The subjective value of social context in people who use cannabis.

Disordered cannabis use is linked to social problems, which could be explained by a subjective devaluation of nondrug social contexts and/or an overvaluation of cannabis-paired options relative to nondrug alternatives. To examine these hypotheses, measures to assess the subjective value of social- and/or cannabis-paired contexts were collected in people who use cannabis ( = 85) and controls ( = 98) using crowdsourcing methods. Measures included a cued concurrent choice task that presented two images (cannabis, social, social cannabis, and neutral images) paired with monetary options, hypothetical purchase tasks that included access to social parties with and without a cannabis "open bar," and the Social Anhedonia Scale (SAS).

A dose-ranging study of the physiological and self-reported effects of repeated, rapid infusion of remifentanil in people with opioid use disorder and physical dependence on fentanyl.

Rationale: Understanding mechanisms of drug use decisions will inform the development of treatments for opioid use disorder (OUD). Decision-making experiments using neurobehavioral approaches require many trials or events of interest for statistical analysis, but the pharmacokinetics of most opioids limit dosing in humans.

Objectives: This experiment characterized the effects of repeated infusions of the ultra-short acting opioid remifentanil in people with OUD and physical opioid dependence.

Cocaine abstinence during the "critical period" of a contingency management trial predicts future abstinence in people with cocaine use disorder.

Background: Contingency Management (CM) is being piloted as a treatment for stimulant use disorder in several US states, highlighting the need for treatment optimization. One important goal of optimization is decreasing drug use during the early stages of treatment, which has predicted success in other interventions. However, this "critical period" has not been reported in CM trials.

Combining noninvasive brain stimulation with behavioral pharmacology methods to study mechanisms of substance use disorder.

Psychotropic drugs and transcranial magnetic stimulation (TMS) are effective for treating certain psychiatric conditions. Drugs and TMS have also been used as tools to explore the relationship between brain function and behavior in humans. Combining centrally acting drugs and TMS has proven useful for characterizing the neural basis of movement.

Use of drug purchase tasks in medications development research: orexin system regulation of cocaine and drug demand.

Commodity purchase tasks provide a useful method for evaluating behavioral economic demand in the human laboratory. Recent research has shown how responding to purchase tasks for blinded drug administration can be used to study abuse liability. This analysis uses data from a human laboratory study to highlight how similar procedures may be particularly useful for understanding momentary changes in drug valuation when screening novel interventions.

Exponentiated model of drug demand is preferred over exponential models in people with daily/near daily cannabis use.

Cannabis use is a growing health concern emphasizing the need to better understand the complexities of drug choice in people with daily/near daily cannabis use. Hypothetical purchasing tasks provide a means to collect data on drug consumption behavior without requiring drug administration and have been used to isolate behavioral economic factors of choice, including facets of drug demand in substance using populations. Various models are used for analyzing hypothetical purchasing task data, but challenges exist in modeling data sets with consumption values of zero.

Naltrexone-bupropion combinations do not affect cocaine self-administration in humans.

The FDA has not yet approved a pharmacotherapy for cocaine use disorder despite nearly four decades of research. This study determined the initial efficacy, safety, and tolerability of naltrexone-bupropion combinations as a putative pharmacotherapy for cocaine use disorder. Thirty-one (31) non-treatment seeking participants with cocaine use disorder completed a mixed-design human laboratory study.

Cannabis Use Disorder Treatment Preferences: A Pilot Survey in Current Users of Cannabis.

Objectives: Highly effective treatments for cannabis use disorder (CUD) are lacking, and patient preferences have not been considered during treatment development. We therefore conducted an exploratory crowdsourced survey of individuals reporting current cannabis use and a willingness to cut down or quit their cannabis use, to determine their interest in various treatment aspects.

Methods: Subjects (n = 63) were queried about their willingness to take medications as a function of type, route, and regimen and to participate in adherence monitoring.

Suvorexant maintenance enhances the reinforcing but not subjective and physiological effects of intravenous cocaine in humans.

Preclinical research has sought to understand the role of the orexin system in cocaine addiction given the connection between orexin producing cells in the lateral hypothalamus and brain limbic areas. Exogenous administration of orexin peptides increased cocaine self-administration whereas selective orexin-1 receptor antagonists reduced cocaine self-administration in non-human animals. The first clinically available orexin antagonist, suvorexant (a dual orexin-1 and orexin-2 receptor antagonist), attenuated motivation for cocaine and cocaine conditioned place preference, as well as cocaine-associated impulsive responding, in rodents.

Differential impacts of economic and demographic variables on substance use patterns during the COVID-19 pandemic.

: The COVID-19 pandemic and subsequent economic crisis has provided a unique opportunity to investigate the effects of economic shifts on substance use. Existing literature on this relationship is limited and conflicting, warranting further exploration.: This study aimed to identify relationships between socioeconomic status (SES), demographic variables, and substance use patterns before and after government-mandated business closures due to COVID-19.

Influence of pregabalin maintenance on cannabis effects and related behaviors in daily cannabis users.

No medications are approved for cannabis use disorder (CUD), though a small clinical trial demonstrated that the voltage-dependent calcium channel (VDCC) ligand gabapentin reduced cannabis use in treatment seekers. VDCCs are modulated by cannabinoid (CB) ligands, and there are shared effects between CB agonists and VDCC ligands. This overlapping neuropharmacology and the initial clinical results supported the evaluation of pregabalin, a "next-generation" VDCC ligand, as a CUD medication.

Exploratory examination of the effects of d-amphetamine on active-state functional connectivity: Influence of impulsivity and sensation-seeking status.

Recent advances in diagnostic research identified that individuals with higher impulsivity and sensation-seeking scores tend to report more positive subjective responses to stimulant drugs such as amphetamine. The current exploratory study hypothesized that differences in underlying mesocorticolimbic circuitry may mediate the relationship between personality and responses to stimulants due to its previously established implication in reward processes as well as the overlap between its dopaminergic projections and the pharmacodynamics of many stimulants. Forty participants (20 female) were recruited with relatively high- and low-impulsivity and sensation-seeking scores as defined by the Zuckerman-Kuhlman Personality Questionnaire (Form IIIR; Zuckerman, Kuhlman, Joireman, Teta, & Kraft, 1993) for a double-blind, placebo-controlled, intranasal amphetamine administration study conducted within an MRI scanner.

Sexually dimorphic neuroimmune response to chronic opioid treatment and withdrawal.

Opioid use disorder is a leading cause of morbidity and mortality in the United States. Increasing pre-clinical and clinical evidence demonstrates sex differences in opioid use and dependence. However, the underlying molecular mechanisms contributing to these effects, including neuroinflammation, are still obscure.

Topiramate-phentermine combinations reduce cocaine self-administration in humans.

Rationale: Cocaine use disorder is an unrelenting public health concern. Despite nearly four decades of research, an FDA approved medication is not yet available.

Objectives: The objective of this human laboratory study was to demonstrate the initial efficacy, safety and tolerability of topiramate-phentermine combinations for cocaine use disorder.

Influence of n-acetylcysteine maintenance on the pharmacodynamic effects of oral ethanol.

Rationale: Glutamate systems play an important role in the abuse related effects of alcohol. n-Acetylcysteine, a drug that promotes glutamate homeostasis, attenuates a range of alcohol effects in preclinical models.

Objectives: This human laboratory study determined the influence of n-acetylcysteine maintenance on alcohol self-administration using a model predictive of treatment effectiveness, along with the subjective, performance and physiological effects of alcohol.

An update on the clinical pharmacology of methylphenidate: therapeutic efficacy, abuse potential and future considerations.

Introduction: Methylphenidate remains a first-line medication for treating ADHD in children and adults. However, its behavioral pharmacological similarities to methamphetamine and cocaine have historically created concern for its potential as a drug of abuse. In September 2019, the FDA published a docket requesting comments for the development of abuse deterrent formulations for CNS stimulants, emphasizing the abuse of methylphenidate as a public health concern.

Acute methylphenidate administration reduces cocaine-cue attentional bias.

Mechanistic research on behavioral processes underlying substance use disorder might help identify novel targets for interventions development. Drug-related attentional bias and response inhibition deficits have received a great deal of consideration in substance use research, broadly, and cocaine use research, specifically. Studies investigating pharmacological mechanisms that may ameliorate, or further impair, these behaviors relevant to cocaine use are relatively lacking.

The state of clinical outcome assessments for cannabis use disorder clinical trials: A review and research agenda.

There is considerable variability in the use of outcome measures in clinical trials for cannabis use disorder (CUD), and a lack of consensus regarding optimal outcomes may have hindered development and approval of new pharmacotherapies. The goal of this paper is to summarize an evaluation of assessment measures and clinical endpoints for CUD clinical trials, and propose a research agenda and priorities to improve CUD clinical outcome assessments. The primary recommendation is that sustained abstinence from cannabis should not be considered the primary outcome for all CUD clinical trials as it has multiple limitations.

Utilizing the commodity purchase task to evaluate behavioral economic demand for illicit substances: a review and meta-analysis.

Background Andaims: The commodity purchase task is a simulated demand procedure that is easy and quick to complete (< 5 minutes) as well as adaptable for remote delivery and use with varied study populations. The purpose of this meta-analysis was to synthesize research using the commodity purchase task with illicit substances to evaluate the magnitude of omnibus effects sizes and moderators of the correlation of demand indices with quantity-frequency (QF) and severity measures.

Design: Random-effects meta-analyses and meta-regressions involving studies with cross-sectional correlational designs.

Pharmacological validation of a translational model of cocaine use disorder: Effects of d-amphetamine maintenance on choice between intravenous cocaine and a nondrug alternative in humans and rhesus monkeys.

Drug self-administration procedures are the gold standard for laboratory research to study mechanisms of drug use disorders and evaluate candidate medications. However, preclinical-to-clinical translation has been hampered by a lack of coordination. To address this limitation, we previously developed homologous intravenous (IV) cocaine choice self-administration procedures in rhesus monkeys and humans, and then demonstrated their functional equivalence.

Contribution of cannabis-related cues to concurrent reinforcer choice in humans.

Background: Drug-related cues play a critical role in the development and persistence of substance use disorder. Few human laboratory studies have evaluated how these cues contribute to decisions between concurrently presented reinforcers, and none have examined the specific role of cannabis cues. This study evaluated the contribution of cannabis-related cues to concurrent monetary reinforcer choice in humans.

Evaluating non-medical prescription opioid demand using commodity purchase tasks: test-retest reliability and incremental validity.

Rationale: Non-medical prescription opioid use and opioid use disorder (OUD) present a significant public health concern. Identifying behavioral mechanisms underlying OUD will assist in developing improved prevention and intervention approaches. Behavioral economic demand has been extensively evaluated as a measure of reinforcer valuation for alcohol and cigarettes, whereas prescription opioids have received comparatively little attention.

Influence of phendimetrazine maintenance on the reinforcing, subjective, performance, and physiological effects of intranasal cocaine.

Rationale: No pharmacotherapies are approved for cocaine use disorder. Phendimetrazine, a prodrug of the monoamine-releaser phenmetrazine, attenuates the reinforcing effects of cocaine in preclinical models, has minimal abuse potential, and is safe when combined with cocaine.

Objectives: This study determined the influence of phendimetrazine maintenance on the reinforcing effects of cocaine (i.