The contribution of cannabis use to variation in the incidence of psychotic disorder across Europe (EU-GEI) : a multicentre case-control study , Marta Di Forti et al., The Lancet, 2019

The contribution of cannabis use to variation in the incidence of psychotic disorder across Europe (EU-GEI) : a multicentre case-control study

Marta Di Forti, Diego Quattrone, Tom P Freeman, Giada Tripoli, Charlotte Gayer-Anderson, Harriet Quigley, Victoria Rodriguez, Hannah E Jongsma, Laura Ferraro, Caterina La Cascia, Daniele La Barbera, Ilaria Tarricone, Domenico Berardi, Andrei Szöke, Celso Arango, Andrea Tortelli, Eva Velthorst,
Miguel Bernardo, Cristina Marta Del-Ben, Paulo Rossi Menezes, Jean-Paul Selten, Peter B Jones, James B Kirkbride, Bart PF Rutten, Lieuwe de Haan, Pak C Sham, Jim van Os, Cathryn M Lewis, Michael Lynskey, Craig Morgan, Robin M Murray, and the EU-GEI WP2 Group*

www.thelancet.com/psychiatry

Published online March 19, 2019

http://dx.doi.org/10.1016/S2215-0366(19)30048-3

 

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.
Commentaire (Dr Christian Sueur) :
Une nouvelle étude qui tend à mettre en lien la consommation de THC, et la production de troubles psychotique; une de plus… mais qui, a la lecture du texte intégral, “bute” toujours sur l’absence de preuve quant à un lien de causalité prouvé, entre THC et psychose, et là, en l’occurrence, entre l’habitude de fumer du Cannabis à forte teneur en THC, et “l’éclosion” de pathologies psychotiques en surnombre, tant il est vrai que ce genre de statistique épidémiologique, dans une problématique comportant de multiples paramètres, échoue à montrer de façon incontestable, des relations de type causalistes univoques.
cf en particulier : https://www.grecc.org/publications/dossiers-scientifiques/les-meta-analyses-et-le-cannabis-ou-la-negation-du-savoir-clinique-21-sep-2011-dr-christian-sueur/
Comme l’écrit un chercheur anglais spécialiste de la question (Dr Amir Englund, chercheur du King’s College de Londres)  : «de telles études ne permettent pas de dire si c’est l’usage fréquent de cannabis fort qui cause la psychose chez ces patients, ni de l’exclure». «Il se peut que le cannabis cause une psychose chez certains, ou que les patients atteints de psychose préfèrent un cannabis plus fort, ou les deux». (…) «Étant donné que la question de la causalité ne sera probablement jamais vraiment prouvée – nous devons assumer le pire et tenter de réduire la consommation fréquente de formes plus fortes de cannabis en particulier chez les personnes vulnérables face à la psychose».
cf :  http://info.sante.lefigaro.fr/article/cannabis-une-teneur-elevee-en-thc-augmenterait-le-risque-de-troubles-mentaux/?utm_source=AM2&utm_medium=email&utm_campaign=Sante
Une autre question non traitée, est celle du taux respectif de THC, et celui du CBD dans la marijuana consommée par les sujets étudiés dans cette étude : “Our potency variable does not include the proportion of another important cannabinoid, cannabidiol (CBD), because reliable data on this were available for only England and Holland
Or, la présence de quantités suffisante de CBD dans la marijuana fortement dosée en THC antagonise cette capacité à provoquer des épisodes psychotiques liée au THC (épisodes psychotiques induits, à la fois par un effet “gachette”, (“trigger”), ainsi que par une potentialisation de cet effet, du fait de caractéristiques “favorables” du système endocannabinoïde “personnel” du sujet considéré, sur un terrain génétique “sensible”)