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Clinical evidence

Cannabis in chronic pain: what the evidence supports

A review of the published literature, including the findings that run against the case for treatment.

September 2026, rewritten against the primary literature 21 September 2026

This article is written for healthcare professionals. It is published openly because the evidence base for this category is poorly served elsewhere, but it is not advice on the treatment of an individual patient.

Around 20% of adults worldwide live with chronic pain, and some estimates put the figure above 30%.1,2 Chronic pain frequently co-occurs with depression, insomnia, anxiety, post-traumatic stress disorder and substance use disorders.3,4 It is also the most common indication for which medical cannabis is prescribed in countries that permit it: 65% of qualifying conditions in US state registries, and 73% of prescriptions in the German companion survey.5,6

A long history and a short evidence base

Cannabis has been used medicinally, including for pain, for at least 2,500 to 3,000 years according to written and archaeological records, with traditions reaching back further.7,8 The modern trial evidence is roughly thirty years old, and it is uneven in quality: most trials are short, many are small, and the products studied range from smoked flower to pharmaceutical extracts, which limits how far any single result carries.

What the major syntheses conclude

Rather than assemble individual studies, a prescriber is better served by the systematic reviews and guideline statements published since 2015. They do not all agree, and the disagreement is itself informative.

Moderate certainty, small effect

Wang et al., BMJ 2021 (32 randomised trials, 5,174 patients, chronic cancer and non-cancer pain). Non-inhaled medical cannabis or cannabinoids give a small to very small improvement in pain: about 10% more patients reach a clinically important reduction than on placebo, with small improvements in physical function and sleep quality and transient adverse effects such as dizziness and cognitive impairment.9 The accompanying BMJ Rapid Recommendation makes a weak recommendation to offer a trial of non-inhaled medical cannabis in addition to standard care for people with chronic pain when other treatments are insufficient.10

Very low quality, not endorsed

Fisher et al., Pain 2021 (36 randomised trials, 7,217 patients, for the IASP task force). The evidence “neither supports nor refutes claims of efficacy and safety”; benefit was seen only in short cannabis trials and in longer nabiximols trials, all at very low quality.11 On that basis the International Association for the Study of Pain stated in March 2021 that it does not endorse the general use of cannabinoids to treat pain, while calling for higher-quality research rather than closing the question.12

Modest benefit, notable harms

Cochrane, Mücke et al. 2018 (16 trials, 1,750 patients, chronic neuropathic pain). 30% pain relief in 39% of patients on cannabis-based medicines against 33% on placebo, a number needed to treat of 11, with more nervous-system and psychiatric adverse events and more withdrawals; the authors concluded the potential benefits “might be outweighed by their potential harms” for many patients.13

Product-specific

McDonagh et al., Annals of Internal Medicine 2022 (AHRQ living review). Synthetic products with high THC:CBD ratios and the 1:1 THC:CBD oromucosal spray may give short-term improvements in pain, with increased dizziness and sedation; the evidence for other products, and for long-term harms, is insufficient.14 A 2024 network meta-analysis of 90 trials found medical cannabis may be similar to opioids in chronic non-cancer pain with fewer discontinuations for adverse events, at low to moderate certainty.15

Read together: a modest average benefit, concentrated in a minority of patients and mainly with non-inhaled THC-containing products; trials that are too short to tell us about long-term use; adverse effects that are common but usually transient; and guideline bodies ranging from a weak recommendation to non-endorsement. The long-term observational data point the same way: in a 2022 meta-analysis of open-label studies, mean pain fell by 1.75 points on a 10-point scale and about one patient in five achieved 50% relief, which the authors considered sufficient to justify a trial of treatment in selected, monitored patients.16

What patients report

In a 2017 survey of 984 dispensary patients in New England, two-thirds had a diagnosis of chronic pain, mainly back and neck pain, neuropathic pain, post-surgical pain and abdominal pain. Patients rated cannabis as about 75% effective on average, and among the health benefits they described, pain relief was the most common, followed by improved sleep.17 This is a self-report survey of people who chose to use cannabis, not a controlled trial, and should be read as a description of patient experience rather than a measure of efficacy.

Opioids

Three findings are widely quoted, and each needs its design stated. A 2016 retrospective survey of 244 Michigan dispensary patients reported a 64% reduction in opioid use, fewer side effects and better quality of life; the authors themselves called for validation in prospective studies.18 A 2021 county-level analysis in the BMJ found that having more cannabis dispensaries was associated with about 17% lower opioid-related mortality, and an earlier economic study found fewer treatment admissions for opioid addiction in states that allowed dispensaries.19,20 These are ecological associations, not proof of cause; a 2019 re-analysis of the original state-level data found the association had reversed once later years were included.21

The randomised evidence is more sober. Animal studies show strong cannabinoid-opioid synergy, and one small clinical study found vaporised cannabis added to a stable opioid dose reduced pain by 27% without changing opioid plasma levels.22 But the 2022 update of the opioid-sparing meta-analysis found that higher-quality randomised trials did not demonstrate an opioid-sparing effect, in either acute or cancer pain.23 Opioid reduction remains a plausible goal for individual patients, monitored, not a demonstrated population effect.

Where the evidence is negative

  • Cancer pain uncontrolled by opioids. Two phase 3 trials of nabiximols added to optimised opioid therapy did not meet their primary endpoints, and a 2020 meta-analysis of six randomised trials found no reduction in cancer pain from adding cannabinoids, with more somnolence and dizziness.24,25,26
  • Acute and post-operative pain. Oral cannabinoids were no better than placebo in a 2020 meta-analysis of six trials, a 2025 review found the evidence contradictory, and randomised trials show no opioid sparing in acute pain.27,28,23
  • Chronic abdominal pain. A trial of oral THC in chronic abdominal pain found no difference from placebo.29
  • Harms. Across the trial literature, cannabinoids increase short-term adverse events, principally dizziness, dry mouth, somnolence, disorientation and confusion, and the neuropathic pain trials show more psychiatric adverse events than placebo.30,13

We report this because a prescriber needs it. A distributor that publishes only the favourable findings is not a useful clinical source.

Drug interactions

THC and CBD are metabolised in the liver by the cytochrome P450 system. In vitro, THC inhibits CYP2C9 most potently, and also CYP1A2, CYP2C19 and CYP3A; CBD inhibits CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A, and their active metabolites 11-hydroxy-THC and 7-hydroxy-CBD inhibit several of the same enzymes.31,32 At the THC doses typical of inhaled or low-dose oral cannabis, clinically relevant inhibition is unlikely. At the high oral CBD doses used in epilepsy (10 to 20 mg/kg) interactions are documented and modelling predicts meaningful increases in exposure to sensitive substrates.33,34

Three interactions deserve specific attention. Co-administration of CBD with clobazam raised clobazam levels by about 60% and its active metabolite N-desmethylclobazam by about 500%, via CYP2C19 and CYP3A4.34 Rises in INR have been reported with warfarin in patients taking CBD and in a patient using THC-containing cannabis, so INR monitoring is prudent when cannabis is started or stopped.35,36 And for medicines with a narrow therapeutic window that depend on these enzymes, such as direct oral anticoagulants metabolised by CYP3A4 or clopidogrel, which needs CYP2C19 to form its active metabolite, the interaction is theoretical rather than documented, and the sensible response is to monitor rather than to avoid.37,38 A practical point from a 2023 randomised study: a CBD-dominant oral extract increased THC exposure and effects compared with THC alone at the same THC dose, so “more CBD” does not mean “less THC effect” by the oral route.39

Mechanism

Cannabis acts through the endocannabinoid system, a signalling system that modulates pain processing in the spinal cord and brain alongside appetite, nausea, inflammation and mood, which is why it can affect conditions as different as pain, spasticity and chemotherapy-induced nausea. Beyond THC and CBD, well over 100 cannabinoids have been identified, and analgesic effects have been described in preclinical studies for several of them, including cannabichromene. More on the endocannabinoid system.

The honest limitation

Many trials of medical cannabis in chronic pain are short and small, and the products studied are heterogeneous. The evidence supports a monitored trial of treatment in selected patients when standard options have failed, with realistic expectations: a small average benefit that a minority of patients will find worthwhile, and side effects that usually settle. It does not support cannabis as a first-line analgesic, and it does not yet tell us much about years of use. Larger and longer trials, including in Europe, are the way that changes.

In preparation

  • Cannabis in oncology: what the evidence supports and what it does not
  • From illicit to prescribed: what changes when a GP takes over a chronic pain patient’s cannabis

References

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  39. Zamarripa CA, Spindle TR, Surujunarain R, et al. Assessment of orally administered Δ9-tetrahydrocannabinol when coadministered with cannabidiol on Δ9-tetrahydrocannabinol pharmacokinetics and pharmacodynamics in healthy adults: a randomized clinical trial. JAMA Network Open 2023;6(2):e2254752. doi:10.1001/jamanetworkopen.2022.54752

Adapted from material originally written for Motagon by Lukáš Hurt, rewritten against the primary literature September 2026. Reviewed by [name, role], Motagon s.r.o. Last reviewed 21 September 2026.

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