourage effect of medicinal cannabis: what it is and what it isn’t. Biomedicines 2023;11(8):2323. doi:10.3390/biomedicines11082323
10. DeLong GT, Wolf CE, Poklis A, Lichtman AH. Pharmacological evaluation of the natural constituent of Cannabis sativa, cannabichromene and its modulation by Δ9-tetrahydrocannabinol. Drug and Alcohol Dependence 2010;112(1-2):126-133. doi:10.1016/j.drugalcdep.2010.05.019
11. Maione S, Piscitelli F, Gatta L, et al. Non-psychoactive cannabinoids modulate the descending pathway of antinociception in anaesthetized rats through several mechanisms of action. British Journal of Pharmacology 2011;162(3):584-596. doi:10.1111/j.1476-5381.2010.01063.x
12. Noyes R, Brunk SF, Avery DH, Canter A. The analgesic properties of delta-9-tetrahydrocannabinol and codeine. Clinical Pharmacology and Therapeutics 1975;18(1):84-89. doi:10.1002/cpt197518184
13. Johnson JR, Burnell-Nugent M, Lossignol D, et al. Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related pain. Journal of Pain and Symptom Management 2010;39(2):167-179. doi:10.1016/j.jpainsymman.2009.06.008
14. Fallon MT, Albert Lux E, McQuade R, et al. Sativex oromucosal spray as adjunctive therapy in advanced cancer patients with chronic pain unalleviated by optimized opioid therapy: two double-blind, randomized, placebo-controlled phase 3 studies. British Journal of Pain 2017;11(3):119-133. doi:10.1177/2049463717710042
15. Boland EG, Bennett MI, Allgar V, Boland JW. Cannabinoids for adult cancer-related pain: systematic review and meta-analysis. BMJ Supportive and Palliative Care 2020;10(1):14-24. doi:10.1136/bmjspcare-2019-002032
16. Nielsen S, Sabioni P, Trigo JM, et al. Opioid-sparing effect of cannabinoids: a systematic review and meta-analysis. Neuropsychopharmacology 2017;42(9):1752-1765. doi:10.1038/npp.2017.51
17. Nielsen S, Picco L, Murnion B, et al. Opioid-sparing effect of cannabinoids for analgesia: an updated systematic review and meta-analysis of preclinical and clinical studies. Neuropsychopharmacology 2022;47(7):1315-1330. doi:10.1038/s41386-022-01322-4
18. Mücke M, Phillips T, Radbruch L, Petzke F, Häuser W. Cannabis-based medicines for chronic neuropathic pain in adults. Cochrane Database of Systematic Reviews 2018;3:CD012182. doi:10.1002/14651858.CD012182.pub2
19. Abrams DI, Jay CA, Shade SB, et al. Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial. Neurology 2007;68(7):515-521. doi:10.1212/01.wnl.0000253187.66183.9c
20. Ellis RJ, Toperoff W, Vaida F, et al. Smoked medicinal cannabis for neuropathic pain in HIV: a randomized, crossover clinical trial. Neuropsychopharmacology 2009;34(3):672-680. doi:10.1038/npp.2008.120
21. Wang L, Hong PJ, May C, et al. Medical cannabis or cannabinoids for chronic non-cancer and cancer related pain: a systematic review and meta-analysis of randomised clinical trials. BMJ 2021;374:n1034. doi:10.1136/bmj.n1034
22. Gazendam A, Nucci N, Gouveia K, Abdel Khalik H, Rubinger L, Johal H. Cannabinoids in the management of acute pain: a systematic review and meta-analysis. Cannabis and Cannabinoid Research 2020;5(4):290-297. doi:10.1089/can.2019.0079
23. González Cárdenas VH, et al. Cannabinoids for acute postoperative pain management: a systematic review and meta-analysis of clinical trials. European Journal of Pain 2025;29(3):e4790. doi:10.1002/ejp.4790
24. Busse JW, Vankrunkelsven P, Zeng L, et al. Medical cannabis or cannabinoids for chronic pain: a clinical practice guideline. BMJ 2021;374:n2040. doi:10.1136/bmj.n2040
25. International Association for the Study of Pain. IASP position statement on the use of cannabinoids to treat pain. 18 March 2021. iasp-pain.org

Adapted from material originally written for Motagon by Lukáš Hurt, revised and referenced September 2026. Reviewed by [name, role], Motagon s.r.o. Last reviewed 21 September 2026.