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6 December 2018

Weighing the Benefits and Risks of Medical Marijuana Use: A Brief Review

PGY2 Psychiatric Pharmacy Resident, Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN 37212, USA
Pharmacy2018, 6(4), 128;https://doi.org/10.3390/pharmacy6040128
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Abstract

Despite federal prohibition of medical marijuana possession, sale, and use, marijuana use continues to escalate as state legalization persists and expands. The purpose of this discussion is to provide a brief summary of the evidence regarding both potential benefits and risks of medical marijuana use.
Despite federal prohibition of medical marijuana possession, sale, and use, marijuana use continues to escalate as individual state legalization persists and expands (Table 1). As the medical marijuana landscape rapidly changes, it is imperative that healthcare providers stay up to date on available evidence regarding both the benefits and risks of use. Although it is important to note potential benefits demonstrated in specific disease states, evidence in most qualifying indications is insufficient, with the majority lacking randomized controlled trials (RCTs) (Table 2).
Table 1. Qualifying indications by state [1].
Table 2. Potential benefits of marijuana [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33].
Marijuana and oral cannabinoids (dronabinol, nabilone, oral THC) have been associated with adverse effects, including serious adverse effects as well as study withdrawal. The most commonly reported adverse effects include asthenia, balance problems, disorientation, gastrointestinal effects, euphoria, somnolence, dry mouth, fatigue, hallucinations, paranoia, and agitation [11,17].
Marijuana use has a negative effect on mental health and neurologic function. Marijuana users are at risk for tolerance, dependence, and withdrawal [4,18,44]. Multiple studies have examined the negative effects of marijuana on acute and long-term cognition, including impairment in attention, impulse control, decision-making processes, working memory, and executive function. Additionally, marijuana has been associated with an early onset of psychotic disorders, an exacerbated course of illness in established psychotic disorders, exacerbation of mania in bipolar disorders, and worsened symptoms of PTSD [4,11,18,41,44].
Pulmonary, cardiovascular, and carcinogenic effects of marijuana remain controversial [4,44,48,49]. In vivo and in vitro studies have demonstrated that marijuana inhibits several hepatic enzymes (CYP2D6, CYP2C19, CYP2C9, CYP3A4), and preliminary evidence in humans suggests that marijuana may interact with serum drug concentrations of warfarin and antiretroviral therapies [16,50,51,52]. However, additional research is warranted in these areas as the risk of clinically significant drug interactions is unknown [53].
When discussing medical marijuana use, pharmacists must be knowledgeable about potential benefits and risks. Disease states with substantial evidence include chronic pain, chemotherapy-induced nausea and vomiting (oral cannabinoids only), and patient-reported spasticity in MS [2]. Further research is warranted, particularly regarding products similar to those currently available in dispensaries. Because medical marijuana lacks quality standards and FDA regulation, available products have shown significant inconsistencies, with one study revealing that only 17% of edible cannabis products were accurately labeled [54]. It is the responsibility of prescribers and pharmacists to educate patients on potential adverse events and drug interactions. Other pertinent issues to consider are marijuana dosing as well as the inability to extrapolate evidence between oral cannabinoids and marijuana due to differences in chemical composition. As a result of limited high-quality evidence and lack of regulation, the potential benefits and risks must be weighed carefully to make appropriate clinical decisions.

Funding

This research received no external funding.

Conflicts of Interest

The author has no potential conflict of interest or financial disclosures to report.

References

  1. State Medical Marijuana Laws. National Conference of State Legislatures Website. Available online: http://www.ncsl.org/research/health/state-medical-marijuana-laws.aspx (accessed on 26 November 2018).
  2. The 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, USA, 2017; Available online: https://www.nap.edu/catalog/24625/the-health-effects-of-cannabis-and-cannabinoids-the-current-state (accessed on 11 November 2018).
  3. Weber, M.; Goldman, B.; Truniger, S. Tetrahydrocannabinol (THC) for cramps in amyotrophic lateral sclerosis: A randomized, double-blind crossover trial. J. Neurol. Neurosurg. Psychiatry 2010, 81, 1135–1140. [Google Scholar] [CrossRef] [PubMed]
  4. Wilkinson, S.T.; Yarnell, S.; Radhakrishnan, R.; Ball, S.A.; D’Souza, D.C. Marijuana legalization: Impact on physicians and public health. Annu. Rev. Med. 2016, 67, 453–466. [Google Scholar] [CrossRef] [PubMed]
  5. Wilkinson, S.T.; Stefanovics, E.; Rosenheck, R.A. Marijuana use is associated with worse outcomes in symptom severity and violent behavior in patients with post-traumatic stress disorder. J. Clin. Psychiatry 2015, 76, 1174–1180. [Google Scholar] [CrossRef] [PubMed]
  6. Krishnan, S.; Cairns, R.; Howard, R. Cannabinoids for the treatment of dementia. Cochrane Database Syst. Rev. 2009, 2. [Google Scholar] [CrossRef]
  7. Volicer, L.; Stelly, M.; Morris, J.; McLaughlin, J.; Volicer, B.J. Effects of Dronabinol on anorexia and disturbed behavior in patients with Alzheimer’s disease. Int. J. Geriatr. Psychiatry 1997, 12, 913–919. [Google Scholar] [CrossRef]
  8. van den Elsen, G.A.; Ahmed, A.I.; Verkes, R.-J.; Feuth, T.; van der Marck, M.A.; Olde Rikkert, M.G. Effects of tetrahydrocannabinol on balance and gait in patients with dementia: A randomized controlled crossover trial. Am. J. Geriatr. Psychiatry 2015, 23, 1214–1224. [Google Scholar] [CrossRef]
  9. Walther, S.; Mahlberg, R.; Eichmann, U.; Kunz, D. Delta-9-tetrahydrocannabinol for nighttime agitation in severe dementia. Psychopharmacology (Berl.) 2006, 185, 524–528. [Google Scholar] [CrossRef]
  10. Hadland, S.E.; Knight, J.R.; Harris, S.K. Medical marijuana: Review of the science and implications for developmental-behavioral pediatric practice. J. Dev. Behav. Prediatr. 2015, 36, 115–123. [Google Scholar] [CrossRef]
  11. Nugent, S.M.; Morasco, B.J.; O’Neil, M.E.; Freeman, M.; Low, A.; Kondo, K.; Elven, C.; Zakher, B.; Motu’apuaka, M.; Paynter, R.; et al. The effects of cannabis among adults with chronic pain and an overview of general harms. Ann. Intern. Med. 2017, 167, 319–332. [Google Scholar] [CrossRef]
  12. Strasser, F.; Luftner, D.; Possinger, K.; Ernst, G.; Ruhstaller, T.; Meissner, W.; Ko, Y.D.; Schnelle, M.; Reif, M.; Cerny, T.; et al. Comparison of orally administered cannabis extra and delta-9-tetrahydrocannabinol in treating patients with cancer-related anorexia-cachexia syndrome: A multicenter phase III, randomized, double-blind placebo-controlled clinical trial from the Cannabis-In-Cachexia-Study-Group. J. Clin. Oncol. 2006, 24, 3394–3400. [Google Scholar]
  13. Foltin, R.W.; Fischman, M.W.; Byrne, M.F. Effects of smoked marijuana on food intake and body weight of humans living in a residential laboratory. Appetite 1988, 11, 1–14. [Google Scholar] [CrossRef]
  14. Haney, M.; Gunderson, E.W.; Rabkin, J.; Hart, C.L.; Vosburg, S.K.; Comer, S.D.; Foltin, R.W. Dronabinol and marijuana in HIV-positive marijuana smokers: Caloric intake, mood, and sleep. J. Acquir. Immune Defic. Syndr. 2007, 45, 545–554. [Google Scholar] [CrossRef] [PubMed]
  15. Jatoi, A.; Windschitl, H.E.; Loprinzi, C.L.; Sloan, J.A.; Dakhil, S.R.; Mailliard, J.A.; Pundaleeka, S.; Kardinal, C.G.; Fitch, T.R.; Krook, J.E.; et al. Dronabinol versus megestrol acetate versus combination therapy for cancer-associated anorexia: A North Central Cancer Treatment Group Study. J. Clin. Oncol. 2002, 20, 567–573. [Google Scholar] [CrossRef] [PubMed]
  16. Birdsall, S.M.; Birdsall, T.C.; Tims, L.A. The use of medical marijuana in cancer. Curr. Oncol. Rep. 2016, 18, 40. [Google Scholar] [CrossRef] [PubMed]
  17. Whiting, P.F.; Wolff, R.F.; Deshpande, S.; Di Nisio, M.; Duffy, S.; Hernandez, A.V. Cannabinoids for medical use: A systematic review and meta-analysis. JAMA 2015, 313, 2456–2473. [Google Scholar] [CrossRef] [PubMed]
  18. Andrade, M.H.; Carter, G.M.; Shaparin, N.; Suslov, K.; Ellis, R.J.; Ware, M.A.; Abrams, D.I.; Prasad, H.; Wilsey, B.; Indyk, D.; et al. Inhaled cannabis for chronic neuropathic pain: A meta-analysis of individual patient data. J. Pain 2015, 16, 1221–1232. [Google Scholar] [CrossRef] [PubMed]
  19. Naftali, T.; Mechulam, R.; Marii, A.; Gabay, G.; Stein, A.; Bronshtain, M.; Laish, I.; Benjaminov, F.; Konikoff, F.M. Lo-dose cannabidiol is safe but not effective in the treatment for chrohn’s disease, a randomized controlled trial. Dig. Dis. Sci. 2017, 62, 1615–1620. [Google Scholar] [CrossRef]
  20. Naftali, T.; Schleider, L.B.; Dotan, I.; Lansky, E.P.; Benjaminov, F.S.; Konikoff, F.M. Cannabis induces a clinical response in patients with crohn’s disease: A prospective placebo-controlled study. Clin. Gastroenterol. Hepatol. 2013, 11, 1276–1280. [Google Scholar] [CrossRef]
  21. Fiz, J.; Duran, M.; Capella, D.; Carbonell, J.; Farre, M. Cannabis use in patients with fibromyalgia: Effect on symptoms relief and health-related quality of life. PLoS ONE 2011, 6, e18440. [Google Scholar] [CrossRef]
  22. 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. [Google Scholar] [CrossRef]
  23. Green, K. Marijuana smoking vs. cannabinoids for glaucoma therapy. Arch. Ophthalmol. 1998, 116, 1433–1437. [Google Scholar] [CrossRef] [PubMed]
  24. Flach, A.J. Delta-9-tetrahydrocannabinol (THC) in the treatment of end-stage open-angle glaucoma. Trans. Am. Ophthalmol. Soc. 2002, 100, 215–222. [Google Scholar] [PubMed]
  25. Jay, W.M.; Green, K. Multiple-drop study of topically applied 1% δ9-tetrahydrocannabinol in human eyes. Arch. Ophthalmol. 1983, 101, 591–593. [Google Scholar] [CrossRef] [PubMed]
  26. Green, K.; Roth, M. Ocular effects of topical administration of delta 9-tetrahydrocannabinol in man. Arch. Ophthalmol. 1982, 100, 265–267. [Google Scholar] [CrossRef] [PubMed]
  27. Sun, X.; Xu, C.S.; Chadha, N.; Chen, A.; Liu, J. Marijuana for Glaucoma: A Recipe for Disaster or Treatment? Yale J. Biol. Med. 2015, 88, 265–269. [Google Scholar] [PubMed]
  28. Abrams, D.I.; Hilton, J.F.; Leiser, R.J.; Shade, S.B.; Elbeik, T.A.; Aweeka, F.T.; Benowitz, N.L.; Bredt, B.M.; Kosel, B.; Aberg, J.A.; et al. Short-term effects of cannabinoids in patients with HIV-1 infection: A randomized, placebo-controlled clinical trial. Ann. Intern. Med. 2003, 139, 258–266. [Google Scholar] [CrossRef] [PubMed]
  29. Timpone, J.G.; Wright, D.J.; Li, N.; Egorin, M.J.; Enama, M.E.; Mayers, J.; Galetto, G. Division of AIDS Treatment Research Initiative. The safety and pharmacokinetics of single-agent and combination therapy with megestrol acetate and dronabinol for the treatment of HIV wasting syndrome: The DATRI 004 Study Group. AIDS Res. Hum. Retroviruses 1997, 13, 305–315. [Google Scholar] [CrossRef]
  30. Struwe, M.; Kaempfer, S.H.; Geiger, C.J.; Pavia, A.T.; Plasse, T.F.; Shepard, K.V.; Ries, K.; Evans, T.G. Effect of dronabinol on nutritional status in HIV infection. Ann. Pharmacother. 1993, 27, 827–831. [Google Scholar] [CrossRef]
  31. Beal, J.E.; Olson, R.; Laubenstein, L.; Morales, J.O.; Bellman, P.; Yangco, B.; Lefkowitz, L.; Plasse, T.F.; Shepard, K.V. Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS. J. Pain Symptom Manag. 1995, 10, 89–97. [Google Scholar] [CrossRef]
  32. Rhyne, D.N.; Anderson, S.L.; Gedde, M.; Borgelt, L.M. Effects of medical marijuana on migraine headache frequency in an adult population. Pharmacotherapy 2016, 36, 505–510. [Google Scholar] [CrossRef]
  33. Corey-Blood, J.; Wolfson, T.; Gamst, A.; Jin, S.; Marcotte, T.D.; Bentley, H.; Gouaux, B. Cmoked cannabis for spasticity in multiple sclerosis: A randomized, placebo-controlled trial. Can. Med. Assoc. J. 2012, 184, 1143–1150. [Google Scholar] [CrossRef] [PubMed]
  34. Zajicek, J.P.; Hobart, J.C.; Slade, A.; Barnes, D.; Mattison, P.G.; MUSEC Research Group. Multiple sclerosis and extract of cannabis: Results of the MUSEC trial. J. Neurol. Neurosurg. Psychiatry 2012, 83, 1125–1132. [Google Scholar] [CrossRef] [PubMed]
  35. Novotna, A.; Mares, J.; Matcliffe, S.; Novakova, I.; Vachova, M.; Zapletalova, O.; Gasperini, C.; Pozzilli, C.; Cefaro, L.; Comi, G.; et al. A randomized, double-blind, placebo-controlled, parallel-group, enriched-design study of nabiximols (Sativex), as add-on therapy, in subjects with refractory spasticity caused by multiple sclerosis. Eur. J. Neurol. 2011, 18, 1122–1131. [Google Scholar] [CrossRef] [PubMed]
  36. Notcutt, W.; Langford, R.; Davies, P.; Ratcliffe, S.; Potts, R. A placebo-controlled, parallel-group, randomized withdrawal study of subjects with symptoms of spasticity due to multiple sclerosis who are receiving long-term Sativex (nabiximols). Mult. Scler. 2012, 18, 219–228. [Google Scholar] [CrossRef] [PubMed]
  37. Todaro, B. Cannabinoids in the treatment of chemotherapy-induced nausea and vomiting. J. Natl. Compr. Cancer Netw. 2012, 10, 487–492. [Google Scholar] [CrossRef]
  38. Carroll, C.B.; Bain, P.G.; Teare, L.; Liu, X.; Joint, C.; Wroath, C.; Parkin, S.G.; Fox, P.; Wright, D.; Hobart, J.; et al. Cannabis for dyskinesia in Parkinson disease: A randomized double-blind crossover study. Neurology 2004, 63, 1245–1250. [Google Scholar] [CrossRef] [PubMed]
  39. 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. Neurology 2014, 82, 1556–1563. [Google Scholar] [CrossRef]
  40. Chagas, M.H.; Zuardi, A.W.; Tumas, V.; Pena-Pereira, M.A.; Sobreira, E.T.; Bergamaschi, M.M.; dos Santos, A.C.; Teixeira, A.L.; Hallak, J.E.; Crippa, J.A. Effects of cannabidiol in the treatment of patients with Parkinson’s disease: An exploratory double-blind trial. J. Psychopharmacol. 2014, 28, 1088–1098. [Google Scholar] [CrossRef]
  41. Yarnell, S. The use of medicinal marijuana for posttraumatic stress disorder: A review of the current literature. Prim Care Companion CNS Disord. 2015, 17. [Google Scholar] [CrossRef]
  42. Jetly, R.; Heber, A.; Fraser, G.; Boisvert, D. The efficacy of nabilone, a synthetic cannabinoid, in the treatment of PTSD-associated nightmares: A preliminary randomized, double-blind, placebo-controlled cross-over design study. Psychoneuroendocrinology 2015, 51, 585–588. [Google Scholar] [CrossRef]
  43. Roitman, P.; Mechoulam, R.; Cooper-Kazaz, R.; Shalev, A. Preliminary, open-label, pilot study of add-on oral delta-9-tetrahydrocannabinol in chronic post-traumatic stress disorder. Clin. Drug Investig. 2014, 34, 587–591. [Google Scholar] [CrossRef] [PubMed]
  44. Wilkinson, S.T.; Radhakrishnan, R.; D’Souza, D.C. A systematic review of the evidence for medical marijuana in psychiatric indications. J. Clin. Psychiatry 2016, 77, 1050–1064. [Google Scholar] [CrossRef] [PubMed]
  45. Devinsky, O.; Cross, J.H.; Laux, L.; Wright, S. Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome. N. Engl. J. Med. 2017, 376, 2011–2020. [Google Scholar] [CrossRef] [PubMed]
  46. Thiele, E.A.; Marsh, E.D.; French, J.A.; Mazurkiewicz-Beldzinska, M.; Benbadis, S.R.; Joshi, C.; Lyons, P.D.; Taylor, A.; Roberts, C.; Sommerville, K.; et al. Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): A randomized, double-blind, placebo-controlled phase 3 trial. Lancet 2018, 391, 1085–1096. [Google Scholar] [CrossRef]
  47. Zuberi, S.; Devinsky, O.; Patel, A.; Cross, J.H.; Villaneuva, V.; Wirrell, E.C.; Roberts, C.; Checketts, D.; van Landingham, K. Cannabidiol (CBD) significantly decreases drop and total seizure frequency in Lennox-Gastaut syndrome (LGS): Results of a dose-ranging, multi-centre, randomised, double-blind, placebo-controlled trial (GWPCARE3). In Proceedings of the 32nd International Epilepsy Congress, Barcelona, Spain, 2–5 September 2017. in press. [Google Scholar]
  48. Andrade, C. Cannabis and neuropsychiatry, 2: The longitudinal risk of psychosis as an adverse outcome. J. Clin. Psychiatry 2016, 77, e739–e741. [Google Scholar] [CrossRef] [PubMed]
  49. Singh, A.; Saluja, S.; Kumar, A.; Agrawal, S.; Thind, M.; Nanda, S.; Shirani, J. Cardiovascular complications of marijuana and related substances: A review. Cardiol. Ther. 2017. [Google Scholar] [CrossRef] [PubMed]
  50. Yamreudeewong, W.; Wong, H.K.; Brausch, L.M.; Pulley, K.R. Probably interaction between warfarin and marijuana smoking. Ann. Pharmacother. 2009, 43, 1347–1353. [Google Scholar] [CrossRef]
  51. Kosel, B.W.; Aweeka, F.T.; Benowitz, N.L.; Shade, S.B.; Hilton, J.F.; Lizak, P.S.; Abrams, D.I. The effects of cannabinoids on the pharmacokinetics of indinavir and nelfinavir. AIDS 2002, 16, 543–550. [Google Scholar] [CrossRef]
  52. Lucas, C.J.; Galettis, P.; Schneider, J. The pharmacokinetics and the pharmacodynamics of cannabinoids. Br. J. Clin. Pharmacol. 2018, 84, 2477–2482. [Google Scholar] [CrossRef]
  53. Stout, S.M.; Ciminco, N.M. Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: A systematic review. Drug Metab. Rev. 2014, 46, 86–95. [Google Scholar] [CrossRef]
  54. 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. [Google Scholar] [CrossRef] [PubMed]

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