There is evidence that large doses of THC can produce an acute psychosis marked by confusion, amnesia, delusions, hallucinations, anxiety, agitation and hypomanic symptoms. Nonetheless, such high THC doses are rare among cannabis smokers, given that they are likely to stop smoking if they experience undesired effects. Cases do exist, however, of high doses following ingestion of cannabis (cannabis cookies, space cake), where the user has less immediate control over THC titration. Such reactions may also occur after heavy cannabis use, or in some instances, after acute cannabis use by sensitive/vulnerable individuals. These effects abate rapidly after discontinuing cannabis use. There is little evidence that cannabis alone produces a psychosis that persists after the period of intoxication in non-vulnerable cannabis users (Joy et al., 1999; Hall and Degenhardt, 2000).
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Cannabis has been found to have an adverse effect on the clinical course of
schizophrenia. In a Dutch prospective study which assessed patients each month over a year, the 24 people in the cannabis-using group had significantly earlier psychotic relapses than the non-cannabis-using group, an effect that was dose-related (Linszen et al., 1994). Similar findings emerged in a 3-year follow-up community study of psychotic and non-psychotic patients also in the Netherlands. The cannabis users at the beginning of the 3-year study were more likely to have psychotic symptoms and particularly severe ones at follow-up. Those who were diagnosed as psychotic at the beginning of the study had more adverse effects from cannabis use than those who were not psychotic at the start of the study (van Os et al., 2002). In a study that followed up 81 patients in acute psychiatric wards weekly for 6 months, a higher frequency of cannabis use led to more psychotic relapses in the patients, after controlling for other established factors leading to relapse in the statistical analysis (Hides et al., 2006). In contrast, a follow-up study of alcohol- and cannabis-using patients in a psychiatric outpatient continuing care programme in Canada found that symptoms of schizophrenia-spectrum disorders were reduced at 12 months (Margolese et al., 2006).
Findings from national surveys in the USA, Australia and the Netherlands have found higher rates of cannabis use in patients with schizophrenia than the general population. For example, the US National Epidemiological Catchment Area study (Robins and Regier, 1991) indicated that 50 % of those identified with schizophrenia also had a diagnosis of substance use disorder (abuse or dependence), compared with 17 % of the general population (Regier et al., 1990). People who used cannabis on a daily basis were 2.4 times more likely to report psychotic experiences than non-daily cannabis users, after controlling for a variety of confounding variables such as socio-demographic factors, social role and psychiatric conditions (Tien and Anthony, 1990). A study of cannabis use and psychotic symptoms at age 18 in a cohort of 3 500 Greek adolescents found positive associations between frequency of cannabis use and psychotic experiences after controlling for other drug use and depressive symptoms in the statistical analysis, with a stronger association for those who started their cannabis use before age 15. However, the rates of cannabis use in the study group was low, with 6 % reporting lifetime cannabis use and 0.9 % reporting daily or near-daily use (Stefanis et al., 2004).
Four main views on the nature of this association have been proposed. Firstly, the link may be due to socio-demographic, economic or genetic factors common to both substance use and schizophrenia. Secondly, the self-medication hypothesis suggests that patients with schizophrenia may be using cannabis and other drugs as a form of self-treatment for their condition. Thirdly, some suggest that cannabis causes psychosis.
Finally, the vulnerability hypothesis proposes that the use of cannabis can increase the risk of schizophrenia among people with a predisposition to the illness.
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129 A number of carefully designed prospective studies have helped to assess the value of these hypotheses. These studies have been used to chart the development of a number of psychosocial and behavioural topics, and cannabis is just one issue the datasets have allowed to be explored. The findings from these studies have been summarised in a number of reviews (Arseneault et al., 2004; Smit et al., 2004; Degenhardt and Hall, 2006) and two meta-analyses and one systematic review (Henquet et al., 2005a;
Semple et al., 2005; Moore et al., 2007).
The Swedish conscript study
A 15-year prospective study of cannabis use and schizophrenia in 50 465 Swedish military conscripts was the first study to report a potential link between cannabis use and later schizophrenia. The study recruited conscripts who were 18–20 years old in 1969–70. Conscripts who were hospitalised for schizophrenia or psychosis and could be linked to their military medical records were identified. Through this linkage, the relationship between cannabis use and the onset of schizophrenia might be established.
The relative risk for a diagnosis of schizophrenia was 1.3 times higher for those who had used cannabis 1–10 times, three times higher for those who had used cannabis 1–50 times and six times higher for heavy users of cannabis (defined as use on more than 50 occasions) than among those who had not used cannabis. However, over half of the heavy users had had a diagnosis of a psychiatric condition other than psychosis at conscription and when the analysis took this factor into account the relative risk fell to 2.3 (Andreasson et al., 1987; Allebeck, 1991).
A follow-up of the conscripts reported in 2002. Again, heavy cannabis users were found to be 6.7 times more likely than non-users to be at risk of a diagnosis of schizophrenia after 27 years. The risk held when the analysis was carried out on a subsample of conscripts who had used cannabis only. While not an exhaustive array, when other possible confounding factors such as psychiatric diagnosis at conscription, IQ, growing up in a city and cigarette smoking were taken into account the risk, though reduced, still remained, with heavy cannabis users having a threefold relative risk of a diagnosis of schizophrenia (Zammit et al., 2002).
The Dunedin Multidisciplinary Health and Development Study
The Dunedin Study from New Zealand has followed a birth cohort of 1 037 people from the general population born in 1972–3. At age 11 they were examined to identify any self-reported psychotic symptoms before cannabis use may have begun. At 15 and 18 they were examined for self-reported cannabis use, enabling the investigation of the age of onset in relation to later outcomes. At age 26 the subjects were interviewed to
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see if they met the criteria of schizophreniform disorder according to DSM-IV diagnostic criteria. A diagnosis of schizophreniform disorder enabled the elimination of psychotic symptoms resulting from being under the influence of alcohol or drugs. Ninety-six per cent of the birth cohort had remained in the study at this point.
Those who used cannabis at ages 15 and 18 had higher rates of psychotic symptoms at age 26 than non-users, a relationship that remained after the analysis controlled for psychotic symptoms predating cannabis use. Those who started using cannabis by the age of 15 showed a fourfold increase in the likelihood of a diagnosis of
schizophreniform disorder by the age of 26. The analysis also showed that cannabis use by age 15 did not predict depression at age 26, suggesting the outcome was specific to the cannabis use.The study reported that 10.3 % of the 15-year-olds using cannabis received a diagnosis of schizophreniform disorder by the age of 26, compared with 3 % of the controls. The number of 15-year-olds smoking cannabis in the study was small, however (Arseneault et al., 2002).
The Christchurch Health and Development Study
Another New Zealand Study followed a birth cohort of 1 265 people born in
Christchurch urban region, with annual measurements up to the age of 16. Additional measurements were taken at age 18, including whether the individuals had a DSM diagnosis of cannabis dependence and whether psychotic symptoms were identified.
This examination was repeated at ages 21 and 25. Researchers were able to draw on a sample of 1 055 participants for whom information on cannabis use and psychotic symptoms were available at ages 18, 21 and 25, when 1 011 people remained in the study. Psychosis symptomatology was measured with psychosis items selected from of the symptom checklist as representative of the psychotic symptoms. This study addressed two main questions about the relationship between cannabis and psychosis in its analysis.
It attempted to control for residual confounding in its analysis and examine whether reverse causality may be in play, with an increased susceptibility to use cannabis resulting from the individual’s psychological state. A wide range of confounding factors were controlled for in the analysis, including family socioeconomic status, family functioning, child abuse including physical punishment, educational achievement and psychotic symptoms at the previous assessment. Analysis also took into account non-observed fixed sources of confounding (Fergusson et al., 2003, 2005).
The results showed that young people using cannabis daily had rates of psychotic symptoms that were between 2.3 and 3.3 times higher than those of non-users. After adjusting the analysis to take into account the confounding factors, this relationship persisted with daily users 1.6–1.8 times more likely to be experiencing rates of psychosis than non-cannabis users. While the study could not control for all possible confounding factors and the diagnostic tools used in the study may not have found all the aspects
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131 of psychosis, the research shows that increasing use of cannabis was associated with increases in the risks of psychotic symptoms, and that the increases in psychotic symptoms were not associated with increased rates of cannabis use, casting doubt on the self-medication hypothesis (Fergusson et al., 2005).
The Netherlands Mental Health Survey and Incidence Study (NEMESIS)
This study followed 7 076 adults aged 18–65 years randomly selected from the Dutch general population, who were examined in 1996, 1997 and 1999. A total of 4 848 people were still in the study at the 1999 follow-up, 4 045 of whom were considered as the ‘at-risk’ set. The attrition of participants was covered in the analysis of findings from the study. At the 3-year point those who used cannabis at baseline were three times more likely to show psychotic symptoms than non-users. This relationship persisted after controlling for a range of factors in the analysis, such as ethnic group, marital status, educational level and urbanicity. The study also found a dose–response relationship, with the highest risk of psychotic symptoms amongst those who used cannabis more frequently at the beginning of the study. Lifetime history of cannabis at baseline was a stronger predictor of later psychosis than cannabis use at follow-up, suggesting that the relationship between cannabis use and psychosis is not simply one resulting from a short-term psychotic episode (van Os et al., 2002).
The early developmental stages of psychopathology (EDSP) study
The EDSP study examined the prevalence, incidence, risk factors and 4-year course of mental disorders in a random representative sample of adolescents and young adults aged 14–24 in Munich. The baseline survey with 3 021 participants was conducted in 1995, with follow-up data for 2 437 participants in 1999. After adjusting for a range of factors in the analysis, cannabis use at baseline moderately increased the risk of psychotic symptoms at follow-up. The effect of cannabis was stronger for those with any predisposition for psychosis at baseline than those without, with a dose–response relation with increasing frequency of use. Predisposition to psychosis did not predict cannabis use at follow-up in the analysis, suggesting that the cannabis was not used as self-medication in this group (Henquet et al., 2005b).