Medical Marijuana and Chronic Pain: a Review of Basic Science and Clinical Evidence
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Cannabinoid compounds include phytocannabinoids, endocannabinoids, and synthetics. The two primary phytocannabinoids are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), with CB1 receptors in the brain and peripheral tissue and CB2 receptors in the immune and hematopoietic systems. The route of delivery of cannabis is important as the bioavailability and metabolism are very different for smoking versus oral/sublingual routes. Gold standard clinical trials are limited; however, some studies have thus far shown evidence to support the use of cannabinoids for some cancer, neuropathic, spasticity, acute pain, and chronic pain conditions.
KeywordsMedical marijuana Chronic pain Cannabis Phytocannabinoids Endocannabinoids Neuropathic pain
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Conflict of Interest
Bjorn Jensen, Jeffrey Chen, Tim Furnish, and Mark Wallace each declare no potential conflicts of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
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- 1.Mechoulam R. The pharmacohistory of cannabis sativa. In: Mechoulam R, editor. Cannabinoids as therapeutic agents. Boca Raton: CRC Press; 1986. p. 1–19.Google Scholar
- 2.O’Shaugnessy WB. On the preparations of the Indian hemp, or gunjah (Cannabis indica): their effects on the animal system in health, and their utility in the treatment of tetanus and other convulsive diseases. Trans Med Phys Soc., Bengal., 71–102, 1838–40;421–46, 1842.Google Scholar
- 4.Fankhauser M. Chapter 4: history of cannabis in Western medicine. In: Grotenhermen F, Russo R, editors. Cannabis and cannabinoids: pharmacology, toxicology and therapeutic potential. New York: The Haworth Integrative Healing Press; 2002. p. 37–51.Google Scholar
- 5.Russo EB, Hohmann AG. Role of cannabinoids in pain management. In: Deer T, Gordin V, editors. Comprehensivetreatment of chronic pain by medical, interventional and behavioral approaches. New York: Springer; 2013. pp. 181–197. Google Scholar
- 7.Ljubiša G. A comparative study on some chemical and biological characteristics of various samples of cannabis resin. Bull Narcotic (UNODC). 1962;3:37–46.Google Scholar
- 15.Szabo B, Schlicker E. Effects of cannabinoids on neurotransmission cannabinoids. In: Pertwee RG, editor. Handbook of experimental pharmacology, vol. 168. Heidelberg: Springer; 2005. p. 327–65.Google Scholar
- 17.Vaughan CW, Christie MJ. Retrograde signaling by endocannabinoids cannabinoids. In: Pertwee RG, editor. Handbook of experimental pharmacology, vol. 168. Heidelberg: Springer; 2005. p. 367–83.Google Scholar
- 19.Cabral GA, Staab A. Effects on the immune system cannabinoids. In: Pertwee RG, editor. Handbook of experimental pharmacology, vol. 168. Heidelberg: Springer; 2005. p. 385–423.Google Scholar
- 20.Pertwee RG. Pharmacological actions of cannabinoids. In: Pertwee RG, editor. Handbook of experimental pharmacology, vol. 168. Heidelberg: Springer; 2005. p. 1–51.Google Scholar
- 29.•Borgelt LL, Franson KM, Nussbaum AM, Wang GS. The pharmacologic and clinical effects of medical cannabis. Pharmacotherapy. 2013;33.3:195–209. Web. A helpful source for describing pharmacodynamics and pharmacokinetics. It also touched on the uses of medical cannabis for pain and muscles spasms, as well as safety concerns with medical cannabis use. CrossRefGoogle Scholar
- 31.Strougo A, Zuurman L, Roy C, et al. Modelling of the concentration–effect relationship of THC on central nervous system parameters and heart rate—insight into its mechanisms of action and a tool for clinical research and development of cannabinoids. J Psychopharmacol. 2008;22:717–26.CrossRefPubMedGoogle Scholar
- 36.Karschner EL, Darwin WD, Goodwin RS, Wright S, Huestis MA. Plasma cannabinoid pharmacokinetics following controlled oral delta9-tetrahydrocannabinol and oromucosal cannabis extract administration. Clin Chem. 2011;57(1):66–75. doi: 10.1373/clinchem.2010.152439. Epub 2010 Nov 15. Gonzalez R, et al. Nonacute neuropsychological effects of cannabis use. J Clin Pharm 2002, 42:48S–57S.PubMedCentralCrossRefPubMedGoogle Scholar
- 37.Grant I et al. Non-acute neurocognitive effects of cannabis use: a metaanalysis. J Int Neuropsych Soc. 2003;9:679–89.Google Scholar
- 38.•Meier MH, et al. Persistent cannabis users show neuropsychological decline from childhood to midlife. 2012; PNAS. 109(40):E2657. These studies provided insight into the debate about the long-term effects of cannabis, especially on our adolescent population. It is important to remember the difficulties associated with studying long-term effects of cannabis in populations without intentionally subjecting them to their effects for significant periods of time. Google Scholar
- 40.••Rogeberg O. Correlations between cannabis use and IQ change in the Dunedin cohort are consistent with confounding from socioeconomic status. Proc Natl Acad Sci U S A. 2013;110(11):4251–4. These studies provided insight into the debate about the long-term effects of cannabis, especially on our adolescent population. It is important to remember the difficulties associated with studying long-term effects of cannabis in populations without intentionally subjecting them to their effects for significant periods of time. (see references 74 and 75 for further reading). PubMedCentralCrossRefPubMedGoogle Scholar
- 41.•Bava S, Jacobus J, Thayer RE, Tapert SF. Longitudinal changes in white matter integrity among adolescent substance users. Alcohol Clin Exp Res. 2013. Alcohol Clin Exp. When considering the dangers of chronic Cannabis use, it is important to use a commonly abused substance such as alcohol as a comparison. This study focused primarily on brain scans, but provided a direct example of alcohol versus marijuana on the brain. Google Scholar
- 42.Watson SJ, Benson JA Jr, Joy JE. Marijuana and medicine: assessing the science base: a summary of the 1999 Institute of Medicine report. Arch Gen Psychiatry. 2000;57(6):547–52.Google Scholar
- 45.Staquet M, Gantt C, Machin D. Effect of a nitrogen analog of tetrahydrocannabinol on cancer pain. Clin J Pharm Therap. 1978;23:397–401.Google Scholar
- 46.Jochimsen PR et al. Effect of benzopyranoperidine a delta-9-THC congener on pain. Clin J Pharm Therap. 1978;24:223–7.Google Scholar
- 47.Johnson JR, Burnell-Nugent M, Lossignol D, Ganae-Motan ED, Fallon PR. Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related pain. J Pain Symp Manag. 2010;39(2):167–79.CrossRefGoogle Scholar
- 51.Wade DT, Robson P, House H, Makela P, Aram J. A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms. Clin Rehabil. 2003;17:18–26.Google Scholar
- 67.Blake DR, Robson P, Ho M, Jubb RW, McCabe CS. 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(1):50–2.Google Scholar
- 69.•Yu XH, Co CQ, Martino G, et al. A peripherally restricted cannabinoid receptor agonist produces robust anti-nociceptive effects in rodent models of inflammatory and neuropathic pain. Pain. 2010;151(2):337–44. Studies on these types of cannabinoid medications are significant because they may provide alternate routes of analgesia while avoiding the psychoactive effects of medical cannabis that normally hinder their use. CrossRefPubMedGoogle Scholar
- 71.•Clapper JR, Moreno-Sanz G, Russo R, et al. Anandamide suppresses pain initiation through a peripheral endocannabinoid mechanism. Nat Neurosci. 2010;13:1265–70. Studies on these types of cannabinoid medications are significant because they may provide alternate routes of analgesia while avoiding the psychoactive effects of medical cannabis that normally hinder their use. PubMedCentralCrossRefPubMedGoogle Scholar
- 72.Wood GW, Bache F. The dispensatory of the United States of America 6th edn. Philadelphia: Grigg and Elliot; 1845: 1238.Google Scholar
- 73.Moffitt TE, Meier MH, Caspi A, Poulton R. Reply to Rogeberg and Daly: no evidence that socioeconomic status or personality differences confound the association between cannabis use and IQ decline. Proc Nat Acad Sci USA. 2013;110.11:E980-982. Web. 28 July 2015. http://www.pnas.org/content/110/11/E980.full.
- 74.Rogeberg O. Reply to Moffitt et al.: causal inference from observational data remains difficult. Proc Nat Acad Sci USA. 2013;110.11:E983. Web. 28 July 2015. http://www.pnas.org/content/110/11/E983.fullElliot. 1845:1238.
- 75.Aldington S, et al. Effects of cannabis on pulmonary structure, function and symptoms. Thorax. 2007;62.12:1058–063. PubMed. Web. 30 July 2015.Google Scholar
- 76.Tashkin DP, Baldwin GC, Sarafian T, Dubinett S, Roth MD. Respiratory and immunologic consequences of marijuana smoking. J Clin Pharmacol. 2002;42(11 Suppl):71S-81S.Google Scholar
- 77.Tetrault JM, Crothers K, Moore BA, Mehra R, Concato J, Fiellin DA. Effects of marijuana smoking on pulmonary function and respiratory complications: a systematic review. Arch Intern Med. 2007;167(3):221–8.Google Scholar
- 79.•Hall W, Degenhardt L. The adverse health effects of chronic cannabis use. Drug Test Anal. 2014;6:39–45. Relevant to the evidence for chronic cannabis use. Important to note that there are still a large amount of research to be completed before actually accepting some of worrisome chronic effects. CrossRefPubMedGoogle Scholar