Cannabis as a cause of psychosis; an ecogenetic study linking cannabis-induced dopamine response to psychotic mechanisms and experiences in daily life
10 / 2007 - unknown
Extensive epidemiological work by me and others links cannabis use to psychotic symptoms and illness. I have argued, however, that epidemiological work now needs to be followed by experimental work on possible mechanisms by which delta-9-THC (THC, the psycho-active component of cannabis) may cause psychosis. Previously, I reported that gene-environment interactions underlie the association between cannabis and psychosis. The biological mechanism through which THC induces psychosis in individuals at increased genetic risk, however, remains largely unknown. I hypothesize that i) THC facilitates the development of psychotic experiences by releasing mesolimbic dopamine and ii) THC-induced dopamine response is moderated by genetic risk for psychosis. Approach:I will assess, in three groups of individuals at high, medium and low genetic risk for psychosis:A) In a double-blind, placebo-controlled Single Photon Emission Computed Tomography (SPECT) study of experimental THC exposure, the acute effects of THC on i) striatal dopamine response and ii) computer-assisted tasks assessing psychotic experiences. B) The degree to which variation in striatal dopamine response predicts daily life psychotic responses to THC in an observational momentary assessment study.C) The moderating effects of genetic risk on i) THC-induced dopamine response, and ii) THC-induced psychotic experiences (assessed both experimentally and in daily life). To this end, two indicators of genetic risk for psychosis will be used: i) a psychometric indicator of genetic risk (questionnaire measure) and ii) catechol-O-methyltransferase (COMT)Val158Met genotype.Significance:Until recently, no specific environmental risk factor was firmly linked to psychotic illness. However, consensus is building that cannabis is of likely causal significance. This is extremely topical, given that poor-prognosis psychotic disorders affect approximately 1-2 out of every 100 young individuals.
Het gebruik van cannabis kan leiden tot het horen van stemmen en het hebben van paranoïde gedachten. Hoe komt dit? De onderzoekers zullen mensen cannabis toedienen en door middel van hersenfoto's bestuderen wat er vervolgens in de hersenen gebeurt.