Cannabis for Chronic Pain
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Summary
Cannabis for Chronic Pain: A Living Systematic Review
This work was based on a living systematic review, Living Systematic Review on Cannabis and Other Plant-Based Treatments for Chronic Pain | Effective Health Care Program (ahrq.gov), by the Evidence-based Practice Center Program at the Agency for Healthcare Research and Quality (AHRQ). Used with authors’ permission. Citation available below.
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Background
- Approximately 100 million people in the US are affected by chronic pain.
- Chronic pain is the most common reason people use cannabis for medical purposes.
- Previous reviews suggest cannabis may hold promise in treating certain subgroups of patients with chronic neuropathic pain over the short term.
- Variation in patient populations and cannabis formulations that have been studied, along with inconsistency of findings across studies has limited the certainty of the available evidence.
- As more studies examining the effects of cannabis emerge, this living systematic review will help clarify and update our understanding of the benefits and harms of cannabis for chronic pain.
Methods
Living systematic review
Search:
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Screening:
Study Selection Criteria
| PICOTS Element | Inclusion Criteria | Exclusion Criteria |
| Population | Adults (including pregnant or breastfeeding women) aged 18 years and older with chronic pain (> 12 weeks or pain persisting past the time for normal tissue healing). See categorization of specifically included pain populations below. | Children and adolescents < 18 years old; adults with acute or subacute pain; patients at end of life or in palliative care (e.g. with late-stage cancer-related pain) |
| Interventions | Cannabinoids (including synthetics) using different delivery mechanisms such as oral, buccal, inhalational, topical, or other administration routes. Co-use of other drugs for pain. | Non-plant-based interventions, capsaicin, herbal supplements |
| Comparators | Any comparator or usual care | No comparison |
| Outcomes | Primary efficacy outcomes (i.e., pain, function, disability, pain interference); harms and adverse effects (e.g., dizziness, nausea, sedation, development of cannabis use disorder); secondary outcomes (i.e., psychological distress including depression and anxiety, quality of life, opioid use, sleep quality, sleep disturbance, health care utilization) | Other outcomes |
| Time of follow-up | Short term (1 to < 6 months), intermediate term (6 to < 12 months), long term (≥ 1 year) | Studies with < 1 month of treatment or follow-up after treatment |
| Setting | Any nonhospital setting or setting of self-directed care | Hospital care, hospice care, emergency department care |
| Study design | RCTs; observational studies with a concurrent control group for harms, and to fill gaps in the evidence for benefits | Other study designs |
Abbreviations. KQ: Key Question; PICOTS: population, interventions, comparators, outcomes, timing, setting; RCT: randomized controlled trial
Data synthesis:
- Random effects meta-analyses were performed when there was sufficient homogeneity among studies.
- Risk of bias assessment:
- Cochrane Back Review Group methods for RCTs
- US Preventive Services Task Force methods for observational studies
Assessing the strength (certainty) of the body of evidence:
- AHRQ Methods Guide approach for all primary comparisons and outcomes.
- Of note, the AHRQ methods are very similar to GRADE with the following exceptions: the term strength of evidence is used rather than certainty of evidence, and the term “insufficient” evidence is used in place of the term “very low” strength (certainty) evidence.
Living systematic review:
- Updates are done quarterly
More detailed information about systematic review methods is available here.
Findings
(Searched as of October 2022)
The tables below summarize the evidence for cannabinoids for chronic pain from 21 trials. For the full results see link below.
- Treatments were grouped according to the ratio of THC to CBD and to the source of the cannabinoids (synthetic, extract, whole plant)
- Effect sizes are classified as no effect, small, moderate, or large according to methods used in other systematic reviews of chronic pain.
- Strength of evidence is indicated by plus signs, except where the effect is unclear.
Definitions of effect sizes
| Effect Size | Definition |
| Small effect | · MD 0.5 to 1.0 points on a 0 to 10-point scale, 5 to 10 points on a 0 to 100-point scale · SMD 0.2 to 0.5 · RR/OR 1.2 to 1.4 |
| Moderate effect | · MD >1 to 2 points on a 0 to10-point scale, >10 to 20 points on a 0 to 100-point scale · SMD >0.5 to 0.8 · RR/OR 1.5 to 1.9 |
| Large effect | · MD >2 points on a 0 to10-point scale, >20 points on a 0 to 100-point scale · SMD >0.8 · RR/OR ≥2.0 |
Abbreviations: MD = mean difference; OR = odds ratio; RR = relative risk; SMD = standardized mean difference.
Example interpretation:
For the outcome of pain severity: From 5 trials, a high THC oral treatment had moderate effect on the severity of pain in adults with chronic pain, and the confidence in this finding is low.
Benefits of cannabinoids for chronic pain compared with placebo in the short term (4 weeks to < 6 months)
| THC to CBD Ratio | Pain Response Effect Size (N Studies) [SOE] |
Pain Severity Effect Size (N Studies) [SOE] |
Overall Function Effect Size (N Studies) [SOE] |
| Comparable THC:CBD Oromucosal Spray |
Potential effect (4)a [+] |
Small effect (7) [++] |
Small effect (6) [++] |
| High-THC – Synthetic, Oral | Moderate effect (1) [+] |
Moderate effect (6) [+] |
No effect (3) [+] |
| High-THC – Extracted from Whole-plant, Oral | No evidence | Insufficient (2) | Insufficient (1) |
| Low-THC – Topical CBD | No evidence | Insufficient (1) | No evidence |
| Low THC – Oral CBD | No evidence | Insufficient (1) | Insufficient (1) |
| Other Cannabinoids – CBDV, Oral | Insufficient (1) | Insufficient (1) | No evidence |
| Whole Plant Cannabis (12% THC)b | No evidence | Insufficient (1) | No evidence |
Abbreviations: CBD = cannabidiol; CBDV = cannabidivarin; SOE = strength of evidence; THC = tetrahydrocannabinol.
a Potential effect: SOE of low or higher; findings indicate at least a small magnitude of effect but not statistically significant.
b Comparison was “usual care.”
Effect size: none (i.e., no effect/no statistically significant effect), small, moderate, or large increased risk; SOE: [+] = low, [++] = moderate, [+++] = high.
Harms of cannabinoids for chronic pain compared with placebo in the short term (4 weeks to < 6 months)
| THC to CBD Ratio | WAE Effect Size (N Studies) [SOE] |
SAE Effect Size (N Studies) [SOE] |
Dizziness Effect Size (N Studies) [SOE] |
Nausea Effect Size (N Studies) [SOE] |
Sedation Effect Size (N Studies) |
| Comparable THC:CBD Oromucosal Spray |
Insufficient (5) | No effect (3) [+] |
Large effect (6) [+] |
Moderate effect (6) [+] |
Large effect (6) [+] |
| High-THC – Synthetic, Oral | Potential effecta(4) [+] |
Insufficient (1) | Large effect (2) [++] |
Potential effectb (2) [+] |
Moderate effect (3) [+] |
| High-THC – Extracted From Whole-plant, Oral | Large effect (1) [+] |
Insufficient (1) | Large effect (1) [+] |
No evidence | No evidence |
| Low-THC – Topical CBD | No evidence | No evidence | No evidence | No evidence | No evidence |
| Low-THC – Oral CBD | Insufficient (1) | Insufficient (1) | No evidence | No evidence | No evidence |
| Other Cannabinoids – CBDV, oral | Insufficient (1) | Insufficient (1) | No evidence | No evidence | No evidence |
| Whole Plant Cannabis (12% THC) | Insufficient (1) | Insufficient (1) | Insufficient (1) | Insufficient (1) | Insufficient (1) |
Abbreviations: CBD = cannabidiol; CBDV = cannabidivarin; SAE = serious adverse event; SOE = strength of evidence; THC = tetrahydrocannabinol; WAE = withdrawal due to adverse event.
a potential effect: SOE of low or higher; findings indicate at least a small magnitude of effect but not statistically significant.
b Comparison was “usual care.”
Effect size: none (i.e., no effect/no statistically significant effect), small, moderate, or large increased risk; SOE: [+] = low, [++] = moderate, [+++] = high.
Conclusions
- An oromucosal spray with comparable amounts of THC and CBD probably reduces pain and improves function to a small extent in patients with neuropathic pain.
- A synthetic form of THC may reduce pain to a moderate extent.
- Compared with placebo, cannabis-related interventions resulted in greater risk of common, but not severe adverse events (e.g., dizziness, nausea, sedation), and withdrawals from studies due to adverse events.
Gaps in Evidence
- Whole plant formulations and CBD-predominant formulations remain understudied.
- No studies examined effects beyond 6 months.
- There was relatively little evidence examining the harms of many preparations in patients with chronic pain.
Chou R, Wagner J, Ahmed AY, Morasco BJ, Kansagara D, Selph S, Holmes R, Fu R. Living Systematic Review on Cannabis and Other Plant-Based Treatments for Chronic Pain: 2022 Update. Comparative Effectiveness Review No. 250. (Prepared by Pacific Northwest Evidence-based Practice Center under Contract No. 75Q80120D00006.) AHRQ Publication No. 22-EHC042. Rockville, MD: Agency for Healthcare Research and Quality; September 2022. DOI: https://doi.org/AHRQEPCCER250UPDATE2022. Posted final reports are located on the Effective Health Care Program search page.
To see this report visit: Living Systematic Review on Cannabis and Other Plant-Based Treatments for Chronic Pain | Effective Health Care Program (ahrq.gov)