Cannabis and Pain: A Clinical Review

Kevin P Hill, Matthew D Palastro, Brian Johnson, Joseph W Ditre, Kevin P Hill, Matthew D Palastro, Brian Johnson, Joseph W Ditre

Abstract

Introduction: Cannabis has been used for medical purposes across the world for centuries. As states and countries implement medical and recreational cannabis policies, increasing numbers of people are using cannabis pharmacotherapy for pain. There is a theoretical rationale for cannabis' efficacy for pain management, although the subjective pain relief from cannabis may not match objective measurements of analgesia. As more patients turn to cannabis for pain relief, there is a need for additional scientific evidence to evaluate this increase. Materials and Methods: Research for this review was performed in the PubMed/National Library of Medicine database. Discussion: Preclinical studies demonstrate a narrow therapeutic window for cannabis as pharmacotherapy for pain; the body of clinical evidence for this indication is not as extensive. A recent meta-analysis of clinical trials of cannabis and cannabinoids for pain found modest evidence supporting the use of cannabinoid pharmacotherapy for pain. Recent epidemiological studies have provided initial evidence for a possible reduction in opioid pharmacotherapy for pain as a result of increased implementation of medical cannabis regimens. Conclusion: With increased use of medical cannabis as pharmacotherapy for pain comes a need for comprehensive risk-benefit discussions that take into account cannabis' significant possible side effects. As cannabis use increases in the context of medical and recreational cannabis policies, additional research to support or refute the current evidence base is essential to attempt to answer the questions that so many healthcare professionals and patients are asking.

Keywords: THC; anandamide; cannabidiol; cannabinoids; endocannabinoid; pain.

Conflict of interest statement

No competing financial interests exist.

Figures

FIG. 1.
FIG. 1.
Opponent process theory.

References

    1. Russo EB. History of cannabis and its preparations in saga, science, and sobriquet. Chem Biodivers. 2007;4:1614–1648
    1. Savage SR, Romero-Sandoval A, Schatman M, et al. . Cannabis in pain treatment: clinical and research considerations. J Pain. 2016;17:654–668
    1. National Conference of State Legislatures. 2016. State medical marijuana laws. November 9 Available at (last accessed November21, 2016)
    1. Bestrashniy J, Winters KC. Variability in medical marijuana laws in the United States. Psychol Addict Behav. 2015;29:639–642
    1. Light MK, Orens A, Lewandowski B, et al. . Market size and demand for marijuana in Colorado. The Marijuana Policy Group. 2014. Available at (last accessed November17, 2016)
    1. Ilgen MA, Bohnert K, Kleinberg F, et al. . Characteristics of adults seeking medical marijuana certification. Drug Alcohol Depen. 2013;132:654–659
    1. Sznitman SR, Bretteville-Jensen AL. Public opinion and medical cannabis policies: examining the role of underlying beliefs and national medical cannabis policies. Harm Reduct J. 2015;12:4–6.
    1. National Academies of Sciences, Engineering, and Medicine. The health effects of cannabis and cannabinoids: the current state of evidence and recommendations for research. The National Academies Press: Washington, DC, 2017
    1. Touw M. The religious and medicinal uses of cannabis in China, India and Tibet. J Psychoactive Drugs. 1981;13:23–34
    1. Li HL, Lin H. An archaeological and historical account of cannabis in China. Econ Bot. 1974;28:437–447
    1. Mikuriya TH. Marijuana in medicine: past, present and future. Calif Med. 1969;110:34–40
    1. Aldrich M. History of therapeutic cannabis. In: Mathre ML, eds. Cannabis in medical practice. McFarland: Jefferson, NC, 1997, pp. 35–55
    1. Fankhauser M. History of cannabis in Western Medicine. In: Grotenhermen F, Russo E, eds. Cannabis and Cannabinoids. Chapter 4. The Haworth Integrative Healing Press: New York, 2002, pp. 37–51
    1. Grinspoon L. Marihuana reconsidered. Harvard University Press: Cambridge, MA, 1971
    1. Grinspoon L, Bakalar JB. Marijuana: the forbidden medicine. Chapter 1. Yale Universty Press: New Haven, CT, 1993
    1. Substance Abuse and Mental Health Services Administration. Results from the 2015 national survey on drug use and health: detailed tables. Center for Behavioral Health Statistics and Quality: Rockville, MD, 2016
    1. Mechoulam RJ. Marijuana: chemistry, pharmacology and clinical effects. Academic Press: New York, 1973, pp. 2–99
    1. Mlezack R, Wall PD. Pain mechanisms: a new theory. Science. 1965;150:971–979
    1. IOM. Relieving pain in america: a blueprint for transforming prevention, care, education, and research. The National Academies Press: Washington, DC, 2011
    1. Tsang A, Von Korff M, Lee S, et al. . Common chronic pain conditions in developed and developing countries: gender and age differences and comorbidity with depression-anxiety disorders. J Pain. 2008;9:883–891
    1. Turk DC, Rudy TE. Towards a comprehensive assessment of chronic pain patients. Behav Res Ther. 1987;25:237–249
    1. Arnold LM, Choy E, Clauw DJ, et al. . Fibromyalgia and chronic pain syndromes: a white paper detailing current challenges in the field. Clin J Pain. 2016;32:737–746
    1. Shubayev VI, Kato K, Myers RR. Cytokines in pain. In: Kruger L, Light AR, eds. Translational pain research: from mouse to man. Chapter 8. CRC Press/Taylor & Francis: Boca Raton, FL, 2010. Available at (last accessed May16, 2017)
    1. Koenig J, Werdenhausen R, Linley JE, et al. . Regulation of the NA(v)1.7: a conserved SCN9A natural antisense transcript expressed in dorsal root ganglia. PLOS One. 2015;10:e012883–0.
    1. Clauw DJ. Fibromyalgia: a clinical review. JAMA. 2014;311:1547–1555
    1. Kremer M. Antidepressants and gabapentinoids in neuropathic pain: mechanistic insights. Neuroscience. 2016;338:183–206
    1. Cheng Y, Chen C, Lin CP, et al. . Love hurts: an fMRI study. Neuroimage. 2010;51:923–929
    1. Platts-Mills TF, Hunold KM, Bortsov AV, et al. . More educated emergency department patients are less likely to receive pain medication. Pain. 2012;153:967–973
    1. Johnson B, Mosri D. The neuropsychoanalytic approach: using neuroscience as the basic science of psychoanalysis. Front Psychol. 2016;7:145–9.
    1. Johnson B, Faraone SV. Outpatient detoxification completion and one month outcomes for opioid dependence: a preliminary open label study of a neuropsychoanalytic treatment in pain patients and addicted patients, Neuropsychoanalysis. 2013;15:145–160
    1. Solomon DH, Rassen JA, Glynn RJ, et al. . The comparative safety of analgesics in older adults with arthritis. Arch Intern Med. 2010;170:1968–1978
    1. Zale EL, Maisto SA, Ditre JW. Interrelations between pain and alcohol: an integrative review. Clin Psychol Rev. 2015;37:57–71
    1. Larson MJ, Paasche-Orlow M, Cheng DM, et al. . Persistent pain is associated with substance use after detoxification: a prospective cohort analysis. Addiction. 2007;102:752–760
    1. Demyttenaere K, Bruffaerts R, Lee S, et al. . Mental disorders among persons with chronic back or neck pain: results from the World Mental Health Surveys. Pain. 2007;129:332–342
    1. Strine TW, Hootman JM. US national prevalence and correlates of low back and neck pain among adults. Arthritis Rheum. 2007;57:656–665
    1. Von Korff M, Crane P, Lane M, et al. . Chronic spinal pain and physical-mental comorbidity in the United States: results from the national comorbidity survey replication. Pain. 2005;113:331–339
    1. National Institute on Alcohol Abuse and Alcoholism. Alcohol overdose: the dangers of drinking too much. 2015. Available at (last accessed May16, 2017)
    1. Jochum T, Boettger MK, Burkhardt C, et al. . Increased pain sensitivity in alcohol withdrawal syndrome. Eur J Pain. 2010;14:713–718
    1. Ditre JW, Brandon TH, Zale EL, et al. . Pain, nicotine, and smoking: research findings and mechanistic considerations. Psychol Bull. 2011;137:1065–1093
    1. Zale EL, Maisto SA, Ditre JW. The role of anxiety and depression in bi-directional relations between pain and tobacco smoking. Behav Modif. 2016;40:7–28
    1. Hooten WM, Shi Y, Gazelka HM, et al. . The effects of depression and smoking on pain severity and opioid use in patients with chronic pain. Pain. 2011;152:223–229
    1. Zvolensky MJ, McMillan KA, Gonzalez A, et al. . Chronic musculoskeletal pain and cigarette smoking among a representative sample of Canadian adolescents and adults. Addict Behav. 2010;35:1008–1012
    1. Michna E, Ross EL, Hynes WL, et al. . Predicting aberrant drug behavior in patients treated for chronic pain: importance of abuse history. J Pain Symptom Manage. 2014;28:250–258
    1. Jamison RN, Stetson BA, Parris WC. The relationship between cigarette smoking and chronic low back pain. Addict Behav. 1991;16:103–110
    1. Ditre JW, Heckman BW, Zale EL, et al. . Acute analgesic effects of nicotine and tobacco in humans: a meta-analysis. Pain. 2016;157:1373–1381
    1. Shiri R, Karppinen J, Leino-Arjas P, et al. . The association between smoking and low back pain: a meta-analysis. Am J Med. 2010;123:e7–e35
    1. Ditre JW, Brandon TH. Pain as a motivator of smoking: effects of pain induction on smoking urge and behavior. J Abnorm Psychol. 2008;117:467–472
    1. Patterson AL, Gritzner S, Resnick MP, et al. . Smoking cigarettes as a coping strategy for chronic pain is associated with greater pain intensity and poorer pain-related function. J Pain. 2012;13:285–292
    1. Zale EL, Dorfman ML, Hooten WM, et al. . Tobacco smoking, nicotine dependence, and patterns of prescription opioid misuse: results from a nationally representative sample. Nicotine Tob Res. 2015;17:1906–1103
    1. ONDCP. Epidemic: responding to America's prescription drug abuse crisis. 2011. Available at (last accessed July7, 2014)
    1. Sehgal N, Manchikanti L, Smith HS. Prescription opioid abuse in chronic pain: a review of opioid abuse predictors and strategies to curb opioid abuse. Pain Physician. 2012;15:ES67–ES92
    1. Turk DC, Swanson KS, Gatchel RJ. Predicting opioid misuse by chronic pain patients: a systematic review and literature synthesis. Clin J Pain. 2008;24:497–508
    1. Brennan F, Carr DB, Cousins M. The role of opioids in pain management. Anesth Analg. 2007;105:205–221
    1. Calcaterra S, Glanz J, Binswanger IA. National trends in pharmaceutical opioid related overdose deaths compared to other substance related overdose death: 1999–2009. Drug Alcohol Depend. 2013;131:263–270
    1. Freiden TR, Houry D. Reducing the risks of relief-the CDC opioid prescribing guideline. N Engl J Med. 2016;374:1501–1504
    1. Koob GF, LeMoal M. Drug addiction, dysregulation of reward and allostasis. Neuropsychopharmacology. 2001;24:98–129
    1. Egli M, Koob GF, Edwards S. Alcohol dependence as a chronic pain disorder. Neurosci Biobehav Rev. 2012;36:2179–2192
    1. Piomelli D, Sasso O. Peripheral gating of pain signals by endogenous lipid mediators. Nat Neurosci. 2014;17:164–174
    1. Rice AS. Cannabinoids and pain. Cuurr Opin Investig Drugs. 2001;2:399–414
    1. Castillo PE, Younts TJ, Chavez AE, et al. . Endocannabinoid signaling and synaptic function. Neuron. 2012;76:70–81
    1. Price TJ, Helesic G, Parghi D, et al. . The neuronal distribution of cannabinoid receptor type 1 in the trigeminal ganglion of the rat. Neuroscience. 2003;120:155–162
    1. Sugawara K, Zakany N, Hudt T, et al. . Cannabinoid receptor 1 controls human mucosal-type mast cell degranulation and maturation in situ. J Allergy Clin Immunol. 2013;132:182–193
    1. Stander S, Schemlz M, Metze D, et al. . Distribution of cannabinoid receptor 1 (CB1) and 2 (CB2) on sensory nerve fibers and adnexal structures in human skin. J Dermatol Sci. 2005;38:177–188
    1. Guindon J, Hohmann AG. The endocannabinoid system and pain. CNS Neurol Disord Drug Targets. 2009;8:403–421
    1. Piomelli D, Astarita G, Rapaka R. A neuroscientist's guide to lipidomics. Nat Rev Neurosci. 2007;8:743–754
    1. Massaro M, Martinelli R, Gatta V, et al. . Transcriptome-based identification of new anti-anti-inflammatory and vasodilating properties of the n-3 fatty acid docosahexaenoic acid in vascular endothelial cell under proinflammatory conditions. PLoS One. 2016;10:e012965–2.
    1. Hohmann AG, Suplita RL, Bolton NM, et al. . An endocannabinoid mechanism for stress-induced analgesia. Nature. 2005;435:1108–1112
    1. Hill KP. Medical marijuana for treatment of chronic pain and other medical and psychiatric problems, a clinical review. JAMA. 2015;313:2474–2483
    1. Lim G, Sung B, Ji RR, et al. . Upregulation of spinal cannabinoid-1-receptors following nerve injury enhances the effect of WIN55,212-2 on neuropathic pain behaviour in rats. Pain. 2003;105:275–283
    1. Johanek LM, Heitmiller DR, Turner M, et al. . Cannabinoids attenuate capsaicin-evoked hyperalgesia through spinal and peripheral mechanisms. Pain. 2001;93:303–315
    1. Wallace M, Schulteis G, Atkinson JH, et al. . Dose-dependent effects of smoked cannabis on capsaicin-induced pain and hyperalgesia in healthy volunteers. Anesthesiology. 2007;107:785–796
    1. Kraft B, Frickey NA, Rainer M, et al. . Lack of analgesia by oral standardized cannabis extract on acute inflammatory pain and hyperalgesia in volunteers. Anesthesiology. 2008;109:101–110
    1. Whiting PF, Wolff RF, Deshpande S, et al. . Cannabinoids for medical use: a systematic review and meta-analysis. JAMA. 2015;313:2456–2473
    1. Wallace MS, Marcotte TD, Umlauf A, et al. . Efficacy of inhaled cannabis on painful diabetic neuropathy. J Pain. 2015;16:616–627
    1. Wilsey BL, Deutsch R, Samara E, et al. . A preliminary evaluation of the relationship of cannabinoid blood concentrations with the analgesic response to vaporized cannabis. J Pain Res. 2016;9:587–598
    1. APA. Diagnostic and statistical manual of mental disorders, 5th ed. Washington, DC, 2013
    1. Florez-Salamanca L, Secades-Villa R, Hasin DS, et al. . Probability and predictors of transition from abuse to dependence on alcohol, cannabis, and cocaine: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Am J Drug Alcohol Abuse. 2013;39:168–179
    1. Hall WD, Pacula RL. Cannabis use and dependence: public health and public policy. Cambridge University Press: Cambridge, UK, 2003
    1. Lopez-Quintero C, Perez de los Cobos J, Hasin DS, et al. . 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
    1. Compton WM, Grant BF, Colliver JD, et al. . Prevalence of marijuana use disorders in the United States: 1991–1992 and 2001–2002. JAMA. 2004;291:2114–2121
    1. Allsop DJ, Copeland J, Norberg MM, et al. . Quantifying the clinical significance of cannabis withdrawal. PLoS One. 2012;7:e4486–4.
    1. Budney AJ, Hughes JR, Moore BA, et al. . Review of the validity and significance of cannabis withdrawal syndrome. Am J Psychiatry. 2004;161:1967–1977
    1. Levin KH, Copersino ML, Heishman SJ, et al. . Cannabis withdrawal symptoms in non-treatment-seeking adult cannabis smokers. Drug Alcohol Depend. 2010;111:120–127
    1. Zale EL, Maisto SA, Ditre JW. Interrelations between pain and alcohol: an integrative review. Clin Psychol Rev. 2015;37:57–71
    1. Wade JB, Dougherty LM, Archer CR, et al. . Assessing the stages of pain processing: a multivariate analytical approach. Pain. 1996;68:157–167
    1. Baker TB, Piper ME, McCarthy DE, et al. . Addiction motivation reformulated: an affective processing model of negative reinforcement. Psychol Rev. 2004;111:33–51
    1. Turk DC, Melzack R. The measurement of pain and the assessment of people experiencing pain. In Turk DC, Melzack R, eds. Handbook of pain assessment, 3rd ed. The Guilford Press: New York, 2011, pp. 3–18
    1. Sewell RA, Poling J, Sofuoglu M. The effect of cannabis compared with alcohol on driving. Am J Addict. 2009;18:185–193
    1. Workman EA, Hubbard JR, Felker BL. Comorbid psychiatric disorders and predictors of pain management program success in patients with chronic pain. Prim Care Companion J Clin Psychiatry. 2002;4:137–140
    1. Bachhuber MA, Saloner B, Cunningham CO, et al. . Medical cannabis laws and opioid analgesic overdose mortality in the United States, 1999–2010. JAMA Intern Med. 2014;174:1668–1673
    1. Bradford AC, Bradford DW. Medical marijuana laws reduce prescription medication use in Medicare part D. Health Affairs. 2016;35:1230–1236

Source: PubMed

3
購読する