title: Orexin A expression and promoter methylation in patients with cannabis dependence in comparison to nicotine-dependent cigarette smokers and nonsmokers.
abstract: BACKGROUND
  The orexins (hypocretins) are neuropeptides with an origin in the lateral hypothalamus. They have been found to be crucial within the context of drug craving, withdrawal und relapse.
  
  
  METHODS
  Therefore, orexin A gene expression and promoter methylation in peripheral blood cells of 77 subjects [36 with tetrahydrocannabinol (THC) dependence, 20 nicotine-dependent cigarette smokers and 21 nonsmokers] were assessed by quantitative real-time PCR and methylation-specific digestion PCR.
  
  
  RESULTS
  There was a statistically significant difference in orexin A expression between the three groups [p = 0.000, F = 131.4, d.f. = 2, analysis of variance (ANOVA)]. Orexin A gene expression was statistically significantly correlated with the Satisfaction with Life Scale (r = -0.28, p = 0.018), a visual analogue scale of craving (r = 0.734, p = 0.000) and three subscales of the World Health Organization Alcohol, Smoking and Substance Involvement Screening Test, i.e. nicotine consumption (r = 0.388, p = 0.001), alcohol consumption (r = 0.354, p = 0.002) and cannabis consumption (r = 0.783, p = 0.000). The mean promoter methylation (as a percentage) was not statistically related to orexin gene expression. However, there was a statistically significant difference in promoter methylation with regard to body mass index in general (F = 2.37, d.f. = 54, p = 0.016, ANOVA).
  
  
  CONCLUSIONS
  Orexin might be a possible target in THC as well as nicotine dependence, taking into account the effect of THC on energy homeostasis in the circuit of reward and motivation and its impact on appetite and body weight.
authors: Department of Psychiatry and Psychotherapy, Friedrich Alexander University, Erlangen-Nuremberg, Germany.
authors: Andrea
authors: A
authors: Rotter
authors: Kristina
authors: K
authors: Bayerlein
authors: Max
authors: M
authors: Hansbauer
authors: Judith
authors: J
authors: Weiland
authors: Wolfgang
authors: W
authors: Sperling
authors: Johannes
authors: J
authors: Kornhuber
authors: Teresa
authors: T
authors: Biermann
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D002189:Marijuana Abuse / Q000235:genetics* / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D000068797:Orexins; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis*; D014029:Tobacco Use Disorder / Q000235:genetics* / Q000378:metabolism
chemical_list: C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D012333:RNA, Messenger