The presence of a biological gradient Is supported by the presence of a dose-response relationship, with increasing amounts of AZD8055 cell line cannabis used associated with Increasing risk for psychosis8

or schizophrenia.6,7 As these are all longitudinal studies, which assessed cannabis use at baseline and ascertained later appearance of psychotic Illness, the temporality Inhibitors,research,lifescience,medical criterion Is clearly met. Coherence refers to how the proposed association relates to the generally known facts regarding the illness. This seems problematic, as the use of cannabis has Increased tremendously over the past four decades: according to the National Survey on Drug Use and Health (NSDUH, previously Inhibitors,research,lifescience,medical known as the National Household Survey on Drug Use) , “… the percentage of young adults aged 18 to 25 who had ever used marijuana was 5.1% In 1965, but Increased steadily to 54.4% In 1982. Although the rate for young adults declined somewhat from 1982 to 1993, it did not drop below 43% and actually Increased to 53.8% by 2002. ”14 This represents an Increase of approximately 10fold In the use of cannabis In adolescents; If cannabis

does, in fact, cause psychotic illness, then one would expect that the prevalence of psychotic illness would Increase In parallel to the greatly Increased use of the “causative” substance In the Western world. This is clearly Inhibitors,research,lifescience,medical not the case, as there are reports both of Increases and decreases In the prevalence of schizophrenia15-18 in the Western world, with no clear evidence of a significantly Increased prevalence that would be expected If the use of a causative substance Increased 10-fold. In addressing this Issue, some authors have suggested that cannabis use in early adolescence Is associated Inhibitors,research,lifescience,medical Inhibitors,research,lifescience,medical with particularly strong association with later psychotic Illness, and that this Is a fairly new phenomenon, In that cannabis use among adolescents under the age of 16 years In the USA has appeared only since the early 1990s.12 This Indicates that the hypothesized effect of cannabis

use on the prevalence of schizophrenia will only be observed Histone demethylase in the years to come. However, data from the NSDUH14 Indicate that there has been a significant Increase in cannabis use In this age group as well: the number of 12 to 17 year olds using cannabis for the first time rose from 9.2 per 1000 in 1965, to 58.2 per 1000 In 1980, and to 83.2 per 1000 in 1996. Thus, there has been a very significant Increase In cannabis use In young adolescents as well, which would be expected to lead to an increase of schizophrenia In the population, If cannabis were In fact causative. Regarding biological plausibility, there are some reports on changes In the endogenous cannabinoid system In schizophrenia, which might be related to the effects of cannabis on the brains of patients; this will be discussed in greater detail below.