Randomized controlled trial of zolpidem as a pharmacotherapy for cannabis use disorder.

BACKGROUND: Sleep disturbance is commonly reported among individuals meeting criteria for cannabis use disorder (CUD), and people who use cannabis frequently report sleep disturbance as a contributor to failed quit attempts. The purpose of this study was to measure sleep in individuals enrolled in treatment for CUD, and to determine whether use of hypnotic medication during treatment increased abstinence rates. METHOD: The study enrolled 127 adults seeking treatment for CUD in a 12-week clinical trial and randomized to receive extended-release zolpidem (zolpidem-XR) or placebo. All participants received computerized behavioral therapy and abstinence-based contingency management. The study conducted in-home ambulatory polysomnography (PSG) assessments at baseline and during treatment to objectively measure sleep. Self-report measures of recent sleep, Insomnia Severity Index (ISI), and drug use (Timeline Follow-Back) were collected at each study visit, and the study confirmed self-reported abstinence via quantitative urine drug testing. RESULT: Participants randomized to placebo, but not zolpidem-XR exhibited significant sleep disturbance during week 1 of treatment. Sleep disturbance emerged in the zolpidem-XR group after study medication was stopped at the end of treatment. Though participants assigned to the zolpidem-XR condition had qualitatively greater rates of abstinence compared with placebo (27 % versus 15 % negative at end of treatment), the difference was not statistically significant. Treatment retention was poor (about 50 % drop out in both groups) and medication adherence was a challenge without the use of contingent incentives. CONCLUSION: Results from this randomized controlled trial suggest that zolpidem-XR can attenuate abstinence-induced sleep disturbance early in treatment for CUD, but that sleep problems are likely to emerge after the medication is stopped. Further research should identify alternative pharmacotherapies and behavioral treatments for CUD and elucidate the role of sleep disturbance in the development and maintenance of CUD.

National Institute on Drug Abuse (NIDA) research priorities to support the development of incentive-based treatments for substance use disorders.

The purpose of this commentary is to highlight current research priorities of National Institute on Drug Abuse (NIDA) Division of Therapeutics and Medical Consequences (DTMC) regarding the development and testing of incentive-based interventions for the treatment of substance use disorders (SUDs). This manuscript summarizes the NIH Stage Model for behavioral intervention development, briefly reviews existing research on incentive-based treatments for SUDs that falls within the scope of DTMC at NIDA and highlights the development of digital therapeutics-based incentive interventions as an exemplar and high priority area. We briefly review how digital therapeutics approaches may address some common limitations to dissemination of incentive-based interventions and highlight opportunities for integrating incentive-based approaches into pharmacotherapy efficacy trials. Finally, we mention several related funding opportunities for researchers interested in developing incentive-based approaches for SUD treatment. The overall goal of this commentary is to inform the research community of current NIDA priority areas for intervention development and funding.

Medication Adherence in Tobacco Cessation Clinical Trials.

Adherence is a critical mediator of treatment outcome across health conditions and low rates of adherence undermine success in smoking cessation treatment. This narrative review provides an overview of different techniques that can be used to measure adherence to smoking cessation treatments and outlines strategies to address treatment adherence. Techniques to measure adherence include conducting pill counts, collecting self-reports of adherence, directly observed therapy, biochemical verification methods, and electronic data collection via medication events monitoring systems. Techniques examined for increasing tobacco cessation treatment adherence include counseling, automated adherence calls, feedback from electronic monitors, contingency management and directly observed therapy. Adherence monitoring and optimization should be a standard component of smoking cessation treatment research.

The Relationship Between Circulating Endogenous Cannabinoids and the Effects of Smoked Cannabis.

Background: The endogenous cannabinoid system (ECS), including the endocannabinoids (eCBs), anandamide (AEA), and 2-arachidonoylglycerol (2-AG), plays an integral role in psychophysiological functions. Although frequent cannabis use is associated with adaptations in the ECS, the impact of acute smoked cannabis administration on circulating eCBs, and the relationship between cannabis effects and circulating eCBs are poorly understood. Methods: This study measured the plasma levels of AEA, 2-AG, and Δ-9-tetrahydrocannabinol (THC), subjective drug-effects ratings, and cardiovascular measures at baseline and 15-180 min after cannabis users (n=26) smoked 70% of a cannabis cigarette (5.6% THC). Results: Cannabis administration increased the ratings of intoxication, heart rate, and plasma THC levels relative to baseline. Although cannabis administration did not affect eCB levels relative to baseline, there was a significant positive correlation between baseline AEA levels and peak ratings of "High" and "Good Drug Effect." Further, baseline 2-AG levels negatively correlated with frequency of cannabis use (mean days/week) and with baseline THC metabolite levels. Conclusions: In a subset of heavy cannabis smokers: (1) more frequent cannabis use was associated with lower baseline 2-AG, and (2) those with lower AEA got less intoxicated after smoking cannabis. These findings contribute to a sparse literature on the interaction between endo- and phyto-cannabinoids. Future studies in participants with varied cannabis use patterns are needed to clarify the association between circulating eCBs and the abuse-related effects of cannabis, and to test whether baseline eCBs predict the intoxicating effects of cannabis and are a potential biomarker of cannabis tolerance.

Impact of cyclooxygenase-2 inhibition on cannabis withdrawal and circulating endocannabinoids in daily cannabis smokers.

Attenuating enzymatic degradation of endocannabinoids (eCBs) by fatty acid amide hydrolase (FAAH) reduces cannabis withdrawal symptoms in preclinical and clinical studies. In mice, blocking cyclooxygenase-2 (COX-2) activity increases central eCB levels by inhibiting fatty acid degradation. This placebo-controlled study examined the effects of the FDA-approved COX-2 selective inhibitor, celecoxib, on cannabis withdrawal, 'relapse', and circulating eCBs in a human laboratory model of cannabis use disorder. Daily, nontreatment-seeking cannabis smokers (12M, 3F) completed a crossover study comprising two 11-day study phases (separated by >14 days for medication clearance). In each phase, the effects of daily BID placebo (0 mg) or celecoxib (200 mg) on cannabis (5.3% THC) intoxication, withdrawal symptoms (4 days of inactive cannabis self-administration) and 'relapse' (3 days of active cannabis self-administration following abstinence) were assessed. Outcome measures included mood, cannabis self-administration, sleep, food intake, cognitive performance, tobacco cigarette use and circulating eCBs and related lipids. Under placebo maintenance, cannabis abstinence produced characteristic withdrawal symptoms (negative mood, anorexia and dreaming) relative to cannabis administration and was associated with increased OEA (a substrate of FAAH) and oleic acid (metabolite of OEA), with no change in eCB levels. Compared to placebo, celecoxib improved subjective (but not objective) measures of sleep and did not affect mood or plasma levels of eCBs or associated lipids and increased cannabis craving. The overall absence of effects on cannabis withdrawal symptoms, self-administration or circulating eCBs relative to placebo, combined with an increase in cannabis craving, suggests celecoxib does not show promise as a potential pharmacotherapy for CUD.

Methamphetamine administration dose effects on sexual desire, sexual decision making, and delay discounting.

Correlational evidence has linked methamphetamine use and HIV sexual risk behavior, but the direct effects of methamphetamine on sexual desire and sexual decision making in humans have not been tested. This study was designed to test the effect of methamphetamine administration on sexual desire and hypothetical condom-use decisions as measured by the Sexual Delay Discounting Task. Recreational stimulant users (n = 19) participated in this within-subject, placebo-controlled study comparing the effects of 0 mg, 20 mg, and 40 mg of oral methamphetamine. Compared to placebo, methamphetamine caused dose-related and time-related increases in a single-item sexual desire rating and some standard stimulant abuse liability ratings, as well as dose-related increases in the Sexual Arousal and Desire Inventory (SADI; a multidimensional scale capturing positive and negative aspects of desire/arousal). However, methamphetamine caused no significant mean differences in likelihood of condom use within the Sexual Delay Discounting Task or the Monetary Discounting Task. SADI scores were negatively correlated with change from placebo in condom use likelihood in the Sexual Delay Discounting Task for some partner conditions (i.e., decreased reported likelihood of condom use in participants who experienced increased desire/arousal and vice versa). These mixed results may be consistent with methamphetamine's role as both a treatment for attention-deficit/hyperactivity disorder and as a drug of abuse associated with increased delay discounting, and they suggest that methamphetamine's effects on discounting may be modulated by the reinforcing properties of what is being discounted. Delay discounting may be an understudied element of risky sexual decision making, particularly among individuals who use methamphetamine. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

A placebo-controlled investigation of the analgesic effects, abuse liability, safety and tolerability of a range of oral cannabidiol doses in healthy humans.

AIMS: Preclinical studies demonstrate that cannabidiol (CBD) elicits an antinociceptive response in animal models of neuropathic pain; in humans, limited data are available to support such analgesic effects. Few studies have examined CBD's analgesic effects when administered without other compounds, and little is known regarding dose-dependent effects in noncannabis users. METHODS: This double-blind, placebo-controlled, within-subject outpatient clinical laboratory study sought to determine the analgesic effects, abuse liability, safety and tolerability of acute CBD (0, 200, 400 and 800 mg orally) in healthy noncannabis-using volunteers (n = 17; 8 men, 9 women). Outcomes included experimental pain threshold and pain tolerance using the cold pressor test (CPT), subjective ratings of CPT painfulness and bothersomeness, subjective ratings of abuse liability and mood, and cardiovascular measures, which were assessed at baseline and several time points after drug administration. Data analyses included repeated measures analysis of variance (ANOVA) with planned comparisons. RESULTS: CBD failed to consistently affect pain threshold and tolerance in the CPT relative to placebo. All doses of CBD increased ratings of painfulness compared to placebo (P < .01). Further, CBD had dose-dependent, modest effects on mood and subjective drug effects associated with abuse liability. Oral CBD was safe and well tolerated, producing small decreases in blood pressure (P < .01). CONCLUSION: CBD did not elicit consistent dose-dependent analgesia and in fact increased pain on some measures. Future studies exploring CBD-induced pain relief should consider using a more extensive pain assessment paradigm in different participant populations.

Impact of smoked cannabis on tobacco cigarette smoking intensity and subjective effects: A placebo-controlled, double-blind, within-subjects human laboratory study.

Co-users of cannabis and tobacco frequently use cannabis, then tobacco cigarettes, in a sequential pattern within an occasion, that is, they "chase" smoked cannabis with a tobacco cigarette. The objective of this placebo-controlled, double-blind, within-subjects human laboratory study was to gather preliminary data on how smoking active versus placebo cannabis impacts tobacco cigarette smoking behavior, craving, and subjective effects. Adult daily cannabis and tobacco co-users (N = 9) were randomly assigned to two experimental visit orders (i.e., active cannabis (5.2% THC) first visit and placebo cannabis second visit, or vice versa). Participants smoked one cannabis cigarette, and approximately 30 min later were given a 5-min ad libitum period to smoke one of their own brand of tobacco cigarette. As expected, boost in plasma THC levels and cannabis-related subjective effects differed between active and placebo cannabis conditions. Tobacco cigarette puff topography measures and tobacco craving did not differ between cannabis conditions, but there appeared to be between-participants heterogeneity in cumulative total puff volume. After smoking active versus placebo cannabis, the changes in subjective effects of tobacco smoking after adjusting for pretobacco smoking levels were not significant. Results do not support the notion that immediate effects of smoked cannabis change the behavior of tobacco smoking. The strong overlap between cannabis and tobacco smoking may not be explained by primarily pharmacological factors, but may be driven by more nuanced and complex mechanisms involving pharmacological processes as well as learning factors. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Sexual discounting: A systematic review of discounting processes and sexual behavior.

Behavioral processes underlying sexual behavior are important for understanding normal human functioning and risk behavior leading to sexually transmitted infections (STIs). This systematic review examines delay and probability discounting in human sexual behavior through synthesis of 50 peer-reviewed, original research articles. Sixteen studies focusing exclusively on monetary delay discounting found small effect size positive correlations with sexual risk behaviors. Eleven studies examined delay or probability discounting of sexual behavior itself using tasks that varied duration, frequency, or quality of sex to determine value. Results show delay and uncertainty of sex causes systematic decreases in value. These studies also show consistent medium effect size relationships between sexual discounting measures and sexual health and substance use, supporting utility above and beyond monetary discounting. Twenty-three studies have modeled clinically relevant decision-making, examining effects of delay until condom availability and STI contraction probability on condom use. Observational and experimental designs found condom-use discounting is elevated in high-risk substance use populations, is sensitive to context (e.g., partner desirability), and is more robustly related to sexual risk compared with monetary discounting or condom use decisions when no delay/uncertainty was involved. Administering cocaine, alcohol, and, for some participants, methamphetamine increased condom-use discounting with minimal effect on monetary discounting or condom use when no delay/uncertainty was involved. Reviewed studies robustly support that sexual behavior is highly dependent on delay and probability discounting, and that these processes strongly contribute to sexual risk. Future research should exploit these systematic relationships to design behavioral and pharmacological approaches to decrease sexual risk behavior. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Pharmacokinetics of Cannabis Brownies: A Controlled Examination of Δ9-Tetrahydrocannabinol and Metabolites in Blood and Oral Fluid of Healthy Adult Males and Females.

Oral cannabis products (a.k.a. "edibles") have increased in popularity in recent years. Most prior controlled pharmacokinetic evaluations of cannabis have focused on smoked cannabis and included males who were frequent cannabis users. In this study, 17 healthy adults (8 females), with no cannabis use in at least the past 2 months, completed 4 double-blind outpatient sessions where they consumed cannabis brownies containing Δ9-tetrahydrocannabinol (THC) doses of 0, 10, 25 or 50 mg. Whole blood and oral fluid specimens were collected at baseline and for 8 h post-brownie ingestion. Enzyme-linked immunosorbent assay (ELISA) and liquid chromatography-tandem mass spectrometry (LC-MS-MS) were used to measure THC and relevant metabolites. In whole blood, concentrations of THC and 11-hydroxy-THC (11-OH-THC) peaked 1.5-2 h after brownie consumption, decreased steadily thereafter, and typically returned to baseline within 8 h. Blood concentrations for 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THCCOOH) and THCCOOH-glucuronide were higher than THC and 11-OH-THC and these metabolites were often still detected 8 h post-brownie consumption. Women displayed higher peak concentrations for THC and all metabolites in whole blood compared to men, at least partially owing to their lower body weight/body mass index. Detection of THC in oral fluid was immediate and appeared to reflect the degree of cannabis deposition in the oral cavity, not levels of THC circulating in the blood. THC concentrations were substantially higher in oral fluid than in blood; the opposite trend was observed for THCCOOH. Agreement between ELISA and LC-MS-MS results was high (i.e., over 90%) for blood THCCOOH and oral fluid THC but comparatively low for oral fluid THCCOOH (i.e., 67%). Following oral consumption of cannabis, THC was detected in blood much later, and at far lower peak concentrations, compared to what has been observed with inhaled cannabis. These results are important given the widespread use of toxicological testing to detect recent use of cannabis and/or to identify cannabis intoxication.

Pharmacodynamic dose effects of oral cannabis ingestion in healthy adults who infrequently use cannabis.

BACKGROUND: Prior controlled cannabis research has mostly focused on smoked cannabis and predominantly included frequent cannabis users. Oral cannabis products ("edibles") make up a large and growing segment of the retail cannabis market. This study sought to characterize the pharmacodynamic effects of oral cannabis among infrequent cannabis users. METHODS: Seventeen healthy adults who had not used cannabis for at least 60 days completed four experimental sessions in which they consumed a cannabis-infused brownie that contained 0, 10, 25, or 50 mg THC. Subjective effects, vital signs, cognitive/psychomotor performance, and blood THC concentrations were assessed before and for 8 h after dosing. RESULTS: Relative to placebo, the 10 mg THC dose produced discriminable subjective drug effects and elevated heart rate but did not alter cognitive/psychomotor performance. The 25 and 50 mg THC doses elicited pronounced subjective effects and markedly impaired cognitive and psychomotor functioning compared with placebo. For all active doses, pharmacodynamic effects did not manifest until 30-60 min after ingestion, and peak effects occurred 1.5-3 h post-administration. Blood THC levels were significantly correlated with some pharmacodynamic drug effects, but were substantially lower than what is typically observed after cannabis inhalation. CONCLUSION: Ingestion of oral cannabis dose-dependently altered subjective drug effects and impaired cognitive performance. Unlike inhaled forms of cannabis for which acute effects occur almost immediately, effects of oral cannabis were considerably delayed. In an era of legalization, education about the time course of drug effects for cannabis edibles is needed to facilitate dose titration and reduce acute overdose incidents.

Demographic and sexual risk predictors of delay discounting of condom-protected sex.

Objective: Sexual delay discounting describes the decreased likelihood of condom-protected sex if a condom is not immediately available, which can be quantitatively summarised using the Sexual Delay Discounting Task (SDDT). The present studies determined the extent to which condom use likelihood as assessed by the SDDT is associated with self-reported sexual risk behaviours and demographics in two online samples of adults. Design: Study 1 (n = 767) assessed demographics, sexual risk behaviour, and delay discounting, and examined relations between these variables using correlation and regression. Study 2 (n = 267) examined whether real-world instances of unprotected sex because a condom was not immediately available predicted greater sexual discounting. Main outcome measures: Sexual delay discounting, condom use. Results: Both studies observed significant positive relations between sexual delay discounting and self-reported sexual risk behaviours, and found that males tended to show greater sexual discounting. In Study 2, 46% of the sample self-reported having unprotected sex because a condom was not immediately available, and these individuals showed significantly greater sexual delay discounting. Conclusion: These results extend prior findings by demonstrating that delay is a critical variable underlying real-life sexual risk behaviour among non-clinical samples. The SDDT is an ecologically valid measure of these processes.

Blunt use and menthol cigarette smoking: An examination of adult marijuana users.

INTRODUCTION: Use of menthol cigarettes remains highly prevalent among African American smokers and has increased among White and Hispanic/Latino smokers. Research is needed to examine if behavioral factors, such as marijuana use, are differentially associated with menthol cigarette use among racially/ethnically diverse samples of marijuana users. METHODS: Using data from the 2017 National Survey on Drug Use and Health, this study examined the association between past month marijuana (blunt versus non-blunt) and cigarette (non-menthol cigarette versus menthol cigarette versus no cigarette) use, as well as racial/ethnic differences in this relationship. RESULTS: Among all marijuana users (N = 5,137), 34.1% smoked blunts, 28.7% smoked non-menthol cigarettes and 18.0% smoked menthol cigarettes, with the highest rates of blunt (63.8%) and menthol cigarette (38.9%) use found among African American adults. Multinomial logistic regression analyses revealed a significant association between blunt use and non-menthol cigarette use (versus non-use) and menthol cigarette use (versus non-menthol cigarette and no cigarette use) among the full sample. When stratified by race/ethnicity, this finding was consistent for non-Hispanic White (n = 3,492) and partially consistent for Hispanic/Latino (n = 839) adults. However, among African American adults (n = 806), blunt use was not significantly associated with non-menthol cigarette use or menthol cigarette use. DISCUSSION: Blunt use is associated with increased odds of non-menthol and menthol cigarette use, but only among Hispanic/Latino and White adults. Examining racial/ethnic differences in the association between marijuana and tobacco use is important to understanding disparities and informing prevention and treatment interventions and drug policies.

Varenicline and nabilone in tobacco and cannabis co-users: effects on tobacco abstinence, withdrawal and a laboratory model of cannabis relapse.

Tobacco and cannabis co-users (T+CUs) have poor cannabis cessation outcomes, but the mechanisms underlying this are not well understood. This laboratory study examined the effects of (1) the partial nicotinic agonist, varenicline, on tobacco cessation among T+CUs, and (2) varenicline, alone, and when combined with the cannabinoid agonist nabilone, on cannabis withdrawal and a laboratory model of cannabis relapse. Non-treatment-seeking T+CUs were randomized to active-varenicline or placebo-varenicline, and completed a 15-day outpatient phase; varenicline was titrated to 1 mg BID during days 1-8, and participants were instructed to abstain from tobacco during days 9-15. Participants then moved inpatient for 16 days, where they continued their outpatient medication and tobacco abstinence. Inpatient testing included two, 8-day medication periods, where active-nabilone and placebo-nabilone were administered in counterbalanced order, and measures of acute cannabis effects (days 1-2), withdrawal (days 4-5) and 'relapse' (days 6-8) were collected. Participants in the active-varenicline group were more likely to achieve cotinine-verified tobacco abstinence during the outpatient period versus placebo-varenicline group (46 percent versus 24 percent, respectively), and also reported less mood disturbance and cigarette craving while inpatient. Active-nabilone attenuated cannabis withdrawal in both groups but did not affect cannabis relapse. Regression analyses revealed that two tobacco-related variables, i.e. age of first cigarette use, and cigarette craving while inpatient, were independent predictors of cannabis relapse outcomes. Thus, varenicline holds promise in this population, as a tool to examine the effects of tobacco abstinence on cannabis use outcomes, and as a component of smoking cessation treatments targeting T+CUs.

Sweet flowers are slow, and weeds make haste: leveraging methodology from research on tobacco, alcohol, and opioid analgesics to make rapid and policy-relevant advances in cannabis science.

The legalization of medical and recreational cannabis use has occurred ahead of science. The current evidence base has poor utility for determining if cannabis products can meet the standards of safety, efficacy, and quality intrinsic to modern medicine, and for informing regulation of cannabis as a legal intoxicant. Individual jurisdictions that pass cannabis reforms may not have adequate resources to support the level of new scientific research needed to inform regulatory actions; this could make it difficult to keep a rapidly growing multi-billion-dollar cannabis industry in check. Further, the present lack of evidence-based regulatory oversight for cannabis parallels the climates that gave rise to the tobacco and prescription opioid epidemics, suggesting that continued omission may result in negative public health consequences. However, translating a methodological framework developed through research on these compounds may promote rapid advances in cannabis science germane to regulatory knowledge gaps. The present review highlights specific advancements in these areas, as well as in alcohol regulation, that are prime for informing policy-relevant cannabis science, and also offers some recommendations for evidence-based regulatory policy. Resulting progress may directly inform both regulation of cannabis in both medical and licit recreational drug frameworks, and new cannabis-related public health initiatives.

Pharmacokinetic Characterization of 11-nor-9-carboxy-Δ9-tetrahydrocannabinol in Urine Following Acute Oral Cannabis Ingestion in Healthy Adults.

Understanding the urine excretion profile for Δ9-tetrahydrocannabinol (THC) metabolites is important for accurate detection and interpretation of toxicological testing for cannabis use. Prior literature has primarily evaluated the urinary pharmacokinetics of the non-psychoactive THC metabolite 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THCCOOH) following smoked cannabis administration. The present study examined the urine THCCOOH excretion profile following oral cannabis administration in 18 healthy adults. Following ingestion of a cannabis-containing brownie with 10, 25 or 50 mg of THC (N = 6 per dose), urine specimens were collected on a closed residential research unit for 6 days, followed by three outpatient visits on Days 7-9. Average maximum concentrations (Cmax) of THCCOOH were 107, 335 and 713 ng/mL, and average times to maximum concentration (Tmax) were 8, 6 and 9 h for the 10, 25 and 50 mg THC doses, respectively. Detection windows to first positive and last positive varied as a function of dose; higher doses had shorter time to first positive and longer time to last positive. Considerable inter-subject variability was observed on study outcomes. Gas chromatography/mass spectrometry (GC/MS; 15 ng/mL cutoff) was used as the criterion to assess sensitivity, specificity and agreement for THCCOOH qualitative immunoassay tests using 20, 50 and 100 ng/mL cutoffs. The 50 ng/mL cutoff displayed good sensitivity (92.5%), specificity (92.4%) and overall agreement (92.4%), whereas the 20 ng/mL cutoff demonstrated poor specificity (58.4%), and the 100 ng/mL cutoff exhibited reduced sensitivity (70.9%). Ingestion of cannabis brownies containing the 10 and 25 mg THC doses yielded THCCOOH concentrations that differed in magnitude and time course from those previously reported for the smoked route of administration of comparable doses.

Sleep continuity, architecture and quality among treatment-seeking cannabis users: An in-home, unattended polysomnographic study.

The objective of the study was to describe self-report and objectively measured sleep characteristics of adult treatment-seeking cannabis users. Study participants (n = 87) were adults who were screened for a 12-week outpatient cannabis treatment research program in Baltimore, MD. Participants completed objective and self-report measures of sleep quality. Data were analyzed for the sample overall and after stratifying by sex (54 men, 33 women). Participants were primarily urban, socioeconomically disadvantaged African Americans. Participants were frequent, heavy cannabis users; among a subset of participants assessed, 76.7% used cannabis on the day/night of the assessment. Participants had low rates of other substance abuse and of psychiatric comorbidities. Polysomnography indicated 19.5% of participants received the recommended 7 to 9 hr of sleep, with women averaging more sleep than men. One third (31.0%) had sleep latencies >30 min, one half spent >30 min awake after sleep onset, and more than one half of the sample (55.2%) had sleep efficiency scores of <85%. Most participants met criteria for subthreshold (36.8%) or clinical insomnia (25.3%) on the Insomnia Severity Index, 77.0% had scores of >5 on the Pittsburgh Sleep Quality Index. Most had average scores on the Dysfunctional Beliefs and Attitudes About Sleep (DBAS) questionnaire (M = 51.1, SD = 18.8) that were higher than average among clinical insomnia patients. Women had higher DBAS scores than men. Most participants exhibited characteristics of disordered sleep, and sex differences were observed on polysomnography and self-report measures. Findings extend prior research concerning the association between cannabis use and disordered sleep. Data presented in this article come from Clinical Trial NCT01685073. (PsycINFO Database Record

Morning administration of oral methamphetamine dose-dependently disrupts nighttime sleep in recreational stimulant users.

INTRODUCTION: Use of amphetamine-type stimulants (e.g., methamphetamine) is associated with acute sleep disruptions. No prior reports have characterized the acute effects of methamphetamine on sleep using polysomnography, the gold standard for objective sleep monitoring. METHODS: Recreational stimulant users (n=19) completed a baseline assessment, which included questionnaires assessing demographic and substance use characteristics, and the Pittsburgh Sleep Quality Index (PSQI), which assesses sleep quality over the past month. Participants were administered 0mg (placebo), 20mg, or 40mg oral methamphetamine at 08:15h on study days, using a double-blind, randomized, within-subjects design. Sleep was monitored using polysomnography from 22:20 that evening until 06:15 the following morning. RESULTS: PSQI scores indicated more than half of participants reported poor sleep quality at baseline. Methamphetamine dose-dependently increased sleep latency, and decreased total sleep time, sleep efficiency, time in NREM 2 sleep, number of REM periods, and total time in REM sleep. Sleep under placebo conditions was consistent with what would be expected from healthy adults. CONCLUSIONS: Morning oral administration of methamphetamine produces robust disruptions in nighttime sleep. Future research should examine relations between stimulant use and sleep disruption in naturalistic settings, with regard to both stimulant abuse and licit prescription use.

Pharmacokinetic Profile of Oral Cannabis in Humans: Blood and Oral Fluid Disposition and Relation to Pharmacodynamic Outcomes.

Most research on cannabis pharmacokinetics has evaluated inhaled cannabis, but oral ("edible") preparations comprise an increasing segment of the cannabis market. To assess oral cannabis pharmacokinetics and pharmacodynamics, healthy adults (N = 6 per dose) were administered cannabis brownies containing 10, 25 or 50 mg 9-tetrahydrocannabinol (THC). Whole blood and oral fluid specimens were obtained at baseline and then for 9 days post-exposure; 6 days in a residential research setting and 3 days as outpatients. Measures of subjective, cardiovascular and performance effects were obtained at baseline and for 8 h post-ingestion. The mean Cmax for THC in whole blood was 1, 3.5 and 3.3 ng/mL for the 10, 25 and 50 mg THC doses, respectively. The mean maximum concentration (Cmax) and mean time to maximum concentration (Tmax) of 11-OH-THC in whole blood were similar to THC. Cmax blood concentrations of THCCOOH were generally higher than THC and had longer Tmax values. The mean Tmax for THC in oral fluid occurred immediately following oral dose administration, and appear to reflect local topical residue rather than systemic bioavailbility. Mean Cmax oral fluid concentrations of THCCOOH were lower than THC, erratic over time and mean Tmax occurred at longer times than THC. The window of THC detection ranged from 0 to 22 h for whole blood (limit of quantitation (LOQ) = 0.5 ng/mL) and 1.9 to 22 h for oral fluid (LOQ = 1.0 ng/mL). Subjective drug and cognitive performance effects were generally dose dependent, peaked at 1.5-3 h post-administration, and lasted 6-8 h. Whole blood cannabinoid concentrations were significantly correlated with subjective drug effects. Correlations between blood cannabinoids and cognitive performance measures, and between oral fluid and all pharmacodynamic outcomes were either non-significant or not orderly by dose. Quantitative levels of cannabinoids in whole blood and oral fluid were low compared with levels observed following inhalation of cannabis. The route of administration is important for interpretation of cannabinoid toxicology.