Skip to main content
    • Aa
    • Aa
  • The International Journal of Neuropsychopharmacology, Volume 13, Issue 9
  • October 2010, pp. 1145-1154

Variable individual sensitivity to cannabis in patients with schizophrenia

  • Céline Goldberger (a1) (a2), Alain Dervaux (a1) (a3), David Gourion (a1) (a2), Marie-Chantal Bourdel (a1), Henri Lôo (a1) (a2), Xavier Laqueille (a3) and Marie-Odile Krebs (a1) (a2)
  • DOI:
  • Published online: 09 June 2010

There is now compelling evidence that cannabis consumption might precipitate psychosis onset. The objective of the present study was to assess the role of individual sensitivity to the psychotogenic effect of cannabis in male patients with schizophrenia. The lifetime diagnosis, disease and substance-use history were determined using a standardized interview in 190 patients with schizophrenia. Of patients with lifetime cannabis use (n=121), 44 were characterized as Cannabis-sensitive (CS) patients if the onset of psychotic symptoms occurred within 1 month following the initiation of cannabis consumption, or following a marked rise of cannabis consumption, or marked aggravation of psychotic symptoms each time the subject used cannabis. Age at onset of psychosis was not different in patients with lifetime cannabis use compared to non-users. By contrast, the first psychotic episode occurred 2.6 yr earlier in CS compared to Non-cannabis-sensitive (NCS) patients (p=0.006). Moreover, a specific excess of family history of psychotic disorder was found in CS patients, but not of any other psychiatric disorder, as well as an earlier age at exposure to cannabis (16.7±2.5 yr, p=0.03). Sensitivity to psychotogenic effects of cannabis in schizophrenia patients could be related to both genetic vulnerability to schizophrenia and the influence of cannabis on brain maturation and could modulate the influence of cannabis on the onset of schizophrenia.

Corresponding author
Address for correspondence: Professor M.-O. Krebs, Service Hospitalo-Universitaire, Hôpital Sainte-Anne, 7 rue Cabanis, 75014Paris, France. Tel.: +33 1 45 65 86 46Fax: +33 1 45 65 81 60Email: (
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

M Arendt , PB Mortensen , R Rosenberg , CB Pedersen , BL Waltoft (2008). Familial predisposition for psychiatric disorder: comparison of subjects treated for cannabis-induced psychosis and schizophrenia. Archives of General Psychiatry 65, 269274.

S Arndt , G Tyrrell , M Flaum , NC Andreasen (1992). Comorbidity of substance abuse and schizophrenia: the role of pre-morbid adjustment. Psychological Medicine 22, 379388.

L Arseneault , M Cannon , R Poulton , R Murray , (2002). Cannabis use in adolescence and risk for adult psychosis: longitudinal prospective study. British Medical Journal 325, 12121213.

L Arseneault , M Cannon , J Witton , RM Murray (2004). Causal association between cannabis and psychosis: examination of the evidence. British Journal of Psychiatry 184, 110117.

I Baeza , M Graell , D Moreno , J Castro-Fornieles , (2009). Cannabis use in children and adolescents with first episode psychosis: influence on psychopathology and short-term outcome (CAFEPS study). Schizophrenia Research 113, 129137.

TR Barnes , SH Mutsatsa , SB Hutton , HC Watt , (2006). Comorbid substance use and age at onset of schizophrenia. British Journal of Psychiatry 188, 237242.

M Beiser , D Erickson , JA Fleming , WG Iacono (1993). Establishing the onset of psychotic illness. American Journal of Psychiatry 150, 13491354.

S Bhattacharyya , P Fusar-Poli , S Borgwardt , (2009). Modulation of mediotemporal and ventrostriatal function in humans by Delta9-tetrahydrocannabinol: a neural basis for the effects of Cannabis sativa on learning and psychosis. Archives of General Psychiatry 66, 442451.

MG Bossong , BN van Berckel , R Boellaard , (2009). 9-tetrahydrocannabinol induces dopamine release in the human striatum. Neuropsychopharmacology 34, 759766.

MF Brunette , KT Mueser , H Xie , RE Drake (1997). Relationships between symptoms of schizophrenia and substance abuse. Journal of Nervous and Mental Disease 185, 1320.

B Bühler , M Hambrecht , W Loffler , W an der Heiden , (2002). Precipitation and determination of the onset and course of schizophrenia by substance abuse. A retrospective and prospective study of 232 population-based first illness episodes. Schizophrenia Research 54, 243251.

A Caspi , TE Moffitt , M Cannon , J McClay , (2005). Moderation of the effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in the catechol-O-methyltransferase gene: longitudinal evidence of a gene×environment interaction. Biological Psychiatry 57, 11171127.

MT Compton , NE Whicker , KM Hochman (2007). Alcohol and cannabis use in urban, African American, first-episode schizophrenia-spectrum patients: associations with positive and negative symptoms. Journal of Clinical Psychiatry 68, 19391945.

A Cougnard , M Marcelis , I Myin-Germeys , R De Graaf , (2007). Does normal developmental expression of psychosis combine with environmental risk to cause persistence of psychosis? A psychosis proneness-persistence model. Psychological Medicine 37, 513527.

DC D'Souza , WM Abi-Saab , S Madonick , K Forselius-Bielen , (2005). Delta-9-tetrahydrocannabinol effects in schizophrenia: implications for cognition, psychosis, and addiction. Biological Psychiatry 57, 594608.

DC D'Souza , RA Sewell , M Ranganathan (2009). Cannabis and psychosis/schizophrenia: human studies. European Archives of Psychiatry and Clinical Neuroscience 259, 413431.

LE DeLisi (1992). The significance of age at onset for schizophrenia. Schizophrenia Bulletin 18, 209215.

H Erhenreich , T Rinn , HJ Kunert , MR Moeller , (1999). Specific attentional dysfunction in adults following early start of cannabis use. Psychopharmacology 142, 295301.

AI Green , DL Noordsy , MF Brunette , C O'Keefe (2008). Substance abuse and schizophrenia: pharmacotherapeutic intervention. Journal of Substance Abuse Treatment 34, 6171.

AI Green , MF Tohen , RM Hamer , SM Strakowski , (2004). First episode schizophrenia-related psychosis and substance use disorders: acute response to olanzapine and haloperidol. Schizophrenia Research 66, 125135.

C Henquet , M Di Forti , P Morrison , (2008). Gene-environment interplay between cannabis and psychosis. Schizophrenia Bulletin 34, 11111121.

C Henquet , L Krabbendam , J Spauwen , C Kaplan , (2005 a). Prospective cohort study of cannabis use, predisposition for psychosis, and psychotic symptoms in young people. British Medical Journal 330, 11.

C Henquet , R Murray , D Linszen , J van Os (2005 b). The environment and schizophrenia: the role of cannabis use. Schizophrenia Bulletin 31, 608612.

L Hides , S Dawe , DJ Kavanagh , RM Young (2006). Psychotic symptom and cannabis relapse in recent-onset psychosis. Prospective study. British Journal of Psychiatry 189, 137143.

A Johns (2001). Psychiatric effects of cannabis. British Journal of Psychiatry 178, 116122.

SH Jones , G Thornicroft , M Coffey , G Dunn (1995). A brief mental health outcome scale-reliability and validity of the Global Assessment of Functioning (GAF). British Journal of Psychiatry 166, 654659.

SR Kay , A Fiszbein , LA Opler (1987). The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophrenia Bulletin 13, 261276.

MO Krebs , C Goldberger , A Dervaux (2005). Cannabis use and schizophrenia. American Journal of Psychiatry 162, 401402.

TK Larsen , I Melle , B Auestad , S Friis , (2006). Substance abuse in first-episode non-affective psychosis. Schizophrenia Research 88, 5562.

A Leung , P Chue (2000). Sex differences in schizophrenia, a review of the literature. Acta Psychiatrica Scandinavica 101, 338.

DC Mathers , AH Ghodse (1992). Cannabis and psychotic illness. British Journal of Psychiatry 161, 648653.

PK McGuire , P Jones , I Harvey , M Williams , (1995). Morbid risk of schizophrenia for relatives of patients with cannabis-associated psychosis. Schizophrenia Research 15, 277281.

P Miller , SM Lawrie , A Hodges , R Clafferty , (2001). Genetic liability, illicit drug use, life stress and psychotic symptoms: preliminary findings from the Edinburgh study of people at high risk for schizophrenia. Social Psychiatry and Psychiatric Epidemiology 36, 338342.

TH Moore , S Zammit , A Lingford-Hughes , TR Barnes , (2007). Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. Lancet 370, 319328.

NIMH Genetics Initiative (1992). Family Interview for Genetic Studies (FIGS). Rockville, MD, National Institute of Mental Health, 1992.

JI Nurnberger Jr., MC Blehar , CA Kaufmann , C York-Cooler , (1994). Diagnostic interview for genetic studies. Rationale, unique features, and training. NIMH Genetics Initiative. Archives of General Psychiatry 51, 849859.

M Pistis , S Perra , G Pillolla , M Melia , (2004). Adolescent exposure to cannabinoids induces long-lasting changes in the response to drugs of abuse of rat midbrain dopamine neurons. Biological Psychiatry 56, 8694.

HG Pope , AJ Gruber , JI Hudson , G Cohane , (2003). Early-onset cannabis use and cognitive deficits: what is the nature of the association? Drug and Alcohol Dependence 69, 303310.

M Rais , W Cahn N Van Haren , H Schnack , (2008). Excessive brain volume loss over time in cannabis-using first-episode schizophrenia patients. American Journal of Psychiatry 165, 490496.

G Scheller-Gilkey , SM Thomas , BJ Woolwine , AH Miller (2002). Increased early life stress and depressive symptoms in patients with comorbid substance abuse and schizophrenia. Schizophrenia Bulletin 28, 223231.

E Schlicker , M Kathmann (2001). Modulation of transmitter release via presynaptic cannabinoid receptors. Trends in Pharmacological Sciences 22, 565572.

M Schneider , M Koch (2003). Chronic pubertal, but not adult chronic cannabinoid treatment impairs sensorimotor gating, recognition memory, and the performance in a progressive ratio task in adult rats. Neuropsychopharmacology 28, 17601769.

M Schneider , M Koch (2005). Deficient social and play behavior in juvenile and adult rats after neonatal cortical lesion: effects of chronic pubertal cannabinoid treatment. Neuropsychopharmacology 30, 944957.

JP Selten , N Veen , W Feller , JD Blom , (2001). Incidence of psychotic disorders in immigrant groups to The Netherlands. British Journal of Psychiatry 178, 367372.

J Van Os , M Bak , M Hanssen , RV Bijl , R De Graaf , (2002). Cannabis use and psychosis: a longitudinal population-based study. American Journal of Epidemiology 156, 319327.

JM Vanelle (1997). Refractory schizophrenia: historical and currently prevailing criteria and definitions. European Psychiatry 12 (Suppl. 5), 321s326s.

ND Veen , JP Selten , I van der Tweel , WG Feller , (2004). Cannabis use and age at onset of schizophrenia. American Journal of Psychiatry 161, 501506.

H Verdoux , F Sorbara , C Gindre , JD Swendsen , (2002). Cannabis use and dimensions of psychosis in a nonclinical population of female subjects. Schizophrenia Research 59, 7784.

LN Voruganti , P Slomka , P Zabel , A Mattar , (2001). Cannabis induced dopamine release: an in-vivo SPECT study. Psychiatry Research 107, 173177.

S Zammit , P Allebeck , S Andreasson , I Lundberg , (2002). Self reported cannabis use as a risk factor for schizophrenia in Swedish conscripts of 1969: historical cohort study. British Medical Journal 325, 11991201.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

The International Journal of Neuropsychopharmacology
  • ISSN: 1461-1457
  • EISSN: 1469-5111
  • URL: /core/journals/the-international-journal-of-neuropsychopharmacology
Please enter your name
Please enter a valid email address
Who would you like to send this to? *


Type Description Title
Supplementary Materials

Goldberger Supplementary Material

 Unknown (49 KB)
49 KB