What chronic pain is
Chronic pain is pain that persists beyond the expected recovery time after an injury or illness, typically defined as lasting longer than three months. It is distinct from acute pain, which acts as a short-term warning signal of tissue damage. In chronic pain, the nervous system can become sensitised, generating pain signals even after the original injury has resolved. Common forms include musculoskeletal pain from conditions such as osteoarthritis and low back pain, neuropathic pain caused by nerve injury or disease, and conditions like fibromyalgia where no clear structural cause is identified.
In the UK, chronic pain affects an estimated one-third to one-half of adults. Management typically includes physical therapies, psychological approaches, and medications such as anti-inflammatories, certain antidepressants, antiepileptic drugs, and opioids. Many people with chronic pain do not achieve adequate relief from available treatments.
Cannabis research on Chronic pain
A 2015 systematic review and meta-analysis published in JAMA by Whiting and colleagues examined 79 randomised controlled trials (RCTs) of cannabinoids across multiple medical conditions. For chronic pain, a pooled analysis of 8 RCTs found that 37 per cent of participants on cannabinoids reported a clinically meaningful pain reduction compared with 31 per cent on placebo. This difference did not reach statistical significance (odds ratio 1.41, 95% CI 0.99 to 2.00). A separate analysis of 6 RCTs using a 0-to-10 numerical pain rating scale found a small, statistically significant reduction in pain intensity with cannabinoids (weighted mean difference minus 0.46 points, 95% CI minus 0.80 to minus 0.11). The review rated the overall quality of evidence for chronic pain as moderate.
In 2019, the National Institute for Health and Care Excellence (NICE) published guideline NG144 on cannabis-based medicinal products. The guideline committee reviewed the available RCT evidence and recommended against prescribing nabilone, dronabinol, THC, or a combination of CBD and THC for chronic pain in adults. The guideline further advises that CBD should not be offered for chronic pain in adults outside a clinical trial. The committee cited insufficient evidence of benefit relative to the risks and noted that existing treatments for chronic pain have more established safety profiles.
The RCT evidence for chronic pain has several structural limitations. Many trials used different cannabinoid preparations, doses, and pain conditions, limiting comparability. Trial durations were short, typically 2 to 15 weeks, which provides limited information about effects in a condition that often lasts years. Several trials excluded people with complex health needs or concurrent medication use who represent a substantial proportion of the chronic pain population.
Neuropathic pain — pain caused by nerve damage — has been studied more extensively than other chronic pain types within the cannabinoid literature. Some individual RCTs of oromucosal cannabinoid sprays and inhaled cannabis reported greater pain reductions in neuropathic pain subgroups. However, the NICE guideline does not distinguish between pain types in its recommendation.
Compounds studied for Chronic pain
THC activates the CB1 receptor, which is widely distributed in brain regions that process pain, including the periaqueductal grey, thalamus, and dorsal horn of the spinal cord. Human laboratory research has shown that THC alters experimental pain perception. The clinical trial evidence for THC-containing preparations in chronic pain populations is summarised above. See THC.
CBD does not activate CB1 receptors in the same manner as THC. No human RCT has demonstrated that isolated CBD reduces chronic pain. Animal research has examined CBD in inflammatory pain models, but these findings are from laboratory studies and do not establish a treatment effect in people. See CBD.
Caryophyllene is a terpene that binds to the CB2 receptor, which is expressed on immune cells and is involved in inflammatory signalling pathways. Laboratory and animal research has examined caryophyllene for anti-inflammatory effects relevant to pain conditions. No human clinical trial has tested isolated caryophyllene for pain outcomes. See beta-caryophyllene.
Myrcene has been studied in rodent models for analgesic and muscle-relaxant effects. Human clinical trial data for myrcene and pain are absent. See myrcene.
Linalool has been examined in animal studies for effects on pain behaviour, with proposed mechanisms involving adenosine and glutamate signalling pathways. Human trial data for linalool in pain do not exist. See linalool.
Limits of the evidence for Chronic pain
The most comprehensive systematic review found that the proportion of participants with chronic pain who improved on cannabinoids was not statistically different from placebo. Where a difference was detected on a continuous pain scale, the size of the effect was small: less than half a point on a standard 0-to-10 scale.
The RCT evidence comes principally from pharmaceutical-grade preparations of specific cannabinoids, not from dried cannabis flower or non-standardised products. An RCT of one cannabinoid formulation does not provide evidence that a different cannabis product containing that cannabinoid would produce the same result.
Most trials lasted weeks, not months or years. Chronic pain conditions persist for years, and the safety and effectiveness of cannabinoid use over extended periods has not been established in controlled trials.
NICE, after reviewing the available evidence, concluded that the benefit did not justify the risks and costs. The guideline notes that existing medicines with better-characterised safety profiles and comparable or greater effect sizes are already available.
No RCT has compared cannabis or cannabinoids against the full range of standard chronic pain treatments, including multidisciplinary pain management programmes that integrate physical and psychological approaches.
Sources
1. NICE guideline NG144 (2019, updated 2021). Cannabis-based medicinal products. Study record
2. Whiting PF, Wolff RF, Deshpande S, et al. Cannabinoids for Medical Use: A Systematic Review and Meta-analysis. JAMA. 2015;313(24):2456-2473. doi:10.1001/jama.2015.6358. PMID: 26103030. Study record
