title: Minocycline reduced craving for cigarettes but did not affect smoking or intravenous nicotine responses in humans.
abstract: In recent preclinical studies, the role of nitric oxide (NO) in nicotine dependence has become increasingly evident. Inhibition of NO synthesis blocks acquisition of conditioned place preference, and attenuates the nicotine abstinence syndrome in rodents. These findings have not been followed up in human studies. In order to obtain preliminary data on NO inhibition in human smokers, we conducted a randomized, double-blind, crossover study (N=12) of minocycline, a tetracycline derivative antibiotic, that inhibits the neuronal nitric oxide (NO) synthase enzyme with resultant inhibition of NO production. Medication effects were assessed through a smoking choice procedure as well as subjective and physiological responses to nicotine administered via the intravenous route (IV). Minocycline treatment did not affect smoking self-administration in our choice procedure and did not affect most of the subjective responses to IV nicotine or sample smoking. Following IV nicotine administration, there was a greater reduction in craving for cigarettes under minocycline, compared to placebo. Similarly, smokers had greater reduction in their craving for cigarettes following sample smoking under minocycline treatment. These findings provide limited support for the potential use of minocycline as a treatment of nicotine dependence.
authors.affiliation: Yale University, School of Medicine, Department of Psychiatry, West Haven, CT, USA. Mehmet.Sofuoglu@yale.edu
authors.forename: Mehmet
authors.initials: M
authors.lastname: Sofuoglu
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Waters
authors.forename: Marc
authors.initials: M
authors.lastname: Mooney
authors.forename: Stephanie S
authors.initials: SS
authors.lastname: O'Malley
mesh_terms: D000328:Adult; D000339:Affect / Q000187:drug effects; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001288:Attention / Q000187:drug effects; D003367:Cotinine / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008911:Minocycline / Q000494:pharmacology*; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects; D012907:Smoking / Q000523:psychology*; D013375:Substance Withdrawal Syndrome / Q000523:psychology; D011795:Surveys and Questionnaires
chemical_list: D000890:Anti-Infective Agents; D018722:Nicotinic Agonists; D009538:Nicotine; D008911:Minocycline; D003367:Cotinine