AKT1 genotype moderates the acute psychotomimetic effects of naturalistically smoked cannabis in young cannabis smokers

C J A Morgan, T P Freeman, J Powell, H V Curran

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Smoking cannabis daily doubles an individual's risk of developing a psychotic disorder, yet indicators of specific vulnerability have proved largely elusive. Genetic variation is one potential risk modifier. Single-nucleotide polymorphisms in the AKT1 and catechol-O-methyltransferase (COMT) genes have been implicated in the interaction between cannabis, psychosis and cognition, but no studies have examined their impact on an individual's acute response to smoked cannabis. A total 442 healthy young cannabis users were tested while intoxicated with their own cannabis-which was analysed for delta-9-tetrahydrocannbinol (THC) and cannabidiol content-and also ± 7 days apart when drug-free. Psychotomimetic symptoms and working memory were assessed on both the sessions. Variation at the rs2494732 locus of the AKT1 gene predicted acute psychotic response to cannabis along with dependence on the drug and baseline schizotypal symptoms. Working memory following cannabis acutely was worse in females, with some suggestion of an impact of COMT polymorphism on working memory when drug-free. These findings are the first to demonstrate that AKT1 mediates the acute response to cannabis in otherwise healthy individuals and implicate the AKT1 pathway as a possible target for prevention and treatment of cannabis psychosis.

Original languageEnglish
Article numbere738
JournalTranslational Psychiatry
Volume6
DOIs
Publication statusPublished - 16 Feb 2016

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Cannabis
Genotype
Short-Term Memory
Psychotic Disorders
Catechol O-Methyltransferase
Marijuana Smoking
Cannabidiol
Pharmaceutical Preparations
Cognition
Genes
Substance-Related Disorders
Single Nucleotide Polymorphism

Keywords

  • Acute Disease
  • Adolescent
  • Adult
  • Cannabinoids/genetics
  • Female
  • Genetic Predisposition to Disease/genetics
  • Genotype
  • Humans
  • Male
  • Marijuana Smoking/genetics
  • Mental Disorders/genetics
  • Polymorphism, Single Nucleotide/genetics
  • Proto-Oncogene Proteins c-akt/genetics
  • Risk
  • Sex Factors
  • Young Adult

Cite this

AKT1 genotype moderates the acute psychotomimetic effects of naturalistically smoked cannabis in young cannabis smokers. / Morgan, C J A; Freeman, T P; Powell, J; Curran, H V.

In: Translational Psychiatry, Vol. 6, e738, 16.02.2016.

Research output: Contribution to journalArticle

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