Monday, November 3, 2014

Cannabis Use and Psychosis: The Still Difficult Question of Causality
Many studies have linked adolescent cannabis use and risk of becoming psychotic later in life. However, the question of whether cannabis use actually causes some people to become psychotic is a difficult one to answer and the evidence remains inconclusive. Although it is possible that cannabis use could be a direct cause of mental illness, it is also possible that both usage and mental illness are caused by an underlying third factor. In support of this latter theory, a recently published study comparing family history of mental illness in people with schizophrenia who either have or have not used cannabis, suggests that heavy cannabis use and risk of mental illness are both related to an underlying genetic predisposition. Furthermore, long-term studies on cannabis use have generally not considered that personality characteristics that have been linked to mental illness might also prompt a person’s decision to use drugs such as cannabis.

Cannabis, commonly known as marijuana and also by many other names, is one of the most popular recreational drugs in the world. Although many people try it without apparent ill effects, a large amount of evidence exists that individuals who engage in heavy cannabis use before the age of 18 have an increased risk of developing a psychotic mental disorder later in life (McLaren, Silins, Hutchinson, Mattick, & Hall, 2010). Testing whether or not cannabis use actually causes people to become psychotic is difficult to do, because the only truly conclusive way to do so would involve experimenting on a bunch of people and randomly assigning them to either be users or non-users for a long period of time, and assessing their mental health status before and after. Due to ethical constraints this is not possible (especially in the current climate of political correctness) so researchers have had to make do with alternative study methods. The strongest evidence for a causal role of cannabis comes from prospective cohort studies in which very large groups of people are initially assessed in regards to their mental health and drug use, preferably in adolescence, and then reassessed over a period of years. A review of 10 studies involving seven cohorts in six different countries showed that all but one of these studies found that there was an association between cannabis use and later risk of psychosis (McLaren, et al., 2010). For example, the first such study, and one the largest, assessed over 45,000 Swedish male conscripts aged 18 and then tracked how many were admitted to hospital for schizophrenia over the next 15 years. This study found that those who had used cannabis between 10 and 50 times before the age of 18 were three times more likely to be hospitalised for schizophrenia compared to non-users, while those who had used more than 50 times before age 18 had a six-fold risk compared to non-users. Several other cohort studies also found that heavier usage was associated with increased risk. To put this in perspective, schizophrenia occurs in less than 1% of the general population (van Os & Kapur, 2009), so even if with increased risk associated with heavy use, only a small minority of cannabis users would be affected.

While these prospective studies are consistent with the idea of cannabis causing later psychosis, insofar as usage preceded the development of symptoms and heavier usage was associated with higher risk, alternative explanations for the relationship between cannabis usage and psychosis cannot be ruled out. It is also possible that people who are at greater risk of becoming mentally ill are also more inclined towards cannabis usage, or that there is some third factor underlying both. For example, a limitation of the Swedish cohort study was that it did not assess whether participants who became mentally ill had also used other drugs after the age of 18, such as amphetamines, that might lead to psychotic symptoms (McLaren, Silins, Hutchinson, Mattick, & Hall, 2010). Furthermore, cohort studies mostly have not considered genetic factors or personality traits that are associated with heavy use of cannabis and with risk of psychotic disorder.[1] People who choose to engage in heavy cannabis usage might do so because they have characteristics that also predispose them to eventually become psychotic.

Artistic view of how the world feels like with schizophrenia

The authors of a recent study have argued that that the genetic/familial risk of schizophrenia is what accounts for the association between cannabis use and schizophrenia (Proal, Fleming, Galvez-Buccollini, & DeLisi, 2014). That is, cannabis use is probably not the cause of schizophrenia but itself a manifestation of the underlying genetic factors that also case schizophrenia. This study compared people diagnosed with schizophrenia, who either did or did not have a history of heavy cannabis use in adolescence prior to the onset of their illness, with two comparison groups of people who did not have schizophrenia and who either did or did not have a history of heavy cannabis use in adolescence.[2] They then determined how many people in each group had first degree relatives who had been diagnosed with a psychiatric illness. This was done in order to assess the genetic/familial risk of schizophrenia for members of each group. If cannabis has a special causative effect in the development of psychosis that goes beyond pre-existing genetic risk, then cannabis users who had become psychotic would be expected to have a lower genetic risk compared to non-users who had become psychotic. What the authors found was that, compared to the two comparison groups, people with schizophrenia had the same elevated level of familial/genetic risk regardless of whether they had or had not used cannabis. Hence, they argued that it is the genetic risk that is most likely the cause of schizophrenia, and that cannabis use is unlikely to be the cause, although they admitted that it might hasten the onset of symptoms. Additionally, relatives of the two cannabis-using groups, had high rates of drug use in general, which is in line with research indicating that some people have a genetic predisposition to use drugs.

As well as family history of mental illness, certain psychological characteristics are associated with an increased risk of developing psychotic symptoms. Specifically, some people who are not clinically disturbed have certain tendencies that resemble mild psychotic symptoms, such as experiencing unusual perceptions (e.g. feeling that strangers can read you mind) and holding peculiar beliefs about the nature of reality (e.g. that aliens are influencing events on earth). Psychologists refer to these tendencies as schizotypy, because of their resemblance to more extreme symptoms observed in people with schizophrenia. People with high levels of schizotypy have an elevated risk of becoming fully psychotic later in life, although it is important to note that this only occurs in a minority of people with these tendencies[3] (Chapman, Chapman, Kwapil, Eckblad, & Zinser, 1994). Many research studies have found that heavy users of cannabis also tend to be high in schizotypy traits compared to non-users (Fridberg, Vollmer, O'Donnell, & Skosnik, 2011). Additionally, older users tend to have more severe schizotypy traits compared to younger users, suggesting that symptoms might increase over time in users. Once again, it is difficult to say whether having schizotypy traits predisposes people to use cannabis, or whether using cannabis increases schizotypy. It is also possible there could be a two-way relationship. However, there is some evidence that schizotypy traits in heavy users tend to emerge before they first start using. One survey of users tested this by asking participants who indicated that they had schizotypy symptoms to estimate when they first noticed them occurring, and to state when they first began to use cannabis (Schiffman, Nakamura, Earleywine, & LaBrie, 2005). In the majority of cases, participants said that they had first noticed having schizotypy symptoms a few years before ever using cannabis. Of course this does not necessarily mean that schizotypy causes people to use cannabis, but it may well be a factor. More to the point, it is possible that heavy cannabis users may have an increased risk of psychosis because they naturally tend to be higher in schizotypy traits, rather than because of their drug use. However, it is also possible that the two act in combination and may be mutually reinforcing. 

Schizotypy also tends to be associated with other personality traits that may be relevant to mental health, such as high neuroticism, and low conscientiousness and agreeableness. Neuroticism has been identified as an independent risk factor for schizophrenia in prospective studies (van Os & Jones, 2001) and for mental disorders in general (Malouff, Thorsteinsson, & Schutte, 2005). Although heavy cannabis users tend to be higher in schizotypy than non-users, they do not tend to be higher on neuroticism, although they do tend to be lower than non-users in conscientiousness and agreeableness, as well as higher in openness to experience (Fridberg, et al., 2011). The majority of users, even heavy users, do not go on to develop psychotic mental disorders, so perhaps there is a particular subset of users who are most at risk. Fridberg et al. suggested that those who are not only high in schizotypy but also high in neuroticism and openness to experience as well as low in conscientiousness and agreeableness might be particularly vulnerable. People who have a family history of mental illness would also be of particular concern. 

To reiterate, determining the nature of the causal connection between cannabis use and psychosis is very difficult. It is possible that cannabis use during adolescence has a direct causal role, perhaps due to the drug’s influence on the developing brain. However, the reasons that a person chooses to take up cannabis use in the first place may reflect pre-existing risk factors for psychosis, such as such as genetic/familial risk and schizotypy traits. Future research studies should take these factors into account in order to better help identify individuals who may be at the greatest risk of harm.


[1] One cohort study using a genetic test found that in heavy users with a specific genetic polymorphism had an increased risk of psychosis compared to heavy users without it (Caspi et al.). However, a later study failed to confirm this result (McLaren, et al., 2010a).
[2] The authors were careful to include only people who had not used any other illicit drugs.
[3] In fact, some people with schizotypal tendencies are otherwise well-adjusted. Schizotypy is often associated with creativity and professional artists and stand-up comedians tend to be high in these traits. 

Image Credits

Mystic Weed Rose by MorbidKittyCorpse at Deviant Art 

Schizophrenia/Internal Symmetry by Craig Finn courtesy of Wikimedia Commons

Use of these artworks is permitted by the Creative Commons Licence and does not imply endorsement by the artists. 

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© Scott McGreal. Please do not reproduce without permission. Brief excerpts may be quoted as long as a link to the original article is provided. 

This article also appears on Psychology Today on my blog Unique - Like Everybody Else.

Posts I have written about psychedelic drugs (which are not linked to psychosis)

Caspi, A., Moffitt, T. E., Cannon, M., McClay, J., Murray, R., Harrington, H., . . . Craig, I. W. 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 X Environment Interaction. Biological Psychiatry, 57(10), 1117-1127. doi: 10.1016/j.biopsych.2005.01.026 
Chapman, L. J., Chapman, J. P., Kwapil, T. R., Eckblad, M., & Zinser, M. C. (1994). Putatively Psychosis-Prone Subjects 10 Years Later. Journal of Abnormal Psychology, 103(2), 171-183.
Fridberg, D. J., Vollmer, J. M., O'Donnell, B. F., & Skosnik, P. D. (2011). Cannabis users differ from non-users on measures of personality and schizotypy. Psychiatry Research, 186(1), 46-52. doi: 
Malouff, J. M., Thorsteinsson, E. B., & Schutte, N. S. (2005). The Relationship Between the Five-Factor Model of Personality and Symptoms of Clinical Disorders: A Meta-Analysis. Journal of Psychopathology and Behavioral Assessment, 27(2), 101-114.
McLaren JA, Silins E, Hutchinson D, Mattick RP, & Hall W (2010). Assessing evidence for a causal link between cannabis and psychosis: a review of cohort studies. The International journal on drug policy, 21 (1), 10-9 PMID: 19783132
Proal, A. C., Fleming, J., Galvez-Buccollini, J. A., & DeLisi, L. E. (2014). A controlled family study of cannabis users with and without psychosis. Schizophrenia Research, 152(1), 283-288.
Schiffman, J., Nakamura, B., Earleywine, M., & LaBrie, J. (2005). Symptoms of schizotypy precede cannabis use. Psychiatry Research, 134(1), 37-42. doi:
van Os, J., & Jones, P. B. (2001). Neuroticism as a risk factor for schizophrenia. Psychol Med, 31, 1129 - 1134.
van Os, J., & Kapur, S. (2009). Schizophrenia. The Lancet, 374(9690), 635-645. 

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