Safety and Toxicology of Cannabinoids

Neurotherapeutics

Volumn 12, Issue 4, 2015, Pages 735-746

  Sachs, Jane ^a   McGlade, Erin ^a   Yurgelun Todd, Deborah ^a  

^a UNIVERSITY OF UTAH SCHOOL OF MEDICINE   (United States)

Author keywords

Cannabis; Cannabis efficacy; Cannabis policy; Cannabis safety

Indexed keywords

CANNABINOID; ENDOCANNABINOID; CANNABIS;

BRAIN FUNCTION; CANNABIS ADDICTION; CANNABIS USE; CARDIOVASCULAR DISEASE; CARDIOVASCULAR EFFECT; CHEMICAL ANALYSIS; CHRONIC PAIN; CLIMATE; CLINICAL RESEARCH; COGNITION; COGNITIVE DEFECT; COMPARATIVE STUDY; DRUG EFFECT; DRUG EFFICACY; DRUG SAFETY; GLAUCOMA; HEALTH; HEALTH CARE POLICY; HIGH RISK PATIENT; HUMAN; IMMUNOPATHOLOGY; LONG TERM CARE; MENTAL DISEASE; NAUSEA AND VOMITING; NEOPLASM; NEUROIMAGING; NEUROLOGIC DISEASE; NEUROTOXICOLOGY; PRACTICE GUIDELINE; PRIORITY JOURNAL; PSYCHOLOGICAL ASPECT; PSYCHOSIS; PUBLIC HEALTH; RANDOMIZED CONTROLLED TRIAL (TOPIC); RESPIRATORY TRACT DISEASE; REVIEW; RISK ASSESSMENT; RISK FACTOR; SLEEP DISORDER; SLEEP TIME; ANIMAL; MARIJUANA ABUSE; TOXICOLOGY;

ANIMALS; CANNABINOIDS; CANNABIS; HEALTH POLICY; HUMANS; MARIJUANA ABUSE; TOXICOLOGY;

EID: 84973911568     PISSN: 19337213     EISSN: 18787479     Source Type: Journal    
DOI: 10.1007/s13311-015-0380-8     Document Type: Review

References (131)

1. UNODC. World Drug Report 2013. United Nations Publication Vienna, 2013.
2. Substance Abuse and Mental Health Services Administration (SAMHSA). Results from the 2013 National Survey on Drug Use and Health: Summary of national findings. Substance Abuse and Mental Health Servicels Administration, Rockville, MD, 2014.
3. Elsohly MA, Slade D. Chemical constituents of marijuana: the complex mixture of natural cannabinoids. Life Sci 2005;78:539-548.
4. Borgelt LM, Franson KL, Nussbaum AM, Wang GS. The pharmacologic and clinical effects of medical cannabis. Pharmacother 2013;33:195-209.
5. McPartland JM, Duncan M, Di Marzo V, Pertwee RG. Are cannabidiol and Delta(9) -tetrahydrocannabivarin negative modulators of the endocannabinoid system? A systematic review. Br J Pharmacol 2015;172:737-753.
6. Benbadis SR, Sanchez-Ramos J, Bozorg A, et al. Medical marijuana in neurology. Exp Rev Neurother 2014;14:1453-1465.
7. Mackie K. Signaling via CNS cannabinoid receptors. Mol Cell Endocrinol 2008;286:S60-S65.
8. Pertwee R. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9‐tetrahydrocannabinol, cannabidiol and Δ9‐tetrahydrocannabivarin. Br J Pharmacol 2008;153:199-215.
9. Pertwee RG. Cannabinoid pharmacology: the first 66 years. Br J Pharmacol 2006;147(Suppl. 1):S163-S171.
10. Piomelli D. The molecular logic of endocannabinoid signalling. Nat Rev Neurosci 2003;4:873-884.
11. Pertwee R. Receptors and channels targeted by synthetic cannabinoid receptor agonists and antagonists. Curr Med Chem 2010;17:1360.
12. Suarez-Pinilla P, Lopez-Gil J, Crespo-Facorro B. Immune system: a possible nexus between cannabinoids and psychosis. Brain Behav Immun 2014;40:269-282.
13. Machado Bergamaschi M, Helena Costa Queiroz R, Waldo Zuardi A, Crippa AS. Safety and side effects of cannabidiol, a Cannabis sativa constituent. Curr Drug Saf 2011;6:237-249.
14. Pope C, Mechoulam R, Parsons L. Endocannabinoid signaling in neurotoxicity and neuroprotection. Neurotoxicology 2010;31:562-571.
15. Schatman ME. Medical Marijuana: the state of the science. Medscape Neurology [Internet] 2015. [cited 2015 April 20]. Available from: http://www.medscape.com/viewarticle/839155
16. Adams IB, Martin BR. Cannabis: pharmacology and toxicology in animals and humans. Addiction 1996;91:1585-11614.
17. Cascini F, Aiello C, Di Tanna G. Increasing delta-9-tetrahydrocannabinol (Δ-9-THC) content in herbal cannabis over time: systematic review and meta-analysis. Curr Drug Abuse Rev 2012;5:32-40.
18. Fitzgerald KT, Bronstein AC, Newquist KL. Marijuana poisoning. Top Companion Anim Med 2013;28:8-12.
19. McLaren J, Swift W, Dillon P, Allsop S. Cannabis potency and contamination: a review of the literature. Addiction 2008;103:1100-1109.
20. Repp K, Raich A. Marijuana and health: a comprehensive review of 20 years of research. Washington County Oregon: Department of Health and Human Services; 2014.
21. Robson P. Human studies of cannabinoids and medicinal cannabis. Handb Exp Pharmacol 2005;(168):719-786.
22. Scallet AC. Neurotoxicology of cannabis and THC: a review of chronic exposure studies in animals. Pharmacol Biochem Behav 1991;40:671-676.
23. Wall ME, Sadler BM, Brine D, Taylor H, Perez‐Reyes M. Metabolism, disposition, and kinetics of delta‐9‐tetrahydrocannabinol in men and women. Clin Pharmacol Ther 1983;34:352-363.
24. Zuurman L, Ippel AE, Moin E, Van Gerven J. Biomarkers for the effects of cannabis and THC in healthy volunteers. Br J Clin Pharmacol 2009;67:5-21.
25. Zuurman L, Passier P, de Kam M, Kleijn H, Cohen A, van Gerven J. Pharmacodynamic and pharmacokinetic effects of the intravenously administered CB1 receptor agonist Org 28611 in healthy male volunteers. J Psychopharmacol 2009;23:633-644.
26. Grotenhermen F. The toxicology of cannabis and cannabis prohibition. Chem Biodivers 2007;4:1744-1769.
27. Hall W. The adverse health effects of cannabis use: what are they, and what are their implications for policy? Int J Drug Policy 2009;20:458-466.
28. Hall W, Degenhardt L. Adverse health effects of non-medical cannabis use. Lancet 2009;374:1383-1391.
29. Reece AS. Chronic toxicology of cannabis. J Clin Toxicol 2009;47:517-524.
30. Thomas G, Kloner RA, Rezkalla S. Adverse cardiovascular, cerebrovascular, and peripheral vascular effects of marijuana inhalation: what cardiologists need to know. Am J Cardiol 2014;113:187-190.
31. Kahan M, Srivastava A, Spithoff S, Bromley L. Prescribing smoked cannabis for chronic noncancer pain: preliminary recommendations. Can Fam Physician 2014;60:1083-1090.
32. Parakh P. Adverse health effects of non-medical cannabis use. Lancet 2010;375:196-197.
33. Tormey W. Adverse health effects of non-medical cannabis use. Lancet 2010;375:196.
34. Volkow ND, Baler RD, Compton WM, Weiss SR. Adverse health effects of marijuana use. N Engl J Med 2014;370:2219-2227.
35. Kalant H. Adverse effects of cannabis on health: an update of the literature since 1996. Prog Neuropsychopharmacol Biol Psychiatry 2004;28:849-863.
36. Hashibe M, Straif K, Tashkin DP, Morgenstern H, Greenland S, Zhang ZF. Epidemiologic review of marijuana use and cancer risk. Alcohol 2005;35:265-275.
37. Maertens RM, White PA, Williams A, Yauk CL. A global toxicogenomic analysis investigating the mechanistic differences between tobacco and marijuana smoke condensates in vitro. Toxicology 2013;308:60-73.
38. Gates PJ, Albertella L, Copeland J. The effects of cannabinoid administration on sleep: a systematic review of human studies. Sleep Med Rev 2014;18:477-487.
39. Tramèr MR, Carroll D, Campbell FA, Reynolds DJM, Moore RA, McQuay HJ. Cannabinoids for control of chemotherapy induced nausea and vomiting: quantitative systematic review. BMJ 2001;323:16.
40. Yamamoto I, Watanabe K, Matsunaga T, Kimura T, Funahashi T, Yoshimura H. Pharmacology and toxicology of major constituents of marijuana—on the metabolic activation of cannabinoids and its mechanism. Toxin Rev 2003;22:577-589.
41. Zhornitsky S, Potvin S. Cannabidiol in humans—the quest for therapeutic targets. Pharmaceuticals 2012;5:529-552.
42. Lynch ME, Campbell F. Cannabinoids for treatment of chronic non‐cancer pain; a systematic review of randomized trials. Br J Clin Pharmacol 2011;72:735-744.
43. Roitman P, Mechoulam R, Cooper-Kazaz R, Shalev A. Preliminary, open-label, pilot study of add-on oral Delta9-tetrahydrocannabinol in chronic post-traumatic stress disorder. Clin Drug Investig 2014;34:587-591.
44. Kobayashi H, Suzuki T, Kamata R, et al. Recent progress in the neurotoxicology of natural drugs associated with dependence or addiction, their endogenous agonists and receptors. J Toxicol Sci 1999;24:1-16.
45. Crane NA, Schuster RM, Fusar-Poli P, Gonzalez R. Effects of cannabis on neurocognitive functioning: recent advances, neurodevelopmental influences, and sex differences. Neuropsychol Rev 2013;23:117-137.
46. Meier MH, Caspi A, Ambler A, et al. Persistent cannabis users show neuropsychological decline from childhood to midlife. Proc Natl Acad Sci 2012;109:E2657-E2664.
47. Schoeler T, Bhattacharyya S. The effect of cannabis use on memory function: an update. Subst Abuse Rehabil 2013;4:11-27.
48. Ehrler M, McGlade EC, Yurgelun-Todd D. Subjective and cognitive effects of cannabinoids in marijuana smokers. In: Campolongo P, Fattore L, editors. Cannabinoid modulation of emotion, memory, and motivation. New York: Springer; 2015. p. 159–181.
49. Wrege J, Schmidt A, Walter A, et al. Effects of cannabis on impulsivity: a systematic review of neuroimaging findings. Curr Pharm Des 2014;20:2126.
50. Crean RD, Crane NA, Mason BJ. An evidence based review of acute and long-term effects of cannabis use on executive cognitive functions. J Addict Med 2011;5:1.
51. Gonzalez R, Carey C, Grant I. Nonacute (residual) neuropsychological effects of cannabis use: a qualitative analysis and systematic review. J Clin Pharmacol 2002;42(Suppl.1):48S-57S.
52. Solowij N, Pesa N. Cognitive abnormalities and cannabis use. Rev Bras Psiquiatr 2010;32:531-540.
53. Pope HG, Gruber AJ, Hudson JI, Huestis MA, Yurgelun‐Todd D. Cognitive Measures in long‐term cannabis users. J Clin Pharmacol 2002;42(Suppl. 1):41S-47S.
54. Pope Jr HG, Gruber AJ, Yurgelun-Todd D. Residual neuropsychologic effects of cannabis. Curr Psychiatry Rep 2001;3:507-512.
55. Grant I, Gonzalez R, Carey CL, Natarajan L, Wolfson T. Non-acute (residual) neurocognitive effects of cannabis use: a meta-analytic study. J Int Neuropsychol Soc 2003;9:679-689.
56. Schweinsburg AD, Brown SA, Tapert SF. The influence of marijuana use on neurocognitive functioning in adolescents. Curr Drug Abuse Rev 2008;1:99.
57. James A, James C, Thwaites T. The brain effects of cannabis in healthy adolescents and in adolescents with schizophrenia: a systematic review. Psychiatry Res 2013;214:181-189.
58. Pope HG, Gruber AJ, Hudson JI, Cohane G, Huestis MA, Yurgelun-Todd D. Early-onset cannabis use and cognitive deficits: what is the nature of the association? Drug Alcohol Depend 2003;69:303-310.
59. Pope HG, Yurgelun-Todd D. The residual cognitive effects of heavy marijuana use in college students. JAMA 1996;275:521-527.
60. Batalla A, Bhattacharyya S, Yucel M, et al. Structural and functional imaging studies in chronic cannabis users: a systematic review of adolescent and adult findings. PloS One 2013;8:e55821.
61. Lorenzetti V, Lubman DI, Whittle S, Solowij N, Yucel M. Structural MRI findings in long-term cannabis users: what do we know? Substance Use Misuse 2010;45:1787-1808.
62. Martin-Santos R, Fagundo AB, Crippa JA, et al. Neuroimaging in cannabis use: a systematic review of the literature. Psychol Med 2010;40:383-398.
63. Rapp C, Bugra H, Riecher-Rössler A, Tamagni C, Borgwardt S. Effects of cannabis use on human brain structure in psychosis: a systematic review combining in vivo structural neuroimaging and post mortem studies. Curr Pharm Des 2012;18:5070.
64. Lopez-Larson MP, Bogorodzki P, Rogowska J, et al. Altered prefrontal and insular cortical thickness in adolescent marijuana users. Behav Brain Res 2011;220:164-172.
65. McCormick MA, Shekhar A. Review of marijuana use in the adolescent population and implications of its legalization in the United States. J Drug Metab Toxicol 2014;5:2.
66. Jacobus J, Squeglia LM, Meruelo AD, et al. Cortical thickness in adolescent marijuana and alcohol users: a three-year prospective study from adolescence to young adulthood. Dev Cog Neurosci 2015 Apr 27 [Epub ahead of print].
67. Wetherill RR, Jagannathan K, Hager N, Childress AR, Rao H, Franklin TR. Cannabis, cigarettes, and their co-occurring use: disentangling differences in gray matter volume. Int J Neuropsychopharmacol 2015:pyv061.
68. Gruber SA, Yurgelun-Todd DA. Neuroimaging of marijuana smokers during inhibitory processing: a pilot investigation. Cog Brain Res 2005;23:107-118.
69. Churchwell JC, Yurgelun-Todd DA. Neuroimaging, adolescence, and risky behavior. In: MT B, DH F, R M (eds) Inhibitory control and drug abuse prevention. Springer, ??, 2011, pp. 101-122.
70. Kanayama G, Rogowska J, Pope HG, Gruber SA, Yurgelun-Todd DA. Spatial working memory in heavy cannabis users: a functional magnetic resonance imaging study. Psychopharmacol 2004;176:239-247.
71. Chang L, Cloak C, Yakupov R, Ernst T. Combined and independent effects of chronic marijuana use and HIV on brain metabolites. J Neuroimmune Pharmacol 2006;1:65-76.
72. Hermann D, Sartorius A, Welzel H, et al. Dorsolateral prefrontal cortex N-acetylaspartate/total creatine (NAA/tCr) loss in male recreational cannabis users. Biol Psychol 2007;61:1281-1289.
73. Prescot AP, Renshaw PF, Yurgelun-Todd DA. γ-Amino butyric acid and glutamate abnormalities in adolescent chronic marijuana smokers. Drug Alcohol Depend 2013;129:232-239.
74. Crippa JAS, Derenusson GN, Ferrari TB, et al. Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report. J Psychopharmacol 2011;25:121-130.
75. Gibbs M, Winsper C, Marwaha S, Gilbert E, Broome M, Singh SP. Cannabis use and mania symptoms: a systematic review and meta-analysis. J Affect Disord 2015;171:39-47.
76. Lev-Ran S, Roerecke M, Le Foll B, George TP, McKenzie K, Rehm J. The association between cannabis use and depression: a systematic review and meta-analysis of longitudinal studies. Psychol Med 2014;44:797-810.
77. Crippa JA, Zuardi AW, Martin-Santos R, et al. Cannabis and anxiety: a critical review of the evidence. Hum Psychopharmacol 2009;24:515-523.
78. Nussbaum AM, Thurstone C, McGarry L, Walker B, Sabel AL. Use and diversion of medical marijuana among adults admitted to inpatient psychiatry. Am J Drug Alcohol Abuse 2015;41:166-172.
79. Ferretjans R, Moreira FA, Teixeira AL, Salgado JV. The endocannabinoid system and its role in schizophrenia: a systematic review of the literature. Rev Bras Psiquiatr 2012;34:163-193.
80. Semple DM, McIntosh AM, Lawrie SM. Cannabis as a risk factor for psychosis: systematic review. J Psychopharmacol 2005;19:187-194.
81. Moore THM, Zammit S, Lingford-Hughes A, et al. Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. Lancet 2007;370:319-328.
82. Szoke A, Galliot AM, Richard JR, et al. Association between cannabis use and schizotypal dimensions—a meta-analysis of cross-sectional studies. Psychiatry Res 2014;219:58-66.
83. Malchow B, Hasan A, Fusar-Poli P, Schmitt A, Falkai P, Wobrock T. Cannabis abuse and brain morphology in schizophrenia: a review of the available evidence. Eur Arch Psychiatry Clin 2013;263:3-13.
84. J van der Meer F, Velthorst E, J Meijer C, WJ Machielsen M, de Haan L. Cannabis use in patients at clinical high risk of psychosis: impact on prodromal symptoms and transition to psychosis. Curr Pharm Des 2012;18:5036-5044.
85. Iseger TA, Bossong MG. A systematic review of the antipsychotic properties of cannabidiol in humans. Schizophr Res 2015;162:153-161.
86. Roser P, S Haussleiter I. Antipsychotic-like effects of cannabidiol and rimonabant: systematic review of animal and human studies. Curr Pharm Des 2012;18:5141-5155.
87. Calabria B, Degenhardt L, Hall W, Lynskey M. Does cannabis use increase the risk of death? Systematic review of epidemiological evidence on adverse effects of cannabis use. Drug Alcohol Rev 2010;29:318-330.
88. Johnston LD, Miech RA, O'Malley PM, Bachman JG, Schulenberg JE. Use of alcohol, cigarettes, and number of illicit drugs declines among U.S. teens. Ann Arbor, MI, 2014/ Retrieved 20 Apr. 2015. Report No.
89. National Intstitute of Drug Abuse (NIDA). Research Report Series: Marijuana. 2015.
90. Goldschmidt L, Day NL, Richardson GA. Effects of prenatal marijuana exposure on child behavior problems at age 10. Neurotoxicol Teratol 2000;22:325-336.
91. Richardson GA, Ryan C, Willford J, Day NL, Goldschmidt L. Prenatal alcohol and marijuana exposure: effects on neuropsychological outcomes at 10 years. Neurotoxicol Teratol 2002;24:309-320.
92. de Moraes Barros MC, Guinsburg R, Mitsuhiro S, Chalem E, Laranjeira RR. Neurobehavioral profile of healthy full-term newborn infants of adolescent mothers. Early Hum Dev 2008;84:281-287.
93. Fried PA, Makin J. Neonatal behavioural correlates of prenatal exposure to marihuana, cigarettes and alcohol in a low risk population. Neurotoxicol Teratol 1987;9:1-7.
94. Mincis M, Pfeferman A, Guimarães R, Ramos O, Zukerman E, Karniol I, et al. [Chronic administration of cannabidiol in man. Pilot study]. AMB Rev Assoc Med Bras 1973;19:185-190 (in Portuguese).
95. Koppel BS, Brust JC, Fife T, et al. 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.
96. Lakhan SE, Rowland M. Whole plant cannabis extracts in the treatment of spasticity in multiple sclerosis: a systematic review. BMC Neurol 2009;9:59.
97. O’Reilly K. AMA meeting: delegates support review of marijuana’s schedule I status. American Medical New [Internet] 2009. [cited 2015 Apr 20]. Available from: http://www.amednews.com/article/20091123/profession/311239968/7/
98. Wade DT, Makela P, House H, Bateman C, Robson P. Long-term use of a cannabis-based medicine in the treatment of spasticity and other symptoms in multiple sclerosis. Multiple Sclerosis 2006;12:639-645.
99. Pavisian B, MacIntosh BJ, Szilagyi G, Staines RW, O'Connor P, Feinstein A. Effects of cannabis on cognition in patients with MS A psychometric and MRI study. Neurology 2014;82:1879-1887.
100. Honarmand K, Tierney MC, O'Connor P, Feinstein A. Effects of cannabis on cognitive function in patients with multiple sclerosis. Neurololgy 2011;76:1153-1160.
101. Ghaffar O, Feinstein A. Multiple sclerosis and cannabis: a cognitive and psychiatric study. Neurology 2008;71:164-169.
102. Gloss D, Vickrey B. Cannabinoids for epilepsy. Cochrane Database Syst Rev 2012;6:CD009270.
103. Krishnan S, Cairns R, Howard R. Cannabinoids for the treatment of dementia. Cochrane Database Syst Rev 2009;(2):CD007204.
104. Solas M, Francis PT, Franco R, Ramirez MJ. CB 2 receptor and amyloid pathology in frontal cortex of Alzheimer's disease patients. Neurobiol Aging 2013;34:805-808.
105. Esposito G, De Filippis D, Carnuccio R, Izzo AA, Iuvone T. The marijuana component cannabidiol inhibits β-amyloid-induced tau protein hyperphosphorylation through Wnt/β-catenin pathway rescue in PC12 cells. J Mol Med 2006;84:253-258.
106. Eubanks LM, Rogers CJ, Beuscher AE, IV, et al. A molecular link between the active component of marijuana and Alzheimer's disease pathology. Mol Pharm 2006;3:773-777.
107. Fox SH, Henry B, Hill M, Crossman A, Brotchie J. Stimulation of cannabinoid receptors reduces levodopa‐induced dyskinesia in the MPTP‐lesioned nonhuman primate model of Parkinson's disease. Mov Disord 2002;17:1180-1187.
108. Sagredo O, Ruth Pazos M, Valdeolivas S, Fernández-Ruiz J. Cannabinoids: novel medicines for the treatment of Huntington's disease. Recent Pat CNS Drug Discov 2012;7:41-48.
109. McLoughlin BC, Pushpa‐Rajah JA, Gillies D, et al. Cannabis and schizophrenia. Cochrane Database Syst Rev 2014;10:CD004837.
110. Zuardi AW, Hallak JE, Dursun SM, et al. Cannabidiol monotherapy for treatment-resistant schizophrenia. J Psychopharmacol 2006;20:683-686.
111. Boychuk DG, Goddard G, Mauro G, Orellana MF. The effectiveness of cannabinoids in the management of chronic nonmalignant neuropathic pain: a systematic review. J Oral Facial Pain Headache 2015;29:7-14.
112. 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.
113. Martin-Sanchez E, Furukawa TA, Taylor J, Martin JL. Systematic review and meta-analysis of cannabis treatment for chronic pain. Pain Med 2009;10:1353-1368.
114. Richards BL, Whittle SL, Buchbinder R. Neuromodulators for pain management in rheumatoid arthritis. Cochrane Database Syst Rev 2012;1:CD008921.
115. Canadian Agency for Drugs and Technologies in Health (CADTH). CADTH rapid response reports. CADTH, Ottawa, 2014.
116. Machado Rocha FC, Stefano SC, De Cassia Haiek R, Rosa Oliveira LM, Da Silveira DX. Therapeutic use of Cannabis sativa on chemotherapy-induced nausea and vomiting among cancer patients: systematic review and meta-analysis. Eur J Cancer Care 2008;17:431-443.
117. Wang T, Collet JP, Shapiro S, Ware MA. Adverse effects of medical cannabinoids: a systematic review. CMAJ 2008;178:1669-1678.
118. Mack A, Joy J. Marijuana as medicine?: the science beyond the controversy: National Academies Press, 2000.
119. Kassirer JP. Federal foolishness and marijuana. N Engl J Med 1997;336:366.
120. Lopez-Pelayo H, Batalla A, Balcells MM, Colom J, Gual A. Assessment of cannabis use disorders: a systematic review of screening and diagnostic instruments. Psychol Med 2015;45:1121-1133.
121. Substance Abuse and Mental Health Services Administration (SAMHSA). Results from the 2012 National Survey on Drug Use and Health: summary of national findings. Substance Abuse and Mental Health Services Administration, Rockville, MD, 2013.
122. Okaneku J, Vearrier D, McKeever RG, LaSala GS, Greenberg MI. Change in perceived risk associated with marijuana use in the United States from 2002 to 2012. Clin Toxicol 2015;53:151-155.
123. Research PHL. Laws, maps & data: law atlas. Robert Wood Johnson Foundation.
124. Pacula RL, Hunt P, Boustead A. Words can be deceiving: a review of variation among legally effective medical marijuana laws in the United States. J Drug Policy Anal 2014;7:1-19.
125. Blumenson E, Nilsen E. No rational basis: the pragmatic case for marijuana law reform. Va J Soc Pol’y & L. 2009;17:43.
126. Bostwick JM. Blurred boundaries: the therapeutics and politics of medical marijuana. Mayo Clin Proc 2012;87:172-186.
127. Bostwick JM. The use of cannabis for management of chronic pain. Gen Hosp Psychiatry 2014;36:2-3.
128. Cohen PJ. Medical marijuana 2010: it's time to fix the regulatory vacuum. J Law Med Ethics 2010;38:654-666.
129. Caulkins JP, Hawken A, Kilmer B, Kleiman MA. Marijuana Legalization: what everyone needs to know. Oxford, Oxford University Press, 2012.
130. Kilmer B. Policy designs for cannabis legalization: starting with the eight Ps. Am J Drug Alcohol Ab 2014;40:259-261.
131. Caulkins JP, Hawken A, Kilmer B, Kleiman MA. High tax states: options for gleaning revenue from legal cannabis. Or L Rev 2012;91:1041.