A cross-sectional survey on cannabis: Characterizing motives, opinions, and subjective experiences associated with the use of various oral cannabis products.

BACKGROUND: Cannabis-infused products available for oral consumption include food and drink items (i.e., edibles) (e.g., baked goods, gummy-, chocolate-, and hard-candies, beverages/drinks) as well as non-food formulations (e.g., oils/tinctures, pills/capsules). This study characterized the motives, opinions, and subjective experiences associated with the use of these seven subtypes of oral cannabis products. METHODS: This web-based survey collected cross-sectional, self-report data from a convenience sample of 370 adults regarding various use-motives, self-reported cannabinoid content, subjective experiences, and opinions related to ingesting oral cannabis products with alcohol and/or food. Advice participants had received about modifying oral cannabis product effects, in general, was also collected. RESULTS: Participants reported consuming cannabis baked goods and gummy candies most frequently over the past year (68% and 63%, respectively). Participants were less likely to use oils/tinctures for enjoyment/desire relative to other product types and more likely to use oils/tinctures for therapeutic purposes (e.g., medication-replacement). Self-reported cannabinoid content was highly variable across participants and within product subtype. Participants reported feeling stronger and longer-lasting effects when consuming oral cannabis products on an empty stomach and 43% received advice to "eat a snack or meal" to mitigate effects that are too strong, which contrasts with controlled studies. Finally, 43% of participants reported modifying their experiences with alcohol at least some of time. CONCLUSIONS: These findings underscore the need to further evaluate use-motives as well as the interaction between dietary factors, cannabinoid pharmacokinetics, and subjective drug effects and the interactive effects of oral cannabis products and alcohol in a controlled laboratory setting.

Cannabinoid Content and Label Accuracy of Hemp-Derived Topical Products Available Online and at National Retail Stores.

Importance: Products containing cannabinoids such as cannabidiol (CBD) have proliferated since 2018, when the Agriculture Improvement Act removed hemp (ie, cannabis containing <0.3% Δ9-tetrahydrocannabinol [THC]) from the US controlled substances list. Topical cannabinoid products can be purchased nationwide at retail stores and over the internet, yet research on these products is scarce. Objective: To evaluate the cannabinoid content (ie, CBD and THC) and label accuracy of topical cannabinoid products and to quantify their therapeutic and nontherapeutic claims. Design, Setting, and Participants: Product inclusion criteria included designation as hemp products, intended for topical or transdermal application, and purported to contain cannabinoids (eg, CBD). All unique products available at each retail store were purchased. Online products were identified via Google using relevant keywords (eg, hemp or CBD topical). Various products (eg, lotions and patches) were purchased from retail stores (eg, pharmacies, grocery stores, and cosmetic or beauty stores) in Baltimore, Maryland, and online. Data analysis was performed from March to June 2022. Main Outcomes and Measures: Labeled and actual total amounts of CBD and THC, measured via gas chromatography-mass spectrometry. Therapeutic and nontherapeutic claims and references to the US Food and Drug Administration were quantified. Results: A total of 105 products were purchased, 45 from retail locations and 60 online. Of the 89 products that listed a total amount of CBD on the label, 18% (16 products) were overlabeled (ie, contained >10% less CBD than advertised), 58% (52 products) were underlabeled (ie, contained >10% more CBD than advertised), and 24% (21 products) were accurately labeled. The median (range) percentage deviation between the actual total amount of CBD and the labeled amount was 21% (-75% to 93%) for in-store products and 10% (-96% to 121%) for online products, indicating that products contained more CBD than advertised overall. THC was detected in 37 of 105 products (35%), although all contained less than 0.3% THC. Among the 37 THC-containing products, 4 (11%) were labeled as THC free, 14 (38%) indicated they contained less than 0.3% THC, and 19 (51%) did not reference THC on the label. Overall, 28% of products (29 products) made therapeutic claims, 14% (15 products) made cosmetic claims, and only 47% (49 products) noted that they were not Food and Drug Administration approved. Conclusions and Relevance: In a case series of topical cannabinoid products purchased online and at popular retail stores, products were often inaccurately labeled for CBD and many contained THC. These findings suggest that clinical studies are needed to determine whether topical cannabinoid products with THC can produce psychoactive effects or positive drug tests for cannabis.

Objective sleep outcomes in randomized-controlled trials in persons with substance use disorders: A systematic review.

BACKGROUND: Improving sleep health is an important target for substance use disorder (SUD) research. However, there is little guidance for SUD researchers regarding the use of technologies to objectively assess sleep outcomes in randomized-controlled trials (RCTs). This systematic review aimed to describe the use of technologies to objectively measure sleep outcomes in RCTs conducted in persons with SUDs, in order to inform future sleep intervention studies in SUD populations. METHODS: This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) on May 7th, 2020 (CRD42020182004). RCTs were reviewed here if they were peer-reviewed manuscripts that included objective measures of sleep in RCTs that sought to improve sleep in persons with SUDs. RESULTS: The initial search yielded 13,403 potential articles, with 27 meeting a priori criteria to be included in this review. The most common SUD was alcohol use disorder (59%). The most common technology used to assess sleep was polysomnography (41%), followed by actigraphy (37%), ambulatory polysomnography or components of polysomnography (e.g., electroencephalography; 19%), and at-home sleep apnea testing (7%). The most common sleep outcome reported was total sleep time (96%). CONCLUSIONS: There are a range of options to assess objective sleep outcomes. Polysomnography or ambulatory devices that directly measure brain activity are critical to advance medications through the regulatory process for the indication of improving sleep duration, continuity, and/or sleep onset latency outcomes. Actigraphy is also useful in preliminary investigations and in detecting the relationship between diurnal and SUD-related behaviors.

Patient-reported sleep outcomes in randomized-controlled trials in persons with substance use disorders: A systematic review.

BACKGROUND: Sleep disturbances and disorders are a common and sometimes recalcitrant problem in persons recovering from substance use disorders (SUDs). As such, several randomized-controlled trials (RCTs) have been conducted to address sleep disturbances in a variety of SUD subpopulations and clinical scenarios. The goal of this systematic review was to collate patient-reported sleep outcomes used in past SUD-related RCTs to provide guidance for future sleep research in persons with SUDs. METHODS: This systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) on May 7th, 2020 (CRD42020182004). Studies were included if they were peer-reviewed manuscripts describing RCTs in an SUD population. RESULTS: The initial search yielded 13,403 candidate articles, and 76 met a priori criteria and were included in this review. Thirty-five (46.1%) assessed sleep as a primary outcome (i.e., sleep improvement was the primary goal of the research) and 41 (53.9%) assessed sleep as a secondary outcome (i.e., sleep improvement was an important outcome, but not the primary outcome). The most commonly used measures included the Pittsburgh Sleep Quality Index, the Insomnia Severity Index, and sleep diaries. However, multiple additional sleep assessments were also used, including visual analogue and Likert scales. CONCLUSIONS: The field of addiction medicine would benefit from a streamlined approach in assessing patient-reported sleep in RCTs, including commonly used and validated assessments of sleep quality, inserting daily or repeated measures into RCTs, and including questionnaires that assess clinically relevant insomnia or other sleep disorders.

Urinary Excretion Profile of Cannabinoid Analytes Following Acute Administration of Oral and Vaporized Cannabis in Infrequent Cannabis Users.

Traditionally, smoking has been the predominant method for administering cannabis, but alternative routes of administration have become more prevalent. Additionally, research examining urinary cannabinoid excretion profiles has primarily focused on 11-nor-9-carboxy-∆9-tetrahydrocannabinol (∆9-THC-COOH), a metabolite of ∆9-tetrahydrocannabinol (∆9-THC), as the primary analyte. The aim of the current study was to characterize the urinary excretion profile of ∆9-THC-COOH, ∆9-THC, ∆8-tetrahydrocannabinol (∆8-THC), 11-hydroxy-∆9-tetrahydrocannabinol (11-OH-∆9-THC), ∆9-tetrahydrocannabivarin (THCV), 11-nor-∆9-tetrahydrocannabivarin-9-carboxlic acid (THCV-COOH), cannabidiol (CBD), cannabinol (CBN) and 8,11-dihydroxytetrahydrocannabinol (8,11-diOH-∆9-THC) following controlled administration of both oral and vaporized cannabis. Participants (n = 21, 11 men/10 women) who were infrequent cannabis users ingested cannabis-containing brownies (0, 10 and 25 mg ∆9-THC) and inhaled vaporized cannabis (0, 5 and 20 mg ∆9-THC) across six double-blind outpatient sessions. Urinary concentrations of ∆9-THC analytes were measured at baseline and for 8 h after cannabis administration. Sensitivity, specificity and agreement between the three immunoassays (IAs) for ∆9-THC-COOH (cutoffs of 20, 50 and 100 ng/mL) and liquid chromatography-tandem mass spectrometry (LC-MS-MS) analyses (confirmatory cutoff concentrations of 15 ng/mL) were assessed. Urinary concentrations for ∆9-THC-COOH, ∆9-THC, 11-OH-∆9-THC, THCV, CBN and 8,11-diOH-∆9-THC all peaked at 5-6 h and 4 h following oral and vaporized cannabis administration, respectively. At each active dose, median maximum concentrations (Cmax) for detected analytes were quantitatively higher after oral cannabis administration compared to vaporized. Using current recommended federal workplace drug-testing criteria (screening via IA with a cutoff of ≥50 ng/mL and confirmation via LC-MS-MS at a cutoff of ≥15 ng/mL), urine specimens tested positive for ∆9-THC-COOH in 97.6% of oral sessions and 59.5% of vaporized sessions with active ∆9-THC doses. These data indicate that while ∆9-THC-COOH may serve as the most consistent confirmatory analyte under the current drug-testing guidelines, future work examining 11-OH-∆9-THC under similar parameters could yield an alternative analyte that may be helpful in distinguishing between licit and illicit cannabis products.

Use patterns, beliefs, experiences, and behavioral economic demand of indica and sativa cannabis: A cross-sectional survey of cannabis users.

Cannabis products available for retail purchase are often marketed based on purported plant species (e.g., "indica" or "sativa"). The cannabis industry frequently claims that indica versus sativa cannabis elicits unique effects and/or is useful for different therapeutic indications. Few studies have evaluated use patterns, beliefs, subjective experiences, and situations in which individuals use indica versus sativa. A convenience sample of cannabis users (n = 179) was surveyed via Amazon Mechanical Turk (mTurk). Participants were asked about their prior use of, subjective experiences with, and opinions on indica versus sativa cannabis and completed hypothetical purchasing tasks for both cannabis subtypes. Participants reported a greater preference to use indica in the evening and sativa in the morning and afternoon. Participants were more likely to perceive feeling "sleepy/tired" or "relaxed" after using indica and "alert," "energized," and "motivated" after using sativa. Respondents were more likely to endorse wanting to use indica if they were going to sleep soon but more likely to use sativa at a party. Hypothetical purchasing patterns (i.e., grams of cannabis purchased as a function of escalating price) did not differ between indica and sativa, suggesting that demand was similar. Taken together, cannabis users retrospectively report feeling different effects from indica and sativa; however, demand generally did not differ between cannabis subtypes, suggesting situational factors could influence whether someone uses indica or sativa. Placebo-controlled, blinded studies are needed to characterize the pharmacodynamics and chemical composition of indica and sativa cannabis and to determine whether user expectancies contribute to differences in perceived indica/sativa effects. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Urinary Pharmacokinetic Profile of Cannabidiol (CBD), Δ9-Tetrahydrocannabinol (THC) and Their Metabolites following Oral and Vaporized CBD and Vaporized CBD-Dominant Cannabis Administration.

The market for products containing cannabidiol (CBD) is booming globally. However, the pharmacokinetics of CBD in different oral formulations and the impact of CBD use on urine drug testing outcomes for cannabis (e.g., 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (Δ9-THCCOOH)) are understudied. This study characterized the urinary pharmacokinetics of CBD (100 mg) following vaporization or oral administration (including three formulations: gelcap, pharmacy-grade syrup and or Epidiolex) as well as vaporized CBD-dominant cannabis (containing 100 mg CBD and 3.7 mg Δ9-THC) in healthy adults (n = 18). A subset of participants (n = 6) orally administered CBD syrup following overnight fasting (versus low-fat breakfast). Urine specimens were collected before and for 58 h after dosing on a residential research unit. Immunoassay (IA) screening (cutoffs: 20, 50 and 100 ng/mL) for Δ9-THCCOOH was performed, and quantitation of cannabinoids was completed via LC-MS-MS. Urinary CBD concentrations (ng/mL) were higher after oral (mean Cmax: 734; mean Tmax: 4.7 h, n = 18) versus vaporized CBD (mean Cmax: 240; mean Tmax: 1.3 h, n = 18), and oral dose formulation significantly impacted mean Cmax (Epidiolex = 1,274 ng/mL, capsule = 776 ng/mL, syrup = 151 ng/mL, n = 6/group) with little difference in Tmax. Overnight fasting had limited impact on CBD excretion in urine, and there was no evidence of CBD conversion to Δ8- or Δ9-THC in any route or formulation in which pure CBD was administered. Following acute administration of vaporized CBD-dominant cannabis, 3 of 18 participants provided a total of six urine samples in which Δ9-THCCOOH concentrations ≥15 ng/mL. All six specimens screened positive at a 20 ng/mL IA cutoff, and two of six screened positive at a 50 ng/mL cutoff. These data show that absorption/elimination of CBD is impacted by drug formulation, route of administration and gastric contents. Although pure CBD is unlikely to impact drug testing, it is possible that hemp products containing low amounts of Δ9-THC may produce a cannabis-positive urine drug test.

Sex differences in the acute effects of oral and vaporized cannabis among healthy adults.

Policy changes have increased access to cannabis for individuals with little or no prior exposure. Few studies have examined sex differences in cannabis effects among individuals with sporadic cannabis use or for nonsmoked routes of cannabis administration. Data from four double-blind, placebo-controlled studies were pooled to compare the acute pharmacodynamic effects of vaporized and oral cannabis in male (n = 27) and female (n = 23) participants who used cannabis infrequently (no use ≥30 days prior to randomization). Analyses compared peak change-from-baseline scores between male and female participants for subjective drug effects, cognitive/psychomotor performance, cardiovascular effects, and blood concentrations of Δ9-tetrahydrocannabinol (THC) and its primary metabolites (11-OH-THC, THC-COOH) after exposure to placebo cannabis or cannabis containing low-dose (5 or 10 mg) or high-dose THC (20 or 25 mg). Overall, cannabis elicited dose-orderly increases in subjective effects, impairment of cognitive/psychomotor performance, heart rate, and blood cannabinoid concentrations. Females exhibited greater peak blood 11-OH-THC concentrations and reported greater peak subjective ratings of "drug effect" that remained when controlling for body weight. When controlling for both body weight and peak blood cannabinoid concentrations, ratings of "anxious/nervous," "heart racing," and "restless" were significantly higher for females than males. Although additional research is needed to elucidate sex differences in responses to cannabis at a wider range of THC doses, other routes of administration, and products with diverse chemical composition, the current data indicate that public health messaging and clinical decision making around the use of cannabinoids should recommend lower starting doses for females and warnings about acute anxiogenic reactions.

Therapeutic potential and safety considerations for the clinical use of synthetic cannabinoids.

The phytocannabinoid Δ9-tetrahydrocannabinol (THC) was isolated and synthesized in the 1960s. Since then, two synthetic cannabinoids (SCBs) targeting the cannabinoid 1 (CB1R) and 2 (CB2R) receptors were approved for medical use based on clinical safety and efficacy data: dronabinol (synthetic THC) and nabilone (synthetic THC analog). To probe the function of the endocannabinoid system further, hundreds of investigational compounds were developed; in particular, agonists with (1) greater CB1/2R affinity relative to THC and (2) full CB1/2R agonist activity. This pharmacological profile may pose greater risks for misuse and adverse effects relative to THC, and these SCBs proliferated in retail markets as legal alternatives to cannabis (e.g., novel psychoactive substances [NPS], "Spice," "K2"). These SCBs were largely outlawed in the U.S., but blanket policies that placed all SCB chemicals into restrictive control categories impeded research progress into novel mechanisms for SCB therapeutic development. There is a concerted effort to develop new, therapeutically useful SCBs that target novel pharmacological mechanisms. This review highlights the potential therapeutic efficacy and safety considerations for unique SCBs, including CB1R partial and full agonists, peripherally-restricted CB1R agonists, selective CB2R agonists, selective CB1R antagonists/inverse agonists, CB1R allosteric modulators, endocannabinoid-degrading enzyme inhibitors, and cannabidiol. We propose promising directions for SCB research that may optimize therapeutic efficacy and diminish potential for adverse events, for example, peripherally-restricted CB1R antagonists/inverse agonists and biased CB1/2R agonists. Together, these strategies could lead to the discovery of new, therapeutically useful SCBs with reduced negative public health impact.

Inherent Motor Impulsivity Associates with Specific Gene Targets in the Rat Medial Prefrontal Cortex.

High impulsivity characterizes a myriad of neuropsychiatric diseases, and identifying targets for neuropharmacological intervention to reduce impulsivity could reveal transdiagnostic treatment strategies. Motor impulsivity (impulsive action) reflects in part the failure of "top-down" executive control by the medial prefrontal cortex (mPFC). The present study profiled the complete set of mRNA molecules expressed from genes (transcriptome) in the mPFC of male, outbred rats stably expressing high (HI) or low (LI) motor impulsivity based upon premature responses in the 1-choice serial reaction time (1-CSRT) task. RNA-sequencing identified expression of 18 genes that was higher in the mPFC of HI vs. LI rats. Functional gene enrichment revealed that biological processes related to calcium homeostasis and G protein-coupled receptor (GPCR) signaling pathways, particularly glutamatergic, were overrepresented in the mPFC of HI vs. LI rats. Transcription factor enrichment identified mothers against decapentaplegic homolog 4 (SMAD4) and RE1 silencing transcription factor (REST) as overrepresented in the mPFC of HI rats relative to LI rats, while in silico analysis predicted a conserved SMAD binding site within the voltage-gated calcium channel subunit alpha1 E (CACNA1E) promoter region. qRT-PCR analyses confirmed that mRNA expression of CACNA1E, as well as expression of leucyl and cystinyl aminopeptidase (LNPEP), were higher in the mPFC of HI vs. LI rats. These outcomes establish a transcriptomic landscape in the mPFC that is related to individual differences in motor impulsivity and propose novel gene targets for future impulsivity research.

Suppression of cocaine relapse-like behaviors upon pimavanserin and lorcaserin co-administration.

Cocaine use disorder (CUD) is a major public health challenge for which there are no pharmacotherapeutics approved by the United States Food and Drug Administration (FDA). The propensity to relapse in CUD involves several vulnerability factors including sensitivity to cues associated with cocaine-taking. Serotonin (5-hydroxytryptamine, 5-HT) neurotransmission, particularly through the 5-HT2A receptor (5-HT2AR) and 5-HT2C receptor (5-HT2CR), is mechanistically linked to cocaine-seeking in preclinical models. In the present experiments, we employed self-administration assays in male rats to investigate whether acute and/or repeated administration of the FDA-approved selective 5-HT2AR antagonist/inverse agonist pimavanserin, selective 5-HT2CR agonist lorcaserin or their combination would alter cocaine intake and/or cocaine-seeking behavior. We found that acute administration of lorcaserin, but not pimavanserin, attenuated cocaine intake while pimavanserin plus lorcaserin did not impact cocaine self-administration. In contrast, 10-days of repeated administration of pimavanserin, lorcaserin, or pimavanserin plus lorcaserin during forced abstinence from cocaine self-administration, blunted cocaine-seeking, similar to the acute administration of each ligand. Taken together, these data reveal the efficacy of repeated treatment with pimavanserin plus lorcaserin to attenuate factors important to relapse-like behaviors in rodent models of CUD. This article is part of the special issue entitled 'Serotonin Research: Crossing Scales and Boundaries'.

Therapeutic Efficacy of Cannabidiol (CBD): A Review of the Evidence from Clinical Trials and Human Laboratory Studies.

PURPOSE OF REVIEW: Global policy changes have increased access to products containing cannabidiol (CBD), a primary constituent of hemp and cannabis. The CBD product industry has experienced tremendous growth, in part, because CBD is widely touted as an effective therapeutic for myriad health conditions. However, only 1 CBD product (Epidiolex®) has been approved by the U.S. Food and Drug Administration (FDA) to date. There is substantial interest among consumers and the medical and scientific communities regarding the therapeutic potential of CBD, including for novel indications that are not recognized by the FDA. The purpose of this review was to synthesize available evidence from clinical research regarding the efficacy of CBD as a therapeutic. RECENT FINDINGS: Human laboratory studies and clinical trials (e.g., randomized controlled trials and single-arm, open label trials) evaluating the efficacy of CBD as a therapeutic were identified for various medical conditions, including epilepsy, anxiety, pain/inflammation, schizophrenia, various substance use disorders, post-traumatic stress disorder, and others. There is clear evidence supporting the utility of CBD to treat epilepsy. For other health conditions reviewed, evidence was often mixed and/or there was a general lack of well-powered randomized, placebo-controlled studies to draw definitive conclusions. SUMMARY: Rigorous, controlled evidence for the therapeutic efficacy of CBD is lacking for many health conditions. Possible concerns with the use of CBD as a therapeutic include the potential for adverse effects (e.g., liver toxicity), drug-drug interactions, and lack of sufficient regulatory oversight of retail CBD products.

Convergent neural connectivity in motor impulsivity and high-fat food binge-like eating in male Sprague-Dawley rats.

Food intake is essential for survival, but maladaptive patterns of intake, possibly encoded by a preexisting vulnerability coupled with the influence of environmental variables, can modify the reward value of food. Impulsivity, a predisposition toward rapid unplanned reactions to stimuli, is one of the multifaceted determinants underlying the etiology of dysregulated eating and its evolving pathogenesis. The medial prefrontal cortex (mPFC) is a major neural director of reward-driven behavior and impulsivity. Compromised signaling between the mPFC and nucleus accumbens shell (NAcSh) is thought to underlie the cognitive inability to withhold prepotent responses (motor impulsivity) and binge intake of high-fat food (HFF) seen in binge eating disorder. To explore the relationship between motor impulsivity and binge-like eating in rodents, we identified high (HI) and low impulsive (LI) rats in the 1-choice serial reaction time task and employed a rat model of binge-like eating behavior. HFF binge rats consumed significantly greater calories relative to control rats maintained on continual access to standard food or HFF. HI rats repeatedly exhibited significantly higher bingeing on HFF vs. LI rats. Next, we employed dual viral vector chemogenetic technology which allows for the targeted and isolated modulation of ventral mPFC (vmPFC) neurons that project to the NAcSh. Chemogenetic activation of the vmPFC to NAcSh pathway significantly suppressed motor impulsivity and binge-like intake for high-fat food. Thus, inherent motor impulsivity and binge-like eating are linked and the vmPFC to NAcSh pathway serves as a 'brake' over both behaviors.

Endogenous Serotonin 5-HT2A and 5-HT2C Receptors Associate in the Medial Prefrontal Cortex.

The 5-HT2A receptor (5-HT2AR) and 5-HT2CR are localized to the same neurons within the medial prefrontal cortex (mPFC), which regulates executive function, decision-making, and reward-guided learning and memory processes. The 5-HT2AR and 5-HT2CR coimmunoprecipitate in the mPFC of male Sprague-Dawley rats, while in vitro studies demonstrate the presence of a physical interaction between the 5-HT2AR and 5-HT2CR. The purpose of this study was to identify mPFC subregions in which the 5-HT2AR and 5-HT2CR physically interact ex vivo in the male Sprague-Dawley rat. We established the expression patterns of 5-HT2AR and 5-HT2CR in layers I-VI of the anterior cingulate cortex (ACC), prelimbic (PL), and infralimbic (IL) subregions using double-label fluorescence immunohistochemistry in male rats. We then employed the proximity ligation assay (PLA) to test the hypothesis that the 5-HT2AR and 5-HT2CR form a close, physical association within these mPFC subregions. Our results demonstrate subregion- and layer-specific expression of the 5-HT2AR and 5-HT2CR proteins using immunofluorescence and single recognition PLA, and a spatially close (within 40 nm) interaction between the 5-HT2AR and 5-HT2CR that occurs along a dorsal-ventral gradient in the rat mPFC.

The 5-HT2A Receptor (5-HT2AR) Regulates Impulsive Action and Cocaine Cue Reactivity in Male Sprague-Dawley Rats.

Impulsivity and the attentional orienting response to cocaine-associated cues (cue reactivity) promote relapse in cocaine-use disorder (CUD). A time-dependent escalation of cue reactivity (incubation) occurs during extended, forced abstinence from cocaine self-administration in rats. The investigational serotonin (5-HT) 5-HT2A receptor (5-HT2AR) antagonist/inverse agonist M100907 suppresses impulsive action, or the inability to withhold premature responses, and cocaine-seeking behaviors. The present preclinical study was designed to establish the potential for repurposing the Food and Drug Administration-approved selective 5-HT2AR antagonist/inverse agonist pimavanserin as a therapeutic agent to forestall relapse vulnerability in CUD. In male Sprague-Dawley rats, pimavanserin suppressed impulsive action (premature responses) measured in the 1-choice serial reaction time (1-CSRT) task, similarly to M100907. We also used the 1-CSRT task to establish baseline levels of impulsive action before cocaine self-administration and evaluation of cue reactivity (lever presses reinforced by the discrete cue complex previously paired with cocaine delivery). We observed an incubation of cocaine cue reactivity between day 1 and day 30 of forced abstinence from cocaine self-administration. Baseline levels of impulsive action predicted incubated levels of cocaine cue reactivity in late abstinence. We also found that baseline impulsive action predicted the effectiveness of pimavanserin to suppress incubated cue reactivity in late abstinence from cocaine self-administration at doses that were ineffective in early abstinence. These data suggest that integration of clinical measures of impulsive action may inform refined, personalized pharmacotherapeutic intervention for the treatment of relapse vulnerability in CUD.