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Validation of a behavioral economic purchase task for assessing drug abuse liability.

ABSTRACT: Behavioral economic purchase tasks quantify drug demand (i.e. reinforcing value of a drug) and have been used extensively to assess the value of various drugs among current users. However, purchase tasks have been rarely used with unfamiliar drugs to address a compound's abuse liability, and the current study sought to validate the paradigm in this capacity. Using a double-blind placebo-controlled within-subjects drug challenge design, the study evaluated differential drug demand on an experimental drug purchase task for a 20 mg dose of oral D-amphetamine (versus placebo), a prototypic psychostimulant, in 98 stimulant-naïve participants. Compared with placebo, amphetamine significantly increased intensity, breakpoint and Omax , and significantly decreased elasticity. Mechanistic analyses revealed that Omax and breakpoint mediated the relationship between subjective drug effects and 'willingness to take again', a putative indicator of liability via motivation for future drug-seeking behavior. These findings validate the purchase task paradigm for quantifying the reinforcing value and, in turn, abuse liability of unfamiliar compounds, providing a foundation for a variety of future applications.

SUBMITTER: MacKillop J

PROVIDER: S-EPMC6351223 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Validation of a behavioral economic purchase task for assessing drug abuse liability.

MacKillop James J Goldenson Nicholas I NI Kirkpatrick Matthew G MG Leventhal Adam M AM

Addiction biology 20180105 2

Behavioral economic purchase tasks quantify drug demand (i.e. reinforcing value of a drug) and have been used extensively to assess the value of various drugs among current users. However, purchase tasks have been rarely used with unfamiliar drugs to address a compound's abuse liability, and the current study sought to validate the paradigm in this capacity. Using a double-blind placebo-controlled within-subjects drug challenge design, the study evaluated differential drug demand on an experimen ...[more]

PMID: 29314376

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Project description:IntroductionBehavioral economic purchase tasks are used to estimate the reinforcing value of drugs by asking participants how much they would purchase across a range of increasing prices. We sought to validate such a task for e-cigarettes in experienced users of advanced generation, tank-style devices.MethodsDual users of cigarettes and e-cigarettes (N = 54) and exclusive e-cigarette users (N = 59) attended one session during which they completed assessments including two versions of the E-cigarette Purchase Task: one that asked how many puffs of their e-cigarette they would purchase in 24 hours at varying prices and one that asked how many mLs of e-liquid they would purchase. We correlated purchase task outcomes with other measures of e-cigarette use. We also compared the tasks across dual and exclusive users.ResultsIndices derived from the mLs-based task were more likely to be correlated with self-reported use rates, e-cigarette dependence, and cotinine levels than the puffs-based task. Exclusive users showed greater demand on than dual users only on the mLs version when using an F-test comparison method, while multivariate analysis of variance (MANOVA) results showed that dual users showed greater demand only on the puffs task.ConclusionsResults indicate that the mLs version had greater validity than the puffs version in terms of clinical indices. Dual users may still be on a trajectory to fully switching to e-cigarettes; thus, puffs as a measure may be more intuitive, as this measure is shared by cigarettes and e-cigarettes. For exclusive users, the unit they purchase their e-liquid in may be the most relevant unit and better capture their demand for that product.ImplicationsBehavioral economic purchase tasks have been widely used to understand nicotine use. We have developed two versions of a purchase task for e-cigarette use and compared the two versions in users of advanced generation e-cigarette devices. We found that the mLs version of the task better-reflected use patterns relative to a puffs version, which suggests that participants struggle to place monetary value on a unit of consumption (ie, puffs). Validated measures of e-cigarette reinforcement will be important as researchers and regulators determine which features of these products contribute to reinforcing efficacy.

Project description:BackgroundAttempts to identify opioid users at increased risk of escalating to opioid use disorder have had limited success. Data from a variety of sources suggest that genetic variation may mediate the subjective response to opioid drugs, and therefore contribute to their abuse potential. The goal of the current study was to observe the relationship between select genetic polymorphisms and the subjective effects of oxycodone under controlled clinical laboratory conditions.MethodsNon-dependent, volunteers with some history of prescription opioid exposure (N = 36) provided a blood sample for analyses of variations in the genes that encode for the μ-, κ- and δ-opioid receptors, and the dopamine metabolizing enzyme, catechol-O-methyltransferase (COMT). Participants then completed a single laboratory test session to evaluate the subjective and analgesic effects of oral oxycodone (0, 10, and 20 mg, cumulative dose = 30 mg).ResultsOxycodone produced typical μ-opioid receptor agonist effects, such as miosis, and decreased pain perception. Oxycodone also produced dose-dependent increases in positive subjective responses such as: drug "Liking" and "Good Effect." Genetic variants in the μ- (rs6848893) and δ-opioid receptor (rs581111) influenced the responses to oxycodone administration. Additionally, self-reported "Stimulated" effects of oxycodone varied significantly as a function of COMT rs4680 genotype.DiscussionThe current study shows that the euphoric and stimulating effects of oxycodone can vary as a function of genetic variation. Though the relationship between the stimulating effects of opioids and their abuse liability is not well established, we know that the ability of opioids to provide intense feelings of pleasure is a significant motivator for continued use. If replicated, specific genetic variants may be useful in predicting who is at increased risk of developing maladaptive patterns of use following medical exposure to opioid analgesics.

Project description:Marijuana substitutes often contain blends of multiple psychoactive synthetic cannabinoids (SCBs), including the prevalent SCBs (1-pentyl-1H-indole-3-yl)-1-naphthalenyl-methanone (JWH-018) and (1-butyl-1H-indole-3-yl)-1-naphthalenyl-methanone (JWH-073). Because SCBs are frequently used in combinations, we hypothesized that coadministering multiple SCBs induces synergistic drug-drug interactions. Drug-drug interactions between JWH-018 and JWH-073 were investigated in vivo for ?(9)-tetrahydrocannabinol (?(9)-THC)-like discriminative stimulus effects, analgesia, task disruption, and hypothermia. Combinations (JWH-018:JWH-073) of these drugs were administered to mice in assays of ?(9)-THC discrimination, tail-immersion, and food-maintained responding, and rectal temperatures were measured. Synergism occurred in the ?(9)-THC discrimination assay for two constant dose ratio combinations (1:3 and 1:1). A 1:1 and 2:3 dose ratio induced additivity and synergy, respectively, in the tail-immersion assay. Both 1:1 and 2:3 dose ratios were additive for hypothermia, whereas a 1:3 dose ratio induced subadditive suppression of food-maintained responding. In vitro drug-drug interactions were assessed using competition receptor-binding assays employing mouse brain homogenates and cannabinoid 1 receptor (CB1R)-mediated inhibition of adenylyl cyclase activity in Neuro2A wild-type cells. Interestingly, synergy occurred in the competition receptor-binding assay for two dose ratios (1:5 and 1:10), but not in the adenylyl cyclase activity assay (1:5). Altogether, these data indicate that drug-drug interactions between JWH-018 and JWH-073 are effect- and ratio-dependent and may increase the relative potency of marijuana substitutes for subjective ?(9)-THC-like effects. Combinations may improve the therapeutic profile of cannabinoids, considering that analgesia but not hypothermia or task disruption was potentiated. Importantly, synergy in the competition receptor-binding assay suggests multiple CB1R-SCB binding sites.

Project description:IntroductionIn the USA, Food and Drug Administration regulations prohibit the sale of flavoured cigarettes, with menthol being the exception. However, the manufacture, advertisement and sale of flavoured cigar products are permitted. Such flavourings influence positive perceptions of tobacco products and are linked to increased use. Flavourings may mask the taste of tobacco and enhance smoke inhalation, influencing toxicant exposure and abuse liability among novice tobacco users. Using clinical laboratory methods, this study investigates how flavour availability affects measures of abuse liability in young adult cigarette smokers. The specific aims are to evaluate the effect of cigar flavours on nicotine exposure, and behavioural and subjective measures of abuse liability.Methods and analysesParticipants (projected n=25) are healthy smokers of five or more cigarettes per day over the past 3 months, 18-25 years old, naive to cigar use (lifetime use of 50 or fewer cigar products and no more than 10 cigars smoked in the past 30 days) and without a desire to quit cigarette smoking in the next 30 days. Participants complete five laboratory sessions in a Latin square design with either their own brand cigarette or a session-specific Black & Mild cigar differing in flavour (apple, cream, original and wine). Participants are single-blinded to cigar flavours. Each session consists of two 10-puff smoking bouts (30 s interpuff interval) separated by 1 hour. Primary outcomes include saliva nicotine concentration, behavioural economic task performance and response to various questionnaire items assessing subjective effects predictive of abuse liability. Differences in outcomes across own brand cigarette and flavoured cigar conditions will be tested using linear mixed models.Ethics and disseminationThe Virginia Commonwealth University Institutional Review Board approved the study (VCU IRB: HM20007848). Dissemination channels for study findings include scientific journals, scientific meetings, and policy briefs.Trial registration numberNCT02937051.

Project description:It is estimated that nearly a third of people who abuse drugs started with prescription opioid medicines. Approximately, 11.5 million Americans used prescription drugs recreationally in 2016, and in 2018, 46,802 Americans died as the result of an opioid overdose, including prescription opioids, heroin, and illicitly manufactured fentanyl (National Institutes on Drug Abuse (2020) Opioid Overdose Crisis. https://www.drugabuse.gov/drugs-abuse/opioids/opioid-overdose-crisis . Accessed 06 June 2020). Yet physicians will continue to prescribe oral opioids for moderate-to-severe pain in the absence of alternative therapeutics, underscoring the importance in understanding how drug choice can influence detrimental outcomes. One of the opioid prescription medications that led to this crisis is oxycodone, where misuse of this drug has been rampant. Being one of the most highly prescribed opioid medications for treating moderate-to-severe pain as reflected in the skyrocketed increase in retail sales of 866% between 1997 and 2007, oxycodone was initially suggested to be less addictive than morphine. The false-claimed non-addictive formulation of oxycodone, OxyContin, further contributed to the opioid crisis. Abuse was often carried out by crushing the pills for immediate burst release, typically by nasal insufflation, or by liquefying the pills for intravenous injection. Here, we review oxycodone pharmacology and abuse liability as well as present the hypothesis that oxycodone may exhibit a unique pharmacology that contributes to its high likability and abuse susceptibility. We will discuss various mechanisms that likely contribute to the high abuse rate of oxycodone including clinical drug likability, pharmacokinetics, pharmacodynamics, differences in its actions within mesolimbic reward circuity compared to other opioids, and the possibility of differential molecular and cellular receptor interactions that contribute to its selective effects. We will also discuss marketing strategies and drug difference that likely contributes to the oxycodone opioid use disorders and addiction.

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Validation of a behavioral economic purchase task for assessing drug abuse liability.

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Validation of a behavioral economic purchase task for assessing drug abuse liability.

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