A study associated FAAH gene variation with differences in self-reported arousal and fatigue after amphetamine. Those findings address subjective drug response, not a demonstrated genetic predictor of cognitive enhancement or impairment.
The researchers examined healthy young adults in a double-blind crossover design involving placebo and oral d-amphetamine at 10 and 20 mg. They studied four FAAH polymorphisms and combinations of variants known as haplotypes.
FAAH is involved in the breakdown of endogenous cannabinoids. The experiment investigated naturally occurring genetic variation; it did not administer cannabis or experimentally change participants’ genes.
The report identified associations involving particular variants and arousal or fatigue ratings after the 10-mg dose. It also reported fatigue-related haplotype associations. These were specific analyses, not a finding that every FAAH variant altered every stimulant response at both doses.
The outcomes came from mood-rating measures. They were not direct tests of sustained attention, memory accuracy, response inhibition or driving.
An inherited variant is different from a drug analyte in blood. Neither the variant nor a subjective arousal score establishes how much amphetamine was present at a particular time or whether an individual was functionally impaired.
The findings are consistent with involvement of endogenous cannabinoid biology, but they do not prove that one pathway completely explains the response differences.
The sample was selected for health and ancestry characteristics. The authors noted that a low minor-allele frequency required pooling some genotypes, limiting comparisons and motivating larger replication studies.
This research supports investigating why people report different experiences after the same nominal dose. It does not validate a personal genetic test for drug preference, addiction risk or safe dosing. Any clinical or forensic use would require prospective predictive evidence and outcomes relevant to the decision being made.
Related reading: COMT genotype and attention effects.