Epidemiology and Pharmacological Effects of Cannabis Use

Abstract

Cannabis (marijuana) is a widely consumed and frequently abused substance worldwide. Shortly after being ingested, the tetrahydrocannabinol (THC) contained within it is known to cause effects such as euphoria, relaxation, and alterations in perception. Cannabis use and the accompanying problems are rapidly increasing globally and in our country. This situation creates serious problems in social, economic, and health domains. Cannabis addiction not only reduces individuals' quality of life but also damages family structures and negatively impacts the overall welfare of society. Economically, the efforts and treatment processes to combat cannabis use incur significant costs and result in loss of workforce productivity. Health-wise, it leads to various physical and psychological problems. Preventing cannabis use is crucial for the welfare of our country and the health of our future generations. Therefore, it is necessary to have a thorough understanding of cannabis, its pharmacological properties, and the side effects it causes in users. This review provides general information on cannabis use, its pharmacological properties, and its effects on users. It is believed that this information can make significant contributions to academic studies aimed at protecting public health and reducing cannabis use.

Keywords

• Addiction
• Cannabis
• Pharmacological Effects
• Tetrahydrocannabinol

Kannabis Kullanımının Epidemiyolojisi ve Farmakolojik Etkileri

Öz

Kannabis (esrar), günümüzde dünya çapında yaygın olarak tüketilen ve sıklıkla suistimal edilen bir maddedir. Vücuda alındıktan kısa bir süre sonra içeriğinde bulunan Tetrahidrokanabinol (THC)'un kullanıcıda keyif, gevşeme ve algıda değişiklikler gibi etkilere neden olduğu bilinmektedir. Kannabis kullanımı ve bunun beraberinde getirdiği sorunlar, dünya genelinde ve ülkemizde hızla artış göstermektedir. Bu durum, sosyal, ekonomik ve sağlık alanlarında ciddi problemler yaratmaktadır. Kannabis bağımlılığı, bireylerin yaşam kalitesini düşürmekle kalmayıp, aile yapısını zedelemekte ve toplumun genel refahını olumsuz etkilemektedir. Ekonomik açıdan, bu mücadele ve tedavi süreçleri büyük maliyetler oluşturmakta, iş gücü kaybına neden olmaktadır. Sağlık açısından ise, çeşitli fiziksel ve psikolojik problemlere yol açmaktadır. Kannabis kullanımının engellenmesi ülkemizin refahı ve geleceğimizin sağlığı için oldukça önemli bir konudur. Bu nedenle; kannabisin iyi tanınması, farmakolojik özellikleri ve kullanıcılarda oluşturduğu etkilerinin iyi bilinmesi gerekir. Bu derlemede, kannabis kullanımı, kannabisin farmakolojik özellikleri ve kullanıcıda oluşturduğu etkiler hakkında genel bilgilere yer verilmiştir. Bu bilgilerin toplum sağlığını koruma ve kannabis kullanımını azaltma hedeflerine yönelik akademik çalışmalara önemli katkılar sağlayabileceği düşünülmektedir.

Anahtar Kelimeler

• Bağımlılık
• Farmakolojik Etkiler
• Kannabis
• Tetrahidrokanabinol

Kaynakça

1. Bussink C, Carpentier C, Davalos L, et al. World Drug Repot 2016. New York: United Nations, 2016.
2. Shao H, Du H, Gan Q, et al. Trends of the global burden of disease attributable to cannabis use disorder in 204 countries and territories 1990–2019 Results from the Disease Burden Study. Int J Ment Health Addict. 2023; doi: 10.1007/s11469-022-00999-4..
3. Pertwee RG. Handbook of Cannabis New York: Oxford University Press, 2014.
4. Degenhardt L, Hall W. Extent of illicit drug use and dependence, and their contribution to the global burden of disease. Lancet 2012; 379(9810): 55-70.
5. Gaoni Y, Mechoulam R. Isolation and structure of. DELTA.+-tetrahydrocannabinol and other neutral cannabinoids from hashish. Chem Bio Eng 1971; 93(1): 217-224.
6. Erkelens JL, Hazekamp A. That which we call Indica, by any other name would smell as sweet. J Cannabis Res 2014; 9(1): 9-15.
7. ElSohly MA, Slade D. Chemical constituents of marijuana: the complex mixture of natural cannabinoids. Life Sci 2005; 78(5): 539-548.
8. ElSohly MA, Mehmedic Z, Foster S, et al. Changes in cannabis potency over the last 2 decades (1995–2014) analysis of current data in the United States. Biol. Psychiatry 2016; 79(7): 613-619.

9. Pertwee RG. Pharmacology of cannabinoid CB1 and CB2 receptors. Clin Pharmacol Ther 1997; 74(2): 129-180.
10. Gaoni Y, Mechoulam R. Isolation, structure, and partial synthesis of an active constituent of hashish. J Am Chem Soc 1964; 86(8): 1646-1647.
11. Evren C, Bozkurt M. Synthetic cannabinoids: crisis of the decade. Dusunen Adam 2013; 26(1): 1-11.
12. Jacobson R. Medical marijuana: how the evidence stacks up. Sci Am Mind 2014; 25(3): 15.
13. Hancock S, McKim W. Drugs and Behavior: An İntroduction to Behavioral Pharmacology, 8th edition. New York: Pearson, 2017.
14. Abel E. Marijuana The First Twelve Thousand Years. New York: Plenum Press, 1980.
15. Heilig S. The pot book: a complete guide to Cannabis, its role in medicine, politics, science, and culture. Cogent Food Agric; 2011.
16. Goode E. Marijuana. London: Routledge; 2017.
17. Bonnie RJ, Whitebread C. The Marijuana Conviction: A History of Marijuana Prohibition in the United States. Srasota, FL: Book World, 1999.
18. Coffey C, Carlin JB, Degenhardt L, et al. Cannabis dependence in young adults: an Australian population study. Addiction 2002; 97(2): 187-194.
19. Agrawal A, Rogers CE, Lessov CN, et al. Alcohol, cigarette, and cannabis use between 2002 and 2016 in pregnant women from a nationally representative sample. JAMA Pediatr 2019; 173(1): 95-96.
20. Hall WD. The contribution of research to the development of a national cannabis policy in Australia. Addiction 2008; 103(5): 712-720.
21. Hall W, Stjepanović D, Caulkins J, et al. Public health implications of legalising the production and sale of cannabis for medicinal and recreational use. Lancet 2019; 394(10208): 1580-1590.
22. European Monitoring Centre for Drugs and Drug Addiction. Avrupa Uyuşturucu Raporu 2023. https://www.emcdda.europa.eu/news/2023. (Accessed 10.06.2024).
23. European Monitoring Centre for Drugs and Drug Addiction, European Drug Report:Trends and Developments; 2023. https://www.euda.europa.eu/publications/european-drug-report/2023 (Accessed 10.06.2024).
24. Kračmarová L, Klusoňová H, Petrelli F, Grappasonni I. Tobacco, alcohol and illegal substances: experiences and attitudes among Italian university students. Rev Assoc Med Bras (1992) 2011; 57(5): 523-528.
25. Majid Z, Mehdi Z, Sheen AI, Karim Z, et al. Prevalence of addiction in university students of asia. Journal of Society of Prevention, Advocacy and Research 2023; 2(1).
26. Yaman ÖM. Türkiye’de Gençlik ve Bağımlılık: Biblyometrik ve Tematik Bir Araştırma (1910-2020), 1.Baskı. İstanbul: Dem Matbaası, 2021.
27. Özer ÖA. Ortaöğrenim Öğrencilerinin Psikoaktif Madde Kullanımına Yaklaşımı ve Demografik Özellikler. Uzmanlık tezi, İstanbul: Bakırköy Ruh ve Sinir Hastalıkları Hastanesi, 1991.
28. Güner B. Üniversite öğrencilerinde uyuşturucu madde kullanım alışkanlıkları ve yaygınlığı: Aydın Adnan Menderes Üniversitesi Örneği. ADUSOBED 2019; 6(2): 81-95.
29. Ögel K. Madde kullanım bozuklukları epidemiyolojisi. Türkiye Klinikleri Dahili Tıp Bilimleri Dergisi Psikiyatri 2005; 1(47): 61-64.
30. Ögel K, Aksoy A. Tutuklu ve hükümlü ergenlerde madde kullanımı. Bağımlılık Dergisi 2007; 8(1): 11-17.
31. Karch SB. Pharmacokinetics and Pharmacodynamics of Abused Drugs. Boca Raton, FL: CRC Press, 2007.
32. Grotenhermen F. Pharmacokinetics and pharmacodynamics of cannabinoids. Clin Pharmacokinet 2003; 42(4): 327-360.
33. WHO. Clinical Descriptions and Diagnostic Requirements for ICD-11 Mental, Behavioural And Neurodevelopmental Disorders. Geneva: World Health Organization, 2024.
34. Murphy L, Bartke A. Marijuana/Cannabinoids: Boca Raton, FL: CRC Press; 1992.
35. Iseger TA, Bossong MG. A systematic review of the antipsychotic properties of cannabidiol in humans. Schizophr Res 2015; 162(1-3): 153-161.
36. Cooper R. Diagnosing the Diagnostic and Statistical Manual of Mental Disorders. New York: Routledge, 2018.
37. Livne O, Shmulewitz D, Lev-Ran S, Hasin DS. DSM-5 cannabis withdrawal syndrome: demographic and clinical correlates in US adults. Drug Alcohol Depend 2019; 195: 170-177.
38. Leweke FM, Koethe D. Cannabis and psychiatric disorders: it is not only addiction. Addict Biol 2008; 13(2): 264-275.
39. Reilly D, Didcott P, Swift W, Hall W. Long‐term cannabis use: characteristics of users in an Australian rural area. Addiction 1998; 93(6): 837-846.
40. Ozaki S, Wada K. Amotivational syndrome in organic solvent abusers. Nihon Yakurigaku Zasshi 2001; 117(1): 42-48.
41. Rovai L, Maremmani AGI, Pacini M, Pani PP, Rugani F, Lamanna F, et al. Negative dimension in psychiatry. Amotivational syndrome as a paradigm of negative symptoms in substance abuse. Riv Psichiatr 2013; 48(1): 1-9.
42. Ohlsson A, Lindgren JE, Wahlen A, et al. Plasma delta‐9‐tetrahydrocannabinol concentrations and clinical effects after oral and intravenous administration and smoking. Clin Pharmacol Ther 1980; 28(3): 409-416.
43. Lindgren J-E, Ohlsson A, Agurell S, et al. Clinical effects and plasma levels of Δ 9-tetrahydrocannabinol (Δ 9-THC) in heavy and light users of cannabis. Psychopharmacology (Berl) 1981; 74(3): 208-212.
44. Azorlosa JL, Heishman SJ, Stitzer ML, Mahaffey JM. Marijuana smoking: effect of varying delta 9-tetrahydrocannabinol content and number of puffs. J Pharmacol Exp Ther 1992; 261(1): 114-122.
45. Brenneisen R, Egli A, Elsohly M, et al. The effect of orally and rectally administered delta 9-tetrahydrocannabinol on spasticity: a pilot study with 2 patients. Int J Clin Pharmacol Ther 1996; 34(10): 446-452.
46. Kelly P, Jones RT. Metabolism of tetrahydrocannabinol in frequent and infrequent marijuana users. J Anal Toxicol 1992; 16(4): 228-235.
47. Brick J, Erickson CK. Drugs, The Brain, and Behavior: The Pharmacology of Abuse and Dependence: Philadelphia, PA: Haworth Press, 1998.
48. Adams IB, Martin BR. Cannabis: pharmacology and toxicology in animals and humans. Addiction 1996; 91(11): 1585-1614.
49. Musshoff F, Madea B. Review of biologic matrices (urine, blood, hair) as indicators of recent or ongoing cannabis use. Ther Drug Monit 2006; 28(2): 155-163.
50. Huestis MA, Henningfield JE, Cone EJ. Blood cannabinoids. I. Absorption of THC and formation of 11-OH-THC and THCCOOH during and after smoking marijuana. J Anal Toxicol 1992; 16(5): 276-282.
51. Halldin M, Widman M, Bahr C, et al. Identification of in vitro metabolites of delta 1-tetrahydrocannabinol formed by human livers. Drug Metab Dispos 1982; 10(4): 297-301.
52. Bloomfield MA, Hindocha C, Green SF, et al. The neuropsychopharmacology of cannabis: A review of human imaging studies. Pharmacol Ther 2019; 195: 132-161.
53. Castillo PE, Younts TJ, Chávez AE, Hashimotodani Y. Endocannabinoid signaling and synaptic function. Neuron 2012; 76(1): 70-81.
54. Howlett AC, Barth F, Bonner T, et al. International Union of Pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol Rev 2002; 54(2): 161-202.
55. Ameri A. The effects of cannabinoids on the brain. Prog Neurobiol 1999; 58(4): 315-348.
56. Munro S, Thomas KL, Abu-Shaar M. Molecular characterization of a peripheral receptor for cannabinoids. Nature 1993; 365(6441): 61-65.
57. Kleber HD, Anton RF, George TP, et al. Treatment of patients with substance use disorders. Am J Psychiatry 2007; 164(4): 3-123.
58. Hillard C, Harris R, Bloom A. Effects of the cannabinoids on physical properties of brain membranes and phospholipid vesicles: fluorescence studies. J Pharmacol Exp Ther 1985; 232(3): 579-588.
59. Pertwee R. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9‐tetrahydrocannabinol, cannabidiol and Δ9‐tetrahydrocannabivarin. Br J Pharmacol 2008; 153(2): 199-215.
60. Chye Y, Suo C, Lorenzetti V, et al. Cortical surface morphology in long-term cannabis users: A multi-site MRI study. Eur Neuropsychopharmacol 2019; 29(2): 257-265.
61. Scott JC, Rosen AF, Moore TM, et al. Cannabis use in youth is associated with limited alterations in brain structure. Neuropsychopharmacology 2019; 44(8): 1362-1369.
62. Lorenzetti V, Chye Y, Silva P, et al. Does regular cannabis use affect neuroanatomy? An updated systematic review and meta-analysis of structural neuroimaging studies. Eur Arch Psychiatry Clin Neurosci 2019; 269: 59-71.
63. Tsou K, Mackie K, Sanudo-Pena M, Walker J. Cannabinoid CB1 receptors are localized primarily on cholecystokinin-containing GABAergic interneurons in the rat hippocampal formation. Neuroscience 1999; 93(3): 969-975.
64. Katona I, Urbán GM, Wallace M, et al. Molecular composition of the endocannabinoid system at glutamatergic synapses. J Neurosci 2006; 26(21): 5628-5637.
65. Hájos N, Katona I, Naiem S, et al. Cannabinoids inhibit hippocampal GABAergic transmission and network oscillations. Eur J Neurosci 2000; 12(9): 3239-3249.
66. Robbe D, Montgomery SM, Thome A, et al. Cannabinoids reveal importance of spike timing coordination in hippocampal function. Nat Neurosci 2006; 9(12): 1526-33.
67. Roser P, Della B, Norra C, et al. Auditory mismatch negativity deficits in long-term heavy cannabis users. Eur Arch Psychiatry Clin Neurosci 2010; 260: 491-498.
68. Chopra GS, Smith JW. Psychotic reactions following cannabis use in East Indians. Arch Gen Psychiatry 1974; 30(1): 24-27.
69. Vaessen TSJ, De Jong L, Schäfer AT, et al. The interaction between cannabis use and the Val158Met polymorphism of the COMT gene in psychosis: A transdiagnostic meta–analysis. PLoS One 2018; 13(2): e0192658.
70. Phan KL, Angstadt M, Golden J, et al. Cannabinoid modulation of amygdala reactivity to social signals of threat in humans. J Neurosci 2008; 28(10): 2313-2319.
71. Fusar-Poli P. Distinct effects of D9-tetrahydrocannabinol and cannabidiol on neural activation during emotional processing. Arch Gen Psychiatry 2009; 24(S1): 1-1.
72. Gruber SA, Rogowska J, Yurgelun-Todd DA. Altered affective response in marijuana smokers: an FMRI study. Drug Alcohol Depend 2009; 105(1-2): 139-153.
73. Tetrault JM, Crothers K, Moore BA, et al. Effects of marijuana smoking on pulmonary function and respiratory complications: a systematic review. Arch Intern Med 2007; 167(3): 221-228.
74. Lee MH, Hancox RJ. Effects of smoking cannabis on lung function. Expert Rev Respir Med 2011;5(4):537-547.
75. Taylor DR, Poulton R, Moffitt TE, et al. The respiratory effects of cannabis dependence in young adults. Addiction 2000; 95(11): 1669-1677.
76. Aldington S, Williams M, Nowitz M, et al. Effects of cannabis on pulmonary structure, function and symptoms. Thorax 2007; 62(12): 1058-1063.
77. Fligiel SE, Roth MD, Kleerup EC, et al. Tracheobronchial histopathology in habitual smokers of cocaine, marijuana, and/or tobacco. Chest 1997; 112(2): 319-326.
78. Pratap B, Korniyenko A. Toxic effects of marijuana on the cardiovascular system. Cardiovasc Toxicol 2012; 12: 143-8.
79. Jones RT. Cardiovascular system effects of marijuana. J Clin Pharmacol 2002; 42(1): 58-63.
80. Reece AS. Chronic toxicology of cannabis. Clin Toxicol (Phila) 2009; 47(6): 517-524.
81. Nawrot TS, Perez L, Künzli N, et al. Public health importance of triggers of myocardial infarction: a comparative risk assessment. Lancet 2011; 377(9767): 732-740.
82. Rumalla K, Reddy AY, Mittal MK. Recreational marijuana use and acute ischemic stroke: a population-based analysis of hospitalized patients in the United States. J Neurol Sci 2016; 364: 191-196.
83. Klein TW, Newton C, Larsen K, et al. The cannabinoid system and immune modulation. J Leukoc Biol 2003; 74(4): 486-496.
84. Nichols JM, Kaplan BL. Immune responses regulated by cannabidiol. Cannabis Cannabinoid Res 2020; 5(1): 12-31.
85. Cabral GA, Staab A. Effects on the immune system. Handb Exp Pharmacol 2005; (168): 385-423..
86. Cho C, Hirsch R, Johnstone S. General and oral health implications of cannabis use. Aust Dent J 2005; 50(2): 70-74.
87. Meah F, Lundholm M, Emanuele N, Amjed H, Poku C, Agrawal L, et al. The effects of cannabis and cannabinoids on the endocrine system. Rev Endocr Metab Disord 2022; 23(3): 401-420.
88. Steger RW, Murphy LL, Bartke A, Smith MS. Effects of psychoactive and nonpsychoactive cannabinoids on the hypothalamic-pituitary axis of the adult male rat. Pharmacol Biochem Behav 1990; 37(2): 299-302.
89. Murphy LL, Steger RW, Smith S, Bartke A. Effects of delta-9-tetrahydrocannabinol, cannabinol and cannabidiol, alone and in combinations, on luteinizing hormone and prolactin release and on hypothalamic neurotransmitters in the male rat. Neuroendocrinology 1990; 52(4): 316-321.
90. Rettori V, Aguila MC, Gimeno MF, et al. In vitro effect of delta 9-tetrahydrocannabinol to stimulate somatostatin release and block that of luteinizing hormone-releasing hormone by suppression of the release of prostaglandin E2. Proc Natl Acad Sci USA 1990; 87(24): 10063-10066.
91. Brents LK. Marijuana, the endocannabinoid system and the female reproductive system. Yale J Biol Med. 2016; 89(2): 175-191.
92. Carvalho RK, Andersen ML, Mazaro‐Costa R. The effects of cannabidiol on male reproductive system: A literature review. J Appl Toxicol 2020; 40(1): 132-150.
93. Du Plessis SS, Agarwal A, Syriac A. Marijuana, phytocannabinoids, the endocannabinoid system, and male fertility. J Assist Reprod Genet 2015; 32(11): 1575-1588.
94. Shamloul R, Bella AJ. Impact of cannabis use on male sexual health. J Sex Med 2011; 8(4): 971-975.
95. Chopra GS, Jandu BS. Psychoclinical effects of long‐term marijuana use in 275 Indian chronic users. A comparative assessment of effects in Indian and USA users. Ann N Y Acad Sci 1976; 282(1): 95-108.
96. Tart CT. Marijuana intoxication: common experiences. Nature 1970; 226(5247): 701-704.
97. Malhotra S, Heptulla RA, Homel P, Motaghedi R. Effect of marijuana use on thyroid function and autoimmunity. Thyroid 2017; 27(2): 167-173.
98. Mendelson JH, Mello NK, Ellingboe J, et al. Marihuana smoking suppresses luteinizing hormone in women. J Pharmacol Exp Ther 1986; 237(3): 862-6.
99. Hollister LE, Reaven GM. Delta‐9‐tetrahydrocannabinol and glucose tolerance. Clin Pharmacol Ther 1974; 16(2): 297-302.
100. Podolsky S, Pattavina CG, Amaral MA. Effect of marijuana on the glucose‐tolerance test. Ann N Y Acad Sci 1971; 191(1): 54-60.
101. Akturk HK, Taylor DD, Camsari UM, et al. Association between cannabis use and risk for diabetic ketoacidosis in adults with type 1 diabetes. JAMA Intern Med 2019; 179(1): 115-118.
102. Hayatbakhsh MR, Flenady VJ, Gibbons KS, et al. Birth outcomes associated with cannabis use before and during pregnancy. Pediatr Res 2012; 71(2): 215-219.
103. Gunn J, Rosales C, Center K, et al. Prenatal exposure to cannabis and maternal and child health outcomes: a systematic review and meta-analysis. BMJ Open 2016; 6(4): 009986.
104. Gray KA, Day NL, Leech S, Richardson GA. Prenatal marijuana exposure: effect on child depressive symptoms at ten years of age. Neurotoxicol Teratol 2005; 27(3): 439-448.
105. Karila L, Cazas O, Danel T, Reynaud M. Short-and long-term consequences of prenatal exposure to cannabis. J Gynecol Obstet Biol Reprod (Paris) 2006; 35(1): 62-70.
106. Jaques S, Kingsbury A, Henshcke P, et al. Cannabis, the pregnant woman and her child: weeding out the myths. J Perinatol 2014; 34(6): 417-424.
107. Alpár A, Di Marzo V, Harkany T. At the tip of an iceberg: prenatal marijuana and its possible relation to neuropsychiatric outcome in the offspring. Biol Psychiatry 2016; 79(7): 33-45.
108. Dong C, Chen J, Harrington A, et al. Cannabinoid exposure during pregnancy and its impact on immune function. Cell Mol Life Sci 2019; 76(4): 729-743.
109. Rawal SY, Tatakis DN, Tipton D. Periodontal and oral manifestations of marijuana use. J Tenn Dent Assoc 2012; 92(2): 26-31.
110. Xie M, Gupta MK, Archibald SD, et al. Marijuana and head and neck cancer: an epidemiological review. J Otolaryngol Head Neck Surg 2018; 47(1): 73.
111. Tennstedt D, Saint-Remy A. Cannabis and skin diseases. Eur J Dermatol 2011; 21(1): 5-11.