Royal gorilla, Girl Scout Cookies and Fat Banana are just a few of the improbably named strains of high-potency cannabis out there. In the former, levels of tetrahydrocannabinol (thc), the chemical behind the psychological effects of cannabis, are above 25%. Reviewers describe it as “overwhelming” for novices and a “beautiful euphoric couch-locking experience” for others.
However enticing that may sound, regular use of cannabis with a potency greater than 10% increases the risk of developing psychosis five-fold, according to a study published this week by the Lancet. It also found that using less potent strains daily increased the risk three-fold. Marta Di Forti, a clinical scientist at Kings College in London, and her colleagues looked at cannabis use among 901 European patients newly diagnosed with psychosis. A non-smoking control group was recruited from the general population.
THE LANCET
Summary
Background
Cannabis use is associated with increased risk of later psychotic disorder but whether it affects incidence of the disorder remains unclear. We aimed to identify patterns of cannabis use with the strongest effect on odds of psychotic disorder across Europe and explore whether differences in such patterns contribute to variations in the incidence rates of psychotic disorder.
Methods
We included patients aged 18–64 years who presented to psychiatric services in 11 sites across Europe and Brazil with first-episode psychosis and recruited controls representative of the local populations. We applied adjusted logistic regression models to the data to estimate which patterns of cannabis use carried the highest odds for psychotic disorder. Using Europe-wide and national data on the expected concentration of Δ9-tetrahydrocannabinol (THC) in the different types of cannabis available across the sites, we divided the types of cannabis used by participants into two categories: low potency (THC <10%) and high potency (THC ≥10%). Assuming causality, we calculated the population attributable fractions (PAFs) for the patterns of cannabis use associated with the highest odds of psychosis and the correlation between such patterns and the incidence rates for psychotic disorder across the study sites.
Findings
Between May 1, 2010, and April 1, 2015, we obtained data from 901 patients with first-episode psychosis across 11 sites and 1237 population controls from those same sites. Daily cannabis use was associated with increased odds of psychotic disorder compared with never users (adjusted odds ratio [OR] 3·2, 95% CI 2·2–4·1), increasing to nearly five-times increased odds for daily use of high-potency types of cannabis (4·8, 2·5–6·3). The PAFs calculated indicated that if high-potency cannabis were no longer available, 12·2% (95% CI 3·0–16·1) of cases of first-episode psychosis could be prevented across the 11 sites, rising to 30·3% (15·2–40·0) in London and 50·3% (27·4–66·0) in Amsterdam. The adjusted incident rates for psychotic disorder were positively correlated with the prevalence in controls across the 11 sites of use of high-potency cannabis (r = 0·7; p=0·0286) and daily use (r = 0·8; p=0·0109).
Interpretation
Differences in frequency of daily cannabis use and in use of high-potency cannabis contributed to the striking variation in the incidence of psychotic disorder across the 11 studied sites. Given the increasing availability of high-potency cannabis, this has important implications for public health.
Funding source
Medical Research Council, the European Community’s Seventh Framework Program grant, São Paulo Research Foundation, National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust and King’s College London and the NIHR BRC at University College London, Wellcome Trust.
Introduction
Many countries have legalised or decriminalised cannabis use, leading to concerns that this might result in an increase in cannabis use and associated harm, even if the latter only affects a minority of the population, Cross-sectional and prospective epidemiological studies as well as biological evidence support a causal link between cannabis use and psychotic disorder. Meta-analysis shows a dose–response association with the highest odds of psychotic disorder in those with the heaviest cannabis use. Nevertheless, it is not clear whether, at a population level, patterns of cannabis use influence rates of psychotic disorder.
A systematic review has described a five-times variation in the incidence of schizophrenia worldwide. A transnational case-control study (EU-GEI) has reported an eight-times difference in the incidence of psychotic disorder across 16 European sites plus one in Brazil.
Differences in the distribution of risk factors for psychosis, such as cannabis use, among the populations studied might contribute to these variations.
Research in context
Evidence before this study
The evidence reporting the dose-dependent association between cannabis use and psychotic disorders has been summarised in the meta-analysis by Marconi and colleagues. We searched PubMed for studies published up to March 31, 2018, that had specifically measured the impact of high-potency cannabis use on the odds of psychotic disorder (not psychotic symptoms or psychosis in general) or that had calculated the proportion of new cases of psychotic disorder arising in specific populations that were attributable to the use of high-potency cannabis, using the terms “psychotic disorders” and “high potency cannabis” or “skunk-super skunk” or “high THC cannabis”; we also included the term “population attributable fraction”. Finally, we searched for studies that reported the impact of any use of cannabis on the incidence of psychotic disorder or schizophrenia. Three studies met our inclusion criteria. Boydell and colleagues speculated that an increase in the incidence rates of schizophrenia between 1965 and 1999 in south London might be related to the increase, over the same period, in the prevalence of cannabis use in the year before first presentation. Our two previous case-control studies showed that high-potency cannabis, especially when used daily, carries the highest risk for psychotic disorder and that, assuming causality, 24% of new cases of psychotic disorder in south London could be attributed to the use of high potency cannabis.
Added value of this study
This multicentre case-control study across ten European and one Brazilian site replicates the strong effect of daily use of high-potency cannabis on the odds for psychotic disorder in the whole sample—which, to our knowledge, is the largest to date to address this question. This effect was particularly visible in London and Amsterdam. Additionally, we show that, assuming causality, if high-potency cannabis types were no longer available, then 12% of cases of first-episode psychosis could be prevented across Europe, rising to 30% in London and 50% in Amsterdam. Most importantly, we provide the first direct evidence that cannabis use has an effect on variation in the incidence of psychotic disorders. We show that differences in the prevalence of daily use of cannabis, and in use of high-potency cannabis, among the controls from the different study sites made a major contribution to the striking variations in the incidence rates of psychotic disorder that we have previously reported across the same sites.
Implications of all available evidence
In the context of the well reviewed epidemiological and biological evidence of a causal link between heavy cannabis use and psychotic disorders, our findings have substantial implications for mental health services and public health. Education is needed to inform the public about the mental health hazards of regular use of high-potency cannabis, which is becoming increasingly available worldwide.
Therefore, using data from the EU-GEI case-control study of first-episode psychosis and the previously published data on incidence, we sought to describe differences in patterns of cannabis use across sites, identify the measure of cannabis use with the strongest impact on odds of psychotic disorder across sites, calculate the population attributable fraction (PAF) for the patterns of cannabis use associated with the highest odds for psychosis, and test whether differences in patterns of cannabis use contribute to variations in the incidence of psychotic disorder across sites.
