title: Intermediate cannabis dependence phenotypes and the FAAH C385A variant: an exploratory analysis.
abstract: BACKGROUND
  Cannabis dependence is a growing problem among individuals who use marijuana frequently, and genetic differences make some users more liable to progress to dependence. The identification of intermediate phenotypes of cannabis dependence may aid candidate genetic analysis. Promising intermediate phenotypes include craving for marijuana, withdrawal symptoms after abstinence, and sensitivity to its acute effects. A single nucleotide polymorphism (SNP) in the gene encoding for fatty acid amide hydrolase (FAAH) has demonstrated association with substance use disorder diagnoses, but has not been studied with respect to these narrower phenotypes. FAAH is an enzyme that inactivates anandamide, an endogenous agonist for CB(1) receptors (to which Delta(9)-tetrahydrocannabinol binds). CB(1) binding modulates mesocorticolimbic dopamine release, which underlies many facets of addiction.
  
  
  OBJECTIVE
  The SNP, FAAH C385A (rs324420), was examined to determine whether its variance was associated with changes in craving and withdrawal after marijuana abstinence, craving after cue exposure, or sensitivity to the acute effects of marijuana.
  
  
  METHODS
  Forty daily marijuana users abstained for 24 h, were presented with a cue-elicited craving paradigm and smoked a marijuana cigarette in the laboratory.
  
  
  RESULTS
  C385A variance was significantly associated with changes in withdrawal after abstinence, and happiness after smoking marijuana in the predicted directions, was associated with changes in heart rate after smoking in the opposite of the predicted direction, and was not associated with changes in craving or other acute effects.
  
  
  CONCLUSIONS
  These data lend support to some previous association studies of C385A, but suggest that further refinement of these intermediate phenotypes is necessary.
authors.affiliation: University of Colorado at Boulder, Boulder, CO, USA. Joseph.Schacht@colorado.edu
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Schacht
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: Selling
authors.forename: Kent E
authors.initials: KE
authors.lastname: Hutchison
mesh_terms: D000328:Adult; D000581:Amidohydrolases / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D002189:Marijuana Abuse / Q000201:enzymology / Q000235:genetics*; D008385:Marijuana Smoking / Q000009:adverse effects*; D020641:Polymorphism, Single Nucleotide; D013375:Substance Withdrawal Syndrome / Q000201:enzymology / Q000235:genetics*; D011795:Surveys and Questionnaires; D055815:Young Adult; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D000099252:Fatty Acid Amide Hydrolases