Cannabis for Chronic Pain

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Surveillance

April 2022
September 2022
January 2023
April 2023

Visual Abstract

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 medical reason people use cannabis.
  • 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: 

  • Ovid MEDLINE
  • PsycINFO
  • Embase
  • Cochrane Library
  • SCOPUS

Screening:

Study Selection Criteria

PICOTS Element Inclusion Criteria Exclusion Criteria
Population Adults (including pregnant or breastfeeding women) and adolescents with subacute (lasting 4-12 weeks) or chronic pain (> 12 weeks or pain persisting past the time for normal tissue healing). See categorization of specifically included pain populations below. Children; adults with acute 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 early July 2023)

    The tables below summarize the evidence for cannabinoids for chronic pain from 23 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 or extracted from 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 7 trials, a synthetic high THC oral treatment had a small 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 Responsea
    Effect Size (N Studies)
    [SOE]
    Pain Severity
    Effect Size (N Studies)
    [SOE]
    Overall Function
    Effect Size (N Studies)
    [SOE]
    Comparable THC to CBD – Oromucosal spray, whole plant extract

    Potential effectb (4)

    [+]

    Small effect (7)

    [++]

    Small effect (6)

    [++]

    High THC – Oral, synthetic

    Insufficient (2)

     

    Small effect (7)

    [+]

    No effect (4)

    [+]

    High THC – Oral, whole plant extract No evidence Insufficient (2) Insufficient (1)
    Low THC – Topical CBD, whole plant extract No evidence Insufficient (1) No evidence
    Low THC – Oral CBD, synthetic No evidence Insufficient (1) Insufficient (1)
    Low THC – Oral CBD or CBD/THC, Unclear origin Insufficient (1) Insufficient (1) Insufficient (1)
    Low THC – Sublingual CBD/THC, whole plant extract No evidence Insufficient (1) No evidence
    Other Cannabinoids – CBDV, Oral Insufficient (1) Insufficient (1) No evidence
    Whole-Plant Cannabis (12% THC)c No evidence Insufficient (1) No evidence

    Abbreviations: CBD = cannabidiol; CBDV = cannabidivarin; SOE = strength of evidence; THC = tetrahydrocannabinol.
    a  ≥30% improvement from baseline.
    b Potential effect: SOE of low or higher; findings indicate at least a small magnitude of effect but not statistically significant.
    cComparison 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)
    [SOE]

    Comparable THC to CBD – Oromucosal spray, whole plant extract

    No effect (5)

    [+]

    No effect (3)

    [+]

    Large effect (6)

    [+]

    Moderate effect (6)

    [+]

    Large effect (6)

    [+]

    High THC – Oral, synthetic

    Potential effecta (5)

    [+]

    Insufficient (1)

    Large effect (3)

    [++]

    Potential effecta (3)

    [+]

    Moderate effect (4)

    [+]

    High THC – Oral, whole plant extract

    Large effect (1)

    [+]

    Insufficient (1)

    Large effect (1)

    [+]

    No evidence No evidence
    Low THC – Topical CBD, whole plant extract No evidence No evidence No evidence No evidence No evidence
    Low THC – Oral CBD, synthetic Insufficient (1) Insufficient (1) No evidence No evidence No evidence
    Low THC – Oral CBD or CBD/THC, Unclear origin Insufficient (1) Insufficient (1) Insufficient (1) Insufficient (1) Insufficient (1)

    Low THC – Sublingual

    CBD/THC, whole plant extract

    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)b 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 adult patients with neuropathic pain.
    • 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.
    • No studies were included that examined the evidence among children or adolescents.
    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.

    Chou R, Ahmed AY, Bougatsos C, Morasco BJ, Dana T, Fu R. Living Systematic Review on Cannabis and Other Plant-Based Treatments for Chronic Pain: 2023 Update—Surveillance Report 1. (Prepared by the Pacific Northwest Evidence-based Practice Center under Contract No. 75Q80120D00006.) AHRQ Publication No. 23-EHC032. Rockville, MD: Agency for Healthcare Research and Quality; September 2023. DOI: https://doi.org/10.23970/AHRQEPCCER250.2023UPDATESR1. 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)