title: Effects of the nicotinic receptor antagonist mecamylamine on ad-lib smoking behavior, topography, and nicotine levels in smokers with and without schizophrenia: a preliminary study.
abstract: Individuals with schizophrenia have higher plasma nicotine levels in comparison to non-psychiatric smokers, even when differences in smoking are equated. This difference may be related to how intensely cigarettes are smoked but this has not been well studied. Mecamylamine (MEC), a non-competitive nicotinic acetylcholine receptor (nAChR) antagonist, which has been shown to increase ad-lib smoking and to affect smoking topography, was used in the current study as a pharmacological probe to increase our understanding of smoking behavior, smoking topography, and resulting nicotine levels in smokers with schizophrenia. This preliminary study used a within-subject, placebo-controlled design in smokers with schizophrenia (n=6) and healthy control smokers (n=8) to examine the effects of MEC (10mg/day) on ad-lib smoking behavior, topography, nicotine levels, and tobacco craving across two smoking deprivation conditions (no deprivation and 12-h deprivation). MEC, compared to placebo, increased the number of cigarettes smoked and plasma nicotine levels. MEC increased smoking intensity and resulted in greater plasma nicotine levels in smokers with schizophrenia compared to controls, although these results were not consistent across deprivation conditions. MEC also increased tobacco craving in smokers with schizophrenia but not in control smokers. Our results suggest that antagonism of high-affinity nAChRs in smokers with schizophrenia may prompt compensatory smoking, increasing the intensity of smoking and nicotine exposure without alleviating craving. Further work is needed to assess whether nicotine levels are directly mediated by how intensely the cigarettes are smoked, and to confirm whether this effect is more pronounced in smokers with schizophrenia.
authors.affiliation: Division of Substance Abuse, Department of Psychiatry, Yale University School of Medicine, 2 Church St South, Suite 109, New Haven, CT 06519, United States. sherry.mckee@yale.edu
authors.forename: Sherry A
authors.initials: SA
authors.lastname: McKee
authors.forename: Andrea H
authors.initials: AH
authors.lastname: Weinberger
authors.forename: Emily L R
authors.initials: EL
authors.lastname: Harrison
authors.forename: Sabrina
authors.initials: S
authors.lastname: Coppola
authors.forename: Tony P
authors.initials: TP
authors.lastname: George
mesh_terms: D000293:Adolescent; D000328:Adult; D016739:Behavior, Addictive; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology* / Q000627:therapeutic use*; D008875:Middle Aged; D009483:Neuropsychological Tests; D018733:Nicotinic Antagonists / Q000494:pharmacology* / Q000627:therapeutic use*; D011930:Reaction Time / Q000187:drug effects; D012559:Schizophrenia / Q000150:complications*; D012646:Self Administration; D012907:Smoking / Q000188:drug therapy*; D016540:Smoking Cessation / Q000379:methods*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy; D011795:Surveys and Questionnaires; D014029:Tobacco Use Disorder / Q000188:drug therapy* / Q000209:etiology; D055815:Young Adult
chemical_list: D018733:Nicotinic Antagonists; D008464:Mecamylamine
references.citation: Addict Behav. 2005 May;30(4):741-53
references.pmid: 15833578
references.citation: Am J Addict. 2005 Mar-Apr;14(2):106-23
references.pmid: 16019961
references.citation: Pharmacol Biochem Behav. 2001 Feb;68(2):187-97
references.pmid: 11267622
references.citation: Pharmacol Biochem Behav. 1989 Apr;32(4):933-8
references.pmid: 2798542
references.citation: Pharmacol Biochem Behav. 2003 Sep;76(2):307-13
references.pmid: 14592683
references.citation: Arch Gen Psychiatry. 2005 Jun;62(6):649-59
references.pmid: 15939842
references.citation: Drug Alcohol Depend. 2005 Nov 1;80(2):259-65
references.pmid: 15869844
references.citation: Br J Psychiatry. 1984 Oct;145:429-32
references.pmid: 6487916
references.citation: Biol Psychiatry. 1997 Jul 1;42(1):1-5
references.pmid: 9193735
references.citation: Psychopharmacology (Berl). 1987;91(3):391-3
references.pmid: 3104964
references.citation: Am J Psychiatry. 1998 Nov;155(11):1490-501
references.pmid: 9812108
references.citation: Psychopharmacology (Berl). 1996 Oct;127(4):328-36
references.pmid: 8923568
references.citation: Nicotine Tob Res. 2001 Feb;3(1):7-16
references.pmid: 11260806
references.citation: J Clin Psychopharmacol. 2000 Dec;20(6):706-7
references.pmid: 11106149
references.citation: Clin Chem. 1988 Apr;34(4):724-9
references.pmid: 3359608
references.citation: Arch Gen Psychiatry. 1986 Mar;43(3):289-94
references.pmid: 3954551
references.citation: J Pharmacol Exp Ther. 2000 Oct;295(1):58-66
references.pmid: 10991961
references.citation: Schizophr Res. 2005 Nov 15;79(2-3):323-35
references.pmid: 15961287
references.citation: J Psychopharmacol. 2004 Dec;18(4):457-74
references.pmid: 15582913
references.citation: Schizophr Res. 2006 Oct;87(1-3):307-15
references.pmid: 16854565
references.citation: JAMA. 2000 Nov 22-29;284(20):2606-10
references.pmid: 11086367
references.citation: Schizophr Bull. 1987;13(2):261-76
references.pmid: 3616518
references.citation: Schizophr Res. 2007 Mar;91(1-3):217-25
references.pmid: 17293085
references.citation: Br J Addict. 1991 Sep;86(9):1119-27
references.pmid: 1932883
references.citation: Addiction. 2007 May;102(5):795-802
references.pmid: 17506156
references.citation: Biol Psychiatry. 2005 Apr 1;57(7):802-8
references.pmid: 15820238
references.citation: Addict Behav. 1978;3(3-4):235-41
references.pmid: 735910
references.citation: Clin Pharmacol Ther. 1994 Jul;56(1):86-99
references.pmid: 8033499