Korean Journal of Biological Psychiatry (생물정신의학)

The Korean Society of Biological Psychiatry (대한생물정신의학회)
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Prospects for the Use of Cannabinoids in Mental Health

정신의학에서 대마 관련 약물의 전망

  • Daeyoung Roh (Department of Psychiatry, Hallym University College of Medicine) ;
  • Ki Won Jang (Mind-Neuromodulation Laboratory, Hallym University College of Medicine) ;
  • Chan-Hyung Kim (Department of Psychiatry and Institute of Behavioural Science in Medicine, Yonsei University College of Medicine)
  • 노대영 (한림대학교 의과대학 정신건강의학교실) ;
  • 장기원 (한림대학교 의과대학 마음신경조절연구소) ;
  • 김찬형 (연세대학교 의과대학 정신과학교실 및 행동과학연구소)
  • Received : 2023.10.12
  • Accepted : 2023.10.20
  • Published : 2023.10.31
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Abstract

Cannabis, presently being one of the most commonly employed psychoactive agents globally, ranks after alcohol and nicotine. Despite the permissibility of employing cannabis for medicinal objectives in Korea, the discussion regarding the authorization and control of cannabis for both recreational and medicinal intentions persists, giving rise to apprehensions about the plausible hazards and repercussions of cannabis on public well-being and health. Cannabis has the potential to induce positive experiences that mitigate certain psychiatric symptoms depending on the individual. However, a multitude of studies have demonstrated a close association between cannabis usage and detrimental effects on the brain, including the onset of schizophrenia and the deterioration of cognitive function. The endocannabinoid (eCB) system, which serves as the primary target for the active components of cannabis, was only recently discovered, and the precise mechanisms through which the intricate substances within cannabis interact with the body remain inadequately comprehended. The use of medical cannabis for mental illness has shown promise in treating anxiety, post-traumatic stress disorder, sleep disorders, and substance use disorders. Recent research has focused on the discovery of the eCB system, which plays a role in the therapeutic effects of cannabinoids. These studies are advancing the development of new treatments for mental disorders through research and clinical trials. In conclusion, while cannabis-related substances carry a risk for mental health, the eCB system also holds potential as a new therapeutic mechanism. Further research is needed to better understand the mechanisms of cannabinoids and determine appropriate medical uses.

Keywords

Acknowledgement

이 연구는 한국연구재단 (NRF) 정부지원사업(NRF-2022R1A2C1005797), 산림청(한국임업진흥원) 산림과학기술 연구개발사업(과제번호 2021390A00-2123-0105)의 지원을 받아 수행되었다.

References

  1. United Nations Office on Drugs and Crime. World drug report 2019. Booklet 5: cannabis and hallucinogens. Vienna: United Nations Office on Drugs and Crime;2019. 
  2. UNODC.org [homepage on the Internet]. Vienna: United Nations Office on Drugs and Crime [updated 2021 Jun 24; cited 2022 Feb 7]. Available from: https://www.unodc.org/unodc/data-and-analysis/wdr2021.html. 
  3. Testai FD, Gorelick PB, Aparicio HJ, Filbey FM, Gonzalez R, Gottesman RF, et al. Use of marijuana: effect on brain health: a scientific statement from the American Heart Association. Stroke 2022;53:e176-e187.  https://doi.org/10.1161/STR.0000000000000396
  4. Ganesh S, D'Souza DC. Cannabis and psychosis: recent epidemiological findings continuing the "causality debate". Am J Psychiatry 2022;179:8-10.  https://doi.org/10.1176/appi.ajp.2021.21111126
  5. Fischer B, Rehm J. Cannabis use, legalization and youth health. CMAJ 2017;189:E971-E972.  https://doi.org/10.1503/cmaj.733215
  6. Edition.CNN.com [homepage on the Internet]. Atlanta, GA: CNN [updated 2018 Oct 17; cited 2023 Aug 30]. Available from: https://edition.cnn.com/2018/10/17/opinions/canadian-cannabis-legalization-chivers-opinion-intl/index.html. 
  7. Hasin DS, Sarvet AL, Cerda M, Keyes KM, Stohl M, Galea S, et al. US adult illicit cannabis use, cannabis use disorder, and medical marijuana laws: 1991-1992 to 2012-2013. JAMA Psychiatry 2017;74:579-588.  https://doi.org/10.1001/jamapsychiatry.2017.0724
  8. Mechoulam R, Parker LA. The endocannabinoid system and the brain. Annu Rev Psychol 2013;64:21-47.  https://doi.org/10.1146/annurev-psych-113011-143739
  9. Scopetti M, Morena D, Manetti F, Santurro A, Fazio ND, D'Errico S, et al. Cannabinoids and brain damage: a systematic review on a frequently overlooked issue. Curr Pharm Biotechnol 2023;24:741-757. 
  10. Gaoni Y, Mechoulam R. Isolation, structure, and partial synthesis of an active constituent of hashish. J Am Chem Soc 1964;86:1646-1647.  https://doi.org/10.1021/ja01062a046
  11. Moffat AC, Osselton MD, Widdop B, Watts J. Clarke's analysis of drugs and poisons. 4th ed. London: Pharmaceutical Press;2011. 
  12. Munro S, Thomas KL, Abu-Shaar M. Molecular characterization of a peripheral receptor for cannabinoids. Nature 1993;365:61-65.  https://doi.org/10.1038/365061a0
  13. Hillard CJ. Stress regulates endocannabinoid-CB1 receptor signaling. Semin Immunol 2014;26:380-388.  https://doi.org/10.1016/j.smim.2014.04.001
  14. Legare CA, Raup-Konsavage WM, Vrana KE. Therapeutic potential of cannabis, cannabidiol, and cannabinoid-based pharmaceuticals. Pharmacology 2022;107:131-149.  https://doi.org/10.1159/000521683
  15. Hill MN, Haney M, Hillard CJ, Karhson DS, Vecchiarelli HA. The endocannabinoid system as a putative target for the development of novel drugs for the treatment of psychiatric illnesses. Psychol Med (in press). 
  16. D'Souza DC, Perry E, MacDougall L, Ammerman Y, Cooper T, Wu YT, et al. The psychotomimetic effects of intravenous delta9-tetrahydrocannabinol in healthy individuals: implications for psychosis. Neuropsychopharmacology 2004;29:1558-1572.  https://doi.org/10.1038/sj.npp.1300496
  17. Rey AA, Purrio M, Viveros MP, Lutz B. Biphasic effects of cannabinoids in anxiety responses: CB1 and GABA(B) receptors in the balance of GABAergic and glutamatergic neurotransmission. Neuropsychopharmacology 2012;37:2624-2634.  https://doi.org/10.1038/npp.2012.123
  18. 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;2:139-154.  https://doi.org/10.1089/can.2016.0034
  19. Sylantyev S, Jensen TP, Ross RA, Rusakov DA. Cannabinoid- and lysophosphatidylinositol-sensitive receptor GPR55 boosts neurotransmitter release at central synapses. Proc Natl Acad Sci USA 2013;110:5193-5198.  https://doi.org/10.1073/pnas.1211204110
  20. Andreasson S, Allebeck P, Engstrom A, Rydberg U. Cannabis and schizophrenia. A longitudinal study of Swedish conscripts. Lancet 1987;2:1483-1486.  https://doi.org/10.1016/S0140-6736(87)92620-1
  21. Strang J, Witton J, Hall W. Improving the quality of the cannabis debate: defining the different domains. BMJ 2000;320:108-110.  https://doi.org/10.1136/bmj.320.7227.108
  22. Silva PA, Stanton WR. From child to adult: the Dunedin multidisciplinary health and development study. Auckland: Oxford University Press;1996. 
  23. Arseneault L, Cannon M, Poulton R, Murray R, Caspi A, Moffitt TE. Cannabis use in adolescence and risk for adult psychosis: longitudinal prospective study. BMJ 2002;325:1212-1213.  https://doi.org/10.1136/bmj.325.7374.1212
  24. Dow-Edwards D, Silva L. Endocannabinoids in brain plasticity: cortical maturation, HPA axis function and behavior. Brain Res 2017;1654(Pt B):157-164.  https://doi.org/10.1016/j.brainres.2016.08.037
  25. Hebert-Chatelain E, Desprez T, Serrat R, Bellocchio L, Soria-Gomez E, Busquets-Garcia A, et al. A cannabinoid link between mitochondria and memory. Nature 2016;539:555-559.  https://doi.org/10.1038/nature20127
  26. Crane NA, Schuster RM, Mermelstein RJ, Gonzalez R. Neuropsychological sex differences associated with age of initiated use among young adult cannabis users. J Clin Exp Neuropsychol 2015;37:389-401.  https://doi.org/10.1080/13803395.2015.1020770
  27. Cloak CC, Alicata D, Ernst TM, Chang L. Psychiatric symptoms, salivary cortisol and cytokine levels in young marijuana users. J Neuroimmune Pharmacol 2015;10:380-390.  https://doi.org/10.1007/s11481-015-9606-0
  28. Wilkinson ST, Radhakrishnan R, D'Souza DC. Impact of cannabis use on the development of psychotic disorders. Curr Addict Rep 2014;1:115-128.  https://doi.org/10.1007/s40429-014-0018-7
  29. D'Souza DC, Radhakrishnan R, Sherif M, Cortes-Briones J, Cahill J, Gupta S, et al. Cannabinoids and psychosis. Curr Pharm Des 2016;22:6380-6391.  https://doi.org/10.2174/1381612822666160826105628
  30. Ganesh S, Cortes-Briones J, Ranganathan M, Radhakrishnan R, Skosnik PD, D'Souza DC. Psychosis-relevant effects of intravenous delta-9-tetrahydrocannabinol: a mega analysis of individual participant-data from human laboratory studies. Int J Neuropsychopharmacol 2020;23:559-570.  https://doi.org/10.1093/ijnp/pyaa031
  31. Hindley G, Beck K, Borgan F, Ginestet CE, McCutcheon R, Kleinloog D, et al. Psychiatric symptoms caused by cannabis constituents: a systematic review and meta-analysis. Lancet Psychiatry 2020;7:344-353.  https://doi.org/10.1016/S2215-0366(20)30074-2
  32. Food and Drug Administration. Marinol®. Silver Spring, MD: Food and Drug Administration;2004. 
  33. European Medicines Agency. Acomplia. Amsterdam: European Medicines Agency;2009. 
  34. Electronic Medicines Compendium. Sativex oromucosal spray. Leatherhead: Electronic Medicines Compendium;2015. 
  35. Epidiolex.com [homepage on the Internet]. Dublin: Jazz Pharmaceuticals [updated 2018; cited 2023 Aug 30]. Available from: https://www.epidiolex.com/sites/default/files/EPIDIOLEX_Full_Prescribing_Information.pdf2018. 
  36. Fda.gov [homepage on the Internet]. Silver Spring, MD: U.S. Food and Drug Administration [updated 2018 Jun 25; cited 2023 Aug 30]. Available from: https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-comprised-active-ingredient-derived-marijuana-treat-rare-severe-forms. 
  37. National Academy of Medicine of Korea. 2021 guidance for prevention of meical marjuana abuse for general public. Seoul: National Academy of Medicine of Korea;2021. 
  38. Graczyk M, Lukowicz M, Dzierzanowski T. Prospects for the use of cannabinoids in psychiatric disorders. Front Psychiatry 2021;12:620073. 
  39. Rutkowska M, Jamontt J, Gliniak H. Effects of cannabinoids on the anxiety-like response in mice. Pharmacol Rep 2006;58:200-206. 
  40. Naderi N, Haghparast A, Saber-Tehrani A, Rezaii N, Alizadeh AM, Khani A, et al. Interaction between cannabinoid compounds and diazepam on anxiety-like behaviour of mice. Pharmacol Biochem Behav 2008;89:64-75.  https://doi.org/10.1016/j.pbb.2007.11.001
  41. Bergamaschi MM, Queiroz RH, Chagas MH, de Oliveira DC, De Martinis BS, Kapczinski F, et al. Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naive social phobia patients. Neuropsychopharmacology 2011;36:1219-1226.  https://doi.org/10.1038/npp.2011.6
  42. Bhattacharyya S, Egerton A, Kim E, Rosso L, Riano Barros D, Hammers A, et al. Acute induction of anxiety in humans by delta9-tetrahydrocannabinol related to amygdalar cannabinoid-1 (CB1) receptors. Sci Rep 2017;7:15025. 
  43. Black N, Stockings E, Campbell G, Tran LT, Zagic D, Hall WD, et al. Cannabinoids for the treatment of mental disorders and symptoms of mental disorders: a systematic review and meta-analysis. Lancet Psychiatry 2019;6:995-1010.  https://doi.org/10.1016/S2215-0366(19)30401-8
  44. Kwee CMB, Leen NA, Van der Kamp RC, Van Lissa CJ, Cath DC, Groenink L, et al. Anxiolytic effects of endocannabinoid enhancing compounds: a systematic review and meta-analysis. Eur Neuropsychopharmacol 2023;72:79-94. 
  45. Whiting PF, Wolff RF, Deshpande S, Di Nisio M, Duffy S, Hernandez AV, et al. Cannabinoids for medical use: a systematic review and meta-analysis. JAMA 2015;313:2456-2473.  https://doi.org/10.1001/jama.2015.6358
  46. Bisson JI, Cosgrove S, Lewis C, Robert NP. Post-traumatic stress disorder. BMJ 2015;351:h6161. 
  47. Betthauser K, Pilz J, Vollmer LE. Use and effects of cannabinoids in military veterans with posttraumatic stress disorder. Am J Health Syst Pharm 2015;72:1279-1284.  https://doi.org/10.2146/ajhp140523
  48. 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.  https://doi.org/10.1016/j.psyneuen.2014.11.002
  49. Corroon J, Phillips JA. A cross-sectional study of cannabidiol users. Cannabis Cannabinoid Res 2018;3:152-161.  https://doi.org/10.1089/can.2018.0006
  50. Moltke J, Hindocha C. Reasons for cannabidiol use: a cross-sectional study of CBD users, focusing on self-perceived stress, anxiety, and sleep problems. J Cannabis Res 2021;3:5. 
  51. Monti JM. Hypnoticlike effects of cannabidiol in the rat. Psychopharmacology (Berl) 1977;55:263-265.  https://doi.org/10.1007/BF00497858
  52. Murillo-Rodriguez E, Millan-Aldaco D, Palomero-Rivero M, Mechoulam R, Drucker-Colin R. Cannabidiol, a constituent of Cannabis sativa, modulates sleep in rats. FEBS Lett 2006;580:4337-4345.  https://doi.org/10.1016/j.febslet.2006.04.102
  53. Chagas MH, Crippa JA, Zuardi AW, Hallak JE, Machado-de-Sousa JP, Hirotsu C, et al. Effects of acute systemic administration of cannabidiol on sleep-wake cycle in rats. J Psychopharmacol 2013;27:312-316.  https://doi.org/10.1177/0269881112474524
  54. Murillo-Rodriguez E, Millan-Aldaco D, Cicconcelli D, Giorgetti V, Arankowsky-Sandoval G, Alcaraz-Silva J, et al. Sleep-wake cycle disturbances and NeuN-altered expression in adult rats after cannabidiol treatments during adolescence. Psychopharmacology (Berl) 2021;238:1437-1447.  https://doi.org/10.1007/s00213-021-05769-z
  55. Bartoli F, Bachi B, Calabrese A, Moretti F, Crocamo C, Carra G. Cannabidiol for mood disorders: a call for more research. Can J Psychiatry 2021;66:182-183.  https://doi.org/10.1177/0706743720926798
  56. Bartoli F, Riboldi I, Bachi B, Calabrese A, Moretti F, Crocamo C, et al. Efficacy of cannabidiol for Δ-9-tetrahydrocannabinol-induced psychotic symptoms, schizophrenia, and cannabis use disorders: a narrative review. J Clin Med 2021;10:1303. 
  57. Rosic T, Kapoor R, Panesar B, Naji L, Chai DB, Sanger N, et al. The association between cannabis use and outcome in pharmacological treatment for opioid use disorder. Harm Reduct J 2021;18:24. 
  58. Hurd YL, Spriggs S, Alishayev J, Winkel G, Gurgov K, Kudrich C, et al. Cannabidiol for the reduction of cue-induced craving and anxiety in drug-abstinent individuals with heroin use disorder: a double-blind randomized placebo-controlled trial. Am J Psychiatry 2019;176:911-922.  https://doi.org/10.1176/appi.ajp.2019.18101191
  59. Kalia LV, Lang AE. Parkinson's disease. Lancet 2015;386:896-912.  https://doi.org/10.1016/S0140-6736(14)61393-3
  60. Thanabalasingam SJ, Ranjith B, Jackson R, Wijeratne DT. Cannabis and its derivatives for the use of motor symptoms in Parkinson's disease: a systematic review and meta-analysis. Ther Adv Neurol Disord 2021;14:17562864211018561. 
  61. Ross CA, Tabrizi SJ. Huntington's disease: from molecular pathogenesis to clinical treatment. Lancet Neurol 2011;10:83-98.  https://doi.org/10.1016/S1474-4422(10)70245-3
  62. Govert F, Schneider SA. Huntington's disease and Huntington's disease-like syndromes: an overview. Curr Opin Neurol 2013;26:420-427.  https://doi.org/10.1097/WCO.0b013e3283632d90
  63. Hillard CJ. The endocannabinoid signaling system in the CNS: a primer. Int Rev Neurobiol 2015;125:1-47.  https://doi.org/10.1016/bs.irn.2015.10.001
  64. Ceccarini J, Kuepper R, Kemels D, van Os J, Henquet C, Van Laere K. [18F]MK-9470 PET measurement of cannabinoid CB1 receptor availability in chronic cannabis users. Addict Biol 2015;20:357-367.  https://doi.org/10.1111/adb.12116
  65. Sideli L, Quigley H, La Cascia C, Murray RM. Cannabis use and the risk for psychosis and affective disorders. J Dual Diagn 2020;16:22-42.  https://doi.org/10.1080/15504263.2019.1674991
  66. Cravatt BF, Giang DK, Mayfield SP, Boger DL, Lerner RA, Gilula NB. Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides. Nature 1996;384:83-87.  https://doi.org/10.1038/384083a0
  67. deRoon-Cassini TA, Stollenwerk TM, Beatka M, Hillard CJ. Meet your stress management professionals: the endocannabinoids. Trends Mol Med 2020;26:953-968.  https://doi.org/10.1016/j.molmed.2020.07.002
  68. Drugfree.or.kr [homepage on the Internet]. Seoul: Korean Association Against Drug Abuse [updated 2018 Aug 28; cited 2023 Aug 30]. Available from: https://www.drugfree.or.kr/webzine/magazine/3/post-38.html. 
  69. UNODC.org [homepage on the Internet]. Vienna: United Nations Office on Drugs and Crime [updated 2018; cited 2023 Aug 30]. Available from: https://www.unodc.org/wdr2018/index.html. 
  70. Giroud C, de Cesare M, Berthet A, Varlet V, Concha-Lozano N, Favrat B. E-cigarettes: a review of new trends in cannabis use. Int J Environ Res Public Health 2015;12:9988-10008.  https://doi.org/10.3390/ijerph120809988
  71. Hill KP, Gold MS, Nemeroff CB, McDonald W, Grzenda A, Widge AS, et al. Risks and benefits of cannabis and cannabinoids in psychiatry. Am J Psychiatry 2022;179:98-109.  https://doi.org/10.1176/appi.ajp.2021.21030320
  72. Hasin DS. US epidemiology of cannabis use and associated problems. Neuropsychopharmacology 2018;43:195-212.  https://doi.org/10.1038/npp.2017.198
  73. De Aquino JP, Sherif M, Radhakrishnan R, Cahill JD, Ranganathan M, D'Souza DC. The psychiatric consequences of cannabinoids. Clin Ther 2018;40:1448-1456.  https://doi.org/10.1016/j.clinthera.2018.03.013
  74. Hill M. Perspective: be clear about the real risks. Nature 2015;525:S14. 
  75. Substance Abuse and Mental Health Services Administration. Key substance use and mental health indicators in the United States: results from the 2019 national survey on drug use and health (HHS publication no. PEP20-07-01-001, NSDUH series H-55). Rockville, MD: Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration;2020. 
  76. Park JY, Wu LT. Prevalence, reasons, perceived effects, and correlates of medical marijuana use: a review. Drug Alcohol Depend 2017;177:1-13.  https://doi.org/10.1016/j.drugalcdep.2017.03.009
  77. Royal College of Psychiatrists. Cannabis-based medicinal products (position statement PS05/19). London: Royal College of Psychiatrists;2019. 
  78. Vinod N. Regulation of appetite for treating obesity: lessons from the rimonabant debacle. Curr Trends Biomedical Eng Biosci 2018;15:555908.