FAAH variant Pro129Thr modulates subjective effects produced by cocaine administration

Area of Science:

• Neuroscience
• Genetics
• Addiction Research

Background:

• The endogenous cannabinoid anandamide (AEA) is metabolized by fatty acid amide hydrolase (FAAH).
• A common FAAH gene variant (rs324420 C->A, Pro129Thr) reduces FAAH activity, increasing endocannabinoid levels.
• This FAAH variant is linked to mood/stress alterations and increased addiction risk.

Purpose of the Study:

• To investigate if the FAAH Pro129Thr variant influences cocaine-induced subjective effects in individuals with cocaine use disorder (CUD).
• To determine if this FAAH variant is more prevalent in a CUD population compared to the general population.

Main Methods:

• 70 CUD participants received intravenous saline or cocaine (20, 40 mg) in a controlled laboratory setting.
• Subjective effects were measured using a Visual Analog Scale (VAS) before and after administration.
• FAAH genotype (Pro129Thr variant) was assessed and correlated with subjective responses and substance use.

Main Results:

• The FAAH Pro129Thr variant was associated with increased subjective ratings of 'Drug Effect,' 'High,' and 'Depressed' following cocaine administration.
• The variant allele (A) and AA genotype frequencies were significantly higher in the CUD group (47% vs. 34%; 30% vs. 13%).
• Individuals with the AC/AA allele reported higher tobacco and cocaine use frequency and amount.

Conclusions:

• The FAAH Pro129Thr variant may be over-represented in individuals with CUD.
• This genetic variant might contribute to CUD risk through enhanced subjective responses to cocaine.
• Findings support a genetic predisposition influencing individual responses to cocaine and addiction vulnerability.