Participant Fraud in Virtual Qualitative Substance Use Research: Recommendations and Considerations for Detection and Prevention Based on a Case Study.

Background: The COVID-19 pandemic has accelerated and amplified the use of virtual research methods. While online research has several advantages, it also provides greater opportunity for individuals to misrepresent their identities to fraudulently participate in research for financial gain. Participant deception and fraud have become a growing concern for virtual research. Reports of deception and preventative strategies have been discussed within online quantitative research, particularly survey studies. Though, there is a dearth of literature surrounding these issues pertaining to qualitative studies, particularly within substance use research. Results: In this commentary, we detail an unforeseen case study of several individuals who appeared to deliberately misrepresent their identities and information during participation in a virtual synchronous qualitative substance use study. Through our experiences, we offer strategies to detect and prevent participant deception and fraud, as well as challenges to consider when implementing these approaches. Conclusions: Without general awareness and protective measures, the integrity of virtual research methods remains vulnerable to inaccuracy. As online research continues to expand, it is essential to proactively design innovative solutions to safeguard future studies against increasingly sophisticated deception and fraud.

Impacts of recreational cannabis legalization on use and harms: A narrative review of sex/gender differences.

Legalization of cannabis use for non-medical (recreational) purposes is changing the global cannabis landscape. As attitudes toward cannabis use become more positive and prevalence of use increases in complex ways, concerns emerge about the potential for increased cannabis-attributable harms. Understanding the who, why, and when of this likely increase in cannabis-attributable harms is thus an important public health priority. Both sex and gender contribute to variability in the use, effects, and harms of cannabis and thus sex/gender considerations are important when evaluating the impacts of cannabis legalization. The goal of this narrative review is to broadly discuss sex/gender differences in attitudes toward and prevalence of cannabis use, whether there are sex/gender differences in the impacts of cannabis legalization, and why these sex/gender differences might exist. One of our strongest conclusions is that men have always been more likely to use cannabis than women, yet the sex/gender gap in prevalence of cannabis use has narrowed over time, and this might be partly due to cannabis legalization. The existing evidence suggests that there have also been sex/gender differences in the impacts of legalization on cannabis-attributable harms such as cannabis-involved motor vehicle collisions and hospitalizations, though these results are more variable. The body of literature reviewed has focused almost exclusively on samples of cisgender research participants, and thus future research should encourage inclusion of transgender and gender-diverse participants. More consideration of sex- and gender-based analysis in research evaluating long-term impacts of cannabis legalization is a clear research priority.

The impact of cannabis legalization for recreational purposes on youth: A narrative review of the Canadian experience.

Cannabis legalization for non-medical purposes (subsequently referred to as "cannabis legalization" or "legalization") took place in Canada in October 2018. One of the federal government's stated goals with cannabis legalization was to protect Canadian youth from cannabis-related harms. The main objective of this narrative review is to describe the impact of cannabis legalization on Canadian youth. To that end, we discuss the regulation of the Canadian cannabis market, outline changes in the epidemiology and parameters of cannabis use (modes of use, potency of cannabis) among youth, and discuss prevention and education initiatives related to cannabis. The Canadian model differs from other jurisdictions that legalized recreational cannabis use, especially with regard to a higher degree of government regulation of the cannabis market. Another difference is the development and endorsement of lower-risk cannabis use guidelines to educate the public and health professionals. The results available for this review cover only 3 years post-legalization. Cannabis legalization in Canada brought an apparent increase in use among Canadian older than 25. However, results for youth are mixed, with the majority of studies showing no pronounced increase. Notably, the trend of a decrease in adolescents' cannabis use seen pre-legalization may have reversed. Emerging evidence also suggests that cannabis-related hospitalizations and emergency department visits among Canadian youth may have increased due to cannabis legalization. Data about changes in the age of initiation, the influence of legalization on sex and gender, and race/ethnicity are limited, with evidence suggesting that the age of initiation slightly increased. So far, there is limited data about the impact of cannabis legalization on Canadian youth. Further long-term monitoring and research to assess the effects of cannabis legalization on Canadian youth.

Sex Differences in the Neuropsychiatric Effects and Pharmacokinetics of Cannabidiol: A Scoping Review.

Cannabidiol (CBD) is a non-intoxicating cannabinoid compound with diverse molecular targets and potential therapeutic effects, including effects relevant to the treatment of psychiatric disorders. In this scoping review, we sought to determine the extent to which sex and gender have been considered as potential moderators of the neuropsychiatric effects and pharmacokinetics of CBD. In this case, 300 articles were screened, retrieved from searches in PubMed/Medline, Scopus, Google Scholar, PsycInfo and CINAHL, though only 12 met our eligibility criteria: eight studies in preclinical models and four studies in humans. Among the preclinical studies, three suggested that sex may influence long-term effects of gestational or adolescent exposure to CBD; two found no impact of sex on CBD modulation of addiction-relevant effects of Δ9-tetrahydrocannabinol (THC); two found antidepressant-like effects of CBD in males only; and one found greater plasma and liver CBD concentrations in females compared to males. Among the human studies, two found no sex difference in CBD pharmacokinetics in patient samples, one found greater plasma CBD concentrations in healthy females compared to males, and one found no evidence of sex differences in the effects of CBD on responses to trauma recall in patients with post-traumatic stress disorder (PTSD). No studies were identified that considered the role of gender in CBD treatment effects. We discuss potential implications and current limitations of the existing literature.

Association between ABCB1 rs2235048 Polymorphism and THC Pharmacokinetics and Subjective Effects following Smoked Cannabis in Young Adults.

Genetic influences on acute responses to psychoactive drugs may contribute to individual variability in addiction risk. ABCB1 is a human gene that encodes P-glycoprotein, an ATP-dependent efflux pump that may influence the pharmacokinetics of delta-9-tetrahydrocannabinol (THC), the primary psychoactive component of cannabis. Using data from 48 young adults (aged 19-25 years) reporting 1-4 days of cannabis use per week who completed a placebo-controlled human laboratory experiment, we tested the hypothesis that the rs2235048 polymorphism of ABCB1 would influence acute responses to smoked cannabis. C-allele carriers reported on average greater frequency of weekly cannabis use compared to the TT genotype carriers (TC/CC mean ± SEM = 2.74 ± 0.14, TT = 1.85 ± 0.24, p = 0.004). After smoking a single cannabis cigarette to their desired high, C-allele carriers had higher area-under-the-curve (AUC) of both THC metabolites (11-OH-THC TC/CC = 7.18 ± 9.64, TT = 3.28 ± 3.40, p = 0.05; THC-COOH TC/CC = 95.21 ± 116.12, TT = 45.92 ± 42.38, p = 0.043), and these results were impact by self-reported ethnicity. There were no significant differences in self-reported subjective drug effects except for a greater AUC of visual analogue scale rating of drug liking (TC/CC = 35,398.33 ± 37,233.72, TT = 15,895.56 ± 13,200.68, p = 0.017). Our preliminary findings suggest that further work in a larger sample should investigate whether human ABCB1 influences cannabis-related phenotypes and plays a role in the risk of developing a cannabis use disorder.

Separate and combined effects of alcohol and cannabis on mood, subjective experience, cognition and psychomotor performance: A randomized trial.

Co-use of alcohol and cannabis is associated with increased frequency and intensity of use and related problems. This study examined acute effects of alcohol and cannabis on mood, subjective experience, cognition, and psychomotor performance. Twenty-eight healthy cannabis users aged 19-29 years with recent history of binge drinking completed this within-subjects, double-blind, double-dummy, placebo-controlled, randomized clinical trial. Participants received: placebo alcohol and placebo cannabis (<0.1% THC); alcohol (target breath alcohol content [BrAC] 80 mg/dL) and placebo cannabis; placebo alcohol and active cannabis (12.5% THC); and active alcohol and cannabis over four sessions. Profile of Mood States (POMS), Addiction Research Centre Inventory (ARCI), verbal free recall (VFR), Digit Symbol Substitution Test (DSST), Continuous Performance Test (CPT), and grooved pegboard (GPB) task were administered before and approximately 75 min after drinking alcohol (1 h after smoking cannabis ad libitum). Significant effects of condition were found for the POMS (Tension-Anxiety, Confusion) and ARCI (MBG, LSD, PCAG, Euphoria, Sedation), predominantly with greater increases emerging after cannabis or alcohol-cannabis combined relative to placebo. Significant effects were found for VFR (immediate total and delayed recall, percent retained), DSST (trials attempted, trials correct, reaction time), and GPB (non-dominant hand) predominantly with greater declines in performance after alcohol and alcohol-cannabis combined relative to placebo and/or cannabis. Cannabis appeared to affect mood and subjective experience, with minimal impact on cognitive performance. Alcohol appeared to impair cognitive and psychomotor performance, with minimal impact on mood and subjective experience. Acute effects of alcohol and cannabis combined were additive at most.

Opioid-sparing effect of cannabinoids for analgesia: an updated systematic review and meta-analysis of preclinical and clinical studies.

Cannabinoid co-administration may enable reduced opioid doses for analgesia. This updated systematic review on the opioid-sparing effects of cannabinoids considered preclinical and clinical studies where the outcome was analgesia or opioid dose requirements. We searched Scopus, Cochrane Central Registry of Controlled Trials, Medline, and Embase (2016 onwards). Ninety-two studies met the search criteria including 15 ongoing trials. Meta-analysis of seven preclinical studies found the median effective dose (ED50) of morphine administered with delta-9-tetrahydrocannabinol was 3.5 times lower (95% CI 2.04, 6.03) than the ED50 of morphine alone. Six preclinical studies found no evidence of increased opioid abuse liability with cannabinoid administration. Of five healthy-volunteer experimental pain studies, two found increased pain, two found decreased pain and one found reduced pain bothersomeness with cannabinoid administration; three demonstrated that cannabinoid co-administration may increase opioid abuse liability. Three randomized controlled trials (RCTs) found no evidence of opioid-sparing effects of cannabinoids in acute pain. Meta-analysis of four RCTs in patients with cancer pain found no effect of cannabinoid administration on opioid dose (mean difference -3.8 mg, 95% CI -10.97, 3.37) or percentage change in pain scores (mean difference 1.84, 95% CI -2.05, 5.72); five studies found more adverse events with cannabinoids compared with placebo (risk ratio 1.13, 95% CI 1.03, 1.24). Of five controlled chronic non-cancer pain trials; one low-quality study with no control arm, and one single-dose study reported reduced pain scores with cannabinoids. Three RCTs found no treatment effect of dronabinol. Meta-analyses of observational studies found 39% reported opioid cessation (95% CI 0.15, 0.64, I2 95.5%, eight studies), and 85% reported reduction (95% CI 0.64, 0.99, I2 92.8%, seven studies). In summary, preclinical and observational studies demonstrate the potential opioid-sparing effects of cannabinoids in the context of analgesia, in contrast to higher-quality RCTs that did not provide evidence of opioid-sparing effects.

Mu opioid receptor gene variant modulates subjective response to smoked cannabis.

The mu-opioid receptor (MOR) mediates the rewarding properties of many psychoactive drugs and is an important target in the treatment of addictions. Functional interactions between the opioid and endocannabinoid systems are established and have been hypothesized to contribute to the effects of cannabis. We investigated associations between three single nucleotide polymorphisms in the MOR gene OPRM1 (rs1799971, rs2281617, and rs510769) and subjective responses to smoked cannabis. Fifty-two regular cannabis users (1-4 days/week) were given a cannabis cigarette (12.5% THC) and rated their subjective responses on visual analog scales at baseline and at multiple time points after smoking. Blood samples were collected for THC quantification. There was a significant impact of the intronic variant rs510769 on subjective cannabis effects and THC blood levels. The influence of this gene variant may thus be mediated by pharmacodynamics and/or pharmacokinetic factors. We provide novel evidence that variability in OPRM1 contributes to individual responses to cannabis and may affect risk of cannabis use disorder. Our findings add to the growing body of literature on the genetic basis of individual responses to cannabis and may have implications for targeting the endogenous opioid system in the treatment of cannabis use disorder.

Effects of combining alcohol and cannabis on driving, breath alcohol level, blood THC, cognition, and subjective effects: A narrative review.

Alcohol and cannabis are the two most commonly found intoxicating substances in fatally injured drivers. Epidemiological studies have demonstrated that the use of alcohol or cannabis can lead to an increase in the risk of a motor vehicle collision. Reducing the risks associated with driving under the influence of alcohol or cannabis is achieved partly through roadside detection of breath alcohol concentrations (BrAC) or blood delta-9-tetrahydrocannabinol (THC) levels. The purpose of the present review is to compile the laboratory studies on the combined effects of alcohol and cannabis on simulated driving as well as those evaluating combinations of these drugs on BrAC or blood THC. Given that driving can be affected by a number of cognitive processes, the literature on the cognitive effects of combinations of alcohol and cannabis is also reviewed, along with a discussion of a potential additive effect on the subjective qualities of these drugs. In sum, it is concluded that alcohol and cannabis have additive effects on driving skills, cognition and subjective effects. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Influence of personality on acute smoked cannabis effects on simulated driving.

A recent study of the impact of smoked cannabis on simulated driver behavior demonstrated a reduction in mean speed after smoked cannabis. Previous research identified an association between personality and individual differences and acute drug effects. The present study examined the impact of personality on the reduction in mean speed after smoking cannabis under single- and dual-task driving conditions originally reported by Brands et al. (2019). Sixty-one participants randomly assigned to the active drug condition completed a battery of self-report questionnaires measuring various personality constructs and subsequently operated a driving simulator before and 30 min after smoking a 12.5% Δ9-tetrahydrocannabinol (THC) cigarette. Linear regression modeling tested the influence of self-reported driving errors, lapses, and violations, driver vengeance, psychological distress, impulsivity, and sensation seeking on the reduction in speed after smoking cannabis. After adjusting for the influence of sex, blood THC concentration, and predrug mean speed, impulsivity was a significant predictor of change in speed under both single- (ß = -.45, t = -3.94, p < .001) and dual- (ß = -.35, t = -2.74, p = .008) task driving conditions after cannabis. Higher trait impulsivity was significantly associated with greater reductions in driving speed after cannabis use, which may reflect greater sensitivity to drug effects and a stronger compensatory response. Further multidisciplinary study, including neurochemical, genetic, and psychological components, would be beneficial in helping to better understand how impulsivity and other personality or individual differences may impact the effects of cannabis on driver behavior and performance. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Combined effect of alcohol and cannabis on simulated driving.

RATIONALE: With alcohol and cannabis remaining the most commonly detected drugs in seriously and fatally injured drivers, there is a need to understand their combined effects on driving. OBJECTIVES: The present study examined the effects of combinations of smoked cannabis (12.5% THC) and alcohol (target BrAC 0.08%) on simulated driving performance, subjective drug effects, cardiovascular measures, and self-reported perception of driving ability. METHODS: In this within-subjects, double-blind, double-dummy, placebo-controlled, randomized clinical trial, cannabis users (1-7 days/week) aged 19-29 years attended four drug administration sessions in which simulated driving, subjective effects, cardiovascular measures, and whole blood THC and metabolite concentrations were assessed following placebo alcohol and placebo cannabis (<0.1% THC), alcohol and placebo cannabis, placebo alcohol and active cannabis, and alcohol and active cannabis. RESULTS: Standard deviation of lateral position in the combined condition was significantly different from the placebo condition (p < 0.001). Standard deviation of lateral position was also significantly different from alcohol and cannabis alone conditions in the single task overall drive (p = 0.029 and p = 0.032, respectively), from the alcohol alone condition in the dual task overall drive (p = 0.022) and the cannabis alone condition in the dual task straightaway drive (p = 0.002). Compared to the placebo condition, the combined and alcohol conditions significantly increased reaction time. Subjective effects in the combined condition were significantly greater than with either of the drugs alone at some time points, particularly later in the session. A driving ability questionnaire showed that participants seemed unaware of their level of impairment. CONCLUSION: Combinations of alcohol and cannabis increased weaving and reaction time, and tended to produce greater subjective effects compared to placebo and the single drug conditions suggesting a potential additive effect. The fact that participants were unaware of this increased effect has important implications for driving safety.

Potential of Fatty Acid Amide Hydrolase (FAAH), Monoacylglycerol Lipase (MAGL), and Diacylglycerol Lipase (DAGL) Enzymes as Targets for Obesity Treatment: A Narrative Review.

The endocannabinoid system (ECS) plays an integral role in maintaining metabolic homeostasis and may affect hunger, caloric intake, and nutrient absorption. Obesity has been associated with higher levels of the endogenous cannabinoid transmitters (endocannabinoids). Therefore, the ECS is an important target in obesity treatment. Modulating the enzymes that synthesize and degrade endocannabinoids, namely fatty acid amide hydrolase (FAAH), monoacylglycerol lipase (MAGL), and diacylglycerol lipase (DAGL), may be a promising strategy to treat obesity. This review aims to synthesize all studies investigating pharmacological or genetic manipulation of FAAH, MAGL, or DAGL enzymes in association with obesity-related measures. Pharmacological inhibition or genetic deletion of FAAH tended to promote an obesogenic state in animal models, though the relationships between human FAAH polymorphisms and obesity-related outcomes were heterogeneous, which could be due to FAAH having both pro-appetitive and anti-appetitive substrates. Genetic deletion of Mgll and Dagla as well as pharmacological inhibition of DAGL tended to reduce body weight and improve metabolic state in animal studies, though the effects of Mgll manipulation were tissue-dependent. Monitoring changes in body weight in ongoing clinical trials of FAAH inhibitors may clarify whether FAAH inhibition is a potential therapeutic strategy for treatment obesity. More preclinical work is needed to characterize the role of MAGL and DAGL modulation in obesity-related outcomes.

Influence of Cannabinoid Receptor 1 Genetic Variants on the Subjective Effects of Smoked Cannabis.

As many jurisdictions consider relaxing cannabis legislation and usage is increasing in North America and other parts of the world, there is a need to explore the possible genetic differences underlying the subjective effects of cannabis. This pilot study investigated specific genetic variations within the cannabinoid receptor 1 (CNR1) gene for association with the subjective effects of smoked cannabis. Data were obtained from a double-blinded, placebo-controlled clinical trial studying the impact of cannabis intoxication on driving performance. Participants randomized to the active cannabis group who consented to secondary genetic analysis (n = 52) were genotyped at the CNR1 rs1049353 and rs2023239 polymorphic areas. Maximum value and area under the curve (AUC) analyses were performed on subjective measures data. Analysis of subjective effects by genotype uncovered a global trend towards greater subjective effects for rs1049353 T-allele- and rs2023239 C-allele-carrying subjects. However, significant differences attributed to allelic identity were only documented for a subset of subjective effects. Our findings suggest that rs1049353 and rs2023239 minor allele carriers experience augmented subjective effects during acute cannabis intoxication.

Sex differences in the acute pharmacological and subjective effects of smoked cannabis combined with alcohol in young adults.

Objective: The prevalence of co-use of alcohol and cannabis is increasing, particularly among young adults. Sex differences in the effects of alcohol alone and cannabis alone have been observed in animals and humans. However, sex differences in the acute pharmacological effects of cannabis combined with alcohol have not yet been studied. In young adults, aged 19-29 years, we aimed to examine sex differences following an intoxicating dose of alcohol (target 0.08% breath alcohol content) combined with a moderate dose of cannabis (12.5% Δ9-tetrahydrocannabinol; THC) using an ad libitum smoking procedure. Method: Using a within-subjects design, 28 regular cannabis users (16 males; 12 females) received in random order: (a) placebo alcohol and placebo cannabis, (b) active alcohol and placebo cannabis, (c) placebo alcohol and active cannabis, and (d) active alcohol and active cannabis. Blood samples for THC were collected and measures of vital signs, subjective drug effects, and cognition were collected. Results: In the alcohol-cannabis combined condition, females smoked significantly less of the cannabis cigarette compared to males (p < .001), although both sexes smoked similar amounts in the other conditions. There was minimal evidence that females and males differed in THC blood concentrations, vitals, subjective effects, or cognitive measures. Conclusions: In the alcohol-cannabis combined condition, females experienced the same acute pharmacological and subjective effects of alcohol and cannabis as males, after smoking less cannabis, which has potential implications for informing education and policy. Further research is warranted on sex differences in cannabis pharmacology, as well as the combined effects of alcohol and cannabis. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Cannabis Legalization and Acute Harm From High Potency Cannabis Products: A Narrative Review and Recommendations for Public Health.

Legalization and commercial sale of non-medical cannabis has led to increasing diversity and potency of cannabis products. Some of the American states that were the first to legalize have seen rises in acute harms associated with cannabis use, e.g. Colorado has seen increases in emergency department visits for cannabis-related acute psychological distress and severe vomiting (hyperemesis), as well as a number of high-profile deaths related to ingestion of high doses of cannabis edibles. Over-ingestion of cannabis is related to multiple factors, including the sale of cannabis products with high levels of THC and consumers' confusion regarding labelling of cannabis products, which disproportionately impact new or inexperienced users. Based on our review of the literature, we propose three approaches to minimizing acute harms: early restriction of cannabis edibles and high-potency products; clear and consistent labelling that communicates dose/serving size and health risks; and implementation of robust data collection frameworks to monitor harms, broken down by cannabis product type (e.g. dose, potency, route of administration) and consumer characteristics (e.g. age, sex, gender, ethnicity). Ongoing data collection and monitoring of harms in jurisdictions that have existing legal cannabis laws will be vital to understanding the impact of cannabis legalization and maximizing public health benefits.

Therapeutic Potential of Peroxisome Proliferator-Activated Receptor (PPAR) Agonists in Substance Use Disorders: A Synthesis of Preclinical and Human Evidence.

Targeting peroxisome proliferator-activated receptors (PPARs) has received increasing interest as a potential strategy to treat substance use disorders due to the localization of PPARs in addiction-related brain regions and the ability of PPAR ligands to modulate dopamine neurotransmission. Robust evidence from animal models suggests that agonists at both the PPAR-α and PPAR-γ isoforms can reduce both positive and negative reinforcing properties of ethanol, nicotine, opioids, and possibly psychostimulants. A reduction in the voluntary consumption of ethanol following treatment with PPAR agonists seems to be the most consistent finding. However, the human evidence is limited in scope and has so far been less promising. There have been no published human trials of PPAR agonists for treatment of alcohol use disorder, despite the compelling preclinical evidence. Two trials of PPAR-α agonists as potential smoking cessation drugs found no effect on nicotine-related outcomes. The PPAR-γ agonist pioglitazone showed some promise in reducing heroin, nicotine, and cocaine craving in two human laboratory studies and one pilot trial, yet other outcomes were unaffected. Potential explanations for the discordance between the animal and human evidence, such as the potency and selectivity of PPAR ligands and sex-related variability in PPAR physiology, are discussed.

Acute and residual mood and cognitive performance of young adults following smoked cannabis.

OBJECTIVES: To examine acute and residual mood and cognitive performance in young adult regular cannabis users following smoked cannabis. METHODS: Ninety-one healthy young adults completed this double-blind, placebo-controlled, parallel-groups study. Participants were randomized to receive active (12.5% THC) or placebo cannabis with a 2:1 allocation ratio, and mood [Profile of Mood States (POMS)] and cognitive performance [Hopkins Verbal Learning Test - Revised (HVLT-R), Digit Symbol Substitution Test (DSST), Continuous Performance Test (CPT), grooved pegboard (GPB)] were assessed before and 1, 24, and 48 (h) after smoking cannabis ad libitum. High and Low THC groups were based on blood THC concentrations. RESULTS: One hour after smoking cannabis, compared to Placebo, in both the High and Low THC groups, there were increases in POMS Arousal and Positive Mood, and in the High THC group only, increases in Confusion, Friendliness, and Elation, and a decrease in Fatigue. Increases in Friendliness and Elation in the High THC group remained significant for 24 h. The only significant acute effect of cannabis on cognition was a decrease in the percent of words retained in the HVLT-R in the High THC group compared to Placebo (mean difference = 15.8%, 95% CI = 3.6-28.0%, p = 0.006). Unexpectedly, compared to Placebo, both the High and Low THC groups improved in DSST performance at 48 h (p ≤ 0.016). CONCLUSIONS: Under the present experimental conditions, in young regular cannabis users, smoking cannabis ad libitum had significant effects on mood, some of which persisted 24 h later, yet minimal effects on cognition, and no evidence of residual cognitive impairment.

Sex differences in the acute effects of smoked cannabis: evidence from a human laboratory study of young adults.

RATIONALE: Animal studies have found robust sex differences in the pharmacokinetics and pharmacodynamics of Δ9-tetrahydrocannabinol (THC). However, the human evidence remains equivocal, despite findings that women may experience more severe consequences of cannabis use than men. OBJECTIVES: The objective of this secondary analysis was to examine sex differences in THC pharmacokinetics and in acute subjective, physiological, and cognitive effects of smoked cannabis in a sample of regular cannabis users (use 1-4 days per week) aged 19-25 years. METHODS: Ninety-one healthy young adults were randomized to receive active (12.5% THC; 17 females, 43 males) or placebo (< 0.1% THC; 9 females, 21 males) cannabis using a 2:1 allocation ratio. Blood samples to quantify concentrations of THC, 11-OH-THC, and 11-Nor-carboxy-THC (THC-COOH), as well as measures of subjective drug effects, vital signs, and cognition were collected over a period of 6 h following ad libitum smoking of a 750-mg cannabis cigarette. RESULTS: Females smoked less of the cannabis cigarette than males (p = 0.008) and had a lower peak concentration of THC and THC-COOH than males (p ≤ 0.01). Blood THC concentrations remained lower in females even when adjusting for differences in estimated dose of THC inhaled. There was very little evidence of sex differences in visual analog scale (VAS) ratings of subjective drug effects, mood, heart rate, blood pressure, or cognitive effects of cannabis. CONCLUSIONS: Females experienced the same acute effects of smoked cannabis as males at a lower observed dose, highlighting the need for more research on sex differences in the pharmacology of THC, especially when administered by routes in which titrating to the desired effect is more difficult (e.g., cannabis edibles).

Acute and residual effects of smoked cannabis: Impact on driving speed and lateral control, heart rate, and self-reported drug effects.

BACKGROUND: Although driving under the influence of cannabis is increasingly common among young adults, little is known about residual effects on driver behavior. This study examined acute and residual effects of smoked cannabis on simulated driving performance of young cannabis users. METHODS: In this double-blind, placebo-controlled, parallel-group randomized clinical trial, cannabis users (1-4 days/week) aged 19-25 years were randomized with a 2:1 allocation ratio to receive active (12.5% THC) or placebo (0.009% THC) cannabis in a single 750 mg cigarette. A median split (based on whole-blood THC concentrations at the time of driving) was used to divide the active group into low and high THC groups. Our primary outcome was simulated driving performance, assessed 30 min and 24 and 48 h after smoking. Secondary outcomes included blood THC concentrations, subjective drug effects, and heart rate. RESULTS: Ninety-six participants were randomized, and 91 were included in the final analysis (30 high THC, 31 low THC, 30 placebo). Mean speed (but not lateral control) significantly differed between groups 30 min after smoking cannabis (p ≤ 0.02); low and high THC groups decreased their speed compared to placebo. Heart rate, VAS drug effect and drug high increased significantly immediately after smoking cannabis and declined steadily after that. There was little evidence of residual effects in any of the measures. CONCLUSION: Acutely, cannabis caused decreased speed, increased heart rate, and increases in VAS drug effect and drug high. There was no evidence of residual effects on these measures over the two days following cannabis administration.

Driving under the influence of prescription opioids: Self-reported prevalence and association with collision risk in a large Canadian jurisdiction.

BACKGROUND: Motor vehicle collisions are an important contributor to prescription opioid use-related morbidity and mortality. The purpose of the current study was to estimate the prevalence of driving under the influence of prescription opioids (DUIPO) in Ontario, Canada, and to measure the association between this behaviour and the risk of a motor vehicle collision. METHODS: Data were based on telephone interviews with 7857 respondents who reported having driven in the past year. Data were derived from the 2011-2016 cycles of the CAMH Monitor, an ongoing cross-sectional representative survey of adults aged 18 years and older. A binary logistic regression analysis of collision involvement in the previous 12 months was conducted and included demographic characteristics (sex, age, marital status, education, income, region), driving exposure, poor mental health, non-medical use of prescription opioids, and driving after use of alcohol. RESULTS: The prevalence of past-year DUIPO was 3.1%. Controlling for demographic characteristics, driving exposure, and other risk factors, self-reported DUIPO significantly increased the odds of a collision (AdjOR = 1.97; 95% CI 1.08, 3.60; p = 0.026). CONCLUSION: Based on these findings, DUIPO is a notable road safety issue. Research focused on better understanding the impact of prescription opioids on driver behaviour, reducing the prevalence of DUIPO, and improving drug-impaired driving policy and interventions should be prioritized in public health strategies.