The Impact of the Opioid Antagonist Naloxone on Experimentally Induced Craving in Nicotine-Dependent Individuals.

OBJECTIVE: Preclinical and clinical findings suggest a substantial association of the endogenous opioid system in nicotine dependence. The present study investigates the possible dose-dependent influence of naloxone, an unspecific opioid-receptor-antagonist, combined with cue exposure on the physiological state, locomotor activity, craving and the hypothalamic-pituitary-adrenal axis in nicotine-dependent humans. METHODS: Twenty nicotine-dependent, outpatient participants were deprived of nicotine for over 4 h, before receiving challenges with naloxone (1.6 mg or 3.2 mg q70 kg IV) or the placebo. Additionally, following drug administration, either smoking-related cues or neutral images were presented. Nicotine withdrawal was monitored by evaluating the following objective signs - skin conductance, heart rate, temperature, respiration, locomotor activity, cortisol, prolactin and ACTH levels as well as craving. RESULTS: With respect to subjective effects, participants administered a higher dosage of naloxone and those who were shown smoking-related cues were significantly less pleased (p = 0.019), felt more depressed (p = 0.033) and thought smoking would make them feel better (p = 0.028) than participants given naloxone and shown neutral cues. Participants given no naloxone but with smoking-related cues felt a higher urge to smoke than participants given naloxone and shown neutral cues (p = 0.042). Naloxone - in both dosages - also decreased the desire and intention to smoke in comparison to placebo. Compared to the placebo group, significantly higher cortisol, prolactin and ACTH values were observed after administration of lower and higher dosage of naloxone followed by smoking-related cues. CONCLUSION: Naloxone influenced nicotine withdrawal and strengthened significantly by cue exposure, both on objective measurement and on craving scales. These findings suggest an involvement of the endogenous opioid system in the development and maintenance of nicotine dependence.

Smoking upregulates alpha4beta2* nicotinic acetylcholine receptors in the human brain.

The role of the alpha4beta2* nicotinic acetylcholine receptors (nAChR) in tobacco addiction in humans is largely unresolved. We visualized brain alpha4beta2* nicotinic acetylcholine receptors of smokers and non-smokers with positron emission tomography using 2-[(18)F]fluoro-3-(2(S)azetidinylmethoxy)pyridine, commonly known as 2-[(18)F]F-A-85380. The total brain distribution volume of 2-[(18)F]F-A-85380 was significantly increased in smokers. Statistical parametric mapping revealed that the most prominent regional differences of distribution volumes (DV) were found in cerebellum and brainstem with an increased uptake in smokers. The up-regulation of alpha4beta2* nAChR upon chronic nicotine exposure via tobacco smoking incorporates subcortical brain regions which may play an important role in nicotine addiction.

[Olfactory delusional syndrome and alcoholism]. / Eigengeruchswahn und Alkoholabhängigkeit.

The olfactory delusional syndrome belongs to the rare delusional diseases. It is characterized by the persuasion of bothering other people by sending out an odour. This case report is about a 52 year old male suffering of alcoholism in addition. Aspects of this special comorbidity are discussed. Neuroleptic treatment with Risperidone led to a partial remission of the delusional syndrome.