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".

Virtual focus groups among individuals with use disorders: assessing feasibility and acceptability in an underserved clinical population.

Objective: There are substantial barriers to conducting research among individuals with stigmatized and complicated health conditions like substance use disorders. These barriers slow progress when developing, refining, and assessing interventions to better treat underserved populations. Virtual focus groups are an innovative method for collecting data from individuals via a discreet and accessible platform which can inform novel as well as existing treatment approaches. This article reports on the feasibility and acceptability of virtual focus groups as a mechanism to recruit and engage geographically and demographically diverse samples of participants with substance use disorders that are otherwise logistically difficult to assess. Method: Participants were assessed for eligibility for a virtual focus group study based on demographic features, drug use history, and psychiatric history via a remote, interview-based screening. Focus groups were completed anonymously without video or name-sharing. Discussion contributions, quantified with number of times speaking and total number of words spoken, were compared across gender, and treatment status. Participants provided quantitative and qualitative feedback on the focus group experience in a follow-up survey. Results: Focus groups (N=26) based in geographical areas throughout the United States were conducted with 88 individuals with opioid use disorder or stimulant use disorder. Discussion contributions were comparable between genders and among individuals in treatment versus those seeking treatment. A follow-up survey (n=50, 57% of focus group participants) reflected high levels of enjoyment, comfort, and honesty during focus group discussions. Discussion: Findings suggest virtual focus groups can be an effective and efficient tool for substance use research.

Polymorphisms in the A118G SNP of the OPRM1 gene produce different experiences of opioids: A human laboratory phenotype-genotype assessment.

Allelic variations in the A118G SNP of the OPRM1 gene change opioid signaling; however, evaluations of how allelic differences may influence opioid effects are lacking. This human laboratory paradigm examined whether the AA versus AG/GG genotypes determined opioid response profiles. Individuals with limited opioid exposure (N = 100) completed a five-day within-subject, double-blind, placebo-controlled, residential study. Participants were admitted (Day 1), received 4 mg hydromorphone (Day 2) and 0 mg, 2 mg and 8 mg hydromorphone in randomized order (Days 3-5) and completed self-reported visual analog scale (VAS) ratings and Likert scales, observed VAS, and physiological responses at baseline and for 6.5 h post-dose. Outcomes were analysed as peak/nadir effects over time as a function of genotype (available for N = 96 individuals; AG/GG = 13.5%, AA = 86.4%). Participants with AG/GG rated low and moderate doses of hydromorphone as significantly more positive (e.g., Good Effects VAS, coasting, drive, friendly, talkative, stimulation) with fewer negative effects (e.g., itchy skin, nausea, sleepiness), and were also observed as being more talkative and energetic relative to persons with AA. Persons with AG/GG were less physiologically reactive as determined by diastolic blood pressure and heart rate, but had more changes in core temperature compared with those with AA. Persons with AA also demonstrated more prototypic agonist effects across doses; persons with AG/GG showed limited response to 2 mg and 4 mg. Data suggest persons with AG/GG genotype experienced more pleasant and fewer unpleasant responses to hydromorphone relative to persons with AA. Future studies should replicate these laboratory findings in clinical populations to support a precision medicine approach to opioid prescribing.

Changes in weight among individuals with psychiatric conditions or socioeconomic disadvantage assigned to smoke very low nicotine content cigarettes.

Nicotine abstinence leads to weight gain, which could be an unintended consequence of a nicotine reduction policy. This secondary analysis used weekly assessments of weight and ratings of "increased appetite/hunger/weight gain" collected in three 12-week, randomized controlled trials evaluating the effects of cigarettes differing in nicotine dose (15.8, 2.4, or 0.4 mg/g) among individuals with affective disorders, opioid use disorder (OUD), and socioeconomically disadvantaged women. Linear mixed models tested differences by dose and time. Analyses first collapsed across populations and then separated out individuals with OUD because biomarkers suggested they used substantially more noncombusted nicotine. Across populations, weight increased significantly over time, averaging 1.03 kg (p < .001), but did not vary by dose nor was there any interaction of dose/time. "Increased appetite/hunger/weight gain" ratings increased significantly as a function of dose, with differences between low and high doses (1.95 and 1.73, respectively, p = .01), but not by time nor any interaction. In the combined group of individuals with affective disorders and socioeconomically disadvantaged women, weight and "increased appetite/hunger/weight gain" ratings increased significantly by dose, with differences between low and high doses (1.43 vs. 0.73 kg, p = .003 and 2.00 vs. 1.76, p = .02, respectively). Among individuals with OUD, there were no significant effects of any kind on either outcome. Individuals with affective disorders and socioeconomically disadvantaged women gained weight and reported more subjective appetite/weight gain when given 0.4, but not 2.4 mg/g cigarettes, despite comparable decreases in nicotine exposure. However, neither change was clinically significant, suggesting minimal short-term adverse consequences of a nicotine reduction policy. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Within subject, double blind, examination of opioid sensitivity in participant-reported, observed, physiologic, and analgesic outcomes.

Background: Inter-individual differences in opioid sensitivity may underlie different opioid risk profiles but have often been researched in persons who have current or past opioid use disorder or physical dependence. This study examined how opioid sensitivity manifests across various assessments of opioid effects in a primarily opioid-naïve population. Procedures: Data were harmonized from two within-subject, double-blind trials wherein healthy participants (N = 123) received placebo and 4 mg oral hydromorphone. Demographics, self-report ratings, observer ratings, physiological, and cold pressor measures were collected. Participants were categorized as being responsive or nonresponsive to the opioid dose tested and compared using mixed-models, Pearson product correlations, and paired t-tests. Findings: Participants were 49.6% female, mean 33.0 (SD=9.3) years old, and 44.7% Black/African American and 41.5% White, with 89.4% reporting no prior exposure to opioids. Within-subject sensitivity to opioids varied depending on the measure. One in five participants did not respond subjectively to the 4 mg hydromorphone dose based on their "Drug Effects" rating. Persons who were responsive showed more evidence of drug-dependent effects than did persons who were not responsive on ratings of Bad Effects (p= .03), feeling High (p= .01), Nausea (p= .03), pupil diameter (p< 0.01), and on the circular lights task (p< 0.001). Conclusions: This study provides initial evidence that the experience of opioids may be domain specific. Data suggest potentially clinically meaningful differences exist regarding opioid response patterns, evident following one dose among opioid inexperienced individuals.

The impact of opioid-stimulant co-use on tonic and cue-induced craving.

The twin opioid-stimulant epidemics have led to increased overdose deaths and present unique challenges for individuals entering treatment with opioid-stimulant polysubstance use. This study examined tonic and cue-induced craving as a primary outcome among persons in substance use treatment who reported primary substances of opioids, methamphetamine, or cocaine. The sample consisted of 1974 individuals in 55 residential substance-use treatment centers in the United States in 2021. Weekly surveys were delivered via a third-party outcomes tracking system, including measures of tonic and cue-induced craving. Initial comparisons on tonic and cue-induced craving were made among those who primarily used opioids, cocaine, or methamphetamine. Further, the effect of opioid/stimulant polysubstance use on tonic and cue-induced craving was evaluated using marginal effect regression models. Primary methamphetamine use was associated with decreased tonic craving compared to primary opioid use (ß = -5.63, p < 0.001) and primary cocaine use was also associate with decreased tonic craving compared to primary opioid use (ß = -6.14, p < 0.001). Primary cocaine use was also associated with lower cue-induced cravings compared to primary opioid use (ß = -0.53, p = 0.037). Opioid-methamphetamine polysubstance use was associated with higher tonic craving (ß = 3.81, p = <0.001) and higher cue-induced craving (ß = 1.55, p = 0.001); however, this was not the case for opioid-cocaine polysubstance use. The results of this study indicate that individuals who primarily use opioids and have secondary methamphetamine use experience higher cue-induced and tonic-induced craving, suggesting that these individuals may benefit from additional interventions that target craving and mitigate relapse risk and other negative sequelae.

Operational definition of precipitated opioid withdrawal.

Background: Opioid withdrawal can be expressed as both a spontaneous and precipitated syndrome. Although spontaneous withdrawal is well-characterized, there is no operational definition of precipitated opioid withdrawal. Methods: People (N = 106) with opioid use disorder maintained on morphine received 0.4 mg intramuscular naloxone and completed self-report (Subjective Opiate Withdrawal Scale, SOWS), visual analog scale (VAS), Bad Effects and Sick, and observer ratings (Clinical Opiate Withdrawal Scale, COWS). Time to peak severity and minimal clinically important difference (MCID) in withdrawal severity were calculated. Principal component analysis (PCA) during peak severity were conducted and analyzed with repeated measures analyses of variance (ANOVA). Results: Within 60 min, 89% of people reported peak SOWS ratings and 90% of people had peak COWS scores as made by raters. Self-reported signs of eyes tearing, yawning, nose running, perspiring, hot flashes, and observed changes in pupil diameter and rhinorrhea/lacrimation were uniquely associated with precipitated withdrawal. VAS ratings of Bad Effect and Sick served as statistically significant severity categories (0, 1-40, 41-80, and 81-100) for MCID evaluations and revealed participants' identification with an increase of 10 [SOWS; 15% maximum percent effect (MPE)] and 6 (COWS; 12% MPE) points as meaningful shifts in withdrawal severity indicative of precipitated withdrawal. Conclusion: Data suggested that a change of 10 (15% MPE) and 6 (12% MPE) points on the SOWS and COWS, respectively, that occurred within 60 min of antagonist administration was identified by participants as a clinically meaningful increase in symptom severity. These data provide a method to begin examining precipitated opioid withdrawal.

Within-subject, double-blind, randomized, placebo-controlled evaluation of combining the cannabinoid dronabinol and the opioid hydromorphone in adults with chronic pain.

The potential synergistic effects of combining cannabinoids and opioids for analgesia has received considerable attention. No studies to date have evaluated this combination in patients with chronic pain. The present study aimed to evaluate the combined analgesic and drug effects of oral opioid (hydromorphone) and delta-9-tetrahydrocannabinol (dronabinol), as well as their effects on physical and cognitive functioning, and human abuse potential (HAP) outcomes among individuals with knee osteoarthritis (KOA). This was a within-subject, double-blind, randomized, placebo-controlled study. Participants (N = 37; 65% women; mean age = 62) diagnosed with knee osteoarthritis of ≥3/10 average pain intensity were included. Participants received (1) placebo-placebo, (2) hydromorphone (4 mg)-placebo; (3) dronabinol (10 mg)-placebo, and (4) hydromorphone (4 mg)-dronabinol (10 mg). Clinical and experimentally-induced pain, physical and cognitive function, subjective drug effects, HAP, adverse events, and pharmacokinetics were evaluated. No significant analgesic effects were observed for clinical pain severity or physical functioning across all drug conditions. Little enhancement of hydromorphone analgesia by dronabinol was observed on evoked pain indices. While subjective drug effects and some HAP ratings were increased in the combined drug condition, these were not significantly increased over the dronabinol alone condition. No serious adverse events were reported; hydromorphone produced more mild adverse events than placebo, but hydromorphone + dronabinol produced more moderate adverse events than both placebo and hydromorphone alone. Only hydromorphone impaired cognitive performance. Consistent with laboratory studies on healthy adults, the present study shows minimal benefit of combining dronabinol (10 mg) and hydromorphone (4 mg) for analgesia and improving physical functioning in adults with KOA.

Prior Periods of Abstinence Among Adults With an Alcohol Use Disorder: A Qualitative Template Analysis.

Abstaining from substance use is a goal of many people with alcohol use disorder (AUD). Understanding patient perspectives of a period of abstinence may assist persons with AUD in achieving this goal. We accessed the electronic health records of adults with AUD entering an emergency department in Baltimore, Maryland, who received a brief peer support intervention for substance use. Data contained open-ended text entered by staff after a patient indicated ever having a sustained period of substance abstinence. Using qualitative template analysis methodology, we identified codes and themes from these open-ended responses from N = 153 adults with AUD. The sample was primarily male (n = 109, 71.2%) and White (n = 98, 64.1%) with an average age of 43.8 years (SD = 11.2). Themes identified included the abstinence length, abstinence reason, relapse, triggers, time of relapse, and treatment. The most common code for abstinence length was "between 1 and 5 years" (n = 55, 35.9%). Other abstinence length codes included "less than 1 year" and "more than 5 years." Relapse triggers included "family (non-death)," "death of a loved one," "social," "economic," and "treatment-related" reasons. Findings from this study could be used to inform strategies for peer support interventions to assist patients with substance abstinence.

A crowdsourcing survey study on the subjective effects of delta-8-tetrahydrocannabinol relative to delta-9-tetrahydrocannabinol and cannabidiol.

Delta-8-tetrahydrocannabinol (Δ8-THC) has emerged as a new retail cannabinoid product in the U.S. This study queried Δ8-THC users about product use characteristics and self-reported drug effects. Participants were recruited via a large online crowdsourcing platform (Amazon Mechanical Turk). Adults (N = 252) with past year Δ8-THC use (35% with at least weekly use) completed surveys and open-ended questions related to their reasons for using and past experiences with Δ8-THC-containing retail products. Participants with past year use of Δ9-tetrahydrocannabinol (Δ9-THC) and/or cannabidiol (CBD; 81% and 63%) compared the effects of Δ8-THC to those of Δ9-THC and/or CBD by rating drug effects on a visual analog scale from -50 to + 50 where negative scores indicated Δ8-THC effects are weaker, positive scores indicated Δ8-THC effects are stronger, and a score of 0 indicated equal effects to Δ9-THC or CBD. Compared to Δ9-THC, self-reported ratings for "Drug effect," "Bad effect," "Sick," "Anxiety," "Paranoia," "Irritability," "Restlessness," "Memory Problems," and "Trouble Performing Routine Tasks" were lower for Δ8-THC (d = -0.21 to -0.44). Compared to CBD, ratings for Δ8-THC effects were higher for "Drug effect," "Good effect," "High," "Relaxed," "Sleepy," "Hunger/Have the Munchies," "Memory Problems," "Trouble Performing Routine Tasks," and "Paranoia" (d = 0.27-1.02). Qualitative responses indicated that participants used Δ8-THC because it is perceived as (a) legal, (b) a substitute or similar to Δ9-THC, and/or (c) less intense than Δ9-THC. Δ8-THC is an understudied psychoactive component of cannabis that shares more characteristics with Δ9-THC than CBD and should be characterized further with human laboratory studies. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

A double-blind, randomized, placebo-controlled, pilot clinical trial examining buspirone as an adjunctive medication during buprenorphine-assisted supervised opioid withdrawal.

Successful management of opioid withdrawal improves long-term treatment outcomes and reduces opioid use-related morbidity and mortality. Mechanistically supported pharmacotherapeutic approaches are needed to effectively manage acute and protracted opioid withdrawal. Buspirone is a D2 antagonist and 5-HT1a agonist that may decrease opioid withdrawal. Individuals (n = 15) admitted to a residential treatment center for opioid use disorder (OUD) were enrolled into a double-blind randomized clinical trial to assess the efficacy and acceptability of buspirone (45 mg/day) as an adjunctive medication to buprenorphine-assisted, supervised opioid withdrawal. Participants completed daily questionnaires which consisted of the Subjective Opiate Withdrawal Scale (SOWS) and a consensus sleep diary, which assessed total sleep time, time to sleep onset, and sleep quality. Total SOWS scores, individual opioid withdrawal symptoms and sleep outcomes were assessed between treatment groups (Placebo and Buspirone) and over time in a repeated measures linear mixed model. Total SOWS scores significantly decreased across study phases for both groups but decreased to a greater extent among individuals assigned to buspirone during both the first and second week of stable buspirone. Greater decreases in withdrawal were observed during Week 2 of stable buspirone relative to Week 1 of stable buspirone. Participants also reported significant increases in sleep duration and significant decreases in latency to sleep onset. This study provides further support that buspirone can help mitigate opioid withdrawal during a supervised opioid taper. Buspirone may confer unique benefits during protracted withdrawal periods. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Can initial experiences with drugs predict future drug abuse risks?

Initial experiences with drugs may influence an individual's motivations for continued use. This study evaluated the relationship between subjective effects elicited by an individual's first use of alcohol or cannabis, Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) alcohol use disorder (AUD) or cannabis use disorder (CUD) severity, and behavioral economic demand for alcohol or cannabis. Self-reports of initial subjective effects associated with drugs were analyzed for N = 463 participants whose first substance use was either alcohol or cannabis. The likelihood that a particular subjective effect at the time of first use was associated with current AUD/CUD was assessed using ordinal logistic regression with subjective effects as predictors of DSM-5 severity. Behavioral economic demand was assessed using a hypothetical purchase task in which participants indicated their hypothetical consumption of alcohol or cannabis as a function of price. Significant associations were observed for initial subjective effects elicited by alcohol or cannabis and increased DSM-5 severity: (alcohol) relief (OR = 2.52 [95% CI 1.51-4.25], p = .0005) and (cannabis) energetic (OR = 2.31 [95% CI 3.27-55.5], p = .0004). The mean (± SEM) Pmax value for the alcohol subgroup endorsing relief ($96.22 ± $26.48) was significantly greater than the Pmax value for the alcohol subgroup not endorsing relief ($33.81 ± $12.93), t(237) = 2.276, p = .0237. These results suggest that the initial subjective effects associated with a given substance may predict the development and/or severity of substance misuse and substance use disorders (SUDs). These findings are consistent with anecdotal reports that persons with SUD feel energized by the use of substances whereas persons without SUD do not report experiencing such subjective effects upon first use. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Clinical Trial Design Challenges and Opportunities for Emerging Treatments for Opioid Use Disorder: A Review.

Importance: Novel treatments for opioid use disorder (OUD) are needed to address both the ongoing opioid epidemic and long-standing barriers to existing OUD treatments that target the endogenous µ-opioid receptor (MOR) system. The goal of this review is to highlight unique clinical trial design considerations for the study of emerging treatments for OUD that address targets beyond the MOR system. In November 2019, the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership with the US Food and Drug Administration sponsored a meeting to discuss the current evidence regarding potential treatments for OUD, including cannabinoids, psychedelics, sedative-hypnotics, and immunotherapeutics, such as vaccines. Observations: Consensus recommendations are presented regarding the most critical elements of trial design for the evaluation of novel OUD treatments, such as: (1) stage of treatment that will be targeted (eg, seeking treatment, early abstinence/detoxification, long-term recovery); (2) role of treatment (adjunctive with or independent of existing OUD treatments); (3) primary outcomes informed by patient preferences that assess opioid use (including changes in patterns of use), treatment retention, and/or global functioning and quality of life; and (4) adverse events, including the potential for opioid-related relapse or overdose, especially if the patient is not simultaneously taking maintenance MOR agonist or antagonist medications. Conclusions and Relevance: Applying the recommendations provided here as well as considering input from people with lived experience in the design phase will accelerate the development, translation, and uptake of effective and safe therapeutics for individuals struggling with OUD.

Relating individual differences in the reinforcing value of smoking and dependence severity to nicotine exposure levels in vulnerable populations.

Cigarette smoking is overrepresented in populations with psychiatric conditions and socioeconomic disadvantage. Greater understanding of the role of reinforcement and nicotine dependence in smoking among vulnerable populations may facilitate development of better targeted interventions to reduce smoking. Prior research demonstrated that individual differences in the reinforcing value of smoking and nicotine-dependence severity predicted total nicotine-exposure in vulnerable populations. The present study uses multivariate regression to address two aims: (1) Quantify the degree to which the reinforcing value of smoking, assessed using the Cigarette Purchase Task (CPT), and dependence severity assessed using the Fagerström Test of Nicotine Dependence and Brief Wisconsin Inventory of Smoking Dependence Motives (B-WISDM) each account for individual differences in cotinine-plus-3'-hydroxycotinine (COT+3HC) levels. (2) Explore whether there is overlap in the variance accounted for by the CTP, FTND, and B-WISDM. Participants were 628 adults with co-morbid psychiatric conditions or socioeconomic disadvantage who smoked daily. The CPT, FTND, and B-WISDM models accounted for 23.76%, 32.45%, and 29.61% of the variance in COT+3HC levels, respectively. Adding CPT to the FTND model failed to increase the variance accounted for and adding it to the B-WISDM model did so by only 1.2% demonstrating considerable overlap in the variance in nicotine exposure levels accounted for by these three instruments. These results provide new knowledge on the relationship between individual differences in the reinforcing value of smoking and nicotine-exposure levels and suggest differences in reinforcing value may underpin a considerable portion of the variance in nicotine exposure accounted for by dependence severity.

Suvorexant ameliorated sleep disturbance, opioid withdrawal, and craving during a buprenorphine taper.

Increased orexin/hypocretin signaling is implicated in opioid withdrawal, sleep disturbances, and drug-seeking behaviors. This study examined whether a dual-orexin receptor antagonist would improve sleep and withdrawal outcomes when compared with placebo during a buprenorphine/naloxone taper. Thirty-eight participants with opioid use disorder were recruited to a clinical research unit and maintained on 8/2 to 16/4 mg of buprenorphine/naloxone treatment for 3 days before being randomized to 20 mg of suvorexant (n = 14), 40 mg of suvorexant (n = 12), or placebo (n = 12); 26 individuals completed the study. After randomization, participants underwent a 4-day buprenorphine/naloxone taper and 4-day post-taper observation period. Total sleep time (TST) was collected nightly with a wireless electroencephalography device and wrist-worn actigraphy; opioid withdrawal symptoms were assessed via the Subjective Opiate Withdrawal Scale (SOWS); and abuse potential was assessed on a 0- to 100-point visual analog scale of "High" every morning. A priori outcomes included two-group (collapsing suvorexant doses versus placebo) and three-group comparisons of area-under-the-curve (AUC) scores for TST, SOWS, and High. In two-group comparisons, participants receiving suvorexant displayed increased TST during the buprenorphine/naloxone taper and decreased SOWS during the post-taper period. In three-group comparisons, participants receiving 20 mg of suvorexant versus placebo displayed increased AUC for TST during the buprenorphine/naloxone taper, but there was no difference in SOWS among groups. There was no evidence of abuse potential in two- or three-group analyses. The results suggest that suvorexant might be a promising treatment for sleep and opioid withdrawal in individuals undergoing a buprenorphine/naloxone taper.

Pharmacokinetic Profile of ∆9-Tetrahydrocannabinol, Cannabidiol and Metabolites in Blood following Vaporization and Oral Ingestion of Cannabidiol Products.

There is limited data on the comparative pharmacokinetics of cannabidiol (CBD) across oral and vaporized formulations. This within-subject, double-blind, double-dummy, placebo-controlled laboratory study analyzed the pharmacokinetic profile of CBD, ∆9-tetrahydrocannabinol (∆9-THC) and related metabolites in blood and oral fluid (OF) after participants (n = 18) administered 100 mg of CBD in each of the following formulations: (1) oral CBD, (2) vaporized CBD and (3) vaporized CBD-dominant cannabis containing 10.5% CBD and 0.39% ∆9-THC (3.7 mg); all participants also completed a placebo condition. Oral CBD was administered in three formulations: (1) encapsulated CBD, (2) CBD suspended in pharmacy-grade syrup and (3) Epidiolex, allowing for pharmacokinetic comparisons across oral formulations (n = 6 per condition). An optional fifth experimental condition was completed for six participants in which they fasted from all food for 12 h prior to oral ingestion of 100 mg of CBD. Blood and OF samples were collected immediately before and for 57-58 h after each drug administration. Immunoassay screening and LC-MS-MS confirmatory tests were performed, the limit of quantitation was 0.5 ng/mL for ∆9-THC and 1 ng/mL for CBD. The mean Cmax and range of CBD blood concentrations for each product were as follows: vaporized CBD-dominant cannabis, 171.1 ng/mL, 40.0-665.0 ng/mL, vaporized CBD 104.6 ng/mL, 19.0-312.0 ng/mL and oral CBD, 13.7 ng/mL, 0.0-50.0 ng/mL. Of the three oral formulations, Epidiolex produced the greatest peak concentration of CBD (20.5 ng/mL, 8.0-37.0 ng/mL) relative to the capsule (17.8 ng/mL, 2.0-50.0 ng/mL) and syrup (2.8 ng/mL, 0-7.0 ng/mL). ∆9-THC was detected in the blood of 12/18 participants after vaporized CBD-dominant cannabis use, but neither ∆9-THC nor its metabolite THC-COOH were detected in the blood of any participants after vaporized or oral CBD-only administration. These data demonstrate that different oral and vaporized formulations produce substantial variability in the pharmacokinetics of CBD and that CBD alone is unlikely to convert to ∆9-THC or produce positive drug tests for ∆9-THC or its metabolite.

Evaluation of Stigma Related to Perceived Risk for Coronavirus-19 Transmission Relative to the Other Stigmatized Conditions Opioid Use and Depression.

Background: The coronavirus-19 (COVID-19) pandemic was initially characterized by misinformation and fear related to transmission that has been previously shown to produce stigma toward persons perceived to be at risk for transmission. This study evaluated perceptions toward scenarios with variable levels of perceived risk for COVID-19 acquisition, and compared stigma to COVID-19 to depression and opioid use disorder. Methods: Respondents (N = 280) from the United States completed a web-based survey 6 months after pandemic declaration. Questions included demographics and COVID-19 misconceptions, expected response to hypothetical scenarios with variable risk for COVID-19, and the Attribution Questionnaire-9 for COVID-19, depression, and opioid use disorder. Results: Participants had several COVID-19 misconceptions, including that opioids increased immunity (63.6%), persons were more susceptible based upon racial/ethnic background (63.2%), and underlying health conditions did not influence risk (58.9%). Respondents were highly likely (64/100) to assume someone coughing had COVID-19 and the majority (93.5%) recommended quarantining persons with recent travel. However, the majority of respondents (>70% in all cases) also believed they would not change their COVID-19-related behavior when interacting with persons of different racial, ethnic, and age backgrounds. Finally, persons with COVID-19 engendered greater pity, less fear, less blame, less anger, and more willingness to help from respondents relative to persons with opioid use disorder. Conclusion: Stigma ratings toward persons perceived at risk of transmitting COVID-19, collected soon after the onset of the pandemic, showed less evidence of stigma relative to persons with opioid use disorder despite pronounced misconceptions regarding COVID-19 risk. Data provide a foundation for additional research in this area.

Treatment Disruption and Childcare Responsibility as Risk Factors for Drug and Alcohol Use in Persons in Treatment for Substance Use Disorders During the COVID-19 Crisis.

OBJECTIVES: The novel 2019 coronavirus (COVID-19) crisis has caused considerable upheaval in the U.S. healthcare system. The current study examined patient-reported experiences in substance use disorder (SUD) treatment during the early stages of the COVID-19 crisis. METHODS: Participants in SUD treatment were recruited via online crowdsourcing from April 14, 2020 to May 26, 2020, during the early stages of the COVID-19 crisis. Participants reported disruptions in SUD treatment, stress and anxiety caused by these disruptions on a 0-100 point visual analogue scale (VAS), stress associated with childcare responsibilities on a 0-100 VAS, current stress on the Perceived Stress Scale (PSS), anxiety symptoms on the Beck Anxiety Inventory (BAI), sleep disturbances on the Insomnia Severity Index (ISI), and whether they used drugs or alcohol during the COVID-19 crisis. RESULTS: Participants (N = 240) endorsed that at least 1 SUD treatment was switched to telemedicine (63.7%), had some appointments cancelled (37.5%), or was discontinued due to COVID-19 (29.6%). Participants who did versus did not endorse drug/alcohol use reported difficulty obtaining medications to treat their SUD (OR = 2.47, 95% CI, 1.17-5.22, χ2 = 5.98, P = .016), greater scores on VAS treatment-related stress (F1,197 = 5.70, P = .018) and anxiety (F1,197 = 4.07, P = .045), greater VAS stress related to childcare (F1,107 = 10.24, P = .002), and greater scores on the PSS (F1,235 = 19.27, P < .001), BAI (F1,235 = 28.59, P < .001), and ISI (F1,235 = 14.41, P < .001). CONCLUSIONS: Providers and public health officials should work to improve continuity and quality of care during the COVID-19 crisis, with special attention on addressing childcare difficulties and providing remote methods to improve stress, anxiety, and sleep for persons in SUD treatment.