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 (n = 85) and controls (n = 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). Little evidence was found to suggest that the cannabis group undervalued social contexts. People who used cannabis demonstrated a preference for social- versus neutral-cued options, and no preference for cannabis- versus social cannabis-cued options on the choice task. In addition, social party demand and SAS scores did not differ between groups. In contrast, we observed evidence for an overvaluation of cannabis context in people who use cannabis, including preference for social cannabis- versus social-cued options, and more disadvantageous choices for cannabis-cued options on the choice task, as well as more intense and inelastic demand for the social cannabis party compared to the social party. These results suggest that social problems associated with cannabis use could be at least partially explained by an overvaluation of cannabis-paired options, rather than devaluation of nondrug social-paired options, in the value calculations underlying drug use decisions. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Opioid craving does not incubate over time in inpatient or outpatient treatment studies: Is the preclinical incubation of craving model lost in translation?

Within addiction science, incubation of craving is an operational label used to describe time-dependent increases in drug seeking during periods of drug deprivation. The purpose of this systematic review was to describe the preclinical literature on incubation of craving and the clinical literature on craving measured over extended periods of abstinence to document this translational homology and factors impacting correspondence. Across the 44 preclinical studies that met inclusion criteria, 31 reported evidence of greater lever pressing, nose pokes, spout licks, or time spent in drug-paired compartments (i.e., drug seeking) relative to neutral compartments after longer periods of abstinence relative to shorter periods of abstinence, labelled as "incubation of craving." In contrast, no clinical studies (n = 20) identified an increase in opioid craving during longer abstinence periods. The lack of clinical evidence for increases in craving in clinical populations weakens the translational utility of operationalizing the time-dependent increase in drug-seeking behavior observed in preclinical models as models of incubation of "craving".

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. METHODS: An inpatient study using a within-subjects, single-blind, escalating, within-session, pre-post design was conducted. Seven (3 female) subjects were maintained on oral oxycodone (40-60 mg, 4x/day = 160-240 total mg/day) for seven days prior to the dose-ranging session. Subjects received infusions of three ascending remifentanil doses (0.03, 0.1, 0.3 mcg/kg/infusion in 2 subjects; 0.1, 0.3, 1.0 mcg/kg/infusion in 5 subjects) every minute for 40 min per dose, with infusions administered over 5 s to model naturalistic delivery rates. End tidal carbon dioxide, respiration rate, oxygen saturation (SpO2) and heart rate were measured continuously. Blood pressure (BP), pupil diameter and self-reported drug effects were measured every 5 min. RESULTS: Pupil diameter, SpO2 and systolic BP decreased, and ratings on prototypic subjective effects questionnaire items increased, as a function of remifentanil dose. The number of infusions held because of sedation or physiological parameters exceeding predetermined cutoffs also increased with dose. CONCLUSIONS: This experiment established doses and procedures for the safe delivery of rapid, repeated remifentanil infusions to individuals with OUD and physical fentanyl dependence, which can be applied to the mechanistic study of opioid use decisions.

Oxycodone withdrawal is associated with increased cocaine self-administration and aberrant accumbens glutamate plasticity in rats.

Individuals with opioid use disorder (OUD) frequently use other substances, including cocaine. Opioid withdrawal is associated with increased likelihood of cocaine use, which may represent an attempt to ameliorate opioid withdrawal effects. Clinically, 30% of co-using individuals take opioids and cocaine exclusively in a sequential manner. Preclinical studies evaluating mechanisms of drug use typically study drugs in isolation. However, polysubstance use is a highly prevalent clinical issue and thus, we established a novel preclinical model of sequential oxycodone and cocaine self-administration (SA) whereby rats acquired oxycodone and cocaine SA in an A-B-A-B design. Somatic signs of withdrawal were evaluated at 0, 22, and 24h following oxycodone SA, with the 24h timepoint representing somatic signs immediately following cocaine SA. Preclinically, aberrant glutamate signaling within the nucleus accumbens core (NAcore) occurs following use of cocaine or opioids, whereby medium spiny neurons (MSNs) rest in a potentiated or depotentiated state, respectively. Further, NAcore glial glutamate transport via GLT-1 is downregulated following SA of either drug alone. However, it is not clear if cocaine can exacerbate opioid-induced changes in glutamate signaling. In this study, NAcore GLT-1 protein and glutamate plasticity were measured (via AMPA/NMDA ratio) following SA. Rats acquired SA of both oxycodone and cocaine regardless of sex, and the acute oxycodone-induced increase in somatic signs at 22h was positively correlated with cocaine consumption during the cocaine testing phase. Cocaine use following oxycodone SA downregulated GLT-1 and reduced AMPA/NMDA ratios compared to cocaine use following food SA. Further, oxycodone SA alone was associated with reduced AMPA/NMDA ratio. Together, behavioral signs of oxycodone withdrawal may drive cocaine use and further dysregulate NAcore glutamate signaling.

Impacts of xylazine on fentanyl demand, body weight, and acute withdrawal in rats: A comparison to lofexidine.

The opioid use landscape has recently shifted to include xylazine, a veterinary anesthetic, as an adulterant in the fentanyl supply. The health impacts of xylazine as an emerging fentanyl adulterant has raised alarm regarding xylazine as a public health threat, warranting research on the impacts of xylazine on fentanyl's behavioral effects. No prior studies have evaluated the effects of xylazine on fentanyl consumption at various unit doses, fentanyl demand, or withdrawal as compared to the Food and Drug Administration-approved opioid withdrawal medication, lofexidine (Lucemyra®). This is important because lofexidine and xylazine are both adrenergic α2a (A2aR) agonists, however, lofexidine is not a noted fentanyl adulterant. Here we evaluated xylazine and lofexidine combined with self-administered fentanyl doses in male and female rats and evaluated fentanyl demand, body weight, and acute withdrawal. Consumption of fentanyl alone increased at various unit doses compared to saline. Xylazine but not lofexidine shifted fentanyl consumption downward at a number of unit doses, however, both lofexidine and xylazine suppressed fentanyl demand intensity as compared to a fentanyl alone control group. Further, both fentanyl + lofexidine and fentanyl + xylazine reduced behavioral signs of fentanyl withdrawal immediately following SA, but signs increased by 12 h only in the xylazine co-exposed group. Weight loss occurred throughout fentanyl SA and withdrawal regardless of group, although the xylazine group lost significantly more weight during the first 24 h of withdrawal than the other two groups. Severity of weight loss during the first 24 h of withdrawal was also correlated with severity of somatic signs of fentanyl withdrawal. Together, these results suggest that body weight loss may be an important indicator of withdrawal severity during acute withdrawal from the xylazine/fentanyl combination, warranting further translational evaluation.

Progress and promise: A brief reflection on my time as editor of Experimental and Clinical Psychopharmacology.

This editorial focuses on William W. Stoops time as editor of Experimental and Clinical Psychopharmacology. Stoops ends his time with gratitude for all who have contributed to the journal's success over the past years, pride for what they have accomplished, and excitement for the journal's future. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

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. The purpose of this analysis was to determine if, after accounting for baseline abstinence and incentive condition, abstinence in a CM trial for people with Cocaine Use Disorder (CUD) could be predicted by cocaine use during a first-week critical period. METHODS: Eighty-seven participants with CUD were randomized to receive contingent high or low value incentives for cocaine abstinence or were in a non-contingent control group. Generalized estimating equations (GEE) were used to analyze urine test results over 36 timepoints during the 12-week intervention. To assess for a critical period, the first three visits were included in the GEE as a covariate for remaining urine test results. RESULTS: Participants who provided more negative samples during the critical period were significantly more likely to produce a negative urine sample during the remainder of the trial, though some effects of group remained after controlling for the critical period. CONCLUSIONS: These results indicate that a critical period exists for CM trials, and it can explain a substantial amount of future performance. Early contact with an abstinence-contingent high magnitude alternative reinforcer may explain additional performance beyond the critical period, further justifying the use of high magnitude alternative reinforcers.

The endowment effect and temporal discounting of drug and non-drug commodities.

OBJECTIVES: Despite a rich history of behavioral economic research on substance use there remains a need for further exploration of behavioral mechanisms that may underlie the etiology or persistence of substance use disorder. The purpose of this study was to measure the association between delay discounting and the endowment effect in people who smoke cigarettes, use cocaine, and controls, using online crowdsourcing. METHODS: Participants were categorized to a cocaine group (n = 36), cigarette group (n = 48), or control group (n = 47) based on recent reported drug use. Based on group, participants completed up to three delay discounting tasks (i.e., money, cigarettes and cocaine), an endowment effect task for multiple commodities, and other questionnaires. RESULTS: Participants in the cocaine and cigarette group demonstrated an increased rate in discounting for money compared to controls. Participants in the cocaine group had a less pronounced endowment effect for beer, compared to controls, as suggested by willingness to accept less to sell beer. A significant negative association was found between endowment ratios for non-drug commodities and delay discounting for cigarettes, but not monetary or cocaine delay discounting, indicating an inconsistent relationship between the two measures. CONCLUSIONS: These results support prior research demonstrating a relationship between cocaine and cigarette use and delay discounting and extend that work by measuring the association between delay discounting and the endowment effect. Future research should include both loss aversion and endowment effect tasks and compare their relationship with delay discounting among people that use drugs.

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. Eight nontreatment-seeking participants with cocaine use disorder (one with partial data) were enrolled in a cross-over, double-blind, randomized inpatient study. Participants were maintained on the Food and Drug Administration-approved insomnia medication suvorexant (oral; 0, 5, 10, 20 mg/day) in randomized order with experimental sessions completed after at least 3 days of maintenance on each suvorexant dose. Experimental sessions included administration of a sample dose of 0, 10 and 30 mg/70 kg intravenous cocaine. Analyses focused on purchase tasks for the blinded sample dose as well as alcohol, cigarettes and chocolate completed 15 min after the sample dose. As expected based on abuse liability, near zero demand was observed for placebo with dose-related increases in cocaine demand. Suvorexant maintenance increased cocaine demand in a dose-related manner with the greatest increase observed for the 10 mg/kg cocaine dose. Increased demand under suvorexant maintenance was also observed for alcohol. No effect of cocaine administration was observed for alcohol, cigarette, or chocolate demand. These data support the validity of demand procedures for measuring blinded drug demand. Findings also parallel self-administration data from this study by showing increases in cocaine use motivation under suvorexant maintenance.

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. Additionally, a single model or approach may not be best for all commodities and drug classes. This study compared two common demand models (exponential vs. exponentiated) applied to identical hypothetical purchasing task data from 21 (n = 21) individuals with daily/near daily cannabis use. The exponential model was fit using three common levels of replacement values for zero consumption (.1, .01, .001) and compared to the exponentiated model without replacement values. We found that the exponentiated model produced significantly better model fits for individual data, compared to all exponential models. Additionally, significant differences for model derived values of demand elasticity and intensity were found between the exponentiated model and different levels of the exponential model. We conclude that the exponentiated model is preferred over the exponential model for performing demand analysis on hypothetical purchasing task data from individuals with daily/near daily cannabis use. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

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. Subjects were also asked about their willingness to engage in behavioral/psychosocial interventions as a function of type, setting, and duration. Measures theorized to be associated with treatment preferences were also collected, including cannabis use variables, readiness to change, reduction or cessation goal, perceived cessation barriers, and medication use beliefs and behaviors. RESULTS: Survey responses indicated that efforts to develop CUD medications should focus on nonsynthetic compounds administered orally or by mouth spray no more than once per day to maximize patient acceptance. Remote adherence monitoring and one-on-one outpatient behavioral treatment approaches, especially contingency management, are also anticipated to enhance participation. Most subjects indicated a preference to reduce their cannabis use rather than quit. CONCLUSIONS: These data provide guidance for the development of CUD interventions based on the preferences of individuals interested in treatment for their cannabis use. Additional research is needed to confirm these results in a larger sample and determine if matching CUD patients with their preferred treatments improves success rates.

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. Participants were randomly assigned to the naltrexone conditions (i.e., 0, 50 mg/day; between-subject factor) and maintained on escalating doses of bupropion (i.e., 0, 100, 200, 400 mg/day; within-subject factor) for at least four days prior to the conduct of experimental sessions. Cocaine self-administration (IN, 0, 40, 80 mg) was then determined using a modified progressive ratio and relapse procedure. Subjective and cardiovascular effects were also measured. Cocaine produced prototypical dose-related increases in self-administration, subjective outcomes (e.g., "Like Drug"), and cardiovascular indices (e.g., heart rate, blood pressure) during placebo maintenance. Naltrexone and bupropion alone, or in combination, did not significantly decrease self-administration on either procedure. Low doses of bupropion (i.e., 100 mg) blunted the effects of the cocaine on subjective measures of "Like Drug" and "Stimulated". No unexpected adverse effects were observed with naltrexone and bupropion, alone and combined, in conjunction with cocaine. Together, these results do not support the use of these bupropion-naltrexone combinations for the treatment of cocaine use disorder. Future research should determine if novel drug combinations may decrease cocaine self-administration.

Substance use disorders and social determinants of health from electronic medical records obtained during Kentucky's "triple wave".

Social determinants of health (SDOH) play a critical role in the risk of harmful drug use. Examining SDOH as a means of differentiating populations with multiple co-occurring substance use disorders (SUDs) is particularly salient in the era of prevalent opioid and stimulant use known as the "Third Wave". This study uses electronic medical records (EMRs) from a safety net hospital system from 14,032 patients in Kentucky from 2017 to 2019 in order to 1) define three types of SUD cohorts with shared/unique risk factors, 2) identify patients with unstable housing using novel methods for EMRs and 3) link patients to their residential neighborhood to obtain quantitative perspective on social vulnerability. We identified patients in three cohorts with statistically significant unique risk factors that included race, biological sex, insurance type, smoking status, and urban/rural residential location. Adjusting for these variables, we found a statistically significant, increasing risk gradient for patients experiencing unstable housing by cohort type: opioid-only (n = 7385, reference), stimulant-only (n = 4794, odds ratio (aOR) 1.86 95 % confidence interval (CI): 1.66-2.09), and co-diagnosed (n = 1853, aOR = 2.75, 95 % CI: 2.39 to 3.16). At the neighborhood-level, we used 8 different measures of social vulnerability and found that, for the most part, increasing proportions of patients with stimulant use living in a census tract was associated with more social vulnerability. Our study identifies potentially modifiable factors that can be tailored by substance type and demonstrates robust use of EMRs to meet national goals of enhancing research on social determinants of health.

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. This study aimed to translate those preclinical findings and determine whether suvorexant maintenance altered the pharmacodynamic effects of cocaine in humans. Seven non-treatment seeking subjects with cocaine use disorder completed this within-subject human laboratory study, and a partial data set was obtained from one additional subject. Subjects were maintained for at least three days on 0, 5, 10 and 20 mg oral suvorexant administered at 2230 h daily in random order. Subjects completed experimental sessions in which cocaine self-administration of 0, 10 and 30 mg/70 kg of intravenous cocaine was evaluated on a concurrent progressive ratio drug versus money choice task. Subjective and physiological effects of cocaine were also determined. Cocaine functioned as a reinforcer and produced prototypic dose-related subjective and physiological effects (e.g., increased ratings of "Stimulated" and heart rate). Suvorexant (10, 20 mg) increased self-administration of 10 mg/70 kg cocaine and decreased oral temperature but did not significantly alter any other effects of cocaine. Future research may seek to evaluate the effects of orexin-1 selective antagonists in combination with cocaine.

A Brief Introduction to Human Behavioral Pharmacology: Methods, Design Considerations and Ethics.

Human behavioral pharmacology methods have been used to rigorously evaluate the effects of a range of centrally acting drugs in humans under controlled conditions for decades. Methods like drug self-administration and drug discrimination have been adapted from nonhuman laboratory animal models. Because humans have the capacity to communicate verbally, self-report methods are also commonly used to understand drug effects. This perspective article provides an overview of these traditional human behavioral pharmacology methods and introduces some novel methodologies that have more recently been adapted for use in the field. Design (e.g., using placebo controls, testing multiple doses) and ethical (e.g., avoiding enrollment of individuals seeking treatment, determining capacity to consent) considerations that must be addressed when conducting these types of studies are also described.

A preliminary investigation of schedule parameters on cocaine abstinence in contingency management.

Contingency management (CM) interventions are the most effective psychosocial interventions for substance use disorders. However, further investigation is needed to create the most robust intervention possible. This study investigated the effects of 1) reinforcer magnitude; and 2) fixed and escalating and resetting incentives on cocaine abstinence in an outpatient trial. In this analysis, 34 treatment-seeking individuals with Cocaine Use Disorder received either high or low value incentives for providing a benzoylecgonine-negative urine sample or were in a control condition and received incentives for providing a urine sample regardless of the results. Participants received either escalating and resetting incentives, wherein the value of each incentive increased with consecutive negative samples and reset to the initial level upon a positive sample (Experiment 1), or fixed incentives, wherein they received the same value incentive for each negative urine sample they provided (Experiment 2). Large incentives produced more abstinence, although escalating and resetting reinforcer values did not have a differential effect. Large, fixed incentives promoted abstinence faster than other reinforcers, whereas smaller incentives resulted in poor abstinence and took many visits to achieve initial abstinence. Future research comparing different schedules on cocaine abstinence in a randomized control trial with a larger sample size is required.

Logical fallacies and misinterpretations that hinder progress in translational addiction neuroscience.

Substance use disorders (SUDs) are heterogeneous and complex, making the development of translationally predictive rodent and nonhuman primate models to uncover their neurobehavioral underpinnings difficult. Neuroscience-focused outcomes have become highly prevalent, and with this, the notion that SUDs are disorders of the brain embraced as a dominant theoretical orientation to understand SUD etiology and treatment. These efforts, however, have led to few efficacious pharmacotherapies, and in some cases (as with cocaine or methamphetamine), no pharmacotherapies have translated from preclinical models for clinical use. In this theoretical commentary, we first describe the development of animal models of substance use behaviors from a historical perspective. We then define and discuss three logical fallacies including 1) circular explanation, 2) affirming the consequent, and 3) reification that can apply to developed models. We then provide three case examples in which conceptual or logical issues exist in common methods (i.e., behavioral economic demand, escalation, and reinstatement). Alternative strategies to refocus behavioral models are suggested for the field to better bridge the translational divide between animal models, the clinical condition of SUDs, and current and future regulatory pathways for intervention development.

Clinical neuropharmacology of cocaine reinforcement: A narrative review of human laboratory self-administration studies.

Cocaine use is an unrelenting public health concern. To inform intervention and prevention efforts, it is crucial to develop an understanding of the clinical neuropharmacology of the reinforcing effects of cocaine. The purpose of this review is to evaluate and synthesize human laboratory studies that assess pharmacological manipulations of cocaine self-administration. Forty-one peer-reviewed, human cocaine self-administration studies in which participants received a pretreatment drug were assessed. The pharmacological action and treatment regimen for all drugs reviewed were considered. Drugs that increase extracellular dopamine tend to have the most consistent effects on cocaine self-administration. The ability of nondopaminergic drugs to impact cocaine reinforcement might be related to their downstream effects on dopamine, though it is difficult to draw conclusions because pharmacologically selective compounds are not widely available for human testing. The ability of acute versus chronic drug treatment to differentially affect human cocaine self-administration was not determined because buprenorphine was the only pretreatment drug that was assessed under both acute and chronic dosing regimens. Future research directly comparing acute and chronic drug treatment and/or comparing drugs with different mechanisms of action, is needed to make more conclusive determinations about the clinical neuropharmacology of cocaine reinforcement.

Human behavioral pharmacology of stimulant drugs: An update and narrative review.

Stimulant use disorders present an enduring public health concern. Chronic stimulant use is associated with a range of health problems, with notable increases in stimulant overdose that disproportionately affect marginalized populations. With these persistent problems, it is important to understand the behavioral and pharmacological factors that contribute to stimulant use in humans. The purpose of this chapter is to provide an update and narrative review on recent human laboratory research that has evaluated the behavioral pharmacology of stimulant drugs. We focus on two prototypic stimulants: cocaine as a prototype monoamine reuptake inhibitor and d-amphetamine as a prototype monoamine releaser. As such, placebo controlled human laboratory studies that involved administration of doses of cocaine or d-amphetamine and were published in peer reviewed journals within the last 10 years (i.e., since 2011) are reviewed. Primary outcomes from these studies are subjective effects, reinforcing effects, cognitive/behavioral effects, and discriminative stimulus effects. Both cocaine and d-amphetamine produce classical stimulant-like behavioral effects (e.g., increase positive subjective effects, function as reinforcers), but there are notable gaps in the literature including understanding sex differences in response to stimulant drugs, cognitive-behavioral effects of stimulants, and influence of use history (e.g., relatively drug naïve vs drug experienced) on stimulant effects.

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

Background: 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.Objective: 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.Methods: Participants were recruited based on self-reported substance use through Amazon's Mechanical Turk (MTurk). Qualifying participants (N = 315, 43% female, mean age = 35.35) reported their substance use and SES for two-week periods before and after pandemic-related business closures. Regression models analyzed relationships between substance use and study variables.Results: Regression models found that, during COVID-19 closures, greater financial strain predicted decreased benzodiazepine (ß = -1.12) and tobacco (ß = 1.59) use. Additionally, certain predictor variables (e.g., participants' age [ß = 1.22], race [ß = -4.43], psychiatric disorders including ADHD [ß = -2.73] and anxiety [ß = 1.53], and concomitant substance use [ß = 3.38]) predicted changes in substance use patterns; however, the directionality of these associations varied across substances.Conclusion: Specific substance use patterns were significantly and differentially impacted by economic strain, psychiatric diagnoses, and concomitant substance use. These results can help direct harm reduction efforts toward populations at greatest risk of harmful substance use following the pandemic.