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 λk₃ 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.

Keywords: [11C]CURB; addiction; anandamide; cannabis; fatty acid amide hydrolase; positron emission tomography.

Figure 1.

Brain [¹¹C]CURB λk₃ values, an index of [¹¹C]CURB binding to fatty acid amide hydrolase (FAAH), for each participant in the HV (triangles) and CU (circles) groups. The C/C and A/C FAAH genotypes (C385A, rs324420) are indicated by white and grey symbols, respectively. The group means presented are the adjusted means to account for FAAH genotype. Percent differences are displayed for each ROI in [¹¹C]CURB λk₃ in CU (n=13) vs HV (n=16).

Figure 2.

Correlation between cannabis use in the past year and [¹¹C]CURB λk₃ in the ventral striatum and (n=13). All [¹¹C]CURB λk₃ values are all corrected for the FAAH C385A single nucleotide polymorphism. In the bottom plot, the values on the x and y-axis reflect a partial correlation, which was corrected or serum THCCOOH levels.