Abstract
There is a growing body of evidence pointing to the co-occurrence of cannabis use and depression. There is also some evidence that the use of cannabis may lead to the onset of depression; however, strong evidence points to the inverse association; i.e. that depression may lead to the onset or increase in cannabis use frequency. Observational and epidemiological studies have not indicated a positive long-term effect of cannabis use on the course and outcome of depression. The association between cannabis use and depression may be stronger among men during adolescence and emerging adulthood and stronger in women during midlife. There is an indication for potential genetic correlation contributing to the comorbidity of cannabis dependence and major depression, namely that serotonin (5-HT) may mediate such association and there is also evidence for specific risk alleles for cannabis addiction. There is preclinical evidence that alteration in the endocannabinoid system could potentially benefit patients suffering from depression. However, the issue of using cannabis as an anti-depressant is at an early stage of examination and there is little evidence to support it. Finally, there has been little support to the notion that selective serotonin reuptake inhibitors (SSRIs) may be effective in decreasing depressive symptoms or rates of substance use in adolescents treated for depression and a co-occurring substance use disorder. In conclusion, despite methodological limitations, research in the past decades has broadened our knowledge on the association between cannabis use and depression from epidemiological, neurological, genetic, and pharmacological perspectives.
Keywords
- Cannabis
- Mental illness
- Mood disorders
- Major Depressive Disorder
- Bipolar Disorder
- Anxiety Disorders
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References
Ablon SL, Goodwin FK (1974) High frequency of dysphoric reactions to tetrahydrocannabinol among depressed patients. Am J Psychiatry 131(4):448–453
Agrawal A, Lynskey MT (2006) The genetic epidemiology of cannabis use, abuse and dependence. [research support, N.I.H., extramural review]. Addiction 101(6):801–812. https://doi.org/10.1111/j.1360-0443.2006.01399.x
Agrawal A, Wetherill L, Dick DM, Xuei X, Hinrichs A, Hesselbrock V, Kramer J, Nurnberger JI, Schuckit M, Bierut LJ, Edenberg HJ, Foroud T (2009) Evidence for association between polymorphisms in the cannabinoid receptor 1 (CNR1) gene and cannabis dependence. Am J Med Genet B Neuropsychiatr Genet 150B(5):736–740
Amato L, Minozzi S, Mitrova Z, Parmelli E, Saulle R, Cruciani F, Davoli M (2017) Systematic review of safeness and therapeutic efficacy of cannabis in patients with multiple sclerosis, neuropathic pain, and in oncological patients treated with chemotherapy. Epidemiol Prev 41(5–6):279–293
American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders, 5th edn. American Psychiatric Publishing, Arlington, VA
Arendt M, Rosenberg R, Fjordback L, Brandholdt J, Foldager L, Sher L, Munk-Jorgensen P (2007) Testing the self-medication hypothesis of depression and aggression in cannabis-dependent subjects. [research support, non-U.S. Gov’t]. Psychol Med 37(7):935–945. https://doi.org/10.1017/S0033291706009688
Ashton CH, Moore PB, Gallagher P, Young AH (2005) Cannabinoids in bipolar affective disorder: a review and discussion of their therapeutic potential. J Psychopharmacol 19:293–300
Aspis I, Feingold D, Weiser M, Rehm J, Shoval G, Lev-Ran S (2015) Cannabis use and mental health-related quality of life among individuals with depressive disorders. Psychiatry Res 230(2):341–349. https://doi.org/10.1016/j.psychres.2015.09.014
Babson KA, Boden MT, Bonn-Miller MO (2013) Sleep quality moderates the relation between depression symptoms and problematic cannabis use among medical cannabis users. Am J Drug Alcohol Abuse 39:211–216
Bahorik AL, Sterling SA, Campbell CI, Weisner C, Ramo D, Satre DD (2018) Medical and non-medical marijuana use in depression: longitudinal associations with suicidal ideation, everyday functioning, and psychiatry service utilization. J Affect Disord 241:8–14. https://doi.org/10.1016/j.jad.2018.05.065
Bambico FR, Katz N, Debonnel G, Gobbi G (2007) Cannabinoids elicit antidepressant-like behavior and activate serotonergic neurons through the medial prefrontal cortex. J Neurosci 27(43):11700–11711
Batalla A, Soriano-Mas C, Lopez-Sola M, Torrens M, Crippa JA, Bhattacharyya S, Blanco-Hinojo L, Fagundo AB, Harrison BJ, Nogue S, de la Torre R, Farre M, Pujol J, Martin-Santos R (2014) Modulation of brain structure by catechol-O-methyltransferase Val(158) met polymorphism in chronic cannabis users. Addict Biol 19:722–732
Benyamina A, Karila L, Lafaye G, Blecha L (2016) Genetic influences in cannabis use disorder and psychosis: dopamine and beyond. Curr Pharm Des 22(42):6392–6396. https://doi.org/10.2174/1381612822666160831095707
Bhattacharyya S, Iyegbe C, Atakan Z, Martin-Santos R, Crippa JA, Xu X, Williams S, Brammer M, Rubia K, Prata D, Collier DA, McGuire PK (2014) Protein kinase B (AKT1) genotype mediates sensitivity to cannabis-induced impairments in psychomotor control. Psychol Med 44:3315–3328
Bolton JM, Robinson J, Sareen J (2009) Self-medication of mood disorders with alcohol and drugs in the National Epidemiologic Survey on alcohol and related conditions. J Affect Disord 115(3):367–375. https://doi.org/10.1016/j.jad.2008.10.003
Borgelt LM, Franson KL, Nussbaum AM, Wang GS (2013) Thepharmacologic and clinical effects of medical cannabis. Pharmacotherapy 33(2):195–209
Bovasso GB (2001) Cannabis abuse as a risk factor for depressive symptoms. [research support, U.S. Gov’t, non-P.H.S. research support, U.S. Gov’t, P.H.S.]. Am J Psychiatry 158(12):2033–2037
Bricker JB, Russo J, Stein MB, Sherbourne C, Craske M, Schraufnagel TJ, Roy-Byrne P (2007) Does occasional cannabis use impact anxiety and depression treatment outcomes?: results from a randomized effectiveness trial. [comparative study multicenter study randomized controlled trial]. Depress Anxiety 24(6):392–398. https://doi.org/10.1002/da.20248
Chen CY, Wagner FA, Anthony JC (2002) Marijuana use and the risk of major depressive episode. Epidemiological evidence from the United States National Comorbidity Survey. [research support, non-U.S. Gov’t research support, U.S. Gov’t, P.H.S.]. Soc Psychiatry Psychiatr Epidemiol 37(5):199–206. https://doi.org/10.1007/s00127-002-0541-z
Choi K, Le T, McGuire J, Xing G, Zhang L, Li H, Ursano RJ (2012) Expression pattern of the cannabinoid receptor genes in the frontal cortex of mood disorder patients and mice selectively bred for high and low fear. J Psychiatr Res 46(7):882–889
Cohen K, Weizman A, Weinstein A (2019) Modulatory effects of cannabinoids on brain neurotransmission. Eur J Neurosci 50:2322–2345. https://doi.org/10.1111/ejn.14407
Colizzi M, Iyegbe C, Powell J, Ursini G, Porcelli A, Bonvino A, Taurisano P, Romano R, Masellis R, Blasi G, Morgan C, Aitchison K, Mondelli V, Luzi S, Kolliakou A, David A, Murray RM, Bertolino A, Di Forti M (2015) Interaction between functional genetic variation of DRD2 and cannabis use on risk of psychosis. Schizophr Bull 41(5):1171–1182
Cornelius JR, Buksteinb OG, Douaihy AB, Clark DB, Chung TA, Daley DC, Wood DS, Brown SJ (2010) Double-blind fluoxetine trial in comorbid MDD–CUD youth and young adults. Drug Alcohol Depend 112:39–45
Cornelius JR, Clark DB, Bukstein OG, Bimaher B, Salloum IM, Brown SA (2005) Acute phase and five year follow up atusy of fluoxetine in adolescents with major depression and comorbid substance abuse disorder: a review. Addict Behav 30:1824–1833
Cuttler C, Spradlin A, McLaughlin RJ (2018) A naturalistic examination of the perceived effects of cannabis on negative affect. J Affect Disord 235:198–205. https://doi.org/10.1016/j.jad.2018.04.054. Epub 2018 Apr 6
D’souza DC, Ranganathan M (2015) Medical marijuana: is the cart before the horse? JAMA 313(24):2431–2432
Danielsson AK, Lundin A, Agardh E, Allebeck P, Forsell Y (2015) Cannabis use, depression and anxiety: a 3-year prospective population-based study. J Affect Disord 193:103–108. https://doi.org/10.1016/j.jad.2015.12.045
Degenhardt L, Bucello C, Calabria B, Nelson P, Roberts A, Hall W, McLaren J (2011) What data are available on the extent of illicit drug use and dependence globally? Results of four systematic reviews. [research support, non-U.S. Gov’t review]. Drug Alcohol Depend 117(2–3):85–101. https://doi.org/10.1016/j.drugalcdep.2010.11.032
Degenhardt L, Coffey C, Romaniuk H, Swift W, Carlin JB, Hall WD, Patton GC (2013) The persistence of the association between adolescent cannabis use and common mental disorders into young adulthood. [research support, non-U.S. Gov’t]. Addiction 108(1):124–133. https://doi.org/10.1111/j.1360-0443.2012.04015.x
Degenhardt L, Hall W, Lynskey M (2003) Exploring the association between cannabis use and depression. [review]. Addiction 98(11):1493–1504
Denson TF, Earleywine M (2006) Decreased depression in marijuana users. Addict Behav 31:738–742
Dierker L, Selya A, Lanza S, Li R, Rose J (2018) Depression and marijuana use disorder symptoms among current marijuana users. Addict Behav 76:161–168. https://doi.org/10.1016/j.addbeh.2017.08.013
Domschke K, Dannlowski U, Ohrmann P, Lawford B, Bauer J, Kugel H, Heindel W, Young R, Morris P, Arolt V et al (2008) Cannabinoid receptor 1 (CNR1) gene: impact on antidepressant treatment response and emotion processing in major depression. Eur Neuropsychopharmacol 18(10):751–759
Eggan SM, Stoyak SR, Verrico CD, Lewis DA (2010) Cannabinoid CB1 receptor immunoreactivity in the prefrontal cortex: comparison of schizophrenia and major depressive disorder. Neuropsychopharmacology 35:2060–2071
EMMDDA (2017) European drug report 2017. European Monitoring Centre for Drugs and Drug Addiction, Luxembourg
Feingold D, Rehm J, Lev-Ran S (2017) Cannabis use and the course and outcome of major depressive disorder: a population based longitudinal study. Psychiatry Res 251:225–234
Feingold D, Weiser M, Rehm J, Lev-Ran S (2015) The association between cannabis use and mood disorders: a longitudinal study. J Affect Disord 172:211–218
Fergusson DM, Horwood LJ (1997) Early onset cannabis use and psychosocial adjustment in young adults. [comparative study research support, non-U.S. Gov’t]. Addiction 92(3):279–296
Ferrari AJ, Somerville AJ, Baxter AJ, Norman R, Patten SB, Vos T, Whiteford HA (2013) Global variation in the prevalence and incidence of major depressive disorder: a systematic review of the epidemiological literature. Psychol Med 43(03):471–481. https://doi.org/10.1017/S0033291712001511
Findling RL, Pagano ME, McNamara NK, Stansbrey RJ, Faber JE, Lingler J, Reed MD (2009) The short-term safety and efficacy of fluoxetine in depressed adolescents with alcohol and cannabis use disorders: a pilot randomized placebo-controlled trial. Child Adolesc Psychiatry Ment Health 3(1):11. https://doi.org/10.1186/1753-2000-3-11
Georgiades K, Boyle MH (2007) Adolescent tobacco and cannabis use: young adult outcomes from the Ontario child health study. [research support, non-U.S. Gov’t]. J Child Psychol Psychiatry 48(7):724–731. https://doi.org/10.1111/j.1469-7610.2007.01740.x
Gorelick DA (2016) Pharmacological treatment of cannabis-related disorders: a narrative review. Curr Pharm Des 22(42):6409–6419. https://doi.org/10.2174/1381612822666160822150822
Grinspoon L, Bakalar JB (1998) The use of cannabis as a mood stabilizer in bipolar disorder: anecdotal evidence and the need for clinical research. J Psychoactive Drugs 30:171–177
Gruber AJ, Pope HG, Brown ME (1996) Do patients use marijuana as an antidepressant? Depression 4:77–80
Gruber AJ, Pope HG, Oliva P (1997) Very long-term users of marijuana in the United States: a pilot study. Subst Use Misuse 32(3):249–264
Guttmannova K, Kosterman R, White HR, Bailey JA, Lee JO, Epstein M, Hawkins JD (2017) The association between regular marijuana use and adult mental health outcomes. [research support, N.I.H., extramural]. Drug Alcohol Depend 179:109–116. https://doi.org/10.1016/j.drugalcdep.2017.06.016
Hasin DS, Kerridge BT, Saha TD, Huang B, Pickering R, Smith SM, Grant BF (2016) Prevalence and correlates of DSM-5 cannabis use disorder, 2012-2013: findings from the National Epidemiologic Survey on alcohol and related conditions–III. Am J Psychiatr 173(6):588–599
Hodgson K, Almasy L, Knowles EE, Kent JW, Curran JE, Dyer TD, Göring HH, Olvera RL, Woolsey MD, Duggirala R, Fox PT, Blangero J, Glahn DC (2017) The genetic basis of the comorbidity between cannabis use and major depression. Addiction 112(1):113–123
Horwood LJ, Fergusson DM, Coffey C, Patton GC, Tait R, Smart D, Hutchinson DM (2012) Cannabis and depression: an integrative data analysis of four Australasian cohorts. Drug Alcohol Depend 126(3):369–378
Hungund BL, Vinod KY, Kassir SA, Basavarajappa BS, Yalamanchili R, Cooper TB, Mann JJ, Arango V (2004) Upregulation of CB1 receptors and agonist-stimulated [35S]GTPγS binding in the prefrontal cortex of depressed suicide victims. Mol Psychiatry 9:184–190
Jacobus J, Squeglia LM, Escobar S, McKenna BM, Hernandez MM, Bagot KS, Huestis MA (2017) Changes in marijuana use symptoms and emotional functioning over 28-days of monitored abstinence in adolescent marijuana users. Psychopharmacology 234(23–24):3431–3442
Juhasz G, Chase D, Pegg E, Downey D, Toth ZG, Stones K, Platt H, Mekli K, Payton A, Elliott R et al (2009) CNR1 gene is associated with high neuroticism and low agreeableness and interacts with recent negative life events to predict current depressive symptoms. Neuropsychopharmacology 34:2019–2027
Kaasbøll C, Hagen R, Gråwe RW (2018) Population-based associations among cannabis use, anxiety, and depression in Norwegian adolescents. J Child Adolesc Subst Abuse 27(4):238–243
Khantzian EJ (1985) The self-medication hypothesis of addictive disorders: focus on heroin and cocaine dependence. [case reports research support, U.S. Gov’t, P.H.S. review]. Am J Psychiatry 142(11):1259–1264
Khantzian EJ, Albanese MJ (2008) Understanding addiction as self medication: finding Hope behind the pain. Rowman & Littlefield Publishers, Inc., New York
Koethe D, Llenos IC, Dulay JR, Hoyer C, Torrey EF, Leweke FM, Weis S (2007) Expression of CB1 cannabinoid receptor in the anterior cingulate cortex in schizophrenia, bipolar disorder, and major depression. J Neural Transm 114:1055–1063
Leadbeater BJ, Ames ME, Linden-Carmichael AN (2018) Age-varying effects of cannabis use frequency and disorder on symptoms of psychosis, depression, and anxiety in adolescents and adults. Addiction
Lev-Ran S, Roerecke M, Le Foll B, George TP, McKenzie K, Rehm J (2013) The association between cannabis use and depression: a systematic review and meta analysis of longitudinal studies. Psychol Med:1–14. https://doi.org/10.1017/S0033291713001438
Lynskey MT, Glowinski AL, Todorov AA, Bucholz KK, Madden PA, Nelson EC, Statham DJ, Martin NG, Heath AC (2004) Major depressive disorder, suicidal ideation, and suicide attempt in twins discordant for cannabis dependence and early-onset cannabis use. Arch Gen Psychiatry 61(10):1026–1032
Mariani JJ, Brooks D, Haney M, Levin FR (2011) Quantification and comparison of marijuana smoking practices: blunts, joints, and pipes. Drug Alcohol Depend 113(2–3):249–251
Meller WH, Rinehart R, Cadoret RJ, Troughton E (1988) Specific familial transmission in substance abuse. Int J Addict 23(10):1029–1039
Mitjans M, Serretti A, Fabbri C, Gastó C, Catalán R, Fañanás L, Arias B (2013) Screening genetic variability at the CNR1 gene in both major depression etiology and clinical response to citalopram treatment. Psychopharmacology 227:509–519
Monteleone P, Bifulco M, Maina G, Tortorella A, Gazzerro P, Proto MC, Di Filippo C, Monteleone F, Canestrelli B, Buonerba G et al (2010) Investigation of CNR1 and FAAH endocannabinoid gene polymorphisms in bipolar disorder and major depression. Pharmacol Res 61:400–404
Moore TH, Zammit S, Lingford-Hughes A, Barnes TR, Jones PB, Burke M, Lewis G (2007) Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. [research support, non-U.S. Gov’t review]. Lancet 370(9584):319–328. https://doi.org/10.1016/S01406736(07)61162-3
National Academies of Sciences, E., & Medicine (2017) The health effects of cannabis and cannabinoids: the current state of evidence and recommendations for research. National Academies Press
Ogborne AC, Smart RG, Weber T, Birchmore-Timney C (2000) Who is using cannabis as a medicine and why: an exploratory study. J Psychoactive Drugs 32(4):435–443
Otten R, Engels RC (2013) Testing bidirectional effects between cannabis use and depressive symptoms: moderation by the serotonin transporter gene. Addict Biol 18(5):826–835. https://doi.org/10.1111/j.1369-1600.2011.00380.x
Pertwee RG (2001) Cannabinoid receptors and pain. Prog Neurobiol 63(5):569–611
Pertwee R (2014) Handbook of cannabis. Oxford University Press, Oxford
Regier DA, Farmer ME, Rae DS, Locke BZ, Keith SJ, Judd LL, Goodwin FK (1990) Comorbidity of mental disorders with alcohol and other drug abuse. Results from the epidemiologic catchment area (ECA) study. [research support, U.S. Gov’t, P.H.S.]. JAMA 264(19):2511–2518
Rhew IC, Fleming CB, Vander Stoep A, Nicodimos S, Zheng C, McCauley E (2017) Examination of cumulative effects of early adolescent depression on cannabis and alcohol use disorder in late adolescence in a community-based cohort. Addiction 112(11):1952–1960
SAMHSA. (2007) Results from the 2006 National Survey on drug use and health: National Findings. Rockville, MD
SAMHSA. (2014) Results from the 2013 National Survey on drug use and health: summary of National Findings Rockville, MD
Scherma, M, Masia P, Deidda M, Fratta W, Tanda G, Fadda P (2018) New perspectives on the use of cannabis in the treatment of psychiatric disorders. Medicines (Basel), 5(4). pii: E107. doi: https://doi.org/10.3390/medicines5040107
Schoeler T, Theobald D, Pingault J-B, Farrington DP, Coid JW, Bhattacharyya S (2018) Developmental sensitivity to cannabis use patterns and risk for major depressive disorder in mid-life: findings from 40 years of follow-up. Psychol Med:1–8
Shearman LP, Rosko KM, Fleischer R, Wang J, Xu S, Tong XS, Rocha BA (2003) Antidepressant-like and anorectic effects of the cannabinoid CB1 receptor inverse agonist AM251 in mice. Behav Pharmacol 14(8):573–582
Sherva R, Wang Q, Kranzler H, Zhao H, Koesterer R, Herman A, Gelernter J (2016) Genome-wide association study of cannabis dependence severity, novel risk variants, and shared genetic risks. JAMA Psychiat 73(5):472–480. https://doi.org/10.1001/jamapsychiatry.2016.0036
Silins E, Horwood LJ, Patton GC, Fergusson DM, Olsson CA, Hutchinson DM, Mattick RP (2014) Young adult sequelae of adolescent cannabis use: an integrative analysis. Lancet Psychiatry 1(4):286–293. https://doi.org/10.1016/S2215-0366(14)70307-4
Stapinski LA, Montgomery AA, Araya R (2016) Anxiety, depression and risk of cannabis use: examining the internalising pathway to use among Chilean adolescents. Drug Alcohol Depend 166:109–115
Stinson FS, Ruan WJ, Pickering R, Grant BF (2006) Cannabis use disorders in the USA: prevalence, correlates and co-morbidity. [research support, N.I.H., extramural research support, N.I.H., intramural]. Psychol Med 36(10):1447–1460. https://doi.org/10.1017/S0033291706008361
Taurisano P, Romano R, Mancini M, Giorgio AD, Antonucci LA, Fazio L, Rampino A, Quarto T, Gelao B, Porcelli A, Papazacharias A, Ursini G, Caforio G, Masellis R, Niccoli-Asabella A, Todarello O, Popolizio T, Rubini G, Blasi G, Bertolino A (2014) Prefronto-striatal physiology is associated with schizotypy and is modulated by a functional variant of DRD2. Front Behav Neurosci 8:235
Turna J, Patterson B, Van Ameringen M (2017) Is cannabis treatment for anxiety, mood, and related disorders ready for prime time? Depress Anxiety 34(11):1006–1017
United Nations Office on Drugs and Crime (2012) World drug report 2012. United Nations, New York
Van Laar M, van Dorsselaer S, Monshouwer K, de Graaf R (2007) Does cannabis use predict the first incidence of mood and anxiety disorders in the adult population? [research support, non-U.S. Gov’t]. Addiction 102(8):1251–1260. https://doi.org/10.1111/j.1360-0443.2007.01875.x
Verweij KJ, Zietsch BP, Lynskey MT, Medland SE, Neale MC, Martin NG, Vink JM (2010) Genetic and environmental influences on cannabis use initiation and problematic use: a meta-analysis of twin studies. Addiction 105(3):417–430. https://doi.org/10.1111/j.1360-0443.2009.02831.x
Walsh Z, Gonzalez R, Crosby K, Thiessen MS, Carroll C, Bonn-Miller MO (2017) Medical cannabis and mental health: a guided systematic review. Clin Psychol Rev 51:15–29
Weinstein AM, Gorelick DA (2011) Pharmacological treatment of cannabis dependence. Curr Pharm Des 17(14):1351–1358
Whiteford HA, Degenhardt L, Rehm J, Baxter AJ, Ferrari AJ, Erskine HE, Vos T (2013) Global burden of disease attributable to mental and substance use disorders: findings from the global burden of disease study 2010. [research support, N.I.H., extramural research support, non-U.S. Gov’t review]. Lancet 382(9904):1575–1586. https://doi.org/10.1016/S0140-6736(13)61611-6
Wittchen HU, Frohlich C, Behrendt S, Gunther A, Rehm J, Zimmermann P, Perkonigg A (2007) Cannabis use and cannabis use disorders and their relationship to mental disorders: a 10-year prospective-longitudinal community study in adolescents. [research support, N.I.H., extramural research support, non-U.S. Gov’t]. Drug Alcohol Depend 88(Suppl 1):S60–S70. https://doi.org/10.1016/j.drugalcdep.2006.12.013
World Health Organization (1992) ICD 10 classifications of mental and Behavioural disorder: clinical descriptions and diagnostic guidelines. World Health Organization, Geneva
World Health Organization (2016) The health and social effects of nonmedical cannabis use. WHO, Geneva, CH
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Feingold, D., Weinstein, A. (2021). Cannabis and Depression. In: Murillo-Rodriguez, E., Pandi-Perumal, S.R., Monti, J.M. (eds) Cannabinoids and Neuropsychiatric Disorders. Advances in Experimental Medicine and Biology, vol 1264. Springer, Cham. https://doi.org/10.1007/978-3-030-57369-0_5
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