Department of Psychiatry and Behavioral Sciences Johns Hopkins University School of Medicine 1 What is the Evidence for an OpioidSparing Effect of Cannabis Assistant Professor Patrick H Finan PhD ID: 766333
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Department of Psychiatry and Behavioral SciencesJohns Hopkins University School of Medicine 1 What is the Evidence for an Opioid-Sparing Effect of Cannabis? Assistant Professor Patrick H. Finan, Ph.D
DisclosuresNone 2
Why are we interested in opioid-sparing?Opioids commonly prescribed for acute pain, e.g., post-surgeryA significant portion of these patients go on to chronic opioid therapy10-22% patients transition from perioperative pain to chronic pain (Lavand’homme, 2018)A single perioperative opioid prescription in tooth extraction patients was associated with 2.7 OR for later chronic opioid use (Harbaugh et al., 2018)3 Compton et al., 2016, NEJM
Rates of Problematic Opioid UseMisuse: 21-29%Abuse: Not enough dataAddiction: 8-12%4
Cost/Benefit: How well do opioids work for chronic pain in the long run?Short answer: Insufficient EvidenceChou et al., 2015, Ann. Int. Med.
Why don’t we just take patients off of chronic opioids?Darnall et al. (2018) voluntary opioid taper (N=82)38% drop outOf completers, <50% median MEU reduction (288 to 150)Pain didn’t significantly change (p = .29) Darnall et al., 2018, JAMA Int. Med.
Search for Non-Opioid Treatments for Chronic PainWidespread effort to identify and test non-opioid treatments for chronic painWidespread interest in “opioid sparing”: treatments that prevent the need for opioids or directly reduce dose and/or frequency of use7
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Cannabinoids and Chronic Pain2 very recent meta-analyses from respected groupsMucke, Radbruch, & Hauser, 2018, Cochrane ReviewsStockings…& Degenhardt, 2018, PainInclusive of multiple pain conditions, multiple study designs, multiple cannabinoid agentsSame general conclusionsStudies to date have been of generally low quality with high heterogeneity and small samplesThe potential harms may outweigh the potential benefits9
Mucke et al. (2018): Chronic Neuropathic Pain10
Stockings et al. (2018): Chronic Non-Cancer Pain47 RCTs and 57 Observational Studies30% Reduction in Pain8 RCTs OR 1.46 (95%CI 1.16-1.84)50% Reduction in Pain5 RCTsOR 1.43 (95%CI 0.97-2.11)11 Change in Pain Intensity 30 RCTs SMD -.14 (95%CI -.20 to -.08)Change in pain = 3/100 greater than placebo Adverse Events OR 2.22 (95%CI 1.60-3.01)
Are Cannabinoids “Opioid-Sparing”?“Opioid-sparing medications, when co-administered with opioids, enable a reduced opioid dose without loss of analgesic efficacy.” Nielsen et al., 2017What if opioids are not efficacious to begin with?Darnall et al. (2018) showed opioid dose reduction via taper with no co-administered medication and pain did not change12
Preclinical Evidence for Cannabinoid and Opioid SynergyCommon receptor co-expression in primary pain-related neural circuitryShared intracellular signaling mechanismsCannabinoids potentiate release of endogenous opioidsCannabinoid antagonists reverse opioid-induced antinociception**Morphine Effective Dose 3.6 times lower when cannabinoid co-administeredNielsen et al., 2017, Neuropsychopharmacology13
Observational Studies14*Participants incentivized with vaporizer! *Participants recruited from dispensary
Epidemiological Evidence**In 2010, 1729 fewer opioid overdose deaths than expected in states with medical marijuana laws15
More Epidemiological EvidenceMedical Marijuana Laws associated with:Fewer opioid prescription refills (Bradford &Bradford, 2016)Fewer opioid-positive tests in young, fatally-injured drivers (Kim et al., 2016)Fewer prescription opioid-related hospitalizations (Shi, 2017)Stronger effects 3-5 years after implementation, and with greater access to dispensaries (Powell et al., 2018)16
But, also this epidemiological evidence…17
Direct Tests of “Opioid Sparing” Effect of Cannabinoids in HumansOnly 6 randomized, controlled studies; only 2 showed significant reduction in opioid dose providing analgesia (Narang et al., 2008; Cooper et al., 2018)Cooper et al., 201818
Do Cannabinoids Improve Opioid Withdrawal Symptoms?*High dose dronabinol (40mg) was poorly tolerated and reduced after 2 subjects—typical starting dose per FDA is 2.5mg19 Jicha et al., 2015Lofwall et al., 2016
SummaryResults from studies investigating cannabis’ effects on opioid use and pain are inconclusiveLarger, better quality studies are neededGreater focus on replication is neededGreater clarity is needed in defining and assessing ‘opioid sparing’ effects20
AcknowledgmentsCurrent Fellows: Janelle Letzen, Ph.D., Chung-Jung Mun, Ph.D.Mentors: Michael Smith, Ph.D.; Jennifer Haythornthwaite, Ph.D.; Eric Strain, M.D.; Una McCann, M.D.; Diego Pizzagalli, Ph.D.; Roy Wise, Ph.D.; Bob Kerns, Ph.D.; Mary Davis, Ph.D.; Howard Tennen, Ph.D.; and Alex Zautra, Ph.D.BMRL Research Staff: Jim Stone, Emily Burton, Alex Kearson, Brook Fulton, Jean-Michel Tremblay, Ph.D., Brandon Boring, Julia Gajewski-NemesBMRL Alumni: Bethany Remeniuk, Ph.D., Sheera Lerman-Zohar, Ph.D., Jessica Richards, Ph.D.21 Support: K23DA035915 (P Finan, PI)R01DA035246 (K Dunn, PI)Johns Hopkins Blaustein Pain Research Grant (P Finan, PI)JHU ICTR/CISRE