Sonija Luzi

What is the mechanism whereby cannabis use increases risk of psychosis

Cannabis use has increased greatly over the last three decades. The various types of cannabis differ in their concentration of the main psychoactive component, Δ9-tetrahydrocannabinol (THC), and the other major ingredient, cannabidiol (CBD). Plant engineering has maximized levels of THC, thus increasing the potency of street cannabis. It is well known that cannabis intoxication can cause brief psychotic symptoms like paranoia, whilst recent evidence demonstrates that heavy use of cannabis increases the risk of chronic psychoses like schizophrenia; genetic vulnerability seems to predispose some people to a higher risk. This paper starts to consider the neurochemical mechanisms whereby cannabis use increases the risk of psychosis.

Catechol-O-methyltransferase (COMT) val158met genotype is associated with BOLD response as a function of task characteristic.

The catechol-O-methyltransferase (COMT) val158met single nucleotide polymorphism (rs4680) has been shown to be associated with brain activation during a number of neurocognitive and emotional tasks. The present study evaluated genotypic associations with brain function during measurement of cognitive stability (prosaccades) and plasticity (antisaccades). A total of 36 healthy volunteers were genotyped for rs4680 and underwent functional magnetic resonance imaging (fMRI) at 1.5 T. Individuals with at least one val158 allele (val158 carriers, N=24) showed lower blood oxygen level-dependent (BOLD) response in ventromedial and dorsomedial prefrontal cortex during antisaccades compared to val158 noncarriers, whereas met158 homozygotes (N=12) showed lower BOLD response in a cluster in the posterior cingulate and precuneus during prosaccades compared to val158 carriers. These findings suggest that associations of COMT val158met genotype with brain function may be mediated by task characteristics. The findings may be compatible with a hypothesis on the role of COMT val158met genotype in tonic and phasic dopamine levels in brain and differential effects on cognitive measures of stability (eg prosaccades) and plasticity (eg antisaccades).

USE OF HIGH POTENCY CANNABIS IS PARTICULARLY ASSOCIATED WITH ONSET OF PSYCHOSIS

Background: Epidemiological studies have reported that the risk of developing psychosis in cannabis users is dose related. Experimental research has shown that the active constituent of cannabis responsible for its psychotogenic effect is Delta-9-Tetrahydrocannabinol (THC). Recent evidence shows the potency (% TCH) of the cannabis seized in the UK is increasing. Previous studies have also suggested that age at first use of cannabis might moderate the degree of risk for developing a psychotic disorder. We predicted that first episode psychosis patients would be more likely to have started using cannabis in early adolescence, to use higher potency cannabis and to use it more frequently than controls. Methods: We collected information concerning socio-demographic and clinical characteristics, and cannabis use (age at first use, frequency, length of use, type of cannabis used) from 280 firstepisode psychosis (FEP) patients and 174 matched healthy volunteers in South London. Results: Therewasno significant difference in the life-timeprevalence of cannabis use or age at first use between cases and controls. Nevertheless, in the cases group age at first use was positively correlated with age of onset of psychosis: the earlier the age at first cannabis use, the earlier the onset of psychosis (z=0.49; p<0.001). After adjusting for age, gender, ethnicity, level of education, employment status other stimulants use, cases were more likely to be regular users (OR=6.4; 95% CI 3.2-28.6) and to have smoked high potency cannabis (skunk), (OR=6.8; 95% CI 2.6-25.4) than controls. Given a prevalence of 44% for skunk use among our cases and an OR=2.6 for skunk use in cases versus controls, we calculated a population attributable fraction (PAF) for skunk use=27%. Discussion: Patients with first episode psychosis have smoked higher potency cannabis (skunk), for longer and with greater frequency, than healthy controls. Moreover, age at first cannabis use significantly moderates age of onset for psychosis. Our findings also suggest that if skunk use was abolished 27% of the psychosis cases in South East London would be prevented.

S06-04 Skunk and psychosis in South East London

Background Epidemiological studies have reported that the increased risk of developing psychosis in cannabis users is dose related. In addition, experimental research has shown that the active constituent of cannabis responsible for its psychotogenic effect is Delta-9-Tetrahydrocannabinol (THC) (Murray et al, 2007). Recent evidence has suggested an increased in potency (% TCH) in the cannabis seized in the UK (Potter et al, 2007). Hypothesis We predicted that first episode psychosis patients are more likely to use higher potency cannabis and more frequently than controls. Methods We collected information concerning socio-demographic, clinical characteristics and cannabis use (age at first use, frequency, length of use, type of cannabis used) from a sample of 191 first-episode psychosis patients and 120 matched healthy volunteers. All were recruited as part of the Genetic and Psychosis (GAP) study which studied all patients who presented to the South London and Maudsley Trust. Results There was no significant difference in the life-time prevalence of cannabis use or age at first use between cases and controls. However, cases were more likely to be regular users (p=0.05), to be current users (p=0.04) and to have smoked cannabis for longer (p=0.01). Among cannabis users, 86.8% of 1st Episode Psychosis Patients preferentially used Skunk/Sinsemilla compared to 27.7% of Controls. Only 13.2 % of 1st Episode psychosis Patients chose to use Resin/Hash compared to 76.3% of controls. The concentration of TCH in these in South East London, ranges between 8.5 and 14 % (Potter et al, 2007). Controls (47%) were more likely to use Hash (Resin) whose average TCH concentration is 3.4% (Potter et al, 2007). Conclusions Patients with first episode psychosis have smoked higher potency cannabis, for longer and with greater frequency, than healthy controls.