People with schizophrenia frequently report cannabis use, and cannabis may be a risk factor for schizophrenia, mediated through effects on brain function and biochemistry. Thus, it is conceivable that cannabis may also influence cognitive functioning in this patient group. We report data from our own laboratory on the use of cannabis by schizophrenia patients, and review the existing literature on the effects of cannabis on cognition in schizophrenia and related psychosis. Of the 23 studies that were found, 14 reported that the cannabis users had better cognitive performance than the schizophrenia non-users. Eight studies reported no or minimal differences in cognitive performance in the two groups, but only one study reported better cognitive performance in the schizophrenia non-user group. Our own results confirm the overall impression from the literature review of better cognitive performance in the cannabis user group. These paradoxical findings may have several explanations, which are discussed. We suggest that cannabis causes a transient cognitive breakdown enabling the development of psychosis, imitating the typical cognitive vulnerability seen in schizophrenia. This is further supported by an earlier age of onset and fewer neurological soft signs in the cannabis-related schizophrenia group, suggesting an alternative pathway to psychosis.

Introduction

Cannabis Use – A Risk Factor for Schizophrenia?

O-methyltransferase (COMT) gene and adolescent cannabis use significantly increased the likelihood of exhibiting psychotic symptoms and the development of schizophreniform disorders ( However, most individuals do not develop schizophrenia after cannabis use, suggesting that a heightened risk for a development of psychosis must be related to other vulnerability factors. Verdoux (2004) found that subjects with established vulnerability for psychoses showed a stronger risk of follow-up psychosis after cannabis use than individuals without such vulnerability. The relationship between cannabis use and psychosis may also be genetically mediated. In a longitudinal study of 803 individuals, an interaction between the Val allele of the Catechol--methyltransferase (COMT) gene and adolescent cannabis use significantly increased the likelihood of exhibiting psychotic symptoms and the development of schizophreniform disorders ( Caspi et al., 2005 ). In accordance with this, an interaction between the COMT Val allele and sensitivity for psychosis and cognitive effects of the psychoactive substance in cannabis has been found in individuals with psychosis and their relatives ( Henquet et al., 2006 2009 ).

Cannabis and Brain Function

A stronger relationship between adolescent cannabis use and psychosis or schizophrenia, as compared to adult use, has been reported in several studies ( Caspi et al., 2005 Konings et al., 2008 ). Even though some of these findings can be explained by an increased cumulative exposure to cannabis with earlier onset of cannabis use, it may also suggest that a developing brain is more vulnerable to the effects of cannabis than a matured brain.

cognitive functioning in schizophrenia. If cannabis influences schizophrenia neurodevelopment and brain functioning, it could be expected that cannabis use may impact on cognitive functioning in this patients group. The aim of the present review was therefore to examine the relationship between cannabis use and cognitive functioning in schizophrenia. However although there seems to be ample evidence for the influence of cannabis on the development and outbreak of psychosis or schizophrenia ( Moore et al., 2007 ), possibly mediated by adverse effects on brain functioning acting on the dopaminergic system ( D’Souza et al., 2005 ), much less is known regarding the effects of cannabis use onin schizophrenia. If cannabis influences schizophrenia neurodevelopment and brain functioning, it could be expected that cannabis use may impact on cognitive functioning in this patients group. The aim of the present review was therefore to examine the relationship between cannabis use and cognitive functioning in schizophrenia.

Cognition in Patients Who Use Cannabis – A Paradox

For this purpose we reanalyzed previously collected data in our laboratory on cognitive performance in schizophrenia patients, including cannabis use as an explanatory variable (data from Løberg et al., 2003 2008 ). Information on the history of cannabis use was based on the patients’ clinical records and therapist questionnaires, and was further validated through SCID-interviews. Surprisingly, we found that patients with schizophrenia who had a history of cannabis use scored significantly above their fellow counterparts without a history of cannabis use (see Figure 1 ). This was found for almost all cognitive functions investigated, such as general intellectual ability, executive functions, attention, working memory and psychomotor speed. These results did not change when other illegal drugs where controlled for, and there were no differences in the two groups with regard to clinical variables ( Løberg et al., 2003 ).

[View Larger Version of this Image] Figure 1. Mean T-scores for the cannabis and no-cannabis group for the five cognitive functions. General abilities = general verbal and visuospatial abilities = WAIS (Information, Vocabulary, Block Design), Verbal Fluency (FAS), Rey-Osterrieth Complex Figure test, Wisconsin Card Sorting Test (WCST). Learning/memory = California Verbal Learning Test (CVLT) II, Rey-Osterrieth Complex Figure Test. Attention/working mem. = attention/working memory = Digit Vigilance Test, Calcap Continuous Performance Test (CPT), Trail Making Test B. Execute functions = Wisconsin Card Sorting Test (WCST), Stroop Test. Psychomotor speed = Trail Making Test A, Grooved Pegboard Test, Fingertapping Test.

In a second, prospective, study of patients with acute psychosis we assessed cognitive function at admission to a psychiatric emergency ward, after 6 weeks, and after 3 months. Information on the history of cannabis use was based on patient’s clinical records and the Clinician Drug Use Scale ( Drake et al., 1990 ), and was further validated through urine samples. The patients with both cannabis use and psychosis showed a significantly larger improvement in their cognitive performance in the three months after admission, as compared to the psychotic patients with no cannabis use. Both groups showed cognitive impairments at admission, but these were more prevalent in the non-cannabis psychosis group (see Figure 2 Løberg et al., 2008 ).

[View Larger Version of this Image] Figure 2. Mean neuropsychological T-scores for the cannabis and no-cannabis group at admission, after 6 weeks and 3 months.

Cognition in Patients Who Use Cannabis – A Literature Review

cannabis, substance, schizophr*, psychos*, cognit* and neuropsych*, and searched the reference lists for all included papers of other studies covering this topic. This resulted in 23 studies comparing schizophrenia and related psychoses with and without cannabis use (alone or in combination with other substances) on cognitive performance (see Table The paradoxical results reported by Løberg et al. (2003 2008 ) seem to be consistent with several other studies on the relationship between cognition, cannabis and/or illegal drugs and schizophrenia ( Joyal et al., 2003 Jockers-Scherubl et al., 2007 ). We performed a PubMed search on all combinations of the following search words:, and searched the reference lists for all included papers of other studies covering this topic. This resulted in 23 studies comparing schizophrenia and related psychoses with and without cannabis use (alone or in combination with other substances) on cognitive performance (see Table 1 for further details).

n”, and may therefore be influenced by Type-II statistical errors (false negatives), underestimating group differences due to lack of power. For instance, Most of the studies in Table 1 have small “”, and may therefore be influenced by Type-II statistical errors (false negatives), underestimating group differences due to lack of power. For instance, Thoma and Daum (2008) suggested that this may have been a problem in their 2008 study, influencing their conclusion of no differences between the groups. Furthermore, some of the studies included diverse drug use in addition to cannabis use, for instance alcohol and opiates in clusters of stimulating and/or hallucinatory illegal drugs. These drugs may have different, and sometimes opposite effects on brain functioning and neurochemistry, and consequently on cognition. In the overview in Table 1 , all studies included cannabis; as a high frequent drug together with other drugs used, or as the only drug used. Thus, no study was included that did not include cannabis. Previous drug use versus current drug use is included in Table 1 as a separate factor since this may have influenced the results. Current drug use may influence cognition by means of persisting intoxication effects or more acute effects on brain functioning, thus creating a “false” cognitive impairment not otherwise present. Furthermore, the use of diagnostic criteria is noted, yielding a SUD, since this usually means that the patients meet criteria for abuse or addictive behavior, and that the drug use has negative consequences for everyday living. This may bias the drug groups to consist of quite heavy users due to the exclusion of patients without a SUD diagnosis who nevertheless may have a frequent drug problem. An example of this is the study by Addington and Addington (1997) where it was reported that the no-drug group actually included 13 patients with previous drug use. Another problem when comparing the studies in Table 1 is the different diagnostic groups included in the studies, possibly with different levels of cognitive vulnerability.

Conclusion Literature Review

Explanations for the Paradoxical Effect

The seemingly paradoxical cognitive findings in cannabis-related schizophrenia could have several explanations. One explanation is that the group differences in cognition are attributed to superior social skills in the cannabis schizophrenia groups, making them “skillful” enough to get hold of illegal drugs. Superior social skills are however not consistent with the finding of poorer prognosis in this group. Few studies have, however, examined this directly, and the issue therefore remains unresolved. Two Norwegian studies reported poorer premorbid functioning in psychosis patients who also abused illegal drugs ( Ringen et al., 2008 ), and better premorbid social functioning and poorer premorbid academic functioning in this group ( Larsen et al., 2006 ), respectively. It has also been suggested that the group differences could be caused by cannabis having a protective or positive influence on brain functioning ( Coulston et al., 2007a ). Based on the effects of cannabis on brain function and prognosis of the psychosis, this is not supported by the existing data.

Concluding Remarks

Cannabis seems to be a risk factor for the development of schizophrenia, mimicking the typical cognitive vulnerability. As an environmental factor, cannabis use has the potential for being influenced by interventions, thus indirectly having an effect on the development of schizophrenia. Accordingly, clinical implications ( Moore et al., 2007 ) and public health implications ( Arseneault et al., 2004a ) have been suggested. A promising clinical intervention would be to monitor cannabis use in patients known to be vulnerable for psychosis, and help them to stay away from cannabis. Cannabis does not appear to create additive cognitive impairments, however, and cannabis-using patients may actually have better cognitive functioning. This could suggest that cannabis-related schizophrenia represents a different subtype, although few consistent clinical differences in regard to symptom profiles have been found ( Boydell et al., 2007 ). This necessitates a better understanding of the paradox of better cognitive functioning, similar clinical profiles, and worse prognosis in this group, through for instance longitudinal studies on the effect of previous and ongoing cannabis use on the fluctuations of cognitive and clinical functioning in schizophrenia.

Possibly cannabis mimics the typical cognitive vulnerability seen in schizophrenia. Solowij and Michie (2007) suggested that cannabis leads to similar cognitive impairment as what is typically seen in schizophrenia, but of a lower magnitude. Several studies have shown cognitive impairment during THC-intoxication ( D’Souza et al., 2005 Morrison et al., 2009 ). The preliminary data from our own laboratory suggest more transient cognitive impairments in the cannabis group ( Løberg et al., 2008 ). Perhaps cannabis causes a transient cognitive breakdown enabling the development of psychosis, in spite of the absence of proper cognitive vulnerability. Thus, the effects of cannabis on cognition and brain functioning model the cognitive vulnerability in schizophrenia, and understanding this cognitive breakdown may provide a unique window to understanding schizophrenia neurodevelopment.

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Acknowledgments

Financial support for the research reported in this article was given by Research Council of Norway (RCN), Haukeland University Hospital Strategic Research Programme, and Health Authority for Western Norway.

References

Arseneault, L., Cannon, M., Witton, J., and Murray, R. (2004a). Cannabis as a potential causal factor in schizophrenia. In Marijuana and Madness, D. Castle and R. Murray, eds (Cambridge, Cambridge University Press), pp. 101–118.

Br. J. Psychiatry 184, 110–117. Arseneault, L., Cannon, M., Witton, J., and Murray, R. M. (2004b). Causal association between cannabis and psychosis: examination of the evidence.184, 110–117. CrossRef Full Text

O-methyltransferase gene: longitudinal evidence of a gene X environment interaction. Biol. Psychiatry 57, 1117–1127. Caspi, A., Moffitt, T. E., Cannon, M., McClay, J., Murray, R., Harrington, H., Taylor, A., Arseneault, L., Williams, B., Braithwaite, A., Poulton, R., and Craig, I. W. (2005). Moderation of the effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in the catechol--methyltransferase gene: longitudinal evidence of a gene X environment interaction.57, 1117–1127. Pubmed Abstract | Pubmed Full Text | CrossRef Full Text

Schizophr. Res. 96, 169–184. Coulston, C. M., Perdices, M., and Tennant, C. C. (2007a). The neuropsychological correlates of cannabis use in schizophrenia: lifetime abuse/dependence, frequency of use, and recency of use.96, 169–184. CrossRef Full Text

Aust. N Z J. Psychiatry, 41, 869–884. Coulston, C. M., Perdices, M., and Tennant, C. C. (2007b). The neuropsychological of cannabis and other substance use in schizophrenia: review of the literature and critical evaluation of methodological issues.41, 869–884. CrossRef Full Text

D’Souza, D. C., Cho, H.-S., Perry, E. B., and Krystal, J. H. (2004). Cannabinoid “model” psychosis, dopamine-cannabinoid interactions and implications for schizophrenia. In Marijuana and Madness, D. Castle and R. Murray, eds (Cambridge, Cambridge University Press), pp. 142–165.

BMJ 330, 11. Henquet, C., Krabbendam, L., Spauwen, J., Kaplan, C., Lieb, R., Wittchen, H. U., and van Os, J. (2005a). Prospective cohort study of cannabis use, predisposition for psychosis, and psychotic symptoms in young people.330, 11. CrossRef Full Text

Prog. Neuropsychopharm. Biol. Psychiatry 31, 1054–1063. Jockers-Scherubl, M. C., Wolf, T., Radzei, N., Schlattmann, P., Rentzsch, J., Gomez-Carrillo de Castro, A., and Kuhl, K. P. (2007). Cannabis induces different cognitive changes in schizophrenic patients and in healthy controls.31, 1054–1063. CrossRef Full Text

Encephale 28, 160–168. Liraud, F., and Verdoux, H. (2002). Effect of comorbid substance use on neuropsychological performance in subjects with psychotic or mood disorders.28, 160–168. Pubmed Abstract | Pubmed Full Text

Schizophr. Res., 98(Suppl. S), 73. Løberg, E. M., Hugdahl, K., and Jørgensen, H. A. (2008). Lower neurocognitive vulnerability in schizophrenia with a history of cannabis abuse? Abstract.., 98(Suppl. S), 73. CrossRef Full Text

J. Int. Neuropsychol. Soc. 9, 172. Løberg, E. M., Jørgensen, H. A., and Hugdahl, K. (2003). The effects of previous drug abuse on neurocognition in schizophrenia. Abstract.9, 172.

Palmer, B. W., Dawes, S. E., and Heaton, R. K. (2009). What do we know about neuropsychological aspects of schizophrenia? Neuropsychol Rev, 19, 365–384. CrossRef Full Text

J. Nervous Mental Disease 178, 473–480. Tien, A. Y., and Anthony, J. C. (1990). Epidemiological analysis of alcohol and drug use as risk factors for psychotic experiences.178, 473–480.