Family-Based Analysis of Genetic Variation Underlying Psychosis-Inducing Effects of Cannabis<subtitle>Sibling Analysis and Proband Follow-up</subtitle><alt-title>Genetic Variation Underlying Cannabis Effects</alt-title>

Abstract

Genetic variation in AKT1 may mediate both short-term as well as longer-term effects on psychosis expression associated with use of cannabis, possibly through a mechanism of cannabinoid-regulated AKT1/GSK-3 signaling downstream of the dopamine D(2) receptor.

Functional Genetic Variation of the Cannabinoid Receptor 1 and Cannabis Use Interact on Prefrontal Connectivity and Related Working Memory Behavior

“…Furthermore, convergent findings suggest that CNR1 signaling may be abnormal in patients with this brain disorder, even if the functional specificity of these anomalies is unclear (Dalton et al, 2011). Moreover, CNR1 has been inconsistently associated with diagnoses of schizophrenia (Chavarría-Siles et al, 2008;Seifert et al, 2007), and genetic variability and cannabis use appear to interact in conferring risk for psychosis (Caspi et al, 2005;van Winkel et al, 2011b, Di Forti et al, 2012. Interestingly, CNR1 signaling has been implicated in dopamine signaling (Bloomfield et al, 2014), which is centrally linked with schizophrenia (Weinberger et al, 2001).…”

1301 – Structural and functional imaging studies in chronic cannabis users: a systematic review of adolescent and adult findings

“…Finally, in a verbal working memory task, Jager et al (2006) [173] found significantly greater activity in the left superior parietal cortex in the cannabis using group despite there being no differences in task performance, which may be consistent with the idea of a compensatory recruitment effect. [166] found in abstinent cannabis users a reduced anterior cingulate activation using H2 15 O-PET during the performance of a modified Stroop test. However, they also reported a reduced dorsolateral prefrontal cortex activation and a greater activation in the hippocampus bilaterally [166].…”

“…In a H2 15 O-PET study, Block et al (2002) [164] found that cannabis users performed verbal memory tasks more poorly than controls. This was associated with reduced activation in the prefrontal cortex and greater activation in the posterior cerebellum, as well as with an absence of lateralization of hippocampal activity.…”

“…Despite the fact that many individuals tend to discontinue cannabis use after their initial experimentation with the drug [1] and the percentage of individuals who develop dependence is lower than that associated with alcohol (15%) or tobacco (32%) use, around 9% of cannabis users develop dependence in the long term [3,4]. Cannabis use has been associated with a range of acute and chronic mental health problems, such as anxiety, depression, neurocognitive alterations and deficits as well as increased risk of psychotic symptoms and disorders, the severity of these effects being dependent on frequency of use, age of onset and genetic vulnerability [5][6][7][8][9][10][11][12][13][14][15]. These effects are probably related to effects on the endocannabinoid system, which can modulate the neuronal activity of other neurotransmitter systems, such as dopamine, through its action on the most abundant cannabinoid receptor in brain, the cannabinoid receptor 1 (CB1) [16,17].…”

Epigenetic epidemiology in psychiatry: A translational neuroscience perspective

“…The age (or developmental stage) at which individuals start using cannabis influences this association [135]. Further evidence suggests that geneenvironment interactions are likely implicated in the association between cannabis and psychosis [133,[136][137][138][139]. For example, the psychotomimetic effect of cannabis is much greater in siblings of patients with a psychotic disorder, who are at increased genetic risk to develop psychotic disorder than in controls [140].…”