In the United States over 6% of individuals greater than 12 years old have used marijuana in the past month and this substance accounts for approximately 55% of the illicit drug use in this country. The perception that cannabis is a """"""""safe"""""""" illicit drug, without long-term adverse consequences, may contribute to the higher rates of use of marijuana when compared with more """"""""hard"""""""" drugs. However, there has been relatively few brain imaging studies exploring the neurobiological effects of cannabis. Two main areas of recent interest with regards to cannabis use, both potentially related to the dopamine (DA) system, highlight the importance of further in vivo human brain imaging studies examining DA function in cannabis users. First, a relatively strong association (odds ratio > 2) between premorbid cannabis use and schizophrenia has been observed, particularly when cannabis use occurs in adolescence. In schizophrenia, abnormalities of the DA system have been observed in receptor imaging studies. Given the epidemiological link between cannabis use in adolescence and schizophrenia a neuroreceptor imaging study of this nature in individuals who use/abuse cannabis is of particular interest. Second, early use of cannabis has been considered a risk factor for the future use of hard drugs. This has been termed the """"""""gateway"""""""" hypothesis and neurobiological factors such as sensitization may play a role. Sensitization refers to the enhanced DA response in the reward pathway of the nucleus accumbens (NAc) that occurs following repeated and chronic exposure to drugs of abuse. If exposure to cannabis can induce a cross- sensitization to other drugs of abuse (i.e. prior exposure to cannabis results in an increased DA release in the NAc on subsequent exposure to another class of drugs) this would be supportive of the gateway effect. This application seeks to examine the effects of repeated cannabis exposure, beginning in adolescent, on DA transmission in vivo within reward system of the ventral striatum (VST), an area which includes the NAc,. This will be accomplished with positron emission tomography (PET) by measuring amphetamine-induced displacement of [11C]raclopride in 8 adult individuals with a history of repeated cannabis use beginning in adolescence and 8 matched controls. If the hypothesis we seek to test is confirmed - that marijuana use beginning in adolescence alters dopamine signaling in the striatum later in life - it would provide a strong neurobiological basis for the epidemiological link between this drug and schizophrenia, have implications for the theory that marijuana serves as a gateway drug, and strengthen the argument that marijuana use cannot be considered a """"""""safe"""""""" drug of abuse. In the United States over 6% of individuals greater than 12 years old have used marijuana in the past month and this substance accounts for approximately 55% of the illicit drug use in this country. However, there has been relatively few brain imaging studies exploring the neurobiological effects of cannabis. If the hypothesis we seek to test is confirmed - that marijuana use beginning in adolescence alters dopamine reward signaling in the brain later in life - it would provide a strong neurobiological basis for the epidemiological link between this drug and schizophrenia, have implications for the theory that marijuana serves as a gateway drug, and strengthen the argument that marijuana use cannot be considered a """"""""safe"""""""" drug of abuse. ? ? ?
