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Cannabis in Pain Treatment: Clinical and Research Considerations

      Highlights

      • Twenty-three U.S. states permit cannabis for clinical use but it remains illegal under federal law.
      • Cannabis strains have variable content of >100 different cannabinoids.
      • U.S. regulatory hurdles result in most cannabis research being done elsewhere.
      • Cannabidiol may be anti-inflammatory, anxiolytic, and anti-seizure with no euphoria.
      • Cannabis addiction develops in approximately 9% of nonmedical users.

      Abstract

      Cannabinoids show promise as therapeutic agents, particularly as analgesics, but their development and clinical use has been complicated by recognition of their botanical source, cannabis, as a substance of misuse. Although research into endogenous cannabinoid systems and potential cannabinoid pharmaceuticals is slowly increasing, there has been intense societal interest in making herbal (plant) cannabis available for medicinal use; 23 U.S. States and all Canadian provinces currently permit use in some clinical contexts. Whether or not individual professionals support the clinical use of herbal cannabis, all clinicians will encounter patients who elect to use it and therefore need to be prepared to advise them on cannabis-related clinical issues despite limited evidence to guide care. Expanded research on cannabis is needed to better determine the individual and public health effects of increasing use of herbal cannabis and to advance understanding of the pharmaceutical potential of cannabinoids as medications. This article reviews clinical, research, and policy issues related to herbal cannabis to support clinicians in thoughtfully advising and caring for patients who use cannabis, and it examines obstacles and opportunities to expand research on the health effects of herbal cannabis and cannabinoids.

      Perspective

      Herbal cannabis is increasingly available for clinical use in the United States despite continuing controversies over its efficacy and safety. This article explores important considerations in the use of plant Cannabis to better prepare clinicians to care for patients who use it, and identifies needed directions for research.

      Key words

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      References

        • Abrams D.I.
        • Couey P.
        • Shade S.B.
        • Kelly M.E.
        • Benowitz N.L.
        Cannabinoid-opioid interaction in chronic pain.
        Clin Pharmacol Ther. 2011; 90: 844-851
        • Abrams D.I.
        • Jay C.A.
        • Shade S.B.
        • Vizoso H.
        • Reda H.
        • Press S.
        • Kelly M.E.
        • Rowbotham M.C.
        • Petersen K.L.
        Cannabis in painful HIV-associated sensory neuropathy: A randomized placebo-controlled trial.
        Neurology. 2007; 68: 515-521
        • Adashi E.Y.
        • Kocher R.P.
        Physician self-referral: Regulation by exceptions.
        JAMA. 2015; 313: 457-458
      1. American Medical Association: H-95.952 Cannabis for Medicinal Use. Available at: https://www.ama-assn.org/ssl3/ecomm/PolicyFinderForm.pl?site=www.ama-assn.org&uri=/resources/html/PolicyFinder/policyfiles/HnE/H-95.952.HTM. Accessed January 14, 2016

      2. American Medical Association: Opinion 8.08 Informed Consent. Available at: http://www.ama-assn.org/ama/pub/physician-resources/medical-ethics/code-medical-ethics/opinion808.page. Accessed July 21, 2015

        • Andreae M.H.
        • Carter G.M.
        • Shaparin N.
        • Suslov K.
        • Ellis R.J.
        • Ware M.A.
        • Abrams D.I.
        • Prasad H.
        • Wilsey B.
        • Indyk D.
        • Johnson M.
        • Sacks H.S.
        Inhaled cannabis for chronic neuropathic pain: A meta-analysis of individual patient data.
        J Pain. 2015; 16: 1221-1232
        • Anthony J.C.
        The epidemiology of cannabis dependence.
        in: Roffman R.A. Stephens R.S. Cannabis Dependence: Its Nature, Consequences and Treatment. Cambridge University Press, Cambridge2006: 58-105
      3. Arizona Department of Health Services. University of Arizona, College of Public Health: Contract No: ADHS12–017291. Report to Arizona Department of Health Services: First Annual Medical Marijuana Report A.R.S. §36-2809. Available at: http://archive.azcentral.com/ic/pdf/MM-annual-final-report.pdf. Accessed March 28, 2015

        • Asbridge M.
        • Hayden J.A.
        • Cartwright J.L.
        Acute cannabis consumption and motor vehicle collision risk: Systematic review of observational studies and meta-analysis.
        BMJ. 2012; 344: e536
      4. Azcentral. Billeaud J: 24 Doctors certify most in Ariz.'s pot program. Available at: http://www.azcentral.com/news/free/20121109arizona-marijuana-program-doctors.html. Accessed July 21, 2015

        • Bachhuber M.A.
        • Saloner B.
        • Cunningham C.O.
        • Barry C.L.
        Medical cannabis laws and opioid analgesic overdose mortality in the United States, 1999-2010.
        JAMA Intern Med. 2014; 174: 1668-1673
        • Bakheit A.M.
        The pharmacological management of post-stroke muscle spasticity.
        Drugs Aging. 2012; 29: 941-947
      5. Beaver WT, Buring J, Goldstein A, Johnson K, Jones R, Kris MC, Mooney K, Palmberg P, Phair J: Report to the Director, National Institutes of Health. Available at: http://www.sky.org/data/laaketiede/MedicalMJ.html. Accessed July 21, 2015

        • Blake D.R.
        • Robson P.
        • Ho M.
        • Jubb R.W.
        • McCabe C.S.
        Preliminary assessment of the efficacy, tolerability and safety of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis.
        Rheumatology (Oxford). 2006; 45: 50-52
      6. Bureau voor Medicinale Cannabis [Office for Medicinal Cannabis]: Available at: https://www.cannabisbureau.nl/english. Accessed July 21, 2015

        • Burns T.L.
        • Ineck J.R.
        Cannabinoid analgesia as a potential new therapeutic option in the treatment of chronic pain.
        Ann Pharmacother. 2006; 40: 251-260
        • Cerda M.
        • Wall M.
        • Keyes K.M.
        • Galea S.
        • Hasin D.
        Medical marijuana laws in 50 states: Investigating the relationship between state legalization of medical marijuana and marijuana use, abuse and dependence.
        Drug Alcohol Depend. 2012; 120: 22-27
      7. ClinicalTrials.gov. Available at: https://clinicaltrials.gov. Accessed March 29, 2016

      8. ClinicalTrials.gov: Vaporized Cannabis and Spinal Cord Injury Pain. Available at: https://clinicaltrials.gov/ct2/show/NCT01555983. Accessed July 21, 2015

        • Cohen P.J.
        Medical marijuana: The conflict between scientific evidence and political ideology. Part one of two.
        J Pain Palliat Care Pharmacother. 2009; 23: 4-25
        • Cohen P.J.
        Medical marijuana: The conflict between scientific evidence and political ideology. Part two of two.
        J Pain Palliat Care Pharmacother. 2009; 23: 120-140
      9. Colorado Department of Public Health & Environment: Approved medical marijuana research grants. Available at: https://www.colorado.gov/pacific/cdphe/approved-medical-marijuana-research-grants. Accessed July 21, 2015

      10. Congressional Research Service. CRS Report for Congress. Eddy M: Medical Marijuana: Review and Analysis of Federal and State Policies. Available at: http://fas.org/sgp/crs/misc/RL33211.pdf. Accessed March 28, 2015

        • Cooper Z.D.
        • Comer S.D.
        • Haney M.
        Comparison of the analgesic effects of dronabinol and smoked marijuana in daily marijuana smokers.
        Neuropsychopharmacology. 2013; 38: 1984-1992
        • Crean R.D.
        • Tapert S.F.
        • Minassian A.
        • Macdonald K.
        • Crane N.A.
        • Mason B.J.
        Effects of chronic, heavy cannabis use on executive functions.
        J Addict Med. 2011; 5: 9-15
        • Cridge B.J.
        • Rosengren R.J.
        Critical appraisal of the potential use of cannabinoids in cancer management.
        Cancer Manag Res. 2013; 5: 301-313
        • Eisenberg E.
        • Ogintz M.
        • Almog S.
        The pharmacokinetics, efficacy, safety, and ease of use of a novel portable metered-dose cannabis inhaler in patients with chronic neuropathic pain: a phase 1a study.
        J Pain Palliat Care Pharmacother. 2014; 28: 216-225
        • Ellis R.J.
        • Toperoff W.
        • Vaida F.
        • van den Brande G.
        • Gonzales J.
        • Gouaux B.
        • Bentley H.
        • Atkinson J.H.
        Smoked medicinal cannabis for neuropathic pain in HIV: A randomized, crossover clinical trial.
        Neuropsychopharmacology. 2009; 34: 672-680
      11. ElSohly MA: National Institute on Drug Abuse, Quarterly Report: Potency Monitoring Project. Available at: https://www.ncjrs.gov/pdffiles1/ondcp/mpmp_report_104.pdf. Accessed March 28, 2015

        • Finkelman M.D.
        • Kulich R.J.
        • Zacharoff K.L.
        • Smits N.
        • Magnuson B.E.
        • Dong J.
        • Butler S.F.
        Shortening the Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R): A proof-of-principle study for customized computer-based testing.
        Pain Med. 2015; 16: 2344-2356
        • Farrimond J.A.
        • Mercier M.S.
        • Whalley B.J.
        • Williams C.M.
        Cannabis sativa and the endogenous cannabinoid system: Therapeutic potential for appetite regulation.
        Phytother Res. 2011; 25: 170-188
        • Gertsch J.
        • Pertwee R.G.
        • Di Marzo V.
        Phytocannabinoids beyond the Cannabis plant - do they exist?.
        Br J Pharmacol. 2010; 160: 523-529
        • Gourlay D.L.
        • Heit H.A.
        • Almahrezi A.
        Universal precautions in pain medicine: A rational approach to the treatment of chronic pain.
        Pain Med. 2005; 6: 107-112
        • Grotenhermen F.
        Pharmacokinetics and pharmacodynamics of cannabinoids.
        Clin Pharmacokinet. 2003; 42: 327-360
        • Guindon J.
        • Hohmann A.G.
        The endocannabinoid system and pain.
        CNS Neurol Disord Drug Targets. 2009; 8: 403-421
        • Hartman R.L.
        • Huestis M.A.
        Cannabis effects on driving skills.
        Clin Chem. 2013; 59: 478-492
        • Hazekamp A.
        • Ruhaak R.
        • Zuurman L.
        • van Gerven J.
        • Verpoorte R.
        Evaluation of a vaporizing device (Volcano) for the pulmonary administration of tetrahydrocannabinol.
        J Pharm Sci. 2006; 95: 1308-1317
      12. Health Canada: Licensed Producers. Available at: http://www.hc-sc.gc.ca/dhp-mps/marihuana/info/index-eng.php. Accessed July 21, 2015

        • Hunault C.C.
        • Bocker K.B.
        • Stellato R.K.
        • Kenemans J.L.
        • de Vries I.
        • Meulenbelt J.
        Acute subjective effects after smoking joints containing up to 69 mg Delta9-tetrahydrocannabinol in recreational users: A randomized, crossover clinical trial.
        Psychopharmacology (Berl). 2014; 231: 4723-4733
        • Issa M.A.
        • Narang S.
        • Jamison R.N.
        • Michna E.
        • Edwards R.R.
        • Penetar D.M.
        • Wasan A.D.
        The subjective psychoactive effects of oral dronabinol studied in a randomized, controlled crossover clinical trial for pain.
        Clin J Pain. 2014; 30: 472-478
        • Jaques S.C.
        • Kingsbury A.
        • Henshcke P.
        • Chomchai C.
        • Clews S.
        • Falconer J.
        • Abdel-Latif M.E.
        • Feller J.M.
        • Oei J.L.
        Cannabis, the pregnant woman and her child: Weeding out the myths.
        J Perinatol. 2014; 34: 417-424
        • Joshi M.
        • Joshi A.
        • Bartter T.
        Marijuana and lung diseases.
        Curr Opin Pulm Med. 2014; 20: 173-179
        • Joy J.E.
        • Watson Jr., S.J.
        • Benson Jr., J.A.
        Marijuana and Medicine: Assessing the Science Base.
        National Academies Press, Washington, D.C.1999
        • Kedzior K.K.
        • Laeber L.T.
        A positive association between anxiety disorders and cannabis use or cannabis use disorders in the general population–a meta-analysis of 31 studies.
        BMC Psychiatry. 2014; 14: 136
        • Kondrad E.
        • Reid A.
        Colorado family physicians' attitudes toward medical marijuana.
        J Am Board Fam Med. 2013; 26: 52-60
        • Koppel B.S.
        • Brust J.C.
        • Fife T.
        • Bronstein J.
        • Youssof S.
        • Gronseth G.
        • Gloss D.
        Systematic review: Efficacy and safety of medical marijuana in selected neurologic disorders: Report of the Guideline Development Subcommittee of the American Academy of Neurology.
        Neurology. 2014; 82: 1556-1563
        • Kupfer D.J.
        • Detre T.
        • Koral J.
        • Fajans P.
        A comment on the “amotivational syndrome” in marijuana smokers.
        Am J Psychiatry. 1973; 130: 1319-1322
        • Lee D.
        • Karschner E.L.
        • Milman G.
        • Barnes A.J.
        • Goodwin R.S.
        • Huestis M.A.
        Can oral fluid cannabinoid testing monitor medication compliance and/or cannabis smoking during oral THC and oromucosal Sativex administration?.
        Drug Alcohol Depend. 2013; 130: 68-76
        • Lee M.H.
        • Hancox R.J.
        Effects of smoking cannabis on lung function.
        Expert Rev Respir Med. 2011; 5 (quiz: 547): 537-546
        • Le Strat Y.
        • Dubertret C.
        • Le Foll B.
        Impact of age at onset of cannabis use on cannabis dependence and driving under the influence in the United States.
        Accid Anal Prev. 2015; 76: 1-5
        • Li M.C.
        • Brady J.E.
        • DiMaggio C.J.
        • Lusardi A.R.
        • Tzong K.Y.
        • Li G.
        Marijuana use and motor vehicle crashes.
        Epidemiol Rev. 2012; 34: 65-72
        • Lopez-Quintero C.
        • Perez de los Cobos J.
        • Hasin D.S.
        • Okuda M.
        • Wang S.
        • Grant B.F.
        • Blanco C.
        Probability and predictors of transition from first use to dependence on nicotine, alcohol, cannabis, and cocaine: Results of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC).
        Drug Alcohol Depend. 2011; 115: 120-130
        • Lubman D.I.
        • Cheetham A.
        • Yucel M.
        Cannabis and adolescent brain development.
        Pharmacol Ther. 2015; 148: 1-16
        • Lynch M.E.
        • Campbell F.
        Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials.
        Br J Clin Pharmacol. 2011; 72: 735-744
        • Lynch M.E.
        • Ware M.A.
        Cannabinoids for the treatment of chronic non-cancer pain: An updated systematic review of randomized controlled trials.
        J Neuroimmune Pharmacol. 2015; 10: 293-301
        • Machado Rocha F.C.
        • Stefano S.C.
        • De Cassia Haiek R.
        • Rosa Oliveira L.M.
        • Da Silveira D.X.
        Therapeutic use of Cannabis sativa on chemotherapy-induced nausea and vomiting among cancer patients: Systematic review and meta-analysis.
        Eur J Cancer Care (Engl). 2008; 17: 431-443
      13. Marijuana Policy Project: State Policy. Available at: http://www.mpp.org/states. Accessed July 21, 2015

        • McGeeney B.E.
        Cannabinoids and hallucinogens for headache.
        Headache. 2013; 53: 447-458
        • Mechoulam R.
        • Devane W.A.
        • Breuer A.
        • Zahalka J.
        A random walk through a cannabis field.
        Pharmacol Biochem Behav. 1991; 40: 461-464
        • Mehmedic Z.
        • Chandra S.
        • Slade D.
        • Denham H.
        • Foster S.
        • Patel A.S.
        • Ross S.A.
        • Khan I.A.
        • ElSohly M.A.
        Potency trends of Delta9-THC and other cannabinoids in confiscated cannabis preparations from 1993 to 2008.
        J Forensic Sci. 2010; 55: 1209-1217
        • Naftali T.
        • Mechulam R.
        • Lev L.B.
        • Konikoff F.M.
        Cannabis for inflammatory bowel disease.
        Dig Dis. 2014; 32: 468-474
      14. National Institutes of Health. Department of Health and Human Services: Notice of Availability of Additional Marijuana Strains through NIDA's Drug Supply Program. Available at: http://grants.nih.gov/grants/guide/notice-files/NOT-DA-15-064.html. Accessed July 21, 2015

      15. National Medical Marijuana Growers Association: About Us. Available at: http://www.medicalmarijuanagrowersassociation.org/#/about-us/4579354785. Accessed July 21, 2015

      16. NIH. National Institute on Drug Abuse: NIDA Research on the Therapeutic Benefits of Cannabis and Cannabinoids. Available at: http://www.drugabuse.gov/drugs-abuse/marijuana/nida-research-therapeutic-benefits-cannabis-cannabinoids. Accessed July 21, 2015

        • O'Connell T.J.
        • Bou-Matar C.B.
        Long-term marijuana users seeking medical cannabis in California (2001-2007): Demographics, social characteristics, patterns of cannabis and other drug use of 4117 applicants.
        Harm Reduct J. 2007; 4: 16
      17. O'Connor A: Israeli Medical Marijuana Creates Buzz But No High—Will It Go Global? Available at: https://www.washingtonpost.com/world/middle_east/israeli-medical-marijuana-creates-buzz-but-no-high-will-it-go-global/2015/01/31/558fe072-a19a-11e4-9f89-561284a573f8_story.html. Accessed March 28, 2015

        • Passie T.
        • Emrich H.M.
        • Karst M.
        • Brandt S.D.
        • Halpern J.H.
        Mitigation of post-traumatic stress symptoms by Cannabis resin: A review of the clinical and neurobiological evidence.
        Drug Test Anal. 2012; 4: 649-659
        • Peppin J.F.
        • Passik S.D.
        • Couto J.E.
        • Fine P.G.
        • Christo P.J.
        • Argoff C.
        • Aronoff G.M.
        • Bennett D.
        • Cheatle M.D.
        • Slevin K.A.
        • Goldfarb N.I.
        Recommendations for urine drug monitoring as a component of opioid therapy in the treatment of chronic pain.
        Pain Med. 2012; 13: 886-896
        • Perez J.
        Combined cannabinoid therapy via an oromucosal spray.
        Drugs Today (Barc). 2006; 42: 495-503
        • Perron B.E.
        • Bohnert K.
        • Perone A.K.
        • Bonn-Miller M.O.
        • Ilgen M.
        Use of prescription pain medications among medical cannabis patients: Comparisons of pain levels, functioning, and patterns of alcohol and other drug use.
        J Stud Alcohol Drugs. 2015; 76: 406-413
        • Pesce A.
        • West C.
        • Rosenthal M.
        • West R.
        • Crews B.
        • Mikel C.
        • Almazan P.
        • Latyshev S.
        • Horn P.S.
        Marijuana correlates with use of other illicit drugs in a pain patient population.
        Pain Physician. 2010; 13: 283-287
        • Portenoy R.K.
        • Ganae-Motan E.D.
        • Allende S.
        • Yanagihara R.
        • Shaiova L.
        • Weinstein S.
        • McQuade R.
        • Wright S.
        • Fallon M.T.
        Nabiximols for opioid-treated cancer patients with poorly-controlled chronic pain: A randomized, placebo-controlled, graded-dose trial.
        J Pain. 2012; 13: 438-449
        • Ramer R.
        • Hinz B.
        New insights into antimetastatic and antiangiogenic effects of cannabinoids.
        Int Rev Cell Mol Biol. 2015; 314: 43-116
        • Robson P.
        Therapeutic aspects of cannabis and cannabinoids.
        Br J Psychiatry. 2001; 178: 107-115
        • Rom S.
        • Persidsky Y.
        Cannabinoid receptor 2: Potential role in immunomodulation and neuroinflammation.
        J Neuroimmune Pharmacol. 2013; 8: 608-620
        • Russo E.B.
        • Taming T.H.C.
        Potential cannabis synergy and phytocannabinoid-terpenoid entourage effects.
        Br J Pharmacol. 2011; 163: 1344-1364
        • Salomonsen-Sautel S.
        • Min S.J.
        • Sakai J.T.
        • Thurstone C.
        • Hopfer C.
        Trends in fatal motor vehicle crashes before and after marijuana commercialization in Colorado.
        Drug Alcohol Depend. 2014; 140: 137-144
      18. Sanchez YW: Medical marijuana purity under a microscope. Available at: http://www.usatoday.com/story/news/nation/2014/01/06/medical-marijuana-purity-laboratories/4336123. Accessed July 21, 2015

        • Schierenbeck T.
        • Riemann D.
        • Berger M.
        • Hornyak M.
        Effect of illicit recreational drugs upon sleep: Cocaine, ecstasy and marijuana.
        Sleep Med Rev. 2008; 12: 381-389
        • Schuermeyer J.
        • Salomonsen-Sautel S.
        • Price R.K.
        • Balan S.
        • Thurstone C.
        • Min S.J.
        • Sakai J.T.
        Temporal trends in marijuana attitudes, availability and use in Colorado compared to non-medical marijuana states: 2003-11.
        Drug Alcohol Depend. 2014; 140: 145-155
        • Sehgal N.
        • Manchikanti L.
        • Smith H.S.
        Prescription opioid abuse in chronic pain: A review of opioid abuse predictors and strategies to curb opioid abuse.
        Pain Physician. 2012; 15: ES67-ES92
        • Simonetto D.A.
        • Oxentenko A.S.
        • Herman M.L.
        • Szostek J.H.
        Cannabinoid hyperemesis: A case series of 98 patients.
        Mayo Clin Proc. 2012; 87: 114-119
        • Skrabek R.Q.
        • Galimova L.
        • Ethans K.
        • Perry D.
        Nabilone for the treatment of pain in fibromyalgia.
        J Pain. 2008; 9: 164-173
      19. State of Oregon: Control, Regulation, and Taxation of Marijuana and Industrial Hemp Act. Available at: http://media.oregonlive.com/mapes/other/SP-2014-051.pdf. Accessed March 28, 2015

      20. The University of Mississippi, National Center for Natural Products Research: Cannabis Research. Available at: http://pharmacy.olemiss.edu/ncnpr/research-programs/cannabis-research. Accessed July 21, 2015

        • Thomas G.
        • Kloner R.A.
        • Rezkalla S.
        Adverse cardiovascular, cerebrovascular, and peripheral vascular effects of marijuana inhalation: What cardiologists need to know.
        Am J Cardiol. 2014; 113: 187-190
        • Toth C.
        • Mawani S.
        • Brady S.
        • Chan C.
        • Liu C.
        • Mehina E.
        • Garven A.
        • Bestard J.
        • Korngut L.
        An enriched-enrolment, randomized withdrawal, flexible-dose, double-blind, placebo-controlled, parallel assignment efficacy study of nabilone as adjuvant in the treatment of diabetic peripheral neuropathic pain.
        Pain. 2012; 153: 2073-2082
      21. Ubelacker S: Quebec Cannabis Registry To Collect Data From Patients Using Medical Marijuana. Available at: http://www.huffingtonpost.ca/2015/05/11/quebec-registry-will-trac_n_7259620.html. Accessed July 21, 2015

      22. United States Department of Justice, Drug Enforcement Administration, Office of Diversion Control: Controlled Substance Schedules. Available at: http://www.deadiversion.usdoj.gov/schedules/index.html#define. Accessed July 21, 2015

      23. United States Department of Justice, Office of Public Affairs: Justice Department Announces Update to Marijuana Enforcement Policy. Available at: http://www.justice.gov/opa/pr/justice-department-announces-update-marijuana-enforcement-policy. Accessed July 21, 2015

      24. Clinicaltrials.gov: Vaporized Cannabis for Chronic Pain Associated With Sickle Cell Disease (Cannabis-SCD). Available at: https://clinicaltrials.gov/ct2/show/NCT01771731. Accessed July 21, 2015

        • van den Elsen G.A.
        • Ahmed A.I.
        • Lammers M.
        • Kramers C.
        • Verkes R.J.
        • van der Marck M.A.
        • Rikkert M.G.
        Efficacy and safety of medical cannabinoids in older subjects: A systematic review.
        Ageing Res Rev. 2014; 14: 56-64
        • Vandrey R.
        • Raber J.C.
        • Raber M.E.
        • Douglass B.
        • Miller C.
        • Bonn-Miller M.O.
        Cannabinoid dose and label accuracy in edible medical cannabis products.
        JAMA. 2015; 313: 2491-2493
        • Volkow N.D.
        • Baler R.D.
        • Compton W.M.
        • Weiss S.R.B.
        Adverse health effects of marijuana use.
        N Engl J Med. 2014; 370: 2219-2227
        • Wall M.M.
        • Poh E.
        • Cerda M.
        • Keyes K.M.
        • Galea S.
        • Hasin D.S.
        Adolescent marijuana use from 2002 to 2008: Higher in states with medical marijuana laws, cause still unclear.
        Ann Epidemiol. 2011; 21: 714-716
        • Wallace M.S.
        • Marcotte T.D.
        • Umlauf A.
        • Gouaux B.
        • Atkinson J.H.
        Efficacy of inhaled cannabis on painful diabetic neuropathy.
        J Pain. 2015; 16: 616-627
        • Wang G.S.
        • Roosevelt G.
        • Heard K.
        Pediatric marijuana exposures in a medical marijuana state.
        JAMA Pediatr. 2013; 167: 630-633
        • Wang T.
        • Collet J.P.
        • Shapiro S.
        • Ware M.A.
        Adverse effects of medical cannabinoids: A systematic review.
        CMAJ. 2008; 178: 1669-1678
        • Ware M.A.
        • Fitzcharles M.A.
        • Joseph L.
        • Shir Y.
        The effects of nabilone on sleep in fibromyalgia: Results of a randomized controlled trial.
        Anesth Analg. 2010; 110: 604-610
        • Ware M.A.
        • Wang T.
        • Shapiro S.
        • Collet J.P.
        COMPASS study team: Cannabis for the Management of Pain: Assessment of Safety Study (COMPASS).
        J Pain. 2015; 16: 1233-1242
        • Ware M.A.
        • Wang T.
        • Shapiro S.
        • Robinson A.
        • Ducruet T.
        • Huynh T.
        • Gamsa A.
        • Bennett G.J.
        • Collet J.P.
        Smoked cannabis for chronic neuropathic pain: A randomized controlled trial.
        CMAJ. 2010; 182: E694-E701
        • Watson S.J.
        • Benson Jr., J.A.
        • Joy J.E.
        Marijuana and medicine: Assessing the science base: A summary of the 1999 Institute of Medicine report.
        Arch Gen Psychiatry. 2000; 57: 547-552
      25. WebMD: MARINOL Side Effects. Available at: http://www.webmd.com/drugs/2/drug-9308/marinol-oral/details/list-sideeffects. Accessed July 21, 2015

        • Weiner S.G.
        • Horton L.C.
        • Green T.C.
        • Butler S.F.
        A comparison of an opioid abuse screening tool and prescription drug monitoring data in the emergency department.
        Drug Alcohol Depend. 2016; 159: 152-157
        • Wiedemer N.L.
        • Harden P.S.
        • Arndt I.O.
        • Gallagher R.M.
        The opioid renewal clinic: A primary care, managed approach to opioid therapy in chronic pain patients at risk for substance abuse.
        Pain Med. 2007; 8: 573-584
        • Wilkerson J.L.
        • Milligan E.D.
        The central role of glia in pathological pain and the potential of targeting the cannabinoid 2 receptor for pain relief.
        ISRN Anesthesiol. 2011; 593894: 2011
        • Wilkinson S.T.
        • Radhakrishnan R.
        • D'Souza D.C.
        Impact of cannabis use on the development of psychotic disorders.
        Curr Addict Rep. 2014; 1: 115-128
        • Wilsey B.
        • Atkinson J.H.
        • Marcotte T.D.
        • Grant I.
        The medicinal cannabis treatment agreement: Providing information to chronic pain patients via a written document.
        Clin J Pain. 2015; 31: 1087-1096
        • Wilsey B.
        • Marcotte T.
        • Deutsch R.
        • Gouaux B.
        • Sakai S.
        • Donaghe H.
        Low-dose vaporized cannabis significantly improves neuropathic pain.
        J Pain. 2013; 14: 136-148
        • Wilsey B.
        • Marcotte T.
        • Tsodikov A.
        • Millman J.
        • Bentley H.
        • Gouaux B.
        • Fishman S.
        A randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain.
        J Pain. 2008; 9: 506-521
      26. World first: Launch of Quebec Registry for Cannabis Users. Press release of McGill University Health Centre. Available at: https://registrecannabisquebec.com/en/world-first-launch-quebec-registry-users-medical-cannabis. Accessed March 29, 2016

        • Zhang L.R.
        • Morgenstern H.
        • Greenland S.
        • Chang S.C.
        • Lazarus P.
        • Teare M.D.
        • Woll P.J.
        • Orlow I.
        • Cox B.
        • Brhane Y.
        • Liu G.
        • Hung R.J.
        • Cannabis and Respiratory Disease Research Group of New Zealand
        Cannabis smoking and lung cancer risk: Pooled analysis in the International Lung Cancer Consortium.
        Int J Cancer. 2015; 136: 894-903