Benjamin Chadwick; Michael L. Miller; Yasmin L. Hurd

“ Numerous human studies, including prospective longitudinal studies, demonstrate that early cannabis use is associated with major depressive disorder and drug addiction. A strong association between schizophrenia and cannabis use is also apparent, especially when considering genetic factors that interact with this environmental exposure. These human studies set a foundation for carefully controlled animal studies which demonstrate similar patterns following early cannabinoid exposure. ”

“ In contrast to most psychiatric disorders, modeling addiction in animals is very predictive of the human condition through the use of self-administration paradigms wherein animals control their own drug intake. ”

“ The emerging evidence strongly suggests that cannabis exposure during adolescence increases an adult’s individual vulnerability to drug addiction and schizophrenia and may also produce long-lasting effects on anxiety and mood disorders. ”

“ Twin-studies, which control for potential confounds such as genetics and shared environmental influences, have also confirmed that early adolescent onset of cannabis use increases the likelihood of developing drug dependence later in life ( [22] ) . ”

“ Although a small fraction of teens that use cannabis develop schizoaffective disorders, a number of epidemiological studies repeatedly demonstrate elevated risk to develop these psychiatric disorders in association with early-life cannabis use. ”

“ Given the vulnerable nature of adolescent neurodevelopment and the persistent changes that follow early cannabis exposure, the experimental findings outlined should be carefully considered by policymakers. In order to fully address the growing issues of psychiatric illnesses and to ensure a healthy future, measures should be taken to reduce cannabis use among teens. ”

“ The high prevalence of cannabis use among teens and the increasing number of states in the USA that legalize cannabis for both medicinal and recreational purposes are concerning given the surprisingly limited information known about the impact of cannabis on the developing brain and individual susceptibility. ”

“ Cannabis use is associated with progression to use other illicit substances in humans. Twin-studies illustrate that cannabis users have an increased risk of developing substance abuse disorder compared to their discordant twin. ”

“ Longitudinal investigations, making use of neuroimaging and genetics, alongside concurrent studies in animal models are needed to fully elucidate molecular mechanisms that could provide novel treatment interventions for individuals with psychiatric disease and comorbid adolescent cannabis use. ”

“ III of the National Longitudinal Study for Adolescent Health recapitulate this pattern of wide spread yet occasional use in adolescents. While the majority of teens have infrequent use, still a significant percentage, 6.6%, report daily use. Determining the long-term impact of occasional and heavy cannabis use during active periods of brain development, such as adolescence, is of critical importance. ”

“ The psychoactive effects of cannabis, principally mediated by THC, occur via its interaction with the endocannabinoid system, which regulates numerous biological processes involved in development and neuroplasticity. ”

“ The first longitudinal studies demonstrating an association between cannabis use before adulthood and schizophrenia were conducted in Swedish conscripts ( [50] , [51] ) Although no information was known about the individuals before conscription, subjects reporting previous cannabis use at the time of conscription were significantly more likely to be diagnosed with schizophrenia later in life. ”

“ Consequently, THC and related compounds could potentially usurp normal adolescent neurodevelopment, shifting the brain’s developmental trajectory toward a disease-vulnerable state, predisposing early cannabis users to motivational, affective, and psychotic disorders. ”

“ Animal studies allow the possibility to directly test the causal relationship between adolescent cannabinoid exposure and subsequent risk for drug addiction, independent of subject-specific factors that confound human investigations. ”

“ Though a causative relationship cannot be determined between marijuana’s glamorization and its increasing use in teenagers, important lessons can be learned from the major inroads made in reducing cigarette use in youths such as interventions through campaigns that made smoking less socially accepted. ”

“ Few animal experimental studies have specifically focused on examining neurobiological mechanisms associated with regulation of emotion in association with adolescent cannabinoid exposure. Of the studies, Page et al. ( [46] ) demonstrated that administration of the cannabinoid agonist WIN-55,212-2 to adolescents, as compared to adult rats, more profoundly and persistently disrupted cells in the locus coeruleus, a midbrain region that contains noradrenergic neurons and is implicated with depression and anxiety. ”

“ These findings suggest that adolescent cannabinoid exposure could affect the liability to mood disorders later in life, and the potential gender differences may relate in those well-documented in human depression. ”

“ Caspi, A & Moffitt, TE (2002) , Cannabis use in adolescence and risk for adult psychosis: longitudinal prospective study, vol. 325, pp. 1212–3, 10.1136/bmj.325.7374.121212446537, pmid:12446537, DOI 10.1136/bmj.325.7374.1212 ↑ Casadio, P; Fernandes, C; Murray, RM & Di Forti, M (2011) , Cannabis use in young people: the risk for schizophrenia, vol. ”