Vitality

A Gene For Psychosis? This Allele Predicts How Susceptible You Are To The Mind-Altering Effects Of Weed

pot smoking
The AKT1 gene can be used to predict a healthy person’s susceptibility to the mind-altering effects of marijuana. daddyboskeazy, cc by 2.0

Around 1 percent of pot smokers develop psychosis; among this select group, there’s a high prevalence of a particular variant of the AKT1 gene. A new study explores this gene and finds it can also be used to predict a healthy person’s susceptibility to the mind-altering effects of marijuana. If you have a particular allele, smoking pot is more likely to make you paranoid, the University of Exeter and University College London scientists say.

Dr. Celia Morgan, lead author and a professor of psychopharmacology, told Medical Daily in an email that "49 percent [of participants in their] study, which is roughly commensurate with the healthy population," have this genetic variation, adding "there were more dependent users with that variant, overall they were more likely to experience the psychotomimetic effects."

Previous research shows THC, the active ingredient in pot, triggers the gene AKT1 both in the petrie dish and in mice, explain the researchers. Yet, THC also induces the release of dopamine, a neurotransmitter in the pleasure center of the brain. Since AKT1 is not only linked to psychosis but also codes for a protein in the dopamine receptor signaling cascade, this suggests the gene is a likely candidate for regulating the effects of marijuana in healthy users.

To explore this possibility, Morgan and Dr. Val Curran, senior author and a professor of psychopharmacology, enlisted the help of 442 cannabis users.

Organic Study Design

Ranging in age from 16 to 23, the pot smokers included 308 males. Their DNA was obtained from cheek swabs, while the genotyping tests focused on variants of the AKT1 and COMT genes. The researchers analyzed cannabis samples for make-up and strength and then tested each of the participants at home on two separate occasions; while they were under the influence of the drug and while sober. Tests measured symptoms of intoxication and cognitive function. 

While under the influence, the pot smokers with an AKT1 gene variation experienced, more strongly than the others, visual distortions, paranoia, and other psychotic-like symptoms, the researches say. Females were more vulnerable than males to impairment in short-term memory. Though they need to verify this effect with more research, the team notes animal studies show males have more cannabinoid receptors in parts of the brain important to short-term memory, including the prefrontal cortex.

According to the researchers, the findings are the very first to demonstrate people with a particular gene variant (specifically, the AKT1 rs2494732 C allele), are more prone to mind-altering effects when smoking cannabis, even if they are otherwise healthy. 

“Our sensitivity analyses suggested that these effects may be confined to dependent cannabis smokers, but further investigation of these data with larger samples is required,” they wrote. Because there may be many other genetic variants at play, the team says these findings are not quite ready for prime time (translation: your doctor’s office).

"It is too early to advise genetic testing on the basis of these findings but we would recommend anyone who is experiencing symptoms like paranoia or visual distortions from smoking cannabis, regardless of genotype, to reduce their use of the drug," Morgan said. Still, these results suggests a promising direction for developing new drugs to help those with cannabis-induced psychosis.

Source: Morgan CJA, Freeman TP, Powell J, Curran HV. AKT1 genotype moderates the acute psychotomimetic effects of naturalistically smoked cannabis in young cannabis smokers. Translational Psychiatry. 2016.

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