Clearing the smoke: What do we know about adolescent cannabis use and schizophrenia?

Abstract

While cannabis has been used as a recreational drug in many cultures around the world for centuries, it is only recently that we have begun to understand the biology of how this drug affects the brain. The discovery of the primary compon ents of the endocannabinoid system (the cannabinoid CB1 and CB2 receptors and the endogenous ligands anandamide and 2-arachidonoylglycerol) in the late 1980s and early 1990s allowed for discrete and focused research to occur. In the last 25 years, it has been determined that many of the prototyp ical effects of cannabis use (increased feeding, sedation, re duced anxiety, reduced blood pressure) mimic the actions of endocannabinoid signalling. 1 That being said, many of the ef fects of cannabis remain a mystery. The past few decades have been rife with debate regarding the safety and medical utility of cannabis, little of which has actually been rooted in scientific evidence. The extremes of these opinions state that cannabis is a completely innocuous and harmless substance, or that it is a highly dangerous drug whose use provokes a series of adverse health complications. While both of these opinions are for the most part inaccurate, these unfortunately are the types of debates that often occur in a political sphere and can have substantial impact on pol icy decisions. The need for evidence-based decisions to guide cannabis access is imperative given that in the states of Col orado and Washington recreational sale of cannabis is now legal and that in Canada there is currently substantial revi sion and overhaul occurring with the medical marijuana pro gram. While many conditions, including lung cancer and car diac arrthymias, have been at the forefront of the cannabis safety debate for some time, interestingly the discussion has predominantly moved to psychiatry — specifically the asso ciation between adolescent cannabis use and the develop ment of schizophrenia. The first study that brought this association to the forefront of the research community was a paper published in Lancet in 1987 that demonstrated a significant association between cannabis use and the development of schizophrenia in a 15year longitudinal study of more than 45 000 healthy Swedish army conscripts. 2 Individuals who consumed a high level of cannabis (defined as use of cannabis on more than 50 occa sions by the age of 18 years) had a greater risk of schizophrenia developing. This finding was interesting, as several historical reports had documented psychotic-like reactions to cannabis, suggesting that there may be a basis for associating cannabis use with the development of schizophrenia. In the decades that followed, several other reports confirmed this association (see the reviews by Malone and colleagues, 3