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Logo of harmredBioMed CentralBiomed Central Web Sitesearchsubmit a manuscriptregisterthis articleHarm Reduction JournalJournal Front Page
Harm Reduct J. 2012; 9: 1.
Published online 2012 January 1. doi:  10.1186/1477-7517-9-1
PMCID: PMC3295721

Prescribing cannabis for harm reduction


Neuropathic pain affects between 5% and 10% of the US population and can be refractory to treatment. Opioids may be recommended as a second-line pharmacotherapy but have risks including overdose and death. Cannabis has been shown to be effective for treating nerve pain without the risk of fatal poisoning. The author suggests that physicians who treat neuropathic pain with opioids should evaluate their patients for a trial of cannabis and prescribe it when appropriate prior to using opioids. This harm reduction strategy may reduce the morbidity and mortality rates associated with prescription pain medications.

Keywords: cannabis, cannabinoids, opioids, neuropathic pain, chronic pain, harm reduction, ethics

Neuropathic pain (NP) is defined as pain caused by a lesion or disease of the central or peripheral somatosensory nervous system [1]. NP affects between 5% and 10% of the US population [2] and examples include diabetic neuropathy, complex regional pain syndrome, radiculopathy, phantom limb pain, HIV sensory neuropathy, multiple sclerosis-related pain, and poststroke pain [3]. Neuropathic pain is difficult to treat and opioid analgesics are often prescribed [4]. Recent science has demonstrated efficacy in treating NP with cannabis, [5-7] a safer drug than opioids [8]. This paper suggests that physicians who treat neuropathic pain should prescribe cannabis prior to using opioids as a harm reduction (HR) strategy. Topics covered include how harm reduction applies to prescription opioid substitution, the legality of medicinal cannabis, a comparison of cannabis to opioids, the science on treating NP with cannabis and cannabinoids, and the ethics of prescribing a drug which is deemed illegal on the federal but not the state level.

Medicine relies upon the principle of, "First, do no harm," and one might supplement the axiom to read - "First, do no harm, and second, reduce all the harm you can." "Harm reduction" or "harm minimization" can be defined in the broadest sense as strategies designed to reduce risk or harm [9]. Those harmed may include the individual, others impacted by the harmed person, and society [9]. The substitution of a safer drug for one that is more dangerous is considered harm reduction [10]. Specific examples of HR include prescribing methadone or buprenorphine to replace heroin, [11] prescribing nicotine patches to be used instead of smoking tobacco, [12] and prescribing intranasal naloxone to patients on opioid therapy to be utilized in case of overdose [13]. Substituting cannabis for prescribed opioids may be considered a harm reduction strategy.

Under the Federal Controlled Substance Act "marihuana" is illegal and classified as a schedule I substance-meaning it has a high potential for abuse and no accepted medical use [14]. However, sixteen states and the District of Columbia have legalized cannabis for medicinal use and these include Alaska, Arizona, California, Colorado, Delaware, Hawaii, Maine, Michigan, Montana, Nevada, New Jersey, New Mexico, Oregon, Rhode Island, Vermont, and Washington [15]. Each state law differs but all allow physicians to "authorize" or "recommend" cannabis for specific ailments [16]. This "recommendation" affords legal protections for patients to obtain and use medicinal cannabis, and may be considered the "prescription."

Cannabis (Cannabis sativa) and the opium poppy (Papaver somniferum) are both ancient plants that have been used medicinally for thousands of years [17,18]. The natural and synthetic derivatives of opium, including morphine, are called "opioids." [19] "Cannabinoids" is the term for a class of compounds within cannabis of which delta-9-tetrahydrocannabinol (THC) is the most familiar [20]. Besides THC, approximately 100 other cannabinoids have been identified [21,22] including one of special scientific interest called "cannabidiol" (CBD) [23]. The human body produces both endogenous cannabinoids (endocannabinoids) and opioids (endorphins) and contains specific receptors for these substances [24,25]. There is an extensive literature on opioids but far less on cannabis/cannabinoids (CC).

Adverse effects from opioids include respiratory depression, sedation, sleep disturbance, cognitive and psychomotor impairment, delirium, hallucinations, seizures, hyperalgesia, constipation, nausea, and vomiting [26-28]. Adverse events from cannabis/cannabinoids include psychotic episodes, anxiety or panic reactions, memory impairment, reduced concentration, disorientation, lowered blood pressure and increased heart rate [7,29-31]. In a systematic review Wang and colleagues found most adverse events for short-term cannabis use were not serious, and there was a lack of evidence to determine adverse effects for long-term use [32]. Opioids and cannabis share issues of addiction, physical dependence, tolerance and withdrawal [5,33,34].

Between 1999 and 2006 approximately 65,000 people died from opioid analgesic overdose [35]. Regarding fatal overdose from cannabis, Carter and colleagues write, "... this well documented fact: no one has ever died from an overdose of cannabis." [8] In addition, there is insufficient data to demonstrate smoking cannabis causes lung cancer [36] but long-term use is associated with an increased risk of respiratory problems [37]. Although, eating cannabis [38] avoids the respiratory issues. In 2001 the total cost of prescription opioid abuse was estimated at $8.6 billion [39]. Unfortunately, there are no comprehensive studies on the total cost of cannabis abuse. However, enforcing the prohibition on cannabis costs an estimated $7.7 billion per year [40]. Since the federal and most state governments view any use of cannabis as abuse - including medicinal use - one might include this cost. According to a report from the Substance Abuse and Mental Health Services Administration between 1999 and 2009 admissions for treatment of nonheroin opioid abuse increased approximately 516% while admissions for cannabis saw a 53% rise [41].

Nerve pain can be refractory to treatment [42] and opioids are often used as a second-line therapy while antidepressants and anticonvulsants are commonly used first [4,43]. Moreover, opioids may provide only limited pain relief and as Henry McQuay writes, " may be able to decrease neuropathic pain with strong opioids, but the decrease is often slight and is achieved with an adverse effect burden that will not be tolerable over weeks to months." [44] Cannabis and cannabinoid research is in its relative infancy and many studies are of short duration and with small sample sizes [6]. However, a number of review articles suggest that treating neuropathic pain with cannabis/cannabinoids is efficacious and with moderate adverse effects [5-7]. The most thorough of the systematic reviews was of randomized controlled trials (RCTs) of CC therapy [6] which looked at nine studies [45-53] whose focus was on treating different types of neuropathic pain with either smoked cannabis, [45-48] a synthetic cannabinoid similar to THC, [49,50] or a whole plant extract of THC and CBD in a 1:1 ratio [51-53]. CBD may moderate the psychoactive effect of THC and have analgesic properties [24]. Seven of the nine studies demonstrated efficacy for using CC for neuropathic pain [45-49,52,53] while two had mixed results, [50,51] and eight of the nine studies found no serious adverse events [45-51,53].

A closer look at the four RCTs which evaluated smoked cannabis for neuropathic pain [45-48] reveals some common and contrasting elements (Table (Table1).1). Two of the studies, Ware et al. [45] and Wilsey et al., [47] examined cannabis in treating a variety of NP conditions; while the other two, Ellis et al. [46] and Abrams et al., [48] explored the effects of cannabis on HIV-related neuropathic pain. Both Wilsey et al. [47] and Abrams et al. [48] required participants to have previously used cannabis in order to reduce the risk of adverse reactions from psychoactive effects. The RCTs used cannabis with a variety of THC strengths ranging from 0% for placebo [45-48] to 9.4% in Ware et al. [45] Each study required participants to continue taking their regular medications during the cannabis trials and all found a significant decrease in pain compared to placebo [45-48]. In addition, adverse events were tolerable for the vast majority of participants [45-48].

Table 1
Comparison of Randomized Controlled Trials of Smoked Cannabis for Neuropathic Pain

Commentators have suggested that patients should use whole plant cannabis, as opposed to chemical derivatives, because of other potentially beneficial compounds [8,19]. In addition, a number of articles have reported on interactions between cannabinoid and opioid receptors which may result in enhanced analgesia and a synergistic effect when CC is added to opioids [54,55]. This may translate into patients being able to reduce their opioid intake with adjuvant cannabinoid therapy [5,29].

Although prescribing cannabis is legal in 16 states and the District of Columbia, it remains illegal at the federal level. Portions of the American Medical Association's Code of Medical Ethics, Opinion 1.02 - The Relation of Law and Ethics reads, "Ethical values and legal principles are usually closely related, but ethical obligations typically exceed legal duties. In some cases, the law mandates unethical conduct." "In exceptional circumstances of unjust laws, ethical responsibilities should supersede legal obligations." [56] An "exceptional circumstance of unjust laws" may be interpreted as the federal ban on cannabis for medical use. Sixteen states and the District of Columbia found the federal government's prohibition on prescribing and using medicinal cannabis so unjust as to create laws in direct violation of federal statute. Therefore, one could surmise that prescribing cannabis for the purpose of harm reduction is ethical even though it violates federal law. In addition, Hayry suggests that the idea of "freedom" also provides an ethical reason for prescribing cannabis and he writes, "... whatever the legal situation, respect for the freedom of the individual would imply that requests like this (for medicinal cannabis) should be granted, either by health professionals, or by society as a whole." [57]

In states where medicinal cannabis is legal, physicians who treat neuropathic pain with opioids should evaluate their patients for a trial of cannabis and prescribe it when appropriate prior to using opioids. There is sufficient evidence of safety and efficacy for the use of CC in the treatment of nerve pain relative to opioids and as Carter et al write, "From a pharmacological prospective, cannabinoids are considerably safer than opioids..." [8] Prescribing cannabis in place of opioids for neuropathic pain may reduce the morbidity and mortality rates associated with prescription pain medications and may be an effective harm reduction strategy.

[The subject of cannabis dosing is beyond the scope of this paper but those interested should consider reading Carter GT, Weydt P, Kyashna-Tocha M, Abrams DI. Medicinal cannabis: rational guidelines for dosing. IDrugs 2004;7:464-70.]


  • International Association for the Study of Pain. IASP Taxonomy., Accessed December 2, 2011.
  • Center for Medicinal Cannabis Research, University of California. Report to the Legislature and Governor of the State of California presenting findings pursuant to SB847 which created the CMCR and provided state funding. 2010.
  • Dworkin RH, Backonja M, Rowbotham MC, Allen RR, Argoff CR, Bennett GJ, Bushnell MC, Farrar JT, Galer BS, Haythornthwaite JA, Hewitt DJ, Loeser JD, Max MB, Saltarelli M, Schmader KE, Stein C, Thompson D, Turk DC, Wallace MS, Watkins LR, Weinstein SM. Advances in neuropathic pain: diagnosis, mechanisms, and treatment recommendations. Arch Neurol. 2003;60:1524–34. doi: 10.1001/archneur.60.11.1524. [PubMed] [Cross Ref]
  • Dworkin RH, O'Connor AB, Audette J, Baron R, Gourlay GK, Haanpää ML, Kent JL, Krane EJ, Lebel AA, Levy RM, Mackey SC, Mayer J, Miaskowski C, Raja SN, Rice AS, Schmader KE, Stacey B, Stanos S, Treede RD, Turk DC, Walco GA, Wells CD. Recommendations for the pharmacological management of neuropathic pain: an overview and literature update. Mayo Clin Proc. 2010;85(Suppl 3):S3–14. [PMC free article] [PubMed]
  • Leung L. Cannabis and its derivatives: review of medical use. J Am Board Fam Med. 2011;24:452–62. doi: 10.3122/jabfm.2011.04.100280. [PubMed] [Cross Ref]
  • Lynch ME, Campbell F. Cannabinoids for Treatment of Chronic Non-Cancer Pain; a Systematic Review of Randomized Trials. Br J Clin Pharmacol. 2011. in press . [PMC free article] [PubMed]
  • Thaler A, Gupta A, Cohen SP. Cannabinoids for pain management. Adv Psychosom Med. 2011;30:125–38. [PubMed]
  • Carter GT, Flanagan AM, Earleywine M, Abrams DI, Aggarwal SK, Grinspoon L. Cannabis in palliative medicine: improving care and reducing opioid-related morbidity. Am J Hosp Palliat Care. 2011;28:297–303. doi: 10.1177/1049909111402318. [PubMed] [Cross Ref]
  • Kleinig J. The ethics of harm reduction. Subst Use Misuse. 2008;43:1–16. doi: 10.1080/10826080701690680. [PubMed] [Cross Ref]
  • Reiman A. Cannabis as a substitute for alcohol and other drugs. Harm Reduct J. 2009;6:35. doi: 10.1186/1477-7517-6-35. [PMC free article] [PubMed] [Cross Ref]
  • Sacerdote P, Franchi S, Gerra G, Leccese V, Panerai AE, Somaini L. Buprenorphine and methadone maintenance treatment of heroin addicts preserves immune function. Brain Behav Immun. 2008;22:606–13. doi: 10.1016/j.bbi.2007.12.013. [PubMed] [Cross Ref]
  • Bailey SR, Fong DM, Bryson SW, Fortmann SP, Killen JD. Perceived drug assignment and treatment outcome in smokers given nicotine patch therapy. J Subst Abuse Treat. 2010;39:150–6. doi: 10.1016/j.jsat.2010.05.013. [PMC free article] [PubMed] [Cross Ref]
  • Wermeling DP. Opioid harm reduction strategies: focus on expanded access to intranasal naloxone. Pharmacotherapy. 2010;30:627–31. doi: 10.1592/phco.30.7.627. [PubMed] [Cross Ref]
  • United States Drug Enforcement Administration. Lists of: Scheduling Actions, Controlled Substances, Regulated Chemicals., Accessed December 2, 2011.
  • The National Organization for the Reform of Marijuana Laws. Active State Medical Marijuana Programs., Accessed August 21, 2011.
  • Medical Marijuana. 16 Legal Medical Marijuana States and DC Laws, Fees, and Possession Limits., Accessed December 2, 2011.
  • Russo EB. History of cannabis and its preparations in saga, science, and sobriquet. Chem Biodivers. 2007;4:1614–48. doi: 10.1002/cbdv.200790144. [PubMed] [Cross Ref]
  • Brownstein MJ. A brief history of opiates, opioid peptides, and opioid receptors. Proc Natl Acad Sci USA. 1993;90:5391–3. doi: 10.1073/pnas.90.12.5391. [PubMed] [Cross Ref]
  • Duarte DF. Opium and opioids: a brief history. Rev Bras Anestesiol. 2005;55:135–46. [PubMed]
  • Di Marzo V. A brief history of cannabinoid and endocannabinoid pharmacology as inspired by the work of British scientists. Trends Pharmacol Sci. 2006;27:134–40. doi: 10.1016/ [PubMed] [Cross Ref]
  • Mehmedic Z, Chandra S, Slade D, Denham H, Foster S, Patel AS, Ross SA, Khan IA, ElSohly MA. Potency trends of Δ9-THC and other cannabinoids in confiscated cannabis preparations from 1993 to 2008. J Forensic Sci. 2010;55:1209–17. doi: 10.1111/j.1556-4029.2010.01441.x. [PubMed] [Cross Ref]
  • Russo EB. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Br J Pharmacol. 2011;163:1344–64. doi: 10.1111/j.1476-5381.2011.01238.x. [PMC free article] [PubMed] [Cross Ref]
  • Russo E, Guy GW. A tale of two cannabinoids: The therapeutic rationale for combining tetrahydrocannabinol and cannabidiol. Med Hypotheses. 2006;66:234–46. doi: 10.1016/j.mehy.2005.08.026. [PubMed] [Cross Ref]
  • Placzek EA, Okamoto Y, Ueda N, Barker EL. Mechanisms for recycling and biosynthesis of endogenous cannabinoids anandamide and 2-arachidonylglycerol. J Neurochem. 2008;107:987–1000. [PMC free article] [PubMed]
  • Bodnar RJ. Endogenous opiates and behavior: 2009. Peptides. 2010;31:2325–59. doi: 10.1016/j.peptides.2010.09.016. [PubMed] [Cross Ref]
  • Vella-Brincat J, Macleod AD. Adverse effects of opioids on the central nervous systems of palliative care patients. J Pain Palliat Care Pharmacother. 2007;21:15–25. doi: 10.1080/J354v21n01_05. [PubMed] [Cross Ref]
  • Furlan AD, Sandoval JA, Mailis-Gagnon A, Tunks E. Opioids for chronic noncancer pain: a meta-analysis of effectiveness and side effects. CMAJ. 2006;174:1589–94. doi: 10.1503/cmaj.051528. [PMC free article] [PubMed] [Cross Ref]
  • Bushlin I, Rozenfeld R, Devi LA. Cannabinoid-opioid interactions during neuropathic pain and analgesia. Curr Opin Pharmacol. 2010;10:80–6. doi: 10.1016/j.coph.2009.09.009. [PMC free article] [PubMed] [Cross Ref]
  • Hosking RD, Zajicek JP. Therapeutic potential of cannabis in pain medicine. Br J Anaesth. 2008;101:59–68. doi: 10.1093/bja/aen119. [PubMed] [Cross Ref]
  • National Institute on Drug Abuse. InfoFacts: Marijuana., Accessed December 2, 2011.
  • Schubart CD, Sommer IE, van Gastel WA, Goetgebuer RL, Kahn RS, Boks MP. Cannabis with high cannabidiol content is associated with fewer psychotic experiences. Schizophr Res. 2011;130:216–21. doi: 10.1016/j.schres.2011.04.017. [PubMed] [Cross Ref]
  • Wang T, Collet JP, Shapiro S, Ware MA. Adverse effects of medical cannabinoids: a systematic review. CMAJ. 2008;178:1669–78. doi: 10.1503/cmaj.071178. [PMC free article] [PubMed] [Cross Ref]
  • Walwyn WM, Miotto KA, Evans CJ. Opioid pharmaceuticals and addiction: the issues, and research directions seeking solutions. Drug Alcohol Depend. 2010;108:156–65. doi: 10.1016/j.drugalcdep.2010.01.001. [PMC free article] [PubMed] [Cross Ref]
  • Lichtman AH, Martin BR. Cannabinoid tolerance and dependence. Handb Exp Pharmacol. 2005;168:691–717. doi: 10.1007/3-540-26573-2_24. [PubMed] [Cross Ref]
  • Warner M, Chen LH, Makuc DM. Increase in fatal poisonings involving opioid analgesics in the United States, 1999-2006. NCHS Data Brief. 2009;22:1–8. [PubMed]
  • Hashibe M, Morgenstern H, Cui Y, Tashkin DP, Zhang ZF, Cozen W, Mack TM, Greenland S. Marijuana use and the risk of lung and upper aerodigestive tract cancers: results of a population-based case-control study. Cancer Epidemiol Biomarkers Prev. 2006;15:1829–34. doi: 10.1158/1055-9965.EPI-06-0330. [PubMed] [Cross Ref]
  • 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;167:221–8. doi: 10.1001/archinte.167.3.221. [PMC free article] [PubMed] [Cross Ref]
  • Peat S. Using cannabinoids in pain and palliative care. Int J Palliat Nurs. 2010;16:481–5. [PubMed]
  • Birnbaum HG, White AG, Reynolds JL, Greenberg PE, Zhang M, Vallow S, Schein JR, Katz NP. Estimated costs of prescription opioid analgesic abuse in the United States in 2001: a societal perspective. Clin J Pain. 2006;22:667–76. doi: 10.1097/ [PubMed] [Cross Ref]
  • Egan D, Miron JA. In: Pot Politics: Marijuana and the Costs of Prohibition. Earleywine M, editor. New York: Oxford University Press; 2007. The budgetary implications of marihuana prohibition; pp. 17–39.
  • Substance Abuse and Mental Health Services Administration. Treatment Episode Data Set (TEDS). 1999-2009. Rockville, MD; Substance Abuse and Mental Health Services Administration; 2011. National Admissions to Substance Abuse Treatment Services, DASIS Series: S-56, HHS Publication No. (SMA) 11-4646.
  • Rahn EJ, Hohmann AG. Cannabinoids as pharmacotherapies for neuropathic pain: from the bench to the bedside. Neurotherapeutics. 2009;6:713–37. doi: 10.1016/j.nurt.2009.08.002. [PMC free article] [PubMed] [Cross Ref]
  • Finnerup NB, Sindrup SH, Jensen TS. Recent advances in pharmacological treatment of neuropathic pain. F1000 Med Rep. 2010;2:52. [PMC free article] [PubMed]
  • McQuay H. Evidence-based medicine: what is the evidence that it has made a difference? Palliat Med. 2011;25(5):394–7. doi: 10.1177/0269216310394707. [PubMed] [Cross Ref]
  • Ware MA, Wang T, Shapiro S, Robinson A, Ducruet T, Huynh T, Gamsa A, Bennett GJ, Collet JP. Smoked cannabis for chronic neuropathic pain: a randomized controlled trial. CMAJ. 2010;182:E694–701. doi: 10.1503/cmaj.091414. [PMC free article] [PubMed] [Cross Ref]
  • Ellis RJ, Toperoff W, Vaida F, van den Brande G, Gonzales J, Gouaux B, Bentley H, Atkinson JH. Smoked medicinal cannabis for neuropathic pain in HIV: a randomized, crossover clinical trial. Neuropsychopharmacology. 2009;34:672–80. doi: 10.1038/npp.2008.120. [PMC free article] [PubMed] [Cross Ref]
  • 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;9:506–21. doi: 10.1016/j.jpain.2007.12.010. [PubMed] [Cross Ref]
  • Abrams DI, Jay CA, Shade SB, Vizoso H, Reda H, Press S, Kelly ME, Rowbotham MC, Petersen KL. Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial. Neurology. 2007;68:515–21. doi: 10.1212/01.wnl.0000253187.66183.9c. [PubMed] [Cross Ref]
  • Karst M, Salim K, Burstein S, Conrad I, Hoy L, Schneider U. Analgesic effect of the synthetic cannabinoid CT-3 on chronic neuropathic pain: a randomized controlled trial. JAMA. 2003;290:1757–62. doi: 10.1001/jama.290.13.1757. [PubMed] [Cross Ref]
  • Frank B, Serpell MG, Hughes J, Matthews JN, Kapur D. Comparison of analgesic effects and patient tolerability of nabilone and dihydrocodeine for chronic neuropathic pain: randomised, crossover, double blind study. BMJ. 2008;336:199–201. doi: 10.1136/bmj.39429.619653.80. [PMC free article] [PubMed] [Cross Ref]
  • Berman JS, Symonds C, Birch R. Efficacy of two cannabis based medicinal extracts for relief of central neuropathic pain from brachial plexus avulsion: results of a randomised controlled trial. Pain. 2004;112:299–306. doi: 10.1016/j.pain.2004.09.013. [PubMed] [Cross Ref]
  • 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;17:21–9. doi: 10.1191/0269215503cr581oa. [PubMed] [Cross Ref]
  • Nurmikko TJ, Serpell MG, Hoggart B, Toomey PJ, Morlion BJ, Haines D. Sativex successfully treats neuropathic pain characterised by allodynia: a randomised, double-blind, placebo-controlled clinical trial. Pain. 2007;133:210–20. doi: 10.1016/j.pain.2007.08.028. [PubMed] [Cross Ref]
  • Welch SP. Interaction of the cannabinoid and opioid systems in the modulation of nociception. Int Rev Psychiatry. 2009;21:143–51. doi: 10.1080/09540260902782794. [PubMed] [Cross Ref]
  • Desroches J, Beaulieu P. Opioids and cannabinoids interactions: involvement in pain management. Curr Drug Targets. 2010;11:462–73. doi: 10.2174/138945010790980303. [PubMed] [Cross Ref]
  • American Medical Association. Code of Medical Ethics. Opinion 1.02-The Relation of Law and Ethics., Accessed December 2, 2011.
  • Hayry M. Prescribing cannabis: freedom, autonomy, and values. J Med Ethics. 2004;30:333–6. doi: 10.1136/jme.2002.001347. [PMC free article] [PubMed] [Cross Ref]

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