Systematically Testing the Evidence on Marijuana

Cannabis as a Substitute for Opioids in Patients with Chronic Pain

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Cannabis as a Substitute for Opioids in Patients with Chronic Pain

By Benjamin J. Morasco, PhD; Devan Kansagara, MD, MCR

Opioid medications remain commonly prescribed for the treatment of chronic pain, though there is mixed evidence on their effectiveness and they are associated with an increased likelihood of adverse events. Cannabis, when used alone, does not seem to be associated with some of the same adverse effects as prescription opioids, such as overdose deaths from respiratory depression. Patients often ask whether cannabis can be used in place of prescription opioids for treatment of chronic pain. This brief summarizes what is currently known about the possibility of substituting cannabis for prescription opioids.

Population-level studies

  • Some population-level studies suggest states that permit medical cannabis have:
    • Lower mean annual opioid overdose mortality compared with states without medical cannabis laws;
    • A reduction in opioid-related deaths;
    • A reduction in opioid prescriptions funded by Medicare Part D;
    • Lower annual opioid prescribing rates for those receiving Medicaid.
  • However, a replication of this work with longer follow-up found increased rates of opioid overdose death among states that allow cannabis use, including those that permit recreational cannabis use.
  • The above studies have a primary limitation of being based on population-level data and do not track individuals over time.

Patient-level studies

  • Analysis of data from 3 randomized clinical trials provides low-certainty evidence that adding medical cannabis was not associated with a reduction in opioid use for patients with chronic cancer pain.
    • The major limitation of this work is patients enrolled in these trials were instructed not to alter their opioid doses. Although opioid doses did not markedly change, this may be due to the instructions that patients received.
  • In open-label cohort studies of patients with chronic pain and no comparison group, new use of medical cannabis has shown to have significant decreases in the use of prescription opioid medications among patients with chronic noncancer pain.
    • The findings are limited due to inconsistent results across studies and patient populations were highly selected.
  • Survey data suggest that some patients with chronic pain who receive medical cannabis report substituting cannabis for prescription opioids.

Clinical considerations

  • The cannabis use characteristics in observational studies have varied widely, and we do not have enough information to recommend cannabis as an opioid alternative, or what doses, routes of administration, or formulations could be effective.
  • A substantial proportion of recreational cannabis users also report use of cannabis for management of symptoms. We know very little about the extent that this type of “self-treatment” using cannabis is associated with reductions in prescription opioid use.
  • Approximately 20-40% of patients prescribed long-term opioid therapy for chronic pain have co-occurring cannabis use. Clinical practice guidelines do not provide recommendations about whether to taper opioids in patients with co-occurring cannabis use. Clinicians’ opinions and practice characteristics vary substantially when addressing patients with co-occurring use. When working with patients who use both prescription opioids and cannabis, it is recommended to work with the patient on goals for opioid and/or cannabis reduction and to be transparent about local health system policies regarding co-occurring use of both substances.
  • For those with opioid use disorder, first-line pharmacotherapies remain buprenorphine, methadone, or naltrexone. There is interest and ongoing research examining the use of cannabis as a treatment for opioid use disorder, but most of the evidence to date is from pre-clinical studies.

Bottom line

  • There are limited good-quality data with evidence for or against substituting prescription opioids with cannabis for the treatment of chronic pain.
  • Several ecological studies suggest decreased opioid use and opioid-related harms in states that permit medical cannabis. However, other research has found the opposite.
  • Self-report survey studies identify a substantial portion of patients who have decreased prescription opioid use after starting medical cannabis.
  • There are not good quality data from randomized trials to provide evidence in support of a clinical recommendation.
  • Results from prospective cohort studies are mixed about whether cannabis use is associated with changes in prescription opioid use.

Suggested citation: Morasco BJ, Kansagara D. Cannabis as a Substitute for Opioids in Patients with Chronic Pain. Portland, OR: The Systematically Testing the Evidence on Marijuana Project; 2021; revised March 2023. Accessed (Month DD, YYYY). https://www.cannabisevidence.org/clinician-resources/clinician-briefs/cannabis-as-a-substitute-for-opioids-in-patients-with-chronic-pain

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Citations

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Bradford AC, Bradford WD, Abraham A, Bagwell Adams G. Association between US state medical cannabis laws and opioid prescribing in the Medicare Part D population. JAMA Intern Med. 2018;178(5):667-672. doi: 10.1001/jamainternmed.2018.0266.

Campbell G, Hall WD, Peacock A, et al. Effect of cannabis use in people with chronic non-cancer pain prescribed opioids: findings from a 4-year prospective cohort study. Lancet Public Health. 2018;3(7):e341-e350. doi: 10.1016/S2468-2667(18)30110-5.

Corroon JM, Jr., Mischley LK, Sexton M. Cannabis as a substitute for prescription drugs – a cross-sectional study. J Pain Res. 2017;10:989-998. doi: 10.2147/JPR.S134330.

Kansagara D, Morasco BJ, Iacocca MO, Bair MJ, Hooker ER, Becker WC. Clinician knowledge, attitudes, and practice regarding cannabis: results from a national Veterans Health Administration survey. Pain Med. 2020;21(11):3180-3186. doi: 10.1093/pm/pnz322.

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Lucas P, Boyd S, Milloy MJ, Walsh Z. Cannabis significantly reduces the use of prescription opioids and improves quality of life in authorized patients: Results of a large prospective study. Pain Med 2021;22:727-739.

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Nguyen T, Li Y, Greene D, Stancliff S, Quackenbush N. Changes in prescribed opioid dosages among patients receiving medical cannabis for chronic pain, New York State, 2017-2019. JAMA Netw Open. 2023;6(1):e2254573. Published 2023 Jan 3. doi:10.1001/jamanetworkopen.2022.54573

Noori A, Miroshnychenko A, Shergill Y, et al. Opioid-sparing effects of medical cannabis or cannabinoids for chronic pain: a systematic review and meta-analysis of randomised and observational studies. BMJ Open. 2021;11(7):e047717. doi: 10.1136/bmjopen-2020-047717.

Okusanya BO, Asaolu IO, Ehiri JE, Kimaru LJ, Okechukwu A, Rosales C. Medical cannabis for the reduction of opioid dosage in the treatment of non-cancer chronic pain: A systematic review. Systematic Reviews 2020;9:167.

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Shover CL, Davis CS, Gordon SC, Humphreys K. Association between medical cannabis laws and opioid overdose mortality has reversed over time. Proc Natl Acad Sci U S A. 2019;116(26):12624-12626. doi: 10.1073/pnas.1903434116.

Wen H, Hockenberry JM. Association of medical and adult-use marijuana laws with opioid prescribing for Medicaid enrollees. JAMA Intern Med. 2018;178(5):673-679. doi: 10.1001/jamainternmed.2018.1007.