1. Fine PG. Long-term consequences of chronic pain: mounting evidence for pain as a neurological disease and parallels with other chronic disease states. Pain Med. 2011;12(7):996-1004. doi:10.1111/j.1526-4637.2011.01187.x
2. Raffaeli W, Arnaudo E. Pain as a disease: an overview. J Pain Res. 2017;10:2003-2008. doi:10.2147/JPR.S138864
3. Dahlhamer J, Lucas J, Zelaya C, et al. Prevalence of Chronic Pain and High-Impact Chronic Pain Among Adults - United States, 2016. MMWR Morb Mortal Wkly Rep. 2018;67(36):1001-1006. doi:10.15585/mmwr.mm6736a2
4. Treede RD, Rief W, Barke A, et al. A classification of chronic pain for ICD-11. Pain. 2015;156(6):1003-1007. doi:10.1097/j.pain.0000000000000160
5. Beal BR, Wallace MS. An Overview of Pharmacologic Management of Chronic Pain. Med Clin North Am. 2016;100(1):65-79. doi:10.1016/j.mcina.2015.08.006
6. Hylands-White N, Duarte RV, Raphael JH. An overview of treatment approaches for chronic pain management. Rheumatol Int. 2017;37(1):29-42. doi:10.1007/s00296-016-3481-8
7. Graham DY, Opekun AR, Willingham FF, Qureshi WA. Visible small-intestinal mucosal injury in chronic NSAID users. Clin Gastroenterol Hepatol. 2005;3(1):55-59. doi:10.1016/s1542-3565(04)00603-2
8. Castellsague J, Pisa F, Rosolen V, et al. Risk of upper gastrointestinal complications in a cohort of users of nimesulide and other nonsteroidal anti-inflammatory drugs in Friuli Venezia Giulia, Italy. Pharmacoepidemiol Drug Saf. 2013;22(4):365-375. doi:10.1002/pds.3385
9. McDowell K, Clements JN. How can NSAIDs harm cardiovascular and renal function? JAAPA. 2014;27(4):12-15. doi:10.1097/01.JAA.0000444738.62411.83
10. Degenhardt L, Charlson F, Mathers B, et al. The global epidemiology and burden of opioid dependence: results from the global burden of disease 2010 study. Addiction. 2014;109(8):1320-1333. doi:10.1111/add.12551
11. Volkow ND, Icaza MEM, Poznyak V, Saxena S, Gerra G, UNODC-WHO Informal Scientific Network. Addressing the opioid crisis globally. World Psychiatry. 2019;18(2):231-232. doi:10.1002/wps.20633
12. Benyamin R, Trescot AM, Datta S, et al. Opioid complications and side effects. Pain Physician. 2008;11(2 Suppl):S105-20.
13. Vowles KE, McEntee ML, Julnes PS, Frohe T, Ney JP, van der Goes DN. Rates of opioid misuse, abuse, and addiction in chronic pain: a systematic review and data synthesis. Pain. 2015;156(4):569-576. doi:10.1097/01.j.pain.0000460357.01998.f1
14. Lucas P. Cannabis as an adjunct to or substitute for opiates in the treatment of chronic pain. J Psychoactive Drugs. 2012;44(2):125-133. doi:10.1080/02791072.2012.684624
15. Bonini SA, Premoli M, Tambaro S, et al. Cannabis sativa: A comprehensive ethnopharmacological review of a medicinal plant with a long history. J Ethnopharmacol. 2018;227:300-315. doi:10.1016/j.jep.2018.09.004
16. Lynch ME. Cannabinoids in the management of chronic pain: a front line clinical perspective. J Basic Clin Physiol Pharmacol. 2016;27(3):189-191. doi:10.1515/jbcpp-2015-0059
17. Fitzcharles MA, Baerwald C, Ablin J, Hauser W. Efficacy, tolerability and safety of cannabinoids in chronic pain associated with rheumatic diseases (fibromyalgia syndrome, back pain, osteoarthritis, rheumatoid arthritis): a systematic review of randomized controlled trials. Schmerz. 2016;30(1):47-61. doi:10.1007/s00482-015-0084-3
18. Hauser W, Petzke F, Fitzcharles MA. Efficacy, tolerability and safety of cannabis-based medicines for chronic pain management - an overview of systematic reviews. Eur J Pain. 2018;22(3):455-470. doi:10.1002/ejp.1118
19. Whiting PF, Wolff RF, Deshpande S, et al. Cannabinoids for Medical Use: A Systematic Review and Meta-analysis. JAMA. 2015;313(24):2456-2473. doi:10.1001/jama.2015.6358
20. Chaves C, Bittencourt PCT, Pelegrini A. Ingestion of a THC-Rich Cannabis Oil in People with Fibromyalgia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Pain Med. 2020;21(10):2212-2218. doi:10.1093/pm/pnaa303
21. Vickery AW, Finch PM. Cannabis: are there any benefits? Intern Med J. 2020;50(11):1326-1332. doi:10.1111/imj.15052
22. Almog S, Aharon-Peretz J, Vulfsons S, et al. The pharmacokinetics, efficacy, and safety of a novel selective-dose cannabis inhaler in patients with chronic pain: a randomized, double-blinded, placebo-controlled trial. Eur J Pain. 2020;24(8):1505-1516. doi:10.1002/ejp.1605
23. Hosseini A, McLachlan AJ, Lickliter JD. A phase I trial of the safety, tolerability and pharmacokinetics of cannabidiol administered as single-dose oil solution and single and multiple doses of a sublingual wafer in healthy volunteers. Br J Clin Pharmacol. 2021;87(4):2070-2077. doi:10.1111/bcp.14617
24. Izgelov D, Davidson E, Barasch D, Regev A, Domb AJ, Hoffman A. Pharmacokinetic investigation of synthetic cannabidiol oral formulations in healthy volunteers. Eur J Pharm Biopharm. 2020;154:108-115. doi:10.1016/j.ejpb.2020.06.021
25. Perkins D, Butler J, Ong K, et al. A Phase 1, Randomised, Placebo-Controlled, Dose Escalation Study to Investigate the Safety, Tolerability and Pharmacokinetics of Cannabidiol in Fed Healthy Volunteers. Eur J Drug Metab Pharmacokinet. 2020;45(5):575-586. doi:10.1007/s13318-020-00624-6
26. Vazquez M, Guevara N, Maldonado C, Guido PC, Schaiquevich P. Potential Pharmacokinetic Drug-Drug Interactions between Cannabinoids and Drugs Used for Chronic Pain. Biomed Res Int. 2020;2020:3902740. doi:10.1155/2020/3902740
27. Zou S, Kumar U. Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System. Int J Mol Sci. 2018;19(3). doi:10.3390/ijms19030833
28. Starowicz K, Finn DP. Cannabinoids and Pain: Sites and Mechanisms of Action. Adv Pharmacol. 2017;80:437-475. doi:10.1016/bs.apha.2017.05.003
29. Silver RJ. The Endocannabinoid System of Animals. Animals (Basel). 2019;9(9). doi:10.3390/ani9090686
30. Chavez AE, Chiu CQ, Castillo PE. TRPV1 activation by endogenous anandamide triggers postsynaptic long-term depression in dentate gyrus. Nat Neurosci. 2010;13(12):1511-1518. doi:10.1038/nn.2684
31. Demuth DG, Molleman A. Cannabinoid signalling. Life Sci. 2006;78(6):549-563. doi:10.1016/j.lfs.2005.05.055
32. Turcotte C, Blanchet MR, Laviolette M, Flamand N. The CB2 receptor and its role as a regulator of inflammation. Cell Mol Life Sci. 2016;73(23):4449-4470. doi:10.1007/s00018-016-2300-4
33. Schmitz K, Mangels N, Haussler A, Ferreiros N, Fleming I, Tegeder I. Pro-inflammatory obesity in aged cannabinoid-2 receptor-deficient mice. Int J Obes (Lond). 2016;40(2):366-379. doi:10.1038/ijo.2015.169
34. Singh UP, Singh NP, Singh B, Price RL, Nagarkatti M, Nagarkatti PS. Cannabinoid receptor-2 (CB2) agonist ameliorates colitis in IL-10(-/-) mice by attenuating the activation of T cells and promoting their apoptosis. Toxicol Appl Pharmacol. 2012;258(2):256-267. doi:10.1016/j.taap.2011.11.005
35. Shang Y, Tang Y. The central cannabinoid receptor type-2 (CB2) and chronic pain. Int J Neurosci. 2017;127(9):812-823. doi:10.1080/00207454.2016.1257992
36. Kano M, Ohno-Shosaku T, Hashimotodani Y, Uchigashima M, Watanabe M. Endocannabinoid-mediated control of synaptic transmission. Physiol Rev. 2009;89(1):309-380. doi:10.1152/physrev.00019.2008
37. Castillo PE, Younts TJ, Chavez AE, Hashimotodani Y. Endocannabinoid signaling and synaptic function. Neuron. 2012;76(1):70-81. doi:10.1016/j.neuron.2012.09.020
38. Staton PC, Hatcher JP, Walker DJ, et al. The putative cannabinoid receptor GPR55 plays a role in mechanical hyperalgesia associated with inflammatory and neuropathic pain. Pain. 2008;139(1):225-236. doi:10.1016/j.pain.2008.04.006
39. Huang SM, Bisogno T, Petros TJ, et al. Identification of a new class of molecules, the arachidonyl amino acids, and characterization of one member that inhibits pain. J Biol Chem. 2001;276(46):42639-42644. doi:10.1074/jbc.M107351200
40. Scavone JL, Sterling RC, Van Bockstaele EJ. Cannabinoid and opioid interactions: implications for opiate dependence and withdrawal. Neuroscience. 2013;248:637-654. doi:10.1016/j.neuroscience.2013.04.034
41. Russo EB, Burnett A, Hall B, Parker KK. Agonistic properties of cannabidiol at 5-HT1a receptors. Neurochem Res. 2005;30(8):1037-1043. doi:10.1007/s1064-005-6978-1
42. O’Sullivan SE. An update on PPAR activation by cannabinoids. Br J Pharmacol. 2016;173(12):1899-1910. doi:10.1111/bph.13497
43. Bakas T, van Nieuwenhuijzen PS, Devenish SO, McGregor IS, Arnold JC, Chebib M. The direct actions of cannabidiol and 2-arachidonoyl glycerol at GABAA receptors. Pharmacol Res. 2017;119:358-370. doi:10.1016/j.phrs.2017.02.022
44. Morales P, Hurst DP, Reggio PH. Molecular Targets of the Phytocannabinoids: A Complex Picture. Prog Chem Org Nat Prod. 2017;103:103-131. doi:10.1007/978-3-319-45541-9_4
45. Iffland K, Grotenhermen F. An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical Data and Relevant Animal Studies. Cannabis Cannabinoid Res. 2017;2(1):139-154. doi:10.1089/can.2016.0034
46. Atalay S, Jarocka-Karpowicz I, Skrzydlewska E. Antioxidative and Anti-Inflammatory Properties of Cannabidiol. Antioxidants (Basel). 2019;9(1). doi:10.3390/antiox9010021
47. Ke P, Shao BZ, Xu ZQ, et al. Activation of Cannabinoid Receptor 2 Ameliorates DSS-Induced Colitis through Inhibiting NLRP3 Inflammasome in Macrophages. PLoS One. 2016;11(9):e0155076. doi:10.1371/journal.pone.0155076
48. Shao BZ, Wei W, Ke P, Xu ZQ, Zhou JX, Liu C. Activating cannabinoid receptor 2 alleviates pathogenesis of experimental autoimmune encephalomyelitis via activation of autophagy and inhibiting NLRP3 inflammasome. CNS Neurosci Ther. 2014;20(12):1021-1028. doi:10.1111/cns.12349
49. Shi CS, Shenderov K, Huang NN, et al. Activation of autophagy by inflammatory signals limits IL-1beta production by targeting ubiquitinated inflammasomes for destruction. Nat Immunol. 2012;13(3):255-263. doi:10.1038/ni.2215
50. Wirth PW, Watson ES, ElSohly M, Turner CE, Murphy JC. Anti-inflammatory properties of cannabichromene. Life Sci. 1980;26(23):1991-1995. doi:10.1016/0024-3205(80)90631-1
51. Zurier RB, Burstein SH. Cannabinoids, inflammation, and fibrosis. FASEB J. 2016;30(11):3682-3689. doi:10.1096/fj.201600646R
52. Do Y, McKallip RJ, Nagarkatti M, Nagarkatti PS. Activation through cannabinoid receptors 1 and 2 on dendritic cells triggers NF-kappaB-dependent apoptosis: novel role for endogenous and exogenous cannabinoids in immunoregulation. J Immunol. 2004;173(4):2373-2382. doi:10.4049/jimmunol.173.4.2373
53. Lu T, Newton C, Perkins I, Friedman H, Klein TW. Cannabinoid treatment suppresses the T-helper cell-polarizing function of mouse dendritic cells stimulated with Legionella pneumophila infection. J Pharmacol Exp Ther. 2006;319(1):269-276. doi:10.1124/jpet.106.108381
54. Parker J, Atez F, Rossetti RG, Skulas A, Patel R, Zurier RB. Suppression of human macrophage interleukin-6 by a nonpsychoactive cannabinoid acid. Rheumatol Int. 2008;28(7):631-635. doi:10.1007/s00296-007-0489-0
55. Puffenbarger RA, Boothe AC, Cabral GA. Cannabinoids inhibit LPS-inducible cytokine mRNA expression in rat microglial cells. Glia. 2000;29(1):58-69.
56. Fiani B, Sarhadi KJ, Soula M, Zafar A, Quadri SA. Current application of cannabidiol (CBD) in the management and treatment of neurological disorders. Neurol Sci. 2020;41(11):3085-3098. doi:10.1007/s10072-020-04514-2
57. Weizman L, Dayan L, Brill S, et al. Cannabis analgesia in chronic neuropathic pain is associated with altered brain connectivity. Neurology. 2018;91(14):e1285-e1294. doi:10.1212/WNL.000000000006293
58. Xu DH, Cullen BD, Tang M, Fang Y. The Effectiveness of Topical Cannabidiol Oil in Symptomatic Relief of Peripheral Neuropathy of the Lower Extremities. Curr Pharm Biotechnol. 2020;21(5):390-402. doi:10.2174/1389201020666191202111534
59. van Amerongen G, Kanhai K, Baakman AC, et al. Effects on Spasticity and Neuropathic Pain of an Oral Formulation of Delta9-tetrahydrocannabinol in Patients With Progressive Multiple Sclerosis. Clin Ther. 2018;40(9):1467-1482. doi:10.1016/j.clinthera.2017.01.016
60. Lichtman AH, Lux EA, McQuade R, et al. Results of a Double-Blind, Randomized, Placebo-Controlled Study of Nabiximols Oromucosal Spray as an Adjunctive Therapy in Advanced Cancer Patients with Chronic Uncontrolled Pain. J Pain Symptom Manage. 2018;55(2):179-188 e1. doi:10.1016/j.jpainsymman.2017.09.001
61. Wright P, Walsh Z, Margolese S, et al. Canadian clinical practice guidelines for the use of plant-based cannabis and cannabinoid-based products in the management of chronic non-cancer pain and co-occurring conditions: protocol for a systematic literature review. BMJ Open. 2020;10(5):e036114. doi:10.1136/bmjopen-2019-036114
62. Berger AA, Keefe J, Winnick A, et al. Cannabis and cannabidiol (CBD) for the treatment of fibromyalgia. Best Pract Res Clin Anaesthesiol. 2020;34(3):617-631. doi:10.1016/j.bpa.2020.08.010
63. van de Donk T, Niesters M, Kowal MA, Olofsen E, Dahan A, van Velzen M. An experimental randomized study on the analgesic effects of pharmaceutical-grade cannabis in chronic pain patients with fibromyalgia. Pain. 2019;160(4):860-869. doi:10.1097/j.pain.0000000000001464
64. Akram H, Mokrysz C, Curran HV. What are the psychological effects of using synthetic cannabinoids? A systematic review. J Psychopharmacol. 2019;33:271-283. doi:10.1177/0269881119826592
65. Karschner EL, Darwin WD, McMahon RP, et al. Subjective and physiological effects after controlled sativex and oral THC administration. Clin Pharmacol Ther. 2011;89:400-407. doi:10.1038/clpt.2010.318
66. Bedi G, Cooper ZD, Haney M. Subjective, cognitive and cardiovascular dose-effect profile of nabilone and dronabinol in marijuana smokers. Addict Biol. 2013;18:872-881. doi:10.1111/j.1369-1600.2011.00427.x
67. Jicha CJ, Lofwall MR, Nuzzo PA, Babalonis S, Elayi SC, Walsh SL. Safety of oral dronabinol during opioid withdrawal in humans. Drug Alcohol Depend. 2015;157:179-183. doi:10.1016/j.drugalcdep.2015.09.031
68. Hemachandra D, McKetin R, Cherbuin N, Anstey KJ. Heavy cannabis users at elevated risk of stroke: evidence from a general population survey. Aust N Z J Public Health. 2016;40:226-230. doi:10.1111/1753-6405.12477
69. Wolff V, Lauer V, Rouyer O, et al. Cannabis use, ischemic stroke, and multifocal intracranial vasoconstriction: a prospective study in 48 consecutive young patients. Stroke. 2011;42:1778-1780. doi:10.1161/STROKEAHA.110.610915
70. Ravi D, Ghasemiesfe M, Korenstein D, Cascino T, Keyhani S. Associations between marijuana use and cardiovascular risk factors and outcomes a systematic review. Ann Intern Med. 2018;168:187-194. doi:10.7326/M17-1548
71. Gilron I, Blyth FM, Degenhardt L, et al. Risks of harm with cannabinoids, cannabis, and cannabis-based medicine for pain management relevant to patients receiving pain treatment: protocol for an overview of systematic reviews. Pain Rep. 2019;4. doi:10.1097/PR9.0000000000000742
72. Korantzopoulos P, Liu T, Papaioannides D, Li G, Goudevenos JA. Atrial fibrillation and marijuana smoking. Int J Clin Pract. 2008;62:308-313. doi:10.1111/j.1742-1241.2007.01505.x
73. Coughlin PA, Mavor AID. Arterial Consequences of Recreational Drug Use. Eur J Vasc Endovasc Surg. 2006;32:389-396. doi:10.1016/j.ejvs.2006.03.003
74. Ghasemiesfe M, Ravi D, Vali M, et al. Marijuana use, respiratory symptoms, and pulmonary function: a systematic review and meta-analysis. Ann Intern Med. 2018;169:106-115. doi:10.7326/M18-0522
75. Martinasek MP, McGrogan JB, Maysonet A. A systematic review of the respiratory effects of inhalational marijuana. Respir Care. 2016;61:1543-1551. doi:10.4187/respcare.04846
76. Mehra R, Moore BA, Crothers K, Tetrault J, Fiellin DA. The association between marijuana smoking and lung cancer: a systematic review. Arch Intern Med. 2006;166:1359-1367. doi:10.1001/archinte.166.13.1359
77. Tan C, Hatam N, Treasure T. Bullous Disease of the Lung and Cannabis Smoking: Insufficient Evidence for a Causative Link. J R Soc Med. 2006;99:77-80. doi:10.1177/014107680609900220
78. 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;167:221-228. doi:10.1001/archinte.167.3.221
79. Borges G, Bagge CL, Orozco R. A literature review and meta-analyses of cannabis use and suicidality. J Affect Disord. 2016;195:63-74. doi:10.1016/j.jad.2016.02.007
80. Gobbi G, Atkin T, Zytynski T, et al. Association of Cannabis Use in Adolescence and Risk of Depression, Anxiety, and Suicidality in Young Adulthood: A Systematic Review and Meta-analysis. JAMA Psychiatry. 2019;76:426-434. doi:10.1001/jamapsychiatry.2018.4500
81. Amar MB, Potvin S. Cannabis and Psychosis: what is the Link? J Psychoact Drugs. 2007;39:131-142. doi:10.1080/02791072.2007.10399871
82. Large M, Sharma S, Compton MT, Slade T, Nielssen O. Cannabis use and earlier onset of psychosis: a systematic meta-analysis. Arch Gen Psychiatry. 2011;68:555-561. doi:10.1001/archgenpsychiatry.2011.5
83. Myles N, Newall H, Nielssen O, Large M. The Association between Cannabis Use and Earlier Age at Onset of Schizophrenia and other Psychoses: Meta-analysis of Possible Confounding Factors. Curr Pharm Des. 2012;18:5055-5069. doi:10.2174/138161212802884816
84. Ragazzi TCC, Shuhama R, Menezes PR, Del-Ben CM. Cannabis use as a risk factor for psychotic-like experiences: a systematic review of non-clinical populations evaluated with the Community Assessment of Psychic Experiences. J Early Interv. 2018;12:1013-1023. doi:10.1111/eip.12693
85. Marconi A, Di Forti M, Lewis CM, Murray RM, Vassos E. Meta-Analysis of the association between the level of cannabis use and risk of psychosis. Schizophr Bull. 2016;42:1262-1269. doi:10.1093/schbul/sbw003
86. Kedzior KK, Laeber LT. A positive association between anxiety disorders and cannabis use or cannabis use disorders in the general population- a meta-analysis of 31 studies. BMC Psychiatry. 2014;14. doi:10.1186/1471-244X-14-136
87. Ganzer F, Bröning S, Kraft S, Sack PM, Thomasius R. Weighing the Evidence: A Systematic Review on Long-Term Neurocognitive Effects of Cannabis Use in Abstinent Adolescents and Adults. Neuropsychol Rev. 2016;26:186-222. doi:10.1007/s11065-016-9316-2
88. 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. doi:10.1017/S1355617703950016
89. Rabin RA, Zakzanis KK, George TP. The effects of cannabis use on neurocognition in schizophrenia: a meta-analysis. Schizophr Res. 2011;128:111-116. doi:10.1016/j.schres.2011.02.017
90. Scott JC, Slomiak ST, Jones JD, Rosen AFG, Moore TM, Gur RC. Association of Cannabis With Cognitive Functioning in Adolescents and Young Adults A Systematic Review and Meta-analysis. JAMA Psychiatry. 2018;75:585-595. doi:10.1001/jamapsychiatry.2018.0335
91. Oomen PP, Van Hell HH, Bossong MG. The acute effects of cannabis on human executive function. Behav Pharmacol. 2018;29:605-616. doi:10.1097/FBP.000000000000426
92. Bogaty SER, Lee RSC, Hickie IB, Hermens DF. Meta-analysis of neurocognition in young psychosis patients with current cannabis use. J Psychiatr Res. 2018;99:22-32. doi:10.1016/j.jpsychires.2018.01.010
93. Schoeler T, Monk A, Sami MB, et al. Continued versus discontinued cannabis use in patients with psychosis: a systematic review and meta-analysis. Lancet Psychiatry. 2016;3:215-225. doi:10.1016/S2215-0366(15)00363-6
94. Platt B, O’Driscoll C, Curran VH, Rendell PG, Kamboj SK. The effects of licit and illicit recreational drugs on prospective memory: a meta-analytic review. Psychopharmacology. 2019;236:1131-1143. doi:10.1007/s00213-019-05245-9
95. Schreiner AM, Dunn ME. Residual effects of cannabis use on neurocognitive performance after prolonged abstinence: a meta-analysis. Exp Clin Psychopharmacol. 2012;20:420-429. doi:10.1037/a0029117
96. Gurney J, Shaw C, Stanley J, Signal V, Sarfati D. Cannabis exposure and risk of testicular cancer: a systematic review and meta-analysis. BMC Cancer. 2015;15. doi:10.1186/s12885-015-1905-6
97. Ghasemiesfe M, Barrow B, Leonard S, Keyhani S, Korenstein D. Association between Marijuana Use and Risk of Cancer: A Systematic Review and Meta-analysis. JAMA Network Open. 2019;2:1-15. doi:10.1001/jamanetworkopen.2019.16318
98. 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. doi:10.1111/j.1465-3362.2009.00149.x
99. 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. doi:10.1016/j.alcohol.2005.04.008
100. Huang YHJ, Zhang ZF, Tashkin DP, Feng B, Straif K, Hashibe M. An epidemiologic review of marijuana and cancer: an update. Cancer Epidemiol Biomark Prev. 2015;24:15-31. doi:10.1158/1055-9965.EPI-14-1026
101. Sharapova SR, Phillips E, Sirocco K, Kaminski JW, Leeb RT, Rolle I. Effects of prenatal marijuana exposure on neuropsychological outcomes in children aged 1-11 years: a systematic review. Paediatr Perinat Epidemiol. 2018;32:512-532. doi:10.1111/ppe.12505
102. Conner SN, Bedell V, Lipsey K, Macones GA, Cahill AG, Tuuli MG. Maternal Marijuana Use and Adverse Neonatal Outcomes: A Systematic Review and Meta-analysis. Obstet Gynecol. 2016;128:713-723. doi:10.1097/AOG.0000000000001649
103. Gunn JKL, Rosales CB, Center KE, et al. Prenatal exposure to cannabis and maternal and child health outcomes: a systematic review and meta-analysis. BMJ Open. 2016;6:1-8. doi:10.1136/bmjopen-2015-009986
104. Tournebize J, Gibaja V, Kahn JP. Acute effects of synthetic cannabinoids: update 2015. Subst Abuse. 2017;38:344-366. doi:10.1080/08897077.2016.1219438
105. Courts J, Maskill V, Gray A, Glue P. Signs and symptoms associated with synthetic cannabinoid toxicity: systematic review. Australas Psychiatry. 2016;24:598-601. doi:10.1177/1039856216663733
106. Haden M, Archer JRH, Dargan PI, Wood DM. MDMB-CHMICA: Availability, Patterns of Use, and Toxicity Associated With This Novel Psychoactive Substance. Subst Use Misuse. 2017;52:223-232. doi:10.1080/10826084.2016.1223692
107. Tait RJ, Caldicott D, Mountain D, Hill SL, Lenton S. A systematic review of adverse events arising from the use of synthetic cannabinoids and their associated treatment. Clin Toxicol. 2016;54:1-13. doi:10.3109/15563650.2015.1110590
108. Mansoor K, Kheetan M, Shahnawaz S, et al. Systematic review of nephrotoxicity of drugs of abuse, 2005-2016. BMC Nephrology. 2017;18:1-15. doi:10.1186/s12882-017-0794-0
109. Panlilio LV, Goldberg SR, Justinova Z. Cannabinoid Abuse and Addiction: Clinical and Preclinical Findings. Clin Pharmacol Ther. 2015;97:616-627. doi:10.1002/cpt.118
110. Budney AJ, Roffman R, Stephens RS, Walker D. Marijuana dependence and its treatment. Addict Sci Clin Pract. 2007;4:4-16. doi:10.1151/ASCP07414
111. Ramesh D, Schlosburg JE, Wiebelhaus JM, Lichtman AH. Marijuana dependence: not just smoke and mirrors. ILAR Journal. 2011;52:295-308. doi:10.1093/ilar.52.3.295
112. Patel J, Marwaha R. Cannabis Use Disorder. In: Clinical Handbook of Adolescent Addiction. ; 2019:202-212.
113. Degenhardt L, Ferrari AJ, Calabria B, et al. The Global Epidemiology and Contribution of Cannabis Use and Dependence to the Global Burden of Disease: Results from the GBD 2010 Study. PLoS ONE. 2013;8:9-37. doi:10.1371/journal.pone.0076635
114. Freeman TP, Hindocha C, Baio G, et al. Europe PMC Funders Group Cannabidiol for the treatment of cannabis use disorder: Phase IIa double-blind placebo-controlled randomised adaptive Bayesian dose-finding trial. 2021;7:865-874. doi:10.1016/S2215-0366(20)30290-X.Cannabidiol
115. Gilbert DG, Rabinovich NE, McDaniel JT. Nicotine patch for cannabis withdrawal symptom relief: a randomized controlled trial. Psychopharmacology. 2020;237:1507-1519. doi:10.1007/s00213-020-05476-1
116. Sherman BJ, Caruso MA, McRae-Clark AL. Exogenous progesterone for cannabis withdrawal in women: feasibility trial of a novel multimodal methodology. Pharmacol Biochem Behav. 2019;179:22-26. doi:10.1016/j.pbb.2019.01.008
117. Allsop DJ, Copeland J, Lintzeris N, et al. Nabiximols as an agonist replacement therapy during cannabis withdrawal: a randomized clinical trial. JAMA Psychiatry. 2014;71:281-291. doi:10.1001/jamapsychiatry.2013.3947
118. Haney M, Hart CL, Vosburg SK, Comer SD, Reed SC, Foltin RW. Effects of THC and lofexidine in a human laboratory model of marijuana withdrawal and relapse. Psychopharmacology. 2008;197:157-168. doi:10.1007/s00213-007-1020-8
119. Walther L, Gantner A, Heinz A, Majic T. Evidenzbasierte Behandlungsoptionen der Cannabisabhängigkeit. Deutsches Arzteblatt International. 2016;113:653-659. doi:10.3238/arztebl.2016.0653
120. Zvonarev V, Fatuki TA, Tregubenko P. The Public Health Concerns of Marijuana Legalization: An Overview of Current Trends. Cureus. 2019;11. doi:10.7759/cureus.5806
121. Turner AR, Agrawal S. Marijuana. In: StatPearls. StatPearls Publishing; 2020.
122. Breijyeh Z, Jubeh B, Bufo SA, Karaman R, Scrano L. Cannabis: A Toxin-Producing Plant with Potential Therapeutic Uses. Toxins. 2021;13:1-2. doi:10.3390/toxins13020117
123. Bahji A, Stephenson C. International perspectives on the implications of cannabis legalization: a systematic review & thematic analysis. Int J Environ Res Public Health. 2019;16. doi:10.3390/ijerph16173095
124. Hall W, Lynskey M. Assessing the public health impacts of legalizing recreational cannabis use: the US experience. World Psychiatry. 2020;19:179-186. doi:10.1002/wps.20735
125. Leyton M. Cannabis legalization: Did we make a mistake? update 2019. J Psychiatry Neurosci. 2019;44:291-293. doi:10.1503/jpn.190136
126. Di Forti M. To legalize or not to legalize cannabis, that is the question! World Psychiatry. 2020;19:188-189. doi:10.1002/wps.20737