1932

Abstract

Cannabis, the most commonly used recreational drug, is illicit in many areas of the world. With increasing decriminalization and legalization, cannabis use is increasing in the United States and other countries. The adverse effects of cannabis are unclear because its status as a Schedule 1 drug in the United States restricts research. Despite a paucity of data, cannabis is commonly perceived as a benign or even beneficial drug. However, recent studies show that cannabis has adverse cardiovascular and pulmonary effects and is linked with malignancy. Moreover, case reports have shown an association between cannabis use and neuropsychiatric disorders. With growing availability, cannabis misuse by minors has led to increasing incidences of overdose and toxicity. Though difficult to detect, cannabis intoxication may be linked to impaired driving and motor vehicle accidents. Overall, cannabis use is on the rise, and adverse effects are becoming apparent in clinical data sets.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-med-052422-020627
2024-01-29
2024-12-12
Loading full text...

Full text loading...

/deliver/fulltext/med/75/1/annurev-med-052422-020627.html?itemId=/content/journals/10.1146/annurev-med-052422-020627&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Bridgeman MB, Abazia DT. 2017. Medicinal cannabis: history, pharmacology, and implications for the acute care setting. PT Pharm. Ther. 42:18088
    [Google Scholar]
  2. 2.
    Page RL 2nd, Allen LA, Kloner RA et al. 2020. Medical marijuana, recreational cannabis, and cardiovascular health: a scientific statement from the American Heart Association. Circulation 142:e13152
    [Google Scholar]
  3. 3.
    Rotermann M. 2020. What has changed since cannabis was legalized?. Health Rep. 31:1120
    [Google Scholar]
  4. 4.
    Martins SS, Segura LE, Levy NS et al. 2021. Racial and ethnic differences in cannabis use following legalization in US states with medical cannabis laws. JAMA Netw. Open 4:e2127002
    [Google Scholar]
  5. 5.
    Atakan Z. 2012. Cannabis, a complex plant: different compounds and different effects on individuals. Ther. Adv. Psychopharmacol. 2:24154
    [Google Scholar]
  6. 6.
    Hoffman AF, Lupica CR. 2013. Synaptic targets of Δ9-tetrahydrocannabinol in the central nervous system. Cold Spring Harb. Perspect. Med. 3:a012237
    [Google Scholar]
  7. 7.
    Ibsen MS, Connor M, Glass M. 2017. Cannabinoid CB1 and CB2 receptor signaling and bias. Cannabis Cannabinoid Res. 2:4860
    [Google Scholar]
  8. 8.
    Bilbao A, Spanagel R. 2022. Medical cannabinoids: a pharmacology-based systematic review and meta-analysis for all relevant medical indications. BMC Med. 20:259
    [Google Scholar]
  9. 9.
    Nagarkatti P, Pandey R, Rieder SA et al. 2009. Cannabinoids as novel anti-inflammatory drugs. Future Med. Chem. 1:133349
    [Google Scholar]
  10. 10.
    Do Y, McKallip RJ, Nagarkatti M, Nagarkatti PS. 2004. Activation through cannabinoid receptors 1 and 2 on dendritic cells triggers NF-κB-dependent apoptosis: novel role for endogenous and exogenous cannabinoids in immunoregulation. J. Immunol. 173:237382
    [Google Scholar]
  11. 11.
    Zhu W, Friedman H, Klein TW 1998. Δ9-Tetrahydrocannabinol induces apoptosis in macrophages and lymphocytes: involvement of Bcl-2 and caspase-1. J. Pharmacol. Exp. Ther 286:11039
    [Google Scholar]
  12. 12.
    Srivastava MD, Srivastava BI, Brouhard B. 1998. Δ9 Tetrahydrocannabinol and cannabidiol alter cytokine production by human immune cells. Immunopharmacology 40:17985
    [Google Scholar]
  13. 13.
    Smith SR, Terminelli C, Denhardt G. 2000. Effects of cannabinoid receptor agonist and antagonist ligands on production of inflammatory cytokines and anti-inflammatory interleukin-10 in endotoxemic mice. J. Pharmacol. Exp. Ther. 293:13650
    [Google Scholar]
  14. 14.
    Pertwee RG. 2002. Cannabinoids and multiple sclerosis. Pharmacol. Ther. 95:16574
    [Google Scholar]
  15. 15.
    Jia W, Hegde VL, Singh NP et al. 2006. Δ9-Tetrahydrocannabinol-induced apoptosis in Jurkat leukemia T cells is regulated by translocation of Bad to mitochondria. Mol. Cancer Res. 4:54962
    [Google Scholar]
  16. 16.
    McKallip RJ, Lombard C, Fisher M et al. 2002. Targeting CB2 cannabinoid receptors as a novel therapy to treat malignant lymphoblastic disease. Blood 100:62734
    [Google Scholar]
  17. 17.
    Soares RZ, Vuolo F, Dall'Igna DM et al. 2015. Evaluation of the role of the cannabidiol system in an animal model of ischemia/reperfusion kidney injury. Rev. Bras. Ter. Intensiva 27:38389
    [Google Scholar]
  18. 18.
    Lowin T, Tingting R, Zurmahr J et al. 2020. Cannabidiol (CBD): a killer for inflammatory rheumatoid arthritis synovial fibroblasts. Cell Death Dis. 11:714
    [Google Scholar]
  19. 19.
    Sánchez AJ, García-Merino A. 2012. Neuroprotective agents: cannabinoids. Clin. Immunol. 142:5767
    [Google Scholar]
  20. 20.
    Vallée A, Lecarpentier Y, Guillevin R, Vallée JN. 2017. Effects of cannabidiol interactions with Wnt/β-catenin pathway and PPARγ on oxidative stress and neuroinflammation in Alzheimer's disease. Acta Biochim. Biophys. Sin. 49:85366
    [Google Scholar]
  21. 21.
    Santos NA, Martins NM, Sisti FM et al. 2015. The neuroprotection of cannabidiol against MPP+-induced toxicity in PC12 cells involves trkA receptors, upregulation of axonal and synaptic proteins, neuritogenesis, and might be relevant to Parkinson's disease. Toxicol. In Vitro 30:23140
    [Google Scholar]
  22. 22.
    Chandy M, Obal D, Wu JC. 2022. Elucidating effects of environmental exposure using human-induced pluripotent stem cell disease modeling. EMBO Mol. Med. 14:e13260
    [Google Scholar]
  23. 23.
    Obal D, Wu JC. 2020. Induced pluripotent stem cells as a platform to understand patient-specific responses to opioids and anaesthetics. Br. J. Pharmacol. 177:458194
    [Google Scholar]
  24. 24.
    Whiting PF, Wolff RF, Deshpande S et al. 2015. Cannabinoids for medical use: a systematic review and meta-analysis. JAMA 313:245673
    [Google Scholar]
  25. 25.
    Hussain SA, Zhou R, Jacobson C et al. 2015. Perceived efficacy of cannabidiol-enriched cannabis extracts for treatment of pediatric epilepsy: a potential role for infantile spasms and Lennox-Gastaut syndrome. Epilepsy Behav 47:13841
    [Google Scholar]
  26. 26.
    Volkow ND, Baler RD, Compton WM, Weiss SR. 2014. Adverse health effects of marijuana use. N. Engl. J. Med. 370:221927
    [Google Scholar]
  27. 27.
    DeFilippis EM, Singh A, Divakaran S et al. 2018. Cocaine and marijuana use among young adults with myocardial infarction. J. Am. Coll. Cardiol. 71:254051
    [Google Scholar]
  28. 28.
    Pacher P, Steffens S, Hasko G et al. 2018. Cardiovascular effects of marijuana and synthetic cannabinoids: the good, the bad, and the ugly. Nat. Rev. Cardiol. 15:15166
    [Google Scholar]
  29. 29.
    Libby P. 2002. Inflammation in atherosclerosis. Nature 420:86874
    [Google Scholar]
  30. 30.
    Everett BM, MacFadyen JG, Thuren T et al. 2020. Inhibition of interleukin-1β and reduction in atherothrombotic cardiovascular events in the CANTOS trial. J. Am. Coll. Cardiol. 76:166070
    [Google Scholar]
  31. 31.
    Shrestha S, Irvin MR, Grunfeld C, Arnett DK. 2014. HIV, inflammation, and calcium in atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 34:24450
    [Google Scholar]
  32. 32.
    Skeoch S, Bruce IN. 2015. Atherosclerosis in rheumatoid arthritis: Is it all about inflammation?. Nat. Rev. Rheumatol. 11:390400
    [Google Scholar]
  33. 33.
    Frostegard J. 2005. SLE, atherosclerosis and cardiovascular disease. J. Intern. Med. 257:48595
    [Google Scholar]
  34. 34.
    Sugamura K, Sugiyama S, Nozaki T et al. 2009. Activated endocannabinoid system in coronary artery disease and antiinflammatory effects of cannabinoid 1 receptor blockade on macrophages. Circulation 119:2836
    [Google Scholar]
  35. 35.
    Liu J, Gao B, Mirshahi F et al. 2000. Functional CB1 cannabinoid receptors in human vascular endothelial cells. Biochem. J. 346:Pt. 383540
    [Google Scholar]
  36. 36.
    Rajesh M, Mukhopadhyay P, Hasko G et al. 2010. Cannabinoid-1 receptor activation induces reactive oxygen species-dependent and -independent mitogen-activated protein kinase activation and cell death in human coronary artery endothelial cells. Br. J. Pharmacol. 160:688700
    [Google Scholar]
  37. 37.
    Rajesh M, Batkai S, Kechrid M et al. 2012. Cannabinoid 1 receptor promotes cardiac dysfunction, oxidative stress, inflammation, and fibrosis in diabetic cardiomyopathy. Diabetes 61:71627
    [Google Scholar]
  38. 38.
    El-Remessy AB, Rajesh M, Mukhopadhyay P et al. 2011. Cannabinoid 1 receptor activation contributes to vascular inflammation and cell death in a mouse model of diabetic retinopathy and a human retinal cell line. Diabetologia 54:156778
    [Google Scholar]
  39. 39.
    Dol-Gleizes F, Paumelle R, Visentin V et al. 2009. Rimonabant, a selective cannabinoid CB1 receptor antagonist, inhibits atherosclerosis in LDL receptor-deficient mice. Arterioscler. Thromb. Vasc. Biol. 29:1218
    [Google Scholar]
  40. 40.
    Netherland CD, Pickle TG, Bales A, Thewke DP. 2010. Cannabinoid receptor type 2 (CB2) deficiency alters atherosclerotic lesion formation in hyperlipidemic Ldlr-null mice. Atherosclerosis 213:1028
    [Google Scholar]
  41. 41.
    Hoyer FF, Steinmetz M, Zimmer S et al. 2011. Atheroprotection via cannabinoid receptor-2 is mediated by circulating and vascular cells in vivo. J. Mol. Cell Cardiol. 51:100714
    [Google Scholar]
  42. 42.
    Draz EI, Oreby MM, Elsheikh EA et al. 2017. Marijuana use in acute coronary syndromes. Am. J. Drug Alcohol Abuse 43:57682
    [Google Scholar]
  43. 43.
    Patel RS, Katta SR, Patel R et al. 2018. Cannabis use disorder in young adults with acute myocardial infarction: trend inpatient study from 2010 to 2014 in the United States. Cureus 10:e3241
    [Google Scholar]
  44. 44.
    Frost L, Mostofsky E, Rosenbloom JI et al. 2013. Marijuana use and long-term mortality among survivors of acute myocardial infarction. Am. Heart J. 165:17075
    [Google Scholar]
  45. 45.
    McEvoy JW, Blaha MJ, DeFilippis AP et al. 2015. Cigarette smoking and cardiovascular events: role of inflammation and subclinical atherosclerosis from the MultiEthnic Study of Atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 35:7009
    [Google Scholar]
  46. 46.
    Wei TT, Chandy M, Nishiga M et al. 2022. Cannabinoid receptor 1 antagonist genistein attenuates marijuana-induced vascular inflammation. Cell 185:167693.e23
    [Google Scholar]
  47. 47.
    Bycroft C, Freeman C, Petkova D et al. 2018. The UK Biobank resource with deep phenotyping and genomic data. Nature 562:2039
    [Google Scholar]
  48. 48.
    Paik DT, Chandy M, Wu JC. 2020. Patient and disease-specific induced pluripotent stem cells for discovery of personalized cardiovascular drugs and therapeutics. Pharmacol. Rev. 72:32042
    [Google Scholar]
  49. 49.
    Steffens S, Veillard NR, Arnaud C et al. 2005. Low dose oral cannabinoid therapy reduces progression of atherosclerosis in mice. Nature 434:78286
    [Google Scholar]
  50. 50.
    Huestis MA. 2007. Human cannabinoid pharmacokinetics. Chem. Biodivers. 4:1770804
    [Google Scholar]
  51. 51.
    Kariyanna PT, Jayarangaiah A, Singh N et al. 2018. Marijuana induced myocarditis: a new entity of toxic myocarditis. Am. J. Med. Case Rep. 6:16972
    [Google Scholar]
  52. 52.
    Sultan SR, Millar SA, O'Sullivan SE, England TJ 2018. A systematic review and meta-analysis of the in vivo haemodynamic effects of Δ9-tetrahydrocannabinol. Pharmaceuticals 11:13
    [Google Scholar]
  53. 53.
    Richards JR, Blohm E, Toles KA et al. 2020. The association of cannabis use and cardiac dysrhythmias: a systematic review. Clin. Toxicol. 58:86169
    [Google Scholar]
  54. 54.
    Patel RS, Gonzalez MD, Ajibawo T, Baweja R. 2021. Cannabis use disorder and increased risk of arrhythmia-related hospitalization in young adults. Am. J. Addict. 30:57884
    [Google Scholar]
  55. 55.
    Chouairi F, Miller PE, Guha A et al. 2021. Cannabis use disorder among atrial fibrillation admissions, 2008–2018. Pacing Clin. Electrophysiol. 44:193438
    [Google Scholar]
  56. 56.
    Ezzati M, Lopez AD. 2003. Estimates of global mortality attributable to smoking in 2000. Lancet 362:84752
    [Google Scholar]
  57. 57.
    Natl. Cent. Chronic Dis. Prev. Health Promot. (US) Off. Smok. Health 2014. The Health Consequences of Smoking—50 Years of Progress: A Report of the Surgeon General Atlanta, GA: CDC
    [Google Scholar]
  58. 58.
    Wu TC, Tashkin DP, Djahed B, Rose JE. 1988. Pulmonary hazards of smoking marijuana as compared with tobacco. N. Engl. J. Med. 318:34751
    [Google Scholar]
  59. 59.
    Jayakumar N, Chaiton M, Goodwin R et al. 2021. Co-use and mixing tobacco with cannabis among Ontario adults. Nicotine Tob. Res. 23:17178
    [Google Scholar]
  60. 60.
    Hancox RJ, Poulton R, Ely M et al. 2010. Effects of cannabis on lung function: a population-based cohort study. Eur. Respir. J. 35:4247
    [Google Scholar]
  61. 61.
    Tan WC, Bourbeau J, Aaron SD et al. 2019. The effects of marijuana smoking on lung function in older people. Eur. Respir. J. 54:1900826
    [Google Scholar]
  62. 62.
    Benowitz NL, Fraiman JB. 2017. Cardiovascular effects of electronic cigarettes. Nat. Rev. Cardiol. 14:44756
    [Google Scholar]
  63. 63.
    Gotts JE, Jordt S-E, McConnell R, Tarran R. 2019. What are the respiratory effects of e-cigarettes?. BMJ 366:l5275
    [Google Scholar]
  64. 64.
    Butt YM, Smith ML, Tazelaar HD et al. 2019. Pathology of vaping-associated lung injury. N. Engl. J. Med. 381:178081
    [Google Scholar]
  65. 65.
    Hayes D Jr., Board A, Calfee CS et al. 2022. Pulmonary and critical care considerations for e-cigarette, or vaping, product use-associated lung injury. Chest 162:25664
    [Google Scholar]
  66. 66.
    Blount BC, Karwowski MP, Shields PG et al. 2019. Vitamin E acetate in bronchoalveolar-lavage fluid associated with EVALI. N. Engl. J. Med. 382:697705
    [Google Scholar]
  67. 67.
    Martin BR, Dewey WL, Harris LS, Beckner J. 1975. Marihuana-like activity of new synthetic tetrahydrocannabinols. Pharmacol. Biochem. Behav. 3:84953
    [Google Scholar]
  68. 68.
    Adams IB, Martin BR. 1996. Cannabis: pharmacology and toxicology in animals and humans. Addiction 91:1585614
    [Google Scholar]
  69. 69.
    Bonnet U, Preuss UW. 2017. The cannabis withdrawal syndrome: current insights. Subst. Abuse Rehabil. 8:937
    [Google Scholar]
  70. 70.
    Gajendran M, Sifuentes J, Bashashati M, McCallum R. 2020. Cannabinoid hyperemesis syndrome: definition, pathophysiology, clinical spectrum, insights into acute and long-term management. J. Investig. Med. 68:130916
    [Google Scholar]
  71. 71.
    Chu F, Cascella M. 2023. Cannabinoid hyperemesis syndrome. StatPearls Treasure Island, FL: StatPearls Updated July 4, 2022. https://www.ncbi.nlm.nih.gov/books/NBK549915/
    [Google Scholar]
  72. 72.
    Patel J, Marwaha R. 2023. Cannabis use disorder. StatPearls Treasure Island, FL: StatPearls Updated July 11, 2022. https://www.ncbi.nlm.nih.gov/books/NBK538131/
    [Google Scholar]
  73. 73.
    Cerda M, Mauro C, Hamilton A et al. 2020. Association between recreational marijuana legalization in the United States and changes in marijuana use and cannabis use disorder from 2008 to 2016. JAMA Psychiatry 77:16571
    [Google Scholar]
  74. 74.
    Lucatch AM, Coles AS, Hill KP, George TP. 2018. Cannabis and mood disorders. Curr. Addict. Rep. 5:33645
    [Google Scholar]
  75. 75.
    Pinto JV, Medeiros LS, Santana da Rosa G et al. 2019. The prevalence and clinical correlates of cannabis use and cannabis use disorder among patients with bipolar disorder: a systematic review with meta-analysis and meta-regression. Neurosci. Biobehav. Rev. 101:7884
    [Google Scholar]
  76. 76.
    Di Forti M, Quattrone D, Freeman TP et al. 2019. The contribution of cannabis use to variation in the incidence of psychotic disorder across Europe (EU-GEI): a multicentre case-control study. Lancet Psychiatry 6:42736
    [Google Scholar]
  77. 77.
    Campolongo P, Trezza V, Cassano T et al. 2007. Perinatal exposure to delta-9-tetrahydrocannabinol causes enduring cognitive deficits associated with alteration of cortical gene expression and neurotransmission in rats. Addict. Biol. 12:48595
    [Google Scholar]
  78. 78.
    Di Forti M, Iyegbe C, Sallis H et al. 2012. Confirmation that the AKT1 (rs2494732) genotype influences the risk of psychosis in cannabis users. Biol. Psychiatry 72:81116
    [Google Scholar]
  79. 79.
    Kochling J, Geis B, Chao CM et al. 2021. The hazardous (mis)perception of Self-estimated Alcohol intoxication and Fitness to drivE—an avoidable health risk: the SAFE randomised trial. Harm. Reduct. J. 18:122
    [Google Scholar]
  80. 80.
    Rogeberg O, Elvik R. 2016. The effects of cannabis intoxication on motor vehicle collision revisited and revised. Addiction 111:134859
    [Google Scholar]
  81. 81.
    Doucette ML, Frattaroli S, Vernick JS. 2018. Oral fluid testing for marijuana intoxication: enhancing objectivity for roadside DUI testing. Inj. Prev. 24:7880
    [Google Scholar]
  82. 82.
    Lynch KL, Luo YR, Hooshfar S, Yun C. 2019. Correlation of breath and blood Δ9-tetrahydrocannabinol concentrations and release kinetics following controlled administration of smoked cannabis. Clin. Chem. 65:117179
    [Google Scholar]
  83. 83.
    Yeung MEM, Weaver CG, Hartmann R et al. 2021. Emergency department pediatric visits in Alberta for cannabis after legalization. Pediatrics 148:e2020045922
    [Google Scholar]
  84. 84.
    Payne KS, Mazur DJ, Hotaling JM, Pastuszak AW. 2019. Cannabis and male fertility: a systematic review. J. Urol. 202:67481
    [Google Scholar]
  85. 85.
    Harlow AF, Wesselink AK, Hatch EE et al. 2021. Male preconception marijuana use and spontaneous abortion: a prospective cohort study. Epidemiology 32:23947
    [Google Scholar]
  86. 86.
    Koren G, Cohen R 2020. The use of cannabis for hyperemesis gravidarum (HG). J. Cannabis Res. 2:4
    [Google Scholar]
  87. 87.
    Natl. Acad. Sci. Eng. Med 2017. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research Washington, DC: Natl. Acad. Press
    [Google Scholar]
  88. 88.
    Gunn JK, Rosales CB, Center KE et al. 2016. Prenatal exposure to cannabis and maternal and child health outcomes: a systematic review and meta-analysis. BMJ Open 6:e009986
    [Google Scholar]
  89. 89.
    Roncero C, Valriberas-Herrero I, Mezzatesta-Gava M et al. 2020. Cannabis use during pregnancy and its relationship with fetal developmental outcomes and psychiatric disorders. A systematic review. Reprod. Health 17:25
    [Google Scholar]
  90. 90.
    Bowles DW, O'Bryant CL, Camidge DR, Jimeno A 2012. The intersection between cannabis and cancer in the United States. Crit. Rev. Oncol. Hematol. 83:110
    [Google Scholar]
  91. 91.
    Guzman M, Duarte MJ, Blazquez C et al. 2006. A pilot clinical study of Δ9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme. Br. J. Cancer 95:197203
    [Google Scholar]
  92. 92.
    Ghasemiesfe M, Barrow B, Leonard S et al. 2019. Association between marijuana use and risk of cancer: a systematic review and meta-analysis. JAMA Netw. Open 2:e1916318
    [Google Scholar]
  93. 93.
    Aldington S, Harwood M, Cox B et al. 2008. Cannabis use and risk of lung cancer: a case-control study. Eur. Respir. J. 31:28086
    [Google Scholar]
  94. 94.
    Pacher P, Mechoulam R. 2011. Is lipid signaling through cannabinoid 2 receptors part of a protective system?. Prog. Lipid Res. 50:193211
    [Google Scholar]
  95. 95.
    Turcotte C, Blanchet MR, Laviolette M, Flamand N. 2016. The CB2 receptor and its role as a regulator of inflammation. Cell Mol. Life Sci. 73:444970
    [Google Scholar]
  96. 96.
    Bie B, Wu J, Foss JF, Naguib M. 2018. An overview of the cannabinoid type 2 receptor system and its therapeutic potential. Curr. Opin. Anaesthesiol. 31:40714
    [Google Scholar]
  97. 97.
    Despres JP, Golay A, Sjostrom L. 2005. Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N. Engl. J. Med. 353:212134
    [Google Scholar]
  98. 98.
    Onakpoya IJ, Heneghan CJ, Aronson JK. 2016. Worldwide withdrawal of medicinal products because of adverse drug reactions: a systematic review and analysis. Crit. Rev. Toxicol. 46:47789
    [Google Scholar]
  99. 99.
    Cinar R, Iyer MR, Kunos G. 2020. The therapeutic potential of second and third generation CB1R antagonists. Pharmacol. Ther. 208:107477
    [Google Scholar]
  100. 100.
    Fulp A, Bortoff K, Seltzman H et al. 2012. Design and synthesis of cannabinoid receptor 1 antagonists for peripheral selectivity. J. Med. Chem. 55:282034
    [Google Scholar]
/content/journals/10.1146/annurev-med-052422-020627
Loading
/content/journals/10.1146/annurev-med-052422-020627
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error