Nicotine nasal spray and vapor inhaler: abuse liability assessment.

Acute subjective and physiological effects were examined to provide information relevant to abuse liability of new nicotine delivery systems. Subjects (n = 12) were overnight-deprived smokers who received 0, 4, 8 and 16 active puffs from nicotine-containing cigarettes (0.1 mg per puff), 0, 1, 2 or 4 nasal sprays (0.5 mg nicotine per spray) and 0, 30, 60 and 120 vapor inhalations (estimated 0.013 mg nicotine per inhalation) in a within-subject single blinded design. While smokers clearly liked cigarette puffs, there was much less evidence of liking produced by either nasal spray or vapor inhaler; only modest elevations on a measure of good drug effects were observed. The novel delivery products engendered unpleasant effects of burning throat and nose, watery eyes, runny nose, coughing and sneezing that might be expected to limit abuse liability. Nicotine plasma level and heart rate increase was dose-related for cigarettes and nasal spray but not for vapor inhaler, indicating limited nicotine delivery with the latter device. Overall, results are consistent with the conclusion that the nicotine nasal spray and vapor inhaler are of substantially lower abuse liability than cigarettes in experienced cigarette smokers receiving initial exposure to these products.

Abuse liability assessment of sibutramine, a novel weight control agent.

RATIONALE: Sibutramine (Meridia) is a serotonin and norepinephrine reuptake inhibitor marketed for weight control. Previous studies demonstrated low abuse potential for 20 and 30 mg sibutramine (doses near the therapeutic range); however, no data existed on supratherapeutic doses. This study, therefore, examined 25 and 75 mg sibutramine in humans compared to d-amphetamine (20 mg) as a positive control and placebo as a negative control. OBJECTIVES: The study examined the acute subjective, reinforcing, and physiological effects of sibutramine to assess its abuse liability. METHODS: Twelve polydrug abusers with no history of drug dependence participated in this double-blind, inpatient/outpatient study. Volunteers participated in four drug sessions, in which they completed subjective effects scales including the Profile of Mood States (POMS), Visual Analog Scales (VAS), and the Addiction Research Center Inventory (ARCI). The Multiple Choice Procedure (MCP) was used to evaluate reinforcing efficacy. RESULTS: Sibutramine 25 mg produced subjective effects that were indistinguishable from placebo. Sibutramine 75 mg produced significant unpleasant effects, such as Anxiety, Confusion, and decreased Vigor. On the MCP, volunteers chose to give up an average of $4.04 from their study pay rather than receive the higher dose of sibutramine again. In contrast, d-amphetamine 20 mg produced positive mood changes and was well liked. CONCLUSIONS: These data indicate sibutramine lacks amphetamine-type abuse liability when administered acutely.

Roux-en-Y gastric bypass patients hospitalized for substance use disorders achieve successful weight loss despite poor psychosocial outcomes.

An emerging body of literature indicates that Roux-en-Y gastric bypass (RYGB) patients may be at a heightened risk for substance use disorders (SUDs) after surgery. Little is known about how weight loss and psychosocial outcomes of RYGB patients who develop SUD differ from those who do not. The present study compared weight loss and psychosocial outcomes of 26 post-RYGB patients in inpatient SUD treatment with those of 26 RYGB patients who did not evidence problematic substance use in the post-operative period. SUD and control cases were matched on age, sex and time lapse since surgery. No significant differences in % total weight loss or % excess weight loss (EWL) were found between groups. Those in SUD treatment were significantly less likely to meet the surgical failure criteria of <50% EWL but evidenced greater symptoms of depression, higher rates of probable major depressive disorder and poorer quality of life. Our findings indicate that RYGB patients hospitalized for SUDs achieve successful weight loss despite having poor psychosocial outcomes.

Subjective and discriminative stimulus effects of two de-nicotinized cigarettes with different tar yields.

The role of tar yield in the subjective and discriminative stimulus effects of cigarette smoking was examined. Current smokers (n=18) smoked two non-nicotine cigarettes with FTC yields of 0.06 mg nicotine and 12.4 mg (low tar) or 17.9 mg tar (high tar). Physiological measures and visual analog scales were completed over a 30-min period. Dosing order was determined randomly and counterbalanced. After sampling both cigarettes, volunteers smoked a third, test cigarette. Half of the volunteers received the low-tar cigarette and half the high-tar cigarette. Volunteers identified the test cigarette (i.e., A or B) at 5, 30, 60, 300, and 900 s after the first puff. Eight of the eighteen participants correctly identified the test cigarette on 4/5 of trials. No significant changes in visual analog scale scores were found among the non-discriminators. However, among discriminators, the low-tar cigarette produced significant positive effects including good drug effects and stimulation relative to the high-tar cigarette. Relative to the low-tar cigarette, the high-tar cigarette produced negative effects including harshness, heaviness, and intensity of flavor. Average tar yield of these participants' usual cigarettes was 9.75 mg, lower than that of the low-tar cigarette used here, possibly accounting for their greater liking of the low-tar cigarette. No changes in blood pressure or heart rate were observed and both cigarettes produced similar carbon monoxide increases, indicating similar depth of inhalation when smoking each. Results suggest cigarette tar yields may play a role in cigarette smoking preferences. Further research is needed to verify whether preferences are maintained after associations with nicotine delivery are extinguished.