Cannabis withdrawal: Epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis
- David A Gorelick, MD, PhD
David A Gorelick, MD, PhD
- Professor of Psychiatry
- University of Maryland School of Medicine
Cannabis (also called marijuana) is the most commonly used illegal psychoactive substance worldwide . Its psychoactive properties are primarily due to one cannabinoid: delta-9-tetrahydrocannabinol (THC); THC concentration is commonly used as a measure of cannabis potency .
Cannabis withdrawal is manifested by a constellation of signs and symptoms occurring within one week after abrupt reduction or cessation of heavy and prolonged cannabis use, including irritability, anger, anxiety, depression, and disturbed sleep .
The epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis, and management of cannabis withdrawal are reviewed here. The treatment of cannabis withdrawal is reviewed separately. The clinical manifestations, course, assessment, and diagnosis of cannabis use disorder are also reviewed separately. The epidemiology and health consequences of cannabis use and cannabis use disorder are also reviewed separately. The pathogenesis, pharmacology, and treatment of cannabis use disorder in adults are also reviewed separately. Acute intoxication from cannabis and synthetic cannabinoids are also reviewed separately. (See "Cannabis use and disorder: Epidemiology, comorbidity, health consequences, and medico-legal status" and "Cannabis use and disorder: Pathogenesis and pharmacology" and "Treatment of cannabis use disorder" and "Cannabis (marijuana): Acute intoxication" and "Synthetic cannabinoids: Acute intoxication".)
Prevalence — There are no definitive data on the prevalence of cannabis withdrawal, in part because of the lack of large-scale, representative studies that attempt to correlate participants’ intensity of cannabis use with their withdrawal experience. A limitation of studies that have been published is that their data were collected a decade or more ago, when the potency (delta-9-tetrahydrocannabinol [THC] concentration) of cannabis used in the United States was about one-third that of currently available cannabis .
Comparison across the studies below suggests that intensity (amount multiplied by duration) of cannabis use is positively correlated with prevalence of cannabis withdrawal, similar to the well-established relationship for other psychoactive substances such as alcohol and opiates. In general, individuals using cannabis daily or almost daily have a greater than 50 percent prevalence of withdrawal, while those using cannabis less than weekly experience little or no withdrawal. The prevalence of withdrawal among individuals with intermediate intensities of cannabis use is not well established and may depend on the presence or absence of other factors. (See 'Risk factors' below.)To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- United Nations Office on Drugs and Crime, World Drug Report 2016, Vienna 2016.
- Swift W, Wong A, Li KM, et al. Analysis of cannabis seizures in NSW, Australia: cannabis potency and cannabinoid profile. PLoS One 2013; 8:e70052.
- Bonnet U, Preuss UW. The cannabis withdrawal syndrome: current insights. Subst Abuse Rehabil 2017; 8:9.
- 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; 79:613.
- Agrawal A, Pergadia ML, Lynskey MT. Is there evidence for symptoms of cannabis withdrawal in the national epidemiologic survey of alcohol and related conditions? Am J Addict 2008; 17:199.
- Swift W, Hall W, Teesson M. Cannabis use and dependence among Australian adults: results from the National Survey of Mental Health and Wellbeing. Addiction 2001; 96:737.
- Gillespie NA, Neale MC, Prescott CA, et al. Factor and item-response analysis DSM-IV criteria for abuse of and dependence on cannabis, cocaine, hallucinogens, sedatives, stimulants and opioids. Addiction 2007; 102:920.
- Gillespie NA, Neale MC, Legrand LN, et al. Are the symptoms of cannabis use disorder best accounted for by dimensional, categorical, or factor mixture models? A comparison of male and female young adults. Psychol Addict Behav 2012; 26:68.
- Verweij KJ, Agrawal A, Nat NO, et al. A genetic perspective on the proposed inclusion of cannabis withdrawal in DSM-5. Psychol Med 2013; 43:1713.
- 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; 35:102.
- Stephens RS, Babor TF, Kadden R, et al. The Marijuana Treatment Project: rationale, design and participant characteristics. Addiction 2002; 97 Suppl 1:109.
- Copeland J, Swift W, Rees V. Clinical profile of participants in a brief intervention program for cannabis use disorder. J Subst Abuse Treat 2001; 20:45.
- 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; 17:642.
- Bonnet U, Specka M, Stratmann U, et al. Abstinence phenomena of chronic cannabis-addicts prospectively monitored during controlled inpatient detoxification: cannabis withdrawal syndrome and its correlation with delta-9-tetrahydrocannabinol and -metabolites in serum. Drug Alcohol Depend 2014; 143:189.
- Preuss UW, Watzke AB, Zimmermann J, et al. Cannabis withdrawal severity and short-term course among cannabis-dependent adolescent and young adult inpatients. Drug Alcohol Depend 2010; 106:133.
- Ehlers CL, Gilder DA, Gizer IR, Wilhelmsen KC. Heritability and a genome-wide linkage analysis of a Type II/B cluster construct for cannabis dependence in an American Indian community. Addict Biol 2009; 14:338.
- Hasin DS, Keyes KM, Alderson D, et al. Cannabis withdrawal in the United States: results from NESARC. J Clin Psychiatry 2008; 69:1354.
- Herrmann ES, Weerts EM, Vandrey R. Sex differences in cannabis withdrawal symptoms among treatment-seeking cannabis users. Exp Clin Psychopharmacol 2015; 23:415.
- Gizer IR, Gilder DA, Lau P, et al. Contributions of ethnicity to differential item functioning of cannabis abuse and dependence symptoms. J Stud Alcohol Drugs 2013; 74:320.
- Soenksen S, Stein LA, Brown JD, et al. Cannabis Withdrawal Among Detained Adolescents: Exploring the Impact of Nicotine and Race. J Child Adolesc Subst Abuse 2015; 24:119.
- 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; 1:60.
- Ceccarini J, Kuepper R, Kemels D, et al. [18F]MK-9470 PET measurement of cannabinoid CB1 receptor availability in chronic cannabis users. Addict Biol 2015; 20:357.
- Gates P, Albertella L, Copeland J. Cannabis withdrawal and sleep: A systematic review of human studies. Subst Abus 2016; 37:255.
- Garcia AN, Salloum IM. Polysomnographic sleep disturbances in nicotine, caffeine, alcohol, cocaine, opioid, and cannabis use: A focused review. Am J Addict 2015; 24:590.
- Bolla KI, Lesage SR, Gamaldo CE, et al. Polysomnogram changes in marijuana users who report sleep disturbances during prior abstinence. Sleep Med 2010; 11:882.
- Allsop DJ, Copeland J, Norberg MM, et al. Quantifying the clinical significance of cannabis withdrawal. PLoS One 2012; 7:e44864.
- Levin KH, Copersino ML, Heishman SJ, et al. Cannabis withdrawal symptoms in non-treatment-seeking adult cannabis smokers. Drug Alcohol Depend 2010; 111:120.
- Vandrey R, Umbricht A, Strain EC. Increased blood pressure after abrupt cessation of daily cannabis use. J Addict Med 2011; 5:16.
- Bonnet U. Abrupt Quitting of Long-term Heavy Recreational Cannabis Use is Not Followed by Significant Changes in Blood Pressure and Heart Rate. Pharmacopsychiatry 2016; 49:23.
- Loeffler G, Delaney E, Hann M. International trends in spice use: Prevalence, motivation for use, relationship to other substances, and perception of use and safety for synthetic cannabinoids. Brain Res Bull 2016; 126:8.
- Cooper ZD. Adverse Effects of Synthetic Cannabinoids: Management of Acute Toxicity and Withdrawal. Curr Psychiatry Rep 2016; 18:52.
- Macfarlane V, Christie G. Synthetic cannabinoid withdrawal: a new demand on detoxification services. Drug Alcohol Rev 2015; 34:147.
- Argamany JR, Reveles KR, Duhon B. Synthetic cannabinoid hyperemesis resulting in rhabdomyolysis and acute renal failure. Am J Emerg Med 2016; 34:765.e1.
- Dines AM, Wood DM, Galicia M, et al. Presentations to the Emergency Department Following Cannabis use--a Multi-Centre Case Series from Ten European Countries. J Med Toxicol 2015; 11:415.
- Vaziri ND, Thomas R, Sterling M, et al. Toxicity with intravenous injection of crude marijuana extract. Clin Toxicol 1981; 18:353.
- Budney AJ, Moore BA, Vandrey RG, Hughes JR. The time course and significance of cannabis withdrawal. J Abnorm Psychol 2003; 112:393.
- Davis JP, Smith DC, Morphew JW, et al. Cannabis Withdrawal, Posttreatment Abstinence, and Days to First Cannabis Use Among Emerging Adults in Substance Use Treatment: A Prospective Study. J Drug Issues 2016; 46:64.
- Budney AJ, Novy PL, Hughes JR. Marijuana withdrawal among adults seeking treatment for marijuana dependence. Addiction 1999; 94:1311.
- American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), American Psychiatric Association, Arlington 2013.
- Budney AJ, Vandrey RG, Hughes JR, et al. Comparison of cannabis and tobacco withdrawal: severity and contribution to relapse. J Subst Abuse Treat 2008; 35:362.
- Chesney T, Matsos L, Couturier J, Johnson N. Cannabis withdrawal syndrome: An important diagnostic consideration in adolescents presenting with disordered eating. Int J Eat Disord 2014; 47:219.
- Agrawal A, Budney AJ, Lynskey MT. The co-occurring use and misuse of cannabis and tobacco: a review. Addiction 2012; 107:1221.
- Vandrey RG, Budney AJ, Moore BA, Hughes JR. A cross-study comparison of cannabis and tobacco withdrawal. Am J Addict 2005; 14:54.
- Vandrey RG, Budney AJ, Hughes JR, Liguori A. A within-subject comparison of withdrawal symptoms during abstinence from cannabis, tobacco, and both substances. Drug Alcohol Depend 2008; 92:48.