Protein kinase B (AKT1) genotype mediates sensitivity to cannabis-induced impairments in psychomotor control

Abstract

These results require independent replication and show that differing vulnerability to acute psychomotor impairments induced by cannabis depends on variation in a gene that influences dopamine function, and is mediated through modulation of the effect of cannabis on the inferior frontal cortex, that is rich in dopaminergic innervation and critical for psychomotor control.

Does cannabis affect dopaminergic signaling in the human brain? A systematic review of evidence to date

“…Importance of genetic differences in mediating variable response to THC is also consistent with evidence suggesting the role of genes regulating central dopaminergic neurotransmission in mediating variability in the acute (Bhattacharyya et al, 2014; and longer-term effects (Di Forti et al, 2012;van Winkel, 2011) of cannabis on behavior and some of its neural underpinnings (Bhattacharyya et al, 2014;. In particular, demonstrated that individuals with a risk variant linked to higher synaptic dopamine levels (Heinz et al, 2000) of the gene coding for the dopamine transporter (DAT1), involved in clearing dopamine from subcortical synapses (Bannon et al, 2001), experienced a stronger effect of THC on neural activation in the striatum (S , a proxy measure that may be linked to local dopamine change in a key dopaminergic area of the brain.…”

GABA Deficits Enhance the Psychotomimetic Effects of Δ9-THC

“…In an experimental study, Bhattacharyya et al, (2012) showed that polymorphisms of the genes for AKT1 and the dopamine transporter (DAT1) influence the psychotomimetic and neurophysiological response to THC. Finally, in a recent study, Bhattacharyya et al, (2014) also showed that the AKT1 genotype mediates the sensitivity to THC-induced impairments in psychomotor control.…”

“…However, the basis of the enhanced vulnerability to the psychosis-inducing effects of CBs in schizophrenia patients is not clear. Several other mechanisms might explain vulnerability to THC effects including polymorphisms of genes for COMT (Henquet et al, 2006), AKT1, and DAT1 (Bhattacharyya et al, 2012(Bhattacharyya et al, , 2014, and γ-aminobutyric acid (GABA) deficits. Furthermore, it is conceivable that combinations of these factors may coexist and have additive or synergistic effects on increasing vulnerability to THC effects.…”

Increased hippocampal engagement during learning as a marker of sensitivity to psychotomimetic effects of δ-9-THC

“…We ensured that the psychotic symptoms experienced by participants classified as part of the transiently psychotic group were qualitatively similar to overt psychotic symptoms such as delusions and hallucinations and not merely a result of behavioural disorganization, by setting a cut-off threshold identical to that employed in clinical practice. It is also worth noting the present study does not account for other factors such as genetic , Bhattacharyya et al, 2014, Di Forti et al, 2012, van Winkel et al, 2011 and personality and familial factors (Henquet et al, 2005, McGuire et al, 1995, Stirling et al, 2008 as well as the composition (Bhattacharyya et al, 2010) and dose (Schoeler et al, 2016c) of cannabis that may also underlie differential sensitivity to the effects of cannabis.…”