title: Nicotinic acetylcholine receptor availability in cigarette smokers: effect of heavy caffeine or marijuana use.
abstract: Upregulation of α4β2* nicotinic acetylcholine receptors (nAChRs) is one of the most well-established effects of chronic cigarette smoking on the brain. Prior research by our group gave a preliminary indication that cigarette smokers with concomitant use of caffeine or marijuana have altered nAChR availability.
  
  
  
  We sought to determine if smokers with heavy caffeine or marijuana use have different levels of α4β2* nAChRs than smokers without these drug usages.
  
  
  
  One hundred and one positron emission tomography (PET) scans, using the radiotracer 2-FA (a ligand for β2*-containing nAChRs), were obtained from four groups of males: non-smokers without heavy caffeine or marijuana use, smokers without heavy caffeine or marijuana use, smokers with heavy caffeine use (mean four coffee cups per day), and smokers with heavy marijuana use (mean 22 days of use per month). Total distribution volume (Vt/fp) was determined for the brainstem, prefrontal cortex, and thalamus, as a measure of nAChR availability.
  
  
  
  A significant between-group effect was found, resulting from the heavy caffeine and marijuana groups having the highest Vt/fp values (especially for the brainstem and prefrontal cortex), followed by smokers without such use, followed by non-smokers. Direct between-group comparisons revealed significant differences for Vt/fp values between the smoker groups with and without heavy caffeine or marijuana use.
  
  
  
  Smokers with heavy caffeine or marijuana use have higher α4β2* nAChR availability than smokers without these drug usages. These findings are likely due to increased nicotine exposure but could also be due to an interaction on a cellular/molecular level.
authors.affiliation: Departments of Psychiatry and Research, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA. abrody@ucla.edu.|Department of Psychiatry, University of California at Los Angeles, Los Angeles, CA, USA. abrody@ucla.edu.|, 300 UCLA Medical Plaza, Suite 2200, Los Angeles, CA, 90095, USA. abrody@ucla.edu.
authors.forename: Arthur L
authors.initials: AL
authors.lastname: Brody
authors.affiliation: Departments of Psychiatry and Research, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Hubert
authors.affiliation: Departments of Psychiatry and Research, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Mamoun
authors.affiliation: Departments of Psychiatry and Research, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Enoki
authors.affiliation: Departments of Psychiatry and Research, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
authors.forename: Lizette Y
authors.initials: LY
authors.lastname: Garcia
authors.affiliation: Departments of Psychiatry and Research, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Abraham
authors.affiliation: Departments of Psychiatry and Research, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
authors.forename: Paulina
authors.initials: P
authors.lastname: Young
authors.affiliation: Departments of Psychiatry and Research, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.|Department of Physics, University of California at Irvine, Irvine, CA, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Mandelkern
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D001933:Brain Stem / Q000000981:diagnostic imaging / Q000378:metabolism; D002110:Caffeine; D016022:Case-Control Studies; D003069:Coffee; D006801:Humans; D008297:Male; D000074609:Marijuana Use / Q000378:metabolism*; D008875:Middle Aged; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism*; D000074285:Smokers; D012907:Smoking / Q000378:metabolism*; D013788:Thalamus / Q000000981:diagnostic imaging / Q000378:metabolism; D000073869:Tobacco Smoking
chemical_list: D003069:Coffee; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2; D002110:Caffeine
keywords: Brain imaging; Caffeine; Cannabis; Cigarette smoking; Human; Marijuana; Neuroimaging; Nicotinic acetylcholine receptors; Positron emission tomography; Tobacco dependence