Evidence of Accidental Dosing Errors with Immediate-Release Sodium Oxybate: Data from the US Food and Drug Administration Adverse Event Reporting System.

Introduction: Sodium oxybate has been approved by the US Food and Drug Administration (FDA) to treat narcolepsy for 20 years; however, the only available products have been immediate-release (IR) formulations given twice nightly-once at bedtime and a second dose 2.5-4 h later-creating inherent risks with dosing administration errors.

Objectives: Evidence and risks associated with accidental ingestion of the second IR oxybate dose < 2.

The reinforcement threshold and elasticity of demand for nicotine in an adolescent rat model of depression.

Background: The Food and Drug Administration (FDA) is considering setting a nicotine standard for tobacco products to reduce their addictiveness. Such a standard should account for the apparent greater vulnerability to nicotine addiction in some subpopulations, such as adolescents with depression. The present study examined whether the reinforcement threshold and elasticity of demand (i.

Substitutability of nicotine alone and an electronic cigarette liquid using a concurrent choice assay in rats: A behavioral economic analysis.

Background: For the Food and Drug Administration to effectively regulate tobacco products, the contribution of non-nicotine tobacco constituents to the abuse liability of tobacco must be well understood. Our previous work compared the abuse liability of electronic cigarette refill liquids (EC liquids) and nicotine (Nic) alone when each was available in isolation and found no difference in abuse liability (i.e.

Self-Administration of Smokeless Tobacco Products in Rats.

Objective: Preclinical abuse liability assessment is an essential component of tobacco regulatory science. The goal of this project was to evaluate the relative abuse liability of smokeless tobacco products in rats using aqueous extracts of those products. These extracts provide exposure to an extensive range of nicotine and non-nicotine tobacco constituents as occurs in humans.

The effects of nicotine self-administration and withdrawal on concurrently available chow and sucrose intake in adult male rats.

Carbohydrate intake, preference, and taste thresholds may be altered in current and former cigarette smokers, which may mediate weight gain and risk for obesity in individuals who quit smoking. Attempts to model these effects in rodents have primarily used noncontingent nicotine administration. The purpose of this research was to characterize changes in chow and sucrose intake in rats during a 23-h access model of i.

Predictors of the nicotine reinforcement threshold, compensation, and elasticity of demand in a rodent model of nicotine reduction policy.

Background: The FDA is considering reducing the nicotine content in tobacco products as a population-based strategy to reduce tobacco addiction. Research is needed to determine the threshold level of nicotine needed to maintain smoking and the extent of compensatory smoking that could occur during nicotine reduction. Sources of variability in these measures across sub-populations also need to be identified so that policies can take into account the risks and benefits of nicotine reduction in vulnerable populations.

Sex differences in nicotine self-administration in rats during progressive unit dose reduction: implications for nicotine regulation policy.

Reducing the nicotine content in tobacco products is being considered by the FDA as a policy to reduce the addictiveness of tobacco products. Understanding individual differences in response to nicotine reduction will be critical to developing safe and effective policy. Animal and human research demonstrating sex differences in the reinforcing effects of nicotine suggests that males and females may respond differently to nicotine-reduction policies.

Combined active and passive immunization against nicotine: minimizing monoclonal antibody requirements using a target antibody concentration strategy.

Nicotine vaccines have shown preliminary evidence of efficacy for enhancing smoking cessation rates, but the serum nicotine-specific antibody (NicAb) concentrations produced are highly variable and many subjects do not develop effective levels. As an alternative to vaccination, passive immunization with nicotine-specific monoclonal antibodies could produce more uniform serum NicAb concentrations, but its use is limited by their high cost and shorter elimination half-life. This study investigated supplementing vaccination with monoclonal antibodies in a targeted fashion to increase vaccine efficacy while minimizing the required monoclonal antibody dose.

A lack of association between severity of nicotine withdrawal and individual differences in compensatory nicotine self-administration in rats.

Rationale: Compensatory smoking may represent an adverse consequence of smoking reduction or the use of reduced-nicotine tobacco products. Factors contributing to individual variability in compensation are poorly understood.

Objective: The objective of this study was to examine whether severity of nicotine withdrawal as measured by elevated intracranial self-stimulation (ICSS) thresholds is related to individual differences in compensatory nicotine self-administration (NSA) following unit dose reduction.

Compensatory nicotine self-administration in rats during reduced access to nicotine: an animal model of smoking reduction.

The ability of smoking reduction (e.g., decreasing cigarettes per day) to produce significant reductions in toxin exposure is limited by compensatory increases in smoking behavior.

Effects of pregnancy on nicotine self-administration and nicotine pharmacokinetics in rats.

Rationale: Because of the adverse effects of smoking during pregnancy, understanding the factors that influence maternal smoking may help in developing better treatments to help women quit smoking during pregnancy. Animal models could be useful for this purpose.

Objective: The purpose of the present study was to begin the development of an animal model of smoking during pregnancy by initially characterizing nicotine self-administration (NSA) in pregnant rats.

Effects of nicotine withdrawal on performance under a progressive-ratio schedule of sucrose pellet delivery in rats.

Although numerous studies have examined the motivational effects of nicotine withdrawal using intracranial self-stimulation (ICSS) threshold assays, relatively few have employed other methods for assessing motivation that use naturally reinforcing stimuli (e.g., food).

Effects of a nicotine conjugate vaccine on the acquisition and maintenance of nicotine self-administration in rats.

Rationale: Immunization of rats against nicotine using a nicotine conjugate vaccine reduces the distribution of nicotine to brain in rats and attenuates some of nicotine's physiological and behavioral effects. It is not known whether such a vaccine can attenuate nicotine's reinforcing effects.

Objective: The present experiment was conducted to determine whether a nicotine conjugate vaccine could interfere with the acquisition and maintenance of nicotine self-administration (NSA) in rats given 23 h day(-1) access to nicotine.

Reinstatement of nicotine self-administration in rats by presentation of nicotine-paired stimuli, but not nicotine priming.

The objective of the present study was to determine the relative efficacy of nicotine priming and nicotine-paired stimuli in reinstating extinguished NSA in rats. The relative efficacy of different stimulus conditions in reinstating NSA was also determined. Rats were trained to self-administer nicotine (0.