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Cannabis Withdrawal

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Cannabinoids and Pain

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Abstract

Cannabis is the most commonly used illicit substance worldwide. Although commonly considered to be a “soft drug,” cannabis use is associated with mental and physical health problems. Abrupt cessation of prolonged cannabis use can lead to a withdrawal syndrome, a new diagnosis included in the Diagnostic and Statistical Manual of Mental Disorders – Fifth Edition (DSM-5)2 and as a criterion for cannabis use disorder. Symptoms of CWS occur reliably following a specific time course with cessation of cannabis use, are transient, can be ameliorated by readministration of cannabis, and are clinically significant.

Cannabis withdrawal is considered a negative reinforcement for relapse, and patients have reported using other substances such as nicotine and alcohol as a reliever. Therefore, much effort has been made to identify treatment options for CWS. Animal study showed that CBD alleviated withdrawal symptoms and reversed gene expression changes induced by cannabis withdrawal including opioid μ receptor (Oprm1), cannabinoid CB1 receptor (Cnr1), and CB2 receptor (Cnr2) in the nucleus accumbens in mice.

While the search for pharmacological agents for CWS treatment remains ongoing, psychotherapy studies have established several evidence-based models and promising techniques in CWS/CUD treatment.

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References

  1. GBD 2016 Alcohol and Drug Use Collaborators. The global burden of disease attributable to alcohol and drug use in 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016 [published correction appears in Lancet Psychiatry. 2019 Jan;6(1):e2]. Lancet Psychiatry. 2018;5(12):987–1012. https://doi.org/10.1016/S2215-0366(18)30337-7.

  2. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington: American Psychiatric Association; 2013.

    Book  Google Scholar 

  3. Arias F, Szerman N, Vega P, et al. Abuse or dependence on cannabis and other psychiatric disorders. Madrid study on dual pathology prevalence. Actas Esp Psiquiatr. 2013;41(2):122–9.

    PubMed  Google Scholar 

  4. Banks DE, Rowe AT, Mpofu P, Zapolski TCB. Trends in typologies of concurrent alcohol, marijuana, and cigarette use among US adolescents: an ecological examination by sex and race/ethnicity. Drug Alcohol Depend. 2017;179:71–7. https://doi.org/10.1016/j.drugalcdep.2017.06.026.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Zuckermann AME, Williams G, Battista K, de Groh M, Jiang Y, Leatherdale ST. Trends of poly-substance use among Canadian youth. Addict Behav Rep. 2019;10:100189. Published 2019 May 10. https://doi.org/10.1016/j.abrep.2019.100189.

  6. Budney AJ, Moore BA, Vandrey RG, Hughes JR. The time course and significance of cannabis withdrawal. J Abnorm Psychol. 2003;112(3):393–402. https://doi.org/10.1037/0021-843x.112.3.393.

    Article  PubMed  Google Scholar 

  7. Budney AJ, Novy PL, Hughes JR. Marijuana withdrawal among adults seeking treatment for marijuana dependence. Addiction. 1999;94(9):1311–22. https://doi.org/10.1046/j.1360-0443.1999.94913114.x.

    Article  CAS  PubMed  Google Scholar 

  8. Allsop DJ, Norberg MM, Copeland J, Fu S, Budney AJ. The Cannabis Withdrawal Scale development: patterns and predictors of cannabis withdrawal and distress. Drug Alcohol Depend. 2011;119(1–2):123–9. https://doi.org/10.1016/j.drugalcdep.2011.06.003.

    Article  PubMed  Google Scholar 

  9. Allsop DJ, Copeland J, Norberg MM, et al. Quantifying the clinical significance of cannabis withdrawal. PLoS One. 2012;7(9):e44864. https://doi.org/10.1371/journal.pone.0044864.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Levin KH, Copersino ML, Heishman SJ, et al. Cannabis withdrawal symptoms in non-treatment-seeking adult cannabis smokers. Drug Alcohol Depend. 2010;111(1–2):120–7. https://doi.org/10.1016/j.drugalcdep.2010.04.010.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Gorelick DA, Levin KH, Copersino ML, et al. Diagnostic criteria for cannabis withdrawal syndrome. Drug Alcohol Depend. 2012;123(1–3):141–7. https://doi.org/10.1016/j.drugalcdep.2011.11.007.

    Article  PubMed  Google Scholar 

  12. Greene MC, Kelly JF. The prevalence of cannabis withdrawal and its influence on adolescents’ treatment response and outcomes: a 12-month prospective investigation. J Addict Med. 2014;8(5):359–67. https://doi.org/10.1097/ADM.0000000000000064.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Sherman BJ, McRae-Clark AL, Baker NL, et al. Gender differences among treatment-seeking adults with cannabis use disorder: clinical profiles of women and men enrolled in the achieving cannabis cessation-evaluating N-acetylcysteine treatment (ACCENT) study. Am J Addict. 2017;26(2):136–44. https://doi.org/10.1111/ajad.12503.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Bahji A, Stephenson C, Tyo R, Hawken ER, Seitz DP. Prevalence of cannabis withdrawal symptoms among people with regular or dependent use of cannabinoids: a systematic review and meta-analysis. JAMA Netw Open. 2020;3(4):e202370. Published 2020 Apr 1. https://doi.org/10.1001/jamanetworkopen.2020.2370.

  15. Hanna RC, Perez JM, Ghose S. Cannabis and development of dual diagnoses: a literature review. Am J Drug Alcohol Abuse. 2017;43(4):442–55. https://doi.org/10.1080/00952990.2016.1213273.

    Article  PubMed  Google Scholar 

  16. Crippa JA, Zuardi AW, Martín-Santos R, et al. Cannabis and anxiety: a critical review of the evidence. Hum Psychopharmacol. 2009;24(7):515–23. https://doi.org/10.1002/hup.1048.

    Article  CAS  PubMed  Google Scholar 

  17. Bahji A, Mazhar MN, Hudson CC, Nadkarni P, MacNeil BA, Hawken E. Prevalence of substance use disorder comorbidity among individuals with eating disorders: a systematic review and meta-analysis. Psychiatry Res. 2019;273:58–66. https://doi.org/10.1016/j.psychres.2019.01.007.

    Article  PubMed  Google Scholar 

  18. Boggs DL, Kelly DL, Liu F, et al. Cannabis withdrawal in chronic cannabis users with schizophrenia. J Psychiatr Res. 2013;47(2):240–5. https://doi.org/10.1016/j.jpsychires.2012.10.010.

    Article  PubMed  Google Scholar 

  19. Koola MM, Kelly DL, McMahon RP, Boggs DL, Liu F, Gorelick DA. Psychoactive substance use by adults with schizophrenia before and during cannabis withdrawal. Prim Care Companion CNS Disord. 2016;18(5). Published 2016 Sep 1. https://doi.org/10.4088/PCC.16l01959.

  20. Grotenhermen F. Pharmacokinetics and pharmacodynamics of cannabinoids. Clin Pharmacokinet. 2003;42(4):327–60. https://doi.org/10.2165/00003088-200342040-00003.

    Article  CAS  PubMed  Google Scholar 

  21. Cooper ZD, Haney M. Cannabis reinforcement and dependence: role of the cannabinoid CB1 receptor. Addict Biol. 2008;13(2):188–95. https://doi.org/10.1111/j.1369-1600.2007.00095.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Ledent C, Valverde O, Cossu G, et al. Unresponsiveness to cannabinoids and reduced addictive effects of opiates in CB1 receptor knockout mice. Science. 1999;283(5400):401–4. https://doi.org/10.1126/science.283.5400.401.

    Article  CAS  PubMed  Google Scholar 

  23. Lichtman AH, Martin BR. Marijuana withdrawal syndrome in the animal model. J Clin Pharmacol. 2002;42(S1):20S–7S. https://doi.org/10.1002/j.1552-4604.2002.tb05999.x.

    Article  CAS  PubMed  Google Scholar 

  24. Hirvonen J, Goodwin RS, Li CT, et al. Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers. Mol Psychiatry. 2012;17(6):642–9. https://doi.org/10.1038/mp.2011.82.

    Article  CAS  PubMed  Google Scholar 

  25. D’Souza DC, Cortes-Briones JA, Ranganathan M, et al. Rapid changes in CB1 receptor availability in cannabis dependent males after abstinence from cannabis. Biol Psychiatry Cogn Neurosci Neuroimaging. 2016;1(1):60–7. https://doi.org/10.1016/j.bpsc.2015.09.008.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Cone EJ, Huestis MA. Relating blood concentrations of tetrahydrocannabinol and metabolites to pharmacologic effects and time of marijuana usage. Ther Drug Monit. 1993;15(6):527–32. https://doi.org/10.1097/00007691-199312000-00013.

    Article  CAS  PubMed  Google Scholar 

  27. Jones RT, Benowitz NL, Herning RI. Clinical relevance of cannabis tolerance and dependence. J Clin Pharmacol. 1981;21(S1):143S–52S. https://doi.org/10.1002/j.1552-4604.1981.tb02589.x.

    Article  CAS  PubMed  Google Scholar 

  28. Budney AJ, Hughes JR, Moore BA, Vandrey R. Review of the validity and significance of cannabis withdrawal syndrome. Am J Psychiatry. 2004;161(11):1967–77. https://doi.org/10.1176/appi.ajp.161.11.1967.

    Article  PubMed  Google Scholar 

  29. 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(1):157–68. https://doi.org/10.1007/s00213-007-1020-8.

    Article  CAS  PubMed  Google Scholar 

  30. Ng Cheong Ton JM, Gerhardt GA, Friedemann M, et al. The effects of delta 9-tetrahydrocannabinol on potassium-evoked release of dopamine in the rat caudate nucleus: an in vivo electrochemical and in vivo microdialysis study. Brain Res. 1988;451(1–2):59–68. https://doi.org/10.1016/0006-8993(88)90749-4.

    Article  CAS  PubMed  Google Scholar 

  31. Oz M. Receptor-independent effects of endocannabinoids on ion channels. Curr Pharm Des. 2006;12(2):227–39. https://doi.org/10.2174/138161206775193073.

    Article  CAS  PubMed  Google Scholar 

  32. Oz M. Receptor-independent actions of cannabinoids on cell membranes: focus on endocannabinoids. Pharmacol Ther. 2006;111(1):114–44. https://doi.org/10.1016/j.pharmthera.2005.09.009.

    Article  CAS  PubMed  Google Scholar 

  33. Agrawal A, Lynskey MT. The genetic epidemiology of cannabis use, abuse and dependence. Addiction. 2006;101(6):801–12. https://doi.org/10.1111/j.1360-0443.2006.01399.x.

    Article  PubMed  Google Scholar 

  34. Ehlers CL, Gizer IR, Vieten C, et al. Cannabis dependence in the San Francisco Family Study: age of onset of use, DSM-IV symptoms, withdrawal, and heritability. Addict Behav. 2010;35(2):102–10. https://doi.org/10.1016/j.addbeh.2009.09.009.

    Article  PubMed  Google Scholar 

  35. Verweij KJ, Agrawal A, Nat NO, et al. A genetic perspective on the proposed inclusion of cannabis withdrawal in DSM-5. Psychol Med. 2013;43(8):1713–22. https://doi.org/10.1017/S0033291712002735.

    Article  CAS  PubMed  Google Scholar 

  36. Cornelius JR, Chung T, Martin C, Wood DS, Clark DB. Cannabis withdrawal is common among treatment-seeking adolescents with cannabis dependence and major depression, and is associated with rapid relapse to dependence. Addict Behav. 2008;33(11):1500–5. https://doi.org/10.1016/j.addbeh.2008.02.001.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Brezing CA, Levin FR. The current state of pharmacological treatments for cannabis use disorder and withdrawal. Neuropsychopharmacology. 2018;43(1):173–94. https://doi.org/10.1038/npp.2017.212.

    Article  CAS  PubMed  Google Scholar 

  38. Navarrete F, Aracil-Fernández A, Manzanares J. Cannabidiol regulates behavioural alterations and gene expression changes induced by spontaneous cannabinoid withdrawal. Br J Pharmacol. 2018;175(13):2676–88. https://doi.org/10.1111/bph.14226Nielsen.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Nielsen S, Gowing L, Sabioni P, Le Foll B. Pharmacotherapies for cannabis dependence. Cochrane Database Syst Rev. 2019;1(1):CD008940. Published 2019 Jan 28. https://doi.org/10.1002/14651858.CD008940.pub3.

  40. Haney M, Ward AS, Comer SD, Hart CL, Foltin RW, Fischman MW. Bupropion SR worsens mood during marijuana withdrawal in humans. Psychopharmacology. 2001;155(2):171–9. https://doi.org/10.1007/s002130000657.

    Article  CAS  PubMed  Google Scholar 

  41. Gray KM, Watson NL, Carpenter MJ, Larowe SD. N-acetylcysteine (NAC) in young marijuana users: an open-label pilot study. Am J Addict. 2010;19(2):187–9. https://doi.org/10.1111/j.1521-0391.2009.00027.x.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Gray KM, Carpenter MJ, Baker NL, et al. A double-blind randomized controlled trial of N-acetylcysteine in cannabis-dependent adolescents [published correction appears in Am J Psychiatry. 2012 Aug 1;169(8):869]. Am J Psychiatry. 2012;169(8):805–12. https://doi.org/10.1176/appi.ajp.2012.12010055.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Gray KM, Sonne SC, McClure EA, et al. A randomized placebo-controlled trial of N-acetylcysteine for cannabis use disorder in adults. Drug Alcohol Depend. 2017;177:249–57. https://doi.org/10.1016/j.drugalcdep.2017.04.020.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Danovitch I, Gorelick DA. State of the art treatments for cannabis dependence. Psychiatr Clin North Am. 2012;35(2):309–26. https://doi.org/10.1016/j.psc.2012.03.003.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Sherman BJ, McRae-Clark AL. Treatment of cannabis use disorder: current science and future outlook. Pharmacotherapy. 2016;36(5):511–35. https://doi.org/10.1002/phar.1747.

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Pain Medicine, Division of Anesthesiology and Critical Care, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Yinan Chen

  2. Department of Pain Medicine, Division of Anesthesiology, Critical Care and Pain Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Christina Le-Short

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  1. Yinan Chen
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Correspondence to Christina Le-Short .

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Editors and Affiliations

  1. Western Reserve Hospital, Center For Pain Medicine, Cuyahoga Falls, OH, USA

    Samer N. Narouze

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Chen, Y., Le-Short, C. (2021). Cannabis Withdrawal. In: Narouze, S.N. (eds) Cannabinoids and Pain. Springer, Cham. https://doi.org/10.1007/978-3-030-69186-8_39

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  • DOI: https://doi.org/10.1007/978-3-030-69186-8_39

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