Medical Cannabis: An Antidote to the Opioid Epidemic?
In the absence of a few basic statistics, the significance of the opioid epidemic in the United States can be easily underappreciated. In 2015, the most recent year for which the Centers for Disease Control and Prevention (CDC) has published data, over 2 million Americans aged 12 years or older had a substance use disorder involving prescription pain-relievers. This estimate increases to 2.5 million when non-prescription opioids are included.1
Why would non-prescription opioids be included? Almost 80% of heroin users report having used prescription opioids before initiating heroin use.2 And often these individuals have their opioid prescriptions discontinued by concerned physicians after dependence has developed. In a 2014 survey, 94% of respondents reported that they decided to use heroin because prescription opioids were “far more expensive and harder to obtain.”3
In 2015, more than a thousand Americans were treated in emergency departments each day across the country for misusing prescription opioids. That’s more than 365 000 visits for the year. Death by a prescription drug is the #1 cause of accidental death in the United States.4 In 2015, drug overdoses accounted for 52 404 deaths. More than 63% involved an opioid, and more than 15 000 of these deaths involved a prescription opioid.5 Put another way, 91 Americans died each day from an opioid overdose in 2015, 44 of whom died from a prescription opoid.1 In the 17-year period from 1999-2015, the opioid overdose mortality rate, and sales of prescription opioids, increased by 500%, while the prevalence of Americans reporting chronic pain remained stable.6,7
In an effort to address this issue, the CDC issued new guidelines for opioid prescribing in March of this year.8
So, what does this have to do with cannabis?
In a comprehensive 2017 report entitled “The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research,” the Health and Medicine Division of the National Academies of Sciences, Engineering and Medicine stated, “There is conclusive or substantial evidence that cannabis or cannabinoids are effective…for the treatment of chronic pain in adults.”9
According to a multitude of surveys, the most common medical reason for using cannabis or cannabinoids (compounds contained in the cannabis plant) is chronic pain.10,11 Survey respondents report that cannabis use is an effective means of managing their pain, both as a solo therapy10 and as an adjunctive therapy when combined with opioids.12,13 They also report substituting cannabis for prescription opioids11,14,15 and reducing their dose of opioids, thereby experiencing a reduction in the associated side effects while also reporting a higher quality of life.13,15
Ecologic data offers a different perspective with a similar conclusion. Studies using state-level data suggest that fewer opioids are prescribed in states with legal access to medical cannabis. A study published in the journal Health Affairs in 2016, using data from Medicare Part D, found that implementing an effective medical cannabis law led to a reduction of 1826 daily doses of opioids filled per physician per year from 2010 to 2013.16 This reduction in prescribing patterns was subsequently corroborated by the same authors in 2017, using Medicaid data from 2007 to 2014.17 The authors speculated that a savings of $1.01 billion might be realized in 2014 if all US states had medical marijuana laws. (It should be noted that the cost of the cannabis was not included in the analysis.) A different study found 23% and 13% fewer opioid abuse-related and opioid overdose-related hospitalizations, respectively, in states with legal access.18 Finally, a third study showed that the opioid mortality rate was almost 25% lower in states with legal access to medical cannabis.19 This reduced rate appears to continue to decline in years subsequent to the passage of medical cannabis laws.
Human clinical trial data also suggest that cannabinoids are effective pain relievers,20,9,21 and that additive analgesia is achieved when cannabinoids are combined with opioids.22 An open-label study published in 2016 found that individuals with treatment-resistant chronic pain reported improvements in pain and pain-related quality-of-life scores with the addition of cannabinoids to their opioid regimen.12 Forty-four percent of subjects in the study discontinued their opioids entirely. Other studies have demonstrated that cannabinoids may delay or prevent the development of opioid tolerance and rekindle opioid analgesia after a prior dosage has become ineffective.
In addition, cannabinoids are extremely safe. In 2015, more than 33 000 Americans died of an opioid overdose. The number of people who died that year of a cannabis overdose was…zero. A systematic review of 31 studies (23 randomized controlled trials and 8 observational studies) found that 96.6% of adverse effects were “not serious.”23 This safety profile is clearly superior to that of opioids, as well as the drugs used to treat opioid addition (eg, methadone, buprenorphine). Respiratory suppression, the most common cause of opioid overdose death,24 is not a risk associated with high-dose cannabis use because there are few cannabinoid receptors located in the cardio-respiratory centers of the brainstem.25,26 Furthermore, concurrent use of cannabinoids and opioids does not appear to increase the risk of serious adverse effects or death when compared to using opioids alone.27 And, unlike opioid withdrawal, cannabis withdrawal is typically mild, short in duration, and self-limited.28 Most people who stop using cannabinoids do so without formal treatment.
Cannabinoids for Opioid Withdrawal
Anecdotal evidence suggests that cannabinoids may effectively treat symptoms of opioid withdrawal (eg, nausea, vomiting, diarrhea, cramping, muscle spasms, anxiety, agitation, restlessness, insomnia). Cannabidiol (CBD), in particular, may hold the greatest potential in treating opioid use disorders due to its non-rewarding and anxiolytic effects. Anxiety is one of the key drivers of addiction and relapse, and CBD has been shown to reduce anxiety in clinical trials involving healthy subjects and those with social anxiety disorders.29
Preclinical experimental models have shown that CBD reduces the rewarding properties of opioids and reduces heroin-seeking behavior.30,31 A small double-blind pilot study of opioid-dependent humans found that a single dose of CBD led to a decrease in general craving 24 hours later. This effect persisted 7 days after the last treatment. Reductions in anxiety were also observed.31 Clearly, more clinical trials are needed, but these data suggest a plausible role for CBD and perhaps other cannabinoids in the treatment of opioid use disorders.
The morbidity and mortality associated with the current opioid epidemic is staggering: 2.5 million Americans in 2015 were diagnosed with a substance-use disorder involving an opioid, and over 33 000 Americans died of an opioid overdose in that same year. This epidemic is a complex problem requiring a variety of solutions. While widespread adoption of cannabis for pain management is no silver bullet, it is an emerging therapy supported by different methodologies in scientific research, with more on the way. This research not only supports its efficacy as an analgesic, but also its safety, especially when compared to opioids and even non-opioid pharmacological medications. It is entirely possible that this plant, which has long been deemed a threat to public health, might actually be an important part of the solution to one of the most pressing public health crises of our time.
- Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain — United States, 2016. JAMA. 2016;315(15):1624-1645.
- National Academies of Sciences, Engineering, Medicine. Report: The Health Effects of Cannabis and Cannabinoids. Washington, DC: National Academies Press; 2017. Available at: . Accessed July 31, 2017.
- Sexton M, Cuttler C, Finnell JS, Mischley LK. A Cross-Sectional Survey of Medical Cannabis Users: Patterns of Use and Perceived Efficacy. Cannabis Cannabinoid Res. 2016;1(1):131-138.
- Lucas P, Walsh Z. Medical cannabis access, use, and substitution for prescription opioids and other substances: A survey of authorized medical cannabis patients. Int J Drug Policy. 2017;42:30-35.
- Haroutounian S, Ratz Y, Ginosar Y, et al. The Effect of Medicinal Cannabis on Pain and Quality of Life Outcomes in Chronic Pain: A Prospective Open-label Study. Clin J Pain. 2016;32(12):1036-1043.
- Boehnke KF, Litinas E, Clauw DJ. Medical cannabis associated with decreased opiate medication use in retrospective cross-sectional survey of chronic pain patients. J Pain. 2016;17(6):1-6.
- Corroon JM, Mischley LK, Sexton M. Cannabis as a substitute for prescription drugs – a cross-sectional study. J Pain Res. 2017;10:989-998.
- Reiman A, Welty M, Solomon P. Cannabis as a Substitute for Opioid-Based Pain Medication: Patient Self-Report. Cannabis Cannabinoid Res. 2017;2(1):160-166.
- Bradford AC, Bradford WD. Medical marijuana laws reduce prescription medication use in medicare part D. Health Aff. 2016;35(7):1230-1236.
- Bradford AC, Bradford WD. Medical Marijuana Laws May Be Associated With A Decline In The Number Of Prescriptions For Medicaid Enrollees. Health Aff (Millwood). 2017;36(5):945-951.
- Shi Y. Medical marijuana policies and hospitalizations related to marijuana and opioid pain reliever. Drug Alcohol Depend. 2017;173:144-150.
- Bachhuber MA, Saloner B, Cunningham CO, Barry CL. Medical cannabis laws and opioid analgesic overdose mortality in the United States, 1999-2010. JAMA Intern Med. 2014;174(10):1668-1673.
- Lynch ME, Ware MA. Cannabinoids for the Treatment of Chronic Non-Cancer Pain: An Updated Systematic Review of Randomized Controlled Trials. J Neuroimmune Pharmacol. 2015;10(2):293-301.
- Ware MA, Wang T, Shapiro S, et al. Smoked cannabis for chronic neuropathic pain: a randomized controlled trial. Can Med Assoc J. 2010;182(14):E694-E701.
- Abrams DI, Couey P, Shade SB, et al. Cannabinoid-opioid interaction in chronic pain. Clin Pharmacol Ther. 2011;90(6):844-851.
- Wang T, Collet JP, Shapiro S, Ware MA. Adverse effects of medical cannabinoids: a systematic review. Can Med Assoc J. 2008;178(13):1669-1678.
- Stolbach A, Hoffman RS. Acute opioid intoxication in adults. Last updated August 21, 2017. UpToDate. Available at: https://www.uptodate.com/contents/acute-opioid-intoxication-in-adults?source=search_result&search=opioid overdose&selectedTitle=1~146#H22. Accessed August 31, 2017.
- Glass M, Dragunow M, Faull RL. Cannabinoid receptors in the human brain: a detailed anatomical and quantitative autoradiographic study in the fetal, neonatal and adult human brain. Neuroscience. 1997;77(2):299-318.
- Herkenham M, Lynn AB, Litrle MD, et al. Cannabinoid receptor localization in brain. Neurobiology. 1990;87(5):1932-1936.
- Ware MA, Wang T, Shapiro S, et al. Cannabis for the Management of Pain: Assessment of Safety Study (COMPASS). J Pain. 2015;16(12):1233-1242.
- Budney AJ, Hughes JR. The cannabis withdrawal syndrome. Curr Opin Psychiatry. 2006;19(3):233-238.
- Blessing EM, Steenkamp MM, Manzanares J, Marmar CR. Cannabidiol as a Potential Treatment for Anxiety Disorders. Neurotherapeutics. 2015;12(4):825-836.
- Hine B, Torrelio M, Gershon S. Differential effect of cannabinol and cannabidiol on THC-induced responses during abstinence in morphine-dependent rats. Res Commun Chem Pathol Pharmacol. 1975;12(1):185-188.
- Ren Y, Whittard J, Higuera-Matas A, Morris C V, Hurd YL. Cannabidiol, a nonpsychotropic component of cannabis, inhibits cue-induced heroin seeking and normalizes discrete mesolimbic neuronal disturbances. J Neurosci. 2009;29(47):14764-14769.