Current Addiction Reports

, Volume 3, Issue 2, pp 189–198 | Cite as

Cannabis Use Disorders and Altered Brain Morphology: Where Is the Evidence?

  • Valentina LorenzettiEmail author
  • Albert Batalla
  • Janna Cousijn
Cannabis (F Filbey, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Cannabis


Cannabis use disorders (CUDs) affect 13.1 million individuals worldwide. Brain morphology specific to CUDs may mediate the adverse behavioral outcomes of CUDs. We reviewed findings from 20 human neuroimaging studies on grey and white matter morphology in cannabis users that specifically included CUD assessments. There is evidence for CUD-specific morphological abnormalities within the striatum, medial temporal lobe, prefrontal cortex, cerebellum, and corpus callosum. Factors that may aggravate morphological abnormalities associated with CUDs include earlier onset age, higher lifetime exposure, and CUD-associated problems, while abstinence may result in (partial) recovery. These observations suggest that the neural substrates of compulsive cannabis use (e.g., striatum) may be distinct from those linked to cannabinoid exposure (e.g., hippocampus). The lack of studies examining individuals with a diagnosed CUD prevents drawing strong conclusions on CUD-specific morphological abnormalities. Comparing cannabis users with and without CUD is essential to delineate the neurobiology and inform new treatment strategies.


Addiction Brain morphology Cannabis Cannabis use disorder Grey matter White matter 


Compliance with Ethical Standards

Conflict of Interest

Valentina Lorenzetti, Albert Batalla, and Janna Cousijn declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. 1.
    United Nations Office on Drugs and Crime. World drug report 2014. In: World drug report series 2014. United Nations Office on Drugs and Crime, available at 2014. [Accessed 12 December 2014].
  2. 2.
    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(5):737–48. doi: 10.1080/09652140020039107.CrossRefPubMedGoogle Scholar
  3. 3.
    Stinson FS, Ruan WJ, Pickering R, Grant BF. Cannabis use disorders in the USA: prevalence, correlates and co-morbidity. Psychol Med. 2006;36(10):1447–60. doi: 10.1017/S0033291706008361.CrossRefPubMedGoogle Scholar
  4. 4.
    Budney AJ, Vandrey RG, Hughes JR, Thostenson JD, Bursac Z. Comparison of cannabis and tobacco withdrawal: severity and contribution to relapse. J Subst Abus Treat. 2008;35(4):362–8. doi: 10.1016/j.jsat.2008.01.002.CrossRefGoogle Scholar
  5. 5.
    Chauchard E, Septfons A, Chabrol H. Motivations for cannabis cessation, coping and adaptation strategies, and perceived benefits: impact on cannabis use relapse and abstinence. L'Encéphale. 2013;39(6):385–92. doi: 10.1016/j.encep.2013.03.008.CrossRefPubMedGoogle Scholar
  6. 6.
    Lorenzetti V, Cousijn J. Cannabis use disorders and brain morphology. In: Preedy VR, editor. Neuropathology of drug addictions and substance misuse volume 1: common substances of abuse—tobacco, alcohol, cannabinoids and opioids. London: Elsevier Inc.; 2014.Google Scholar
  7. 7.
    Meier MH, Caspi A, Ambler A, Harrington H, Houts R, Keefe RS, et al. Persistent cannabis users show neuropsychological decline from childhood to midlife. Proc Natl Acad Sci U S A. 2012;109(40):E2657–64. doi: 10.1073/pnas.1206820109.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Solowij N, Battisti R. The chronic effects of cannabis on memory in humans: a review. Curr Drug Abus Rev. 2008;1(1):81–98.CrossRefGoogle Scholar
  9. 9.••
    van der Pol P, Liebregts N, de Graaf R, Ten Have M, Korf DJ, van den Brink W, et al. Mental health differences between frequent cannabis users with and without dependence and the general population. Addiction. 2013;108(8):1459–69. doi: 10.1111/add.12196. Internalising mental health problems like depression and anxiety might be specific to dependent compared to non-dependent frequent cannabis users. CrossRefPubMedGoogle Scholar
  10. 10.
    Everitt BJ, Robbins TW. Neural systems of reinforcement for drug addiction: from actions to habits to compulsion. Nat Neurosci. 2005;8(11):1481–9. doi: 10.1038/nn1579.CrossRefPubMedGoogle Scholar
  11. 11.
    Koob GF, Volkow ND. Neurocircuitry of addiction. Neuropsychopharmacology. 2010;35(1):217–38. doi: 10.1038/npp.2009.110.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Wilson SJ, Sayette MA, Fiez JA. Prefrontal responses to drug cues: a neurocognitive analysis. Nat Neurosci. 2004;7(3):211–4. doi: 10.1038/nn1200.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Burns HD, Van Laere K, Sanabria-Bohorquez S, Hamill TG, Bormans G, Eng WS, et al. [18F]MK-9470, a positron emission tomography (PET) tracer for in vivo human PET brain imaging of the cannabinoid-1 receptor. Proc Natl Acad Sci U S A. 2007;104(23):9800–5. doi: 10.1073/pnas.0703472104.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Landfield PW, Cadwallader LB, Vinsant S. Quantitative changes in hippocampal structure following long-term exposure to delta 9-tetrahydrocannabinol: possible mediation by glucocorticoid systems. Brain Res. 1988;443(1–2):47–62.CrossRefPubMedGoogle Scholar
  15. 15.
    Everitt BJ, Robbins TW. From the ventral to the dorsal striatum: devolving views of their roles in drug addiction. Neurosci Biobehav Rev. 2013;37(9 Pt A):1946–54. doi: 10.1016/j.neubiorev.2013.02.010.CrossRefPubMedGoogle Scholar
  16. 16.
    Cousijn J, Wiers RW, Ridderinkhof KR, van den Brink W, Veltman DJ, Goudriaan AE. Grey matter alterations associated with cannabis use: results of a VBM study in heavy cannabis users and healthy controls. NeuroImage. 2012;59(2012):3845–51. doi: 10.1016/j.neuroimage.2011.09.046.CrossRefPubMedGoogle Scholar
  17. 17.••
    Lorenzetti V, Solowij N, Yucel M. The role of cannabinoids in neuroanatomic alterations in cannabis users. Biol Psychiatry. 2015. doi: 10.1016/j.biopsych.2015.11.013. Cannabis use is associated with morphological alterations in cannabinoid receptor-rich brain regions. Greater cannabis exposure and earlier initiation of cannabis use are associated with these alterations. PubMedGoogle Scholar
  18. 18.
    Lorenzetti V, Solowij N, Fornito A, Lubman DI, Yucel M. The association between regular cannabis exposure and alterations of human brain morphology: an updated review of the literature. Curr Pharm Des. 2014;20(13):2138–67.CrossRefPubMedGoogle Scholar
  19. 19.
    Batalla A, Bhattacharyya S, Yucel M, Fusar-Poli P, Crippa JA, Nogue S, et al. Structural and functional imaging studies in chronic cannabis users: a systematic review of adolescent and adult findings. PLoS One. 2013;8(2):e55821. doi: 10.1371/journal.pone.0055821.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Yip SW, DeVito EE, Kober H, Worhunsky PD, Carroll KM, Potenza MN. Pretreatment measures of brain structure and reward-processing brain function in cannabis dependence: an exploratory study of relationships with abstinence during behavioral treatment. Drug Alcohol Depend. 2014;140:33–41. doi: 10.1016/j.drugalcdep.2014.03.031.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Gilman JM, Kuster JK, Lee S, Lee MJ, Kim BW, Makris N, et al. Cannabis use is quantitatively associated with nucleus accumbens and amygdala abnormalities in young adult recreational users. J Neurosci. 2014;34(16):5529–38. doi: 10.1523/JNEUROSCI.4745-13.2014.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    McQueeny T, Padula CB, Price J, Medina KL, Logan P, Tapert SF. Gender effects on amygdala morphometry in adolescent marijuana users. Behav Brain Res. 2011;224(1):128–34.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Yücel M, Solowij N, Respondek C, Whittle S, Fornito A, Pantelis C, et al. Regional brain abnormalities associated with heavy long-term cannabis use. Arch Gen Psychiatry. 2008;65(6):1–8.CrossRefGoogle Scholar
  24. 24.
    Tzilos GK, Cintron CB, Wood JBR, DSimpson NS, Young AD, Pope HGJ, et al. Lack of hippocampal volume change in long-term heavy cannabis users. Am J Addict. 2005;14:64–72.CrossRefPubMedGoogle Scholar
  25. 25.
    Ashtari M, Avants B, Cyckowski L, Cervellione KL, Roofeh D, Cook P, et al. Medial temporal structures and memory functions in adolescents with heavy cannabis use. J Psychiatr Res. 2011;45(8):1055–66. doi: 10.1016/j.jpsychires.2011.01.004.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Medina KL, Schweinsburg AD, Cohen-Zion M, Nagel BJ, Tapert SF. Effects of alcohol and combined marijuana and alcohol use hippocampal volume and asymmetry. Neurotoxicol Teratol. 2007;29:141–52.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Rocchetti M, Crescini A, Borgwardt S, Caverzasi E, Politi P, Atakan Z, et al. Is cannabis neurotoxic for the healthy brain? A meta-analytical review of structural brain alterations in non-psychotic users. Psychiatry Clin Neurosci. 2013;67(7):483–92. doi: 10.1111/pcn.12085.CrossRefPubMedGoogle Scholar
  28. 28.
    Churchwell JC, Lopez-Larson M, Yurgelun-Todd DA. Altered frontal cortical volume and decision making in adolescent cannabis users. Front Psychol. 2010;1:225. doi: 10.3389/fpsyg.2010.00225.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Medina KL, McQueeny T, Nagel BJ, Hanson KL, Yang TT, Tapert SF. Prefrontal cortex morphometry in abstinent adolescent marijuana users: subtle gender effects. Addict Biol. 2009;14(4):457–68. doi: 10.1111/j.1369-1600.2009.00166.x.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Battistella G, Fornari E, Annoni JM, Chtioui H, Dao K, Fabritius M, et al. Long-term effects of cannabis on brain structure. Neuropsychopharmacology. 2014;39(9):2041–8. doi: 10.1038/npp.2014.67.PubMedPubMedCentralGoogle Scholar
  31. 31.
    Mata I, Perez-Iglesias R, Roiz-Santianez R, Tordesillas-Gutierrez D, Pazos A, Gutierrez A, et al. Gyrification brain abnormalities associated with adolescence and early-adulthood cannabis use. Brain Res. 2010;1317:297–304. doi: 10.1016/j.brainres.2009.12.069.CrossRefPubMedGoogle Scholar
  32. 32.
    Medina KL, Nagel BJ, Tapert SF. Abnormal cerebellar morphometry in abstinent adolescent marijuana users. Psychiatry Res. 2010;182(2):152–9. doi: 10.1016/j.pscychresns.2009.12.004.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Solowij N, Yucel M, Respondek C, Whittle S, Lindsay E, Pantelis C, et al. Cerebellar white-matter changes in cannabis users with and without schizophrenia. Psychol Med. 2011;41(11):2349–59. doi: 10.1017/S003329171100050X.CrossRefPubMedGoogle Scholar
  34. 34.••
    Zalesky A, Solowij N, Yucel M, Lubman DI, Takagi M, Harding IH, et al. Effect of long-term cannabis use on axonal fibre connectivity. Brain. 2012;135(Pt7):2245–55. doi: 10.1093/brain/aws136. Long-term cannabis use might negatively affect white matter structure of the developing brain. CrossRefPubMedGoogle Scholar
  35. 35.
    Gruber SA, Silveri MM, Dahlgren MK, Yurgelun-Todd D. Why so impulsive? White matter alterations are associated with impulsivity in chronic marijuana smokers. Exp Clin Psychopharmacol. 2011;19(3):231–42. doi: 10.1037/a0023034.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Ashtari M, Cervellione K, Cottone J, Ardekani BA, Sevy S, Kumra S. Diffusion abnormalities in adolescents and young adults with a history of heavy cannabis use. J Psychiatr Res. 2009;43(3):189–204. doi: 10.1016/j.jpsychires.2008.12.002.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Arnone D, Barrick TR, Chengappa S, Mackay CE, Clark CA, Abou-Saleh MT. Corpus callosum damage in heavy marijuana use: preliminary evidence from diffusion tensor tractography and tract-based spatial statistics. NeuroImage. 2008;41(3):1067–74. doi: 10.1016/j.neuroimage.2008.02.064.CrossRefPubMedGoogle Scholar
  38. 38.
    Medina KL, Nagel BJ, Park A, McQueeny T, Tapert SF. Depressive symptoms in adolescents: associations with white matter volume and marijuana use. J Child Psychol Psychiatry. 2007;48(6):592–600. doi: 10.1111/j.1469-7610.2007.01728.x.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Kumra S, Robinson P, Tambyraja R, Jensen D, Schimunek C, Houri A, et al. Parietal lobe volume deficits in adolescents with schizophrenia and adolescents with cannabis use disorders. J Am Acad Child Adolesc Psychiatry. 2012;51(2):171–80. doi: 10.1016/j.jaac.2011.11.001.CrossRefPubMedGoogle Scholar
  40. 40.
    Winsauer PJ, Daniel JM, Filipeanu CM, Leonard ST, Hulst JL, Rodgers SP, et al. Long-term behavioral and pharmacodynamic effects of delta-9-tetrahydrocannabinol in female rats depend on ovarian hormone status. Addict Biol. 2011;16(1):64–81.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Filbey FM, McQueeny T, Kadamangudi S, Bice C, Ketcherside A. Combined effects of marijuana and nicotine on memory performance and hippocampal volume. Behav Brain Res. 2015;293:46–53. doi: 10.1016/j.bbr.2015.07.029.CrossRefPubMedGoogle Scholar
  42. 42.
    Gotgay N, Giedd JN, Lusk L, Hayashi KM, Greenstein D, Vaituzis AC, et al. Dynamic mapping of human cortical development during childhood through early adulthood. Proc Natl Acad Sci U S A. 2004;101(21):8174–9.CrossRefGoogle Scholar
  43. 43.
    Dorard G, Berthoz S, Phan O, Corcos M, Bungener C. Affect dysregulation in cannabis abusers: a study in adolescents and young adults. Eur Child Adolesc Psychiatry. 2008;17(5):274–82. doi: 10.1007/s00787-007-0663-7.CrossRefPubMedGoogle Scholar
  44. 44.
    Moore TH, Zammit S, Lingford-Huges A, Barnes TR, Jones PB, Burke M, et al. Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. Lancet. 2007;370:319–28.CrossRefPubMedGoogle Scholar
  45. 45.
    Skinner R, Conlon L, Gibbons D, McDonald C. Cannabis use and non-clinical dimensions of psychosis in university students presenting to primary care. Acta Psychiatr Scand. 2011;123(1):21–7. doi: 10.1111/j.1600-0447.2010.01546.x.CrossRefPubMedGoogle Scholar
  46. 46.
    Cousijn J. Embracing comorbidity: a way toward understanding the role of motivational and control processes in cannabis use disorders. Front Psychol. 2015;6:677. doi: 10.3389/fpsyg.2015.00677.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    World Health Organization. The ICD-10 classification of mental and behavioural disorders: clinical descriptions and diagnostic guidelines. Geneva, available at 1992. [Accessed 15 December 2014].
  48. 48.
    Jager G, Van Hell HH, De Win MML, Kahn RS, Van Den Brink W, Van Ree JM, et al. Effects of frequent cannabis use on hippocampal activity during an associative learning memory task. Eur Neuropsychopharmacol. 2007;17:289–97.CrossRefPubMedGoogle Scholar
  49. 49.
    Lopez-Pelayo H, Batalla A, Balcells MM, Colom J, Gual A. Assessment of cannabis use disorders: a systematic review of screening and diagnostic instruments. Psychol Med. 2014;45:1–13. doi: 10.1017/S0033291714002463.Google Scholar
  50. 50.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-5, fifth ed. Washington DC: 2013.Google Scholar
  51. 51.
    American Psychiatric Association. DSM-IV Diagnostic and Statistical Manual of Mental Disorders. fourth ed. Washington DC: 1996.Google Scholar

Copyright information

© Springer International Publishing AG 2016

Authors and Affiliations

  • Valentina Lorenzetti
    • 1
    Email author
  • Albert Batalla
    • 2
    • 3
  • Janna Cousijn
    • 4
  1. 1.Brain & Mental Health Laboratory, Monash Institute of Cognitive & Clinical Neurosciences and School of Psychological SciencesMonash UniversityMelbourneAustralia
  2. 2.Department of PsychiatryRadboud University Medical CentreNijmegenThe Netherlands
  3. 3.Nijmegen Institute for Scientist-Practitioners in Addiction (NISPA)Radboud UniversityNijmegenThe Netherlands
  4. 4.Department of Developmental PsychologyUniversity of AmsterdamAmsterdamThe Netherlands

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