Fatty acid amide hydrolase is lower in young cannabis users

Abstract

We have recently shown that levels of fatty acid amide hydrolase (FAAH), the enzyme that metabolizes the endocannabinoid anandamide, are lower in the brains of adult cannabis users (CUs) (34 ± 11 years of age), tested during early abstinence. Here, we examine replication of the lower FAAH levels in a separate, younger cohort (23 ± 5 years of age). Eighteen healthy volunteers (HVs) and fourteen CUs underwent a positron emission tomography scan using the FAAH radioligand [ 11 C]CURB. Regional [ 11 C]CURB binding was calculated using an irreversible two-tissue compartment model with a metabolite-corrected arterial plasma input function. The FAAH C385A genetic polymorphism (rs324420) was included as a covariate. All CUs underwent a urine screen to confirm recent cannabis use and had serum cannabinoids measured. One CU screened negative for cannabinoids via serum and was removed from analysis. All HVs reported less than five lifetime cannabis exposures more than a month prior to study initiation. There was a significant effect of group (F 1,26 = 4.31; P = .048) when two A/A (rs324420) HVs were removed from analysis to match the genotype of the CU group (n = 16 HVs, n = 13 CUs). Overall, [ 11 C]CURB λk 3 was 12% lower in CU compared with HV. Exploratory correlations showed that lower brain [ 11 C]CURB binding was related to greater use of cannabis throughout the past year. We confirmed our previous report and extended these findings by detecting lower [ 11 C]CURB binding in a younger cohort with less cumulative cannabis exposure.

Imaging Brain Fatty Acid Amide Hydrolase in Untreated Patients With Psychosis

“…No biological mechanism for these associations has been identified. Prior reports showing significantly lower brain FAAH in cannabis use disorders (24,25) position FAAH as a potential molecular link between cannabis use and psychosis.…”

“…Duration of untreated psychosis was calculated per participants' own recollection and clinical notes when available of commencement of symptoms until first antipsychotic exposure. The present analysis includes twenty-seven healthy control participants that have been reported in prior publications (22)(23)(24)(25).…”

Sphingolipid and Endocannabinoid Profiles in Adult Attention Deficit Hyperactivity Disorder

“…The FAAH rs2295633 polymorphism also has been associated with posttraumatic stress disorder [ 57 ]. Other FAAH variants were genetically linked with addiction, anxiety, eating disorders, depression, and obesity [ 58 , 59 , 60 , 61 , 62 , 63 ], emphasizing the endocannabinoid system’s importance for mental health but not specifically for ADHD. Presently, it is not known whether the ADHD-associated FAAH variant reduces or increases reuptake or degradation of AEA.…”

Serum lipid analysis and isotopic enrichment is suggestive of greater lipogenesis in young long‐term cannabis users: A secondary analysis of a case–control study

“…Blood samples were collected from NCU and CU prior to the injection of PET radiotracers scan for previous studies reported elsewhere (Da Silva et al, 2019; Hafizi et al, 2017; Jacobson et al, 2021; Watts et al, 2020). Whole‐blood samples were centrifuged at 3000× g for 5 min at 4°C to isolate serum.…”

“…With its legalization in several countries, including Canada, stigmatization of cannabis use has steadily decreased (Budney et al, 2007; CRIME, 2011; Jacobson et al, 2021). Cannabis is a plant of the Cannabaceae family and contains several active phytocannabinoids, among which delta9‐tetrahydrocannabinol (D 9 ‐THC) and cannabidiol (CBD) are the most studied.…”