Cannabis and Driving in Older Adults.

Importance: Epidemiological studies have found that cannabis increases the risk of a motor vehicle collision. Cannabis use is increasing in older adults, but laboratory studies of the association between cannabis and driving in people aged older than 65 years are lacking. Objective: To investigate the association between cannabis, simulated driving, and concurrent blood tetrahydrocannabinol (THC) levels in older adults. Design, Setting, and Participants: Using an ecologically valid counterbalanced design, in this cohort study, regular cannabis users operated a driving simulator before, 30 minutes after, and 180 minutes after smoking their preferred legal cannabis or after resting. This study was conducted in Toronto, Canada, between March and November 2022 with no follow-up period. Data were analyzed from December 2022 to February 2023. Exposures: Most participants chose THC-dominant cannabis with a mean (SD) content of 18.74% (6.12%) THC and 1.46% (3.37%) cannabidiol (CBD). Main outcomes and measures: The primary end point was SD of lateral position (SDLP, or weaving). Secondary outcomes were mean speed (MS), maximum speed, SD of speed, and reaction time. Driving was assessed under both single-task and dual-task (distracted) conditions. Blood THC and metabolites of THC and CBD were also measured at the time of the drives. Results: A total of 31 participants (21 male [68%]; 29 White [94%], 1 Latin American [3%], and 1 mixed race [3%]; mean [SD] age, 68.7 [3.5] years), completed all study procedures. SDLP was increased and MS was decreased at 30 but not 180 minutes after smoking cannabis compared with the control condition in both the single-task (SDLP effect size [ES], 0.30; b = 1.65; 95% CI, 0.37 to 2.93; MS ES, -0.58; b = -2.46; 95% CI, -3.56 to -1.36) and dual-task (SDLP ES, 0.27; b = 1.75; 95% CI, 0.21 to 3.28; MS ES, -0.47; b = -3.15; 95% CI, -5.05 to -1.24) conditions. Blood THC levels were significantly increased at 30 minutes but not 180 minutes. Blood THC was not correlated with SDLP or MS at 30 minutes, and SDLP was not correlated with MS. Subjective ratings remained elevated for 5 hours and participants reported that they were less willing to drive at 3 hours after smoking. Conclusions and relevance: In this cohort study, the findings suggested that older drivers should exercise caution after smoking cannabis.

Use of cannabidiol (CBD) for the treatment of cognitive impairment in psychiatric and neurological illness: A narrative review.

Cannabidiol (CBD) is one of the major phytocannabinoids present in the cannabis plant, with no acute psychotropic effects and a favorable safety and abuse liability profile. Animal and limited controlled human studies have demonstrated CBD to have analgesic, anxiolytic, anti-inflammatory, antipsychotic, and anticonvulsant effects, to name a few possible indications. There is growing evidence for the use of CBD to treat neurological disorders such as epilepsy, multiple sclerosis, Parkinson's disease, and Alzheimer's disease. It has been suggested that CBD improves cognition and neurogenesis. Cognitive impairment is associated with numerous disorders and can involve deficits in learning, memory, executive functioning, and attention. The purpose of this review will be to evaluate the available preclinical and clinical data on CBD for the treatment of the cognitive impairment associated with several disorders including schizophrenia, epilepsy, Alzheimer's disease, and others. Preclinical, but not clinical, studies found evidence for an improvement in cognitive performance after treatment with CBD. More research is needed to determine whether CBD can be effectively used as a monotherapy to treat cognitive dysfunction. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

On offer to Ontario consumers three years after legalization: A profile of cannabis products, cannabinoid content, plant type, and prices.

Introduction: Cannabis was legalized in Canada in October 2018, regulating the production, distribution, sale, and possession of dried cannabis and cannabis oils. Additional products were legalized 1 year later, including edibles, concentrates, and topicals, with new lines of commercial products coming to market. Ontario is the most populous province in Canada and has the largest cannabis market with the highest number of in-person retail stores and the most cannabis products available online. This study aims to create a profile of products available to consumers three years after legalization by summarizing types of products, THC and CBD potency, plant type, and prices of product sub-categories. Methods: We extracted data from the website of the Ontario Cannabis Store (OCS)-the public agency overseeing the only online store and sole wholesaler to all authorized in-person stores-in the first quarter of 2022 (January 19-March 23). We used descriptive analyses to summarize the data. A total of 1,771 available products were mapped by route of administration into inhalation (smoking, vaping, and concentrates), ingestible (edibles, beverages, oils, and capsules) and topical. Results: Most inhalation products included ≥20%/g THC (dried flower: 94%; cartridges: 96%; resin: 100%) while ingestible products had similar proportions of THC and CBD content. Indica-dominant products tend to be more prominent in inhalation products while sativa-dominant products tend to be more prominent in ingestible products. The average sale price of cannabis was 9.30 $/g for dried flower, 5.79 $/0.1g for cartridges, 54.82 $/g for resin, 3.21 $/unit for soft chews, 1.37 $/ml for drops, 1.52 $/unit for capsules, and 39.94 $/product for topicals. Discussion: In summary, a wide variety of cannabis products were available to Ontarians for different routes of administration and provides numerous indica-dominant, sativa-dominant, and hybrid/blend options. The current market for inhalation products however is geared towards the commercialization of high-THC products.

The Utility of THC Cutoff Levels in Blood and Saliva for Detection of Impaired Driving.

Background: Δ9-Tetrahydrocannabinol (THC) is the psychoactive component in cannabis and a relationship of THC to driving impairment is expected. Despite this, there are discrepant findings with respect to the relationship of blood THC to driving. This study investigated the relationship of blood, urine, and saliva THC/THC-COOH levels to "weaving," as measured by a driving simulator. Methods: Participants smoked cannabis alone or with alcohol. THC/THC-COOH levels in blood, urine, and saliva were correlated with standard deviation of lateral position (SDLP), measuring "weaving." In addition, SDLP after cannabis and/or alcohol were compared with SDLP after placebo when THC/THC-COOH levels were above or below specified thresholds in blood (5 ng/mL), urine (50 ng/mL), or saliva (25 ng/mL). Results: A clear linear relationship between blood THC concentration and SDLP was not observed based on calculation of Spearman coefficients. When compared with placebo, SDLP was significantly increased after cannabis and cannabis combined with alcohol when THC in the blood was above the legal limit. SDLP was increased in drug conditions when saliva cutoffs were above the legal limit. Conclusions: The findings of this study suggest that specified thresholds for THC in blood and saliva may be able to detect driving impairment, but future studies are needed. ClinicalTrials.gov ID: NCT03106363.

The effect of tetrahydrocannabinol:cannabidiol oromucosal spray on cognition: a systematic review.

PURPOSE: Previous studies have shown that tetrahydrocannabinol (THC), the main psychoactive component of cannabis, can impair cognitive abilities. There is also some evidence that cannabidiol (CBD), the most abundant non-intoxicating constituent of cannabis, can attenuate these effects. The purpose of this study was to investigate the effects of THC:CBD oromucosal spray (with equal parts THC and CBD) on cognition compared with control conditions in human studies. METHODS: A systematic literature search was performed on four major bibliographic databases. Studies were included in the present review if they evaluated the cognitive effects of THC:CBD oromucosal spray compared with a control condition. RESULTS: Ten studies were identified (7 on patients with multiple sclerosis, 1 on those with Huntington, and 2 on healthy volunteers) with 510 participants in total. There was considerable heterogeneity among the studies in terms of dose and duration of administration. All studies have used an equal or nearly equal dose of THC and CBD. CONCLUSIONS: Although the results across studies were somewhat inconsistent, most evidence revealed that there is no significant difference between THC:CBD oromucosal spray and control treatments in terms of cognitive outcomes. However, more trials are needed with longer follow-up periods, and dose considerations, particularly comparing lower and higher doses of the spray.

The Role of Dopamine D3 Receptors in Tobacco Use Disorder: A Synthesis of the Preclinical and Clinical Literature.

Tobacco smoking is a significant cause of preventable morbidity and mortality globally. Current pharmacological approaches to treat tobacco use disorder (TUD) are only partly effective and novel approaches are needed. Dopamine has a well-established role in substance use disorders, including TUD, and there has been a long-standing interest in developing agents that target the dopaminergic system to treat substance use disorders. Dopamine has 5 receptor subtypes (DRD1 to DRD5). Given the localization and safety profile of the dopamine receptor D3 (DRD3), it is of therapeutic potential for TUD. In this chapter, the preclinical and clinical literature investigating the role of DRD3 in processes relevant to TUD will be reviewed, including in nicotine reinforcement, drug reinstatement, conditioned stimuli and cue-reactivity, executive function, and withdrawal. Similarities and differences in findings from the animal and human work will be synthesized and findings will be discussed in relation to the therapeutic potential of targeting DRD3 in TUD.

Therapeutic Potential of Histamine H3 Receptors in Substance Use Disorders.

Substance use disorders are a leading cause of morbidity and mortality, and available pharmacological treatments are of modest efficacy. Histamine is a biogenic amine with four types of receptors. The histamine H3 receptor (H3R) is an autoreceptor and also an heteroreceptor. H3Rs are highly expressed in the basal ganglia, hippocampus and cortex, and regulate a number of neurotransmitters including acetylcholine, norepinephrine, GABA and dopamine. Its function and localization suggest that the H3R may be relevant to a number of psychiatric disorders and could represent a potential therapeutic target for substance use disorders. The purpose of the present review is to summarize preclinical studies investigating the effects of H3R agonists and antagonists on animal models of alcohol, nicotine and psychostimulant use. At present, the effects of H3R antagonists such as thioperamide, pitolisant or ciproxifan have been investigated in drug-induced locomotion, conditioned place preference, drug self-administration, reinstatement, sensitization and drug discrimination. For alcohol and nicotine, the effects of H3R ligands on two-bottle choice and memory tasks, respectively, have also been investigated. The results of these studies are inconsistent. For alcohol, H3R antagonists generally decreased the reward-related properties of ethanol, which suggests that H3R antagonists may be effective as a treatment option for alcohol use disorder. However, the effects of H3R antagonists on nicotine and psychostimulant motivation and reward are less clear. H3R antagonists potentiated the abuse-related properties of nicotine, but only a handful of studies have been conducted. For psychostimulants, evidence is mixed and suggests that more research is needed to establish whether H3R antagonists are a viable therapeutic option. The fact that different drugs of abuse have different brain targets may explain the differential effects of H3R ligands.

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.

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).

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.

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).

Are vaporizers a lower-risk alternative to smoking cannabis?

Cannabis use is associated with various adverse physical and mental health outcomes as well as increased risk of motor vehicle collision. Many organizations and the "Lower-Risk Cannabis Use Guidelines" have recommended to use cannabis vaporizers instead of smoking to reduce the associated health risk. This commentary draws attention to the present evidence regarding harm reduction potential of cannabis vaping. Cannabis vaporizer use can reduce the emission of carbon monoxide, chronic respiratory symptoms, and exposure to several toxins while producing similar subjective effects and blood THC concentration compared with smoking cannabis, holding potential for harm reduction among habitual cannabis smokers. However, new cannabis users, regardless of method of administration of cannabis, may experience intense subjective effects and cognitive impairment with increased susceptibility to dependence. Hence, policy makers should consider limiting access to cannabis among young people and adopting strategies to reduce impaired driving under influence of cannabis. Future research should focus on impact of switching from cannabis smoking to dried herb vaping using cannabis vaporizers among chronic cannabis smokers, and long-term outcomes of medical cannabis vaping, and further explore association of vaping-associated lung injury with THC-containing e-liquids.

RéSUMé: L'usage du cannabis est associé à une panoplie de résultats de santé physique et mentale indésirables et à un risque accru de collision entre véhicules automobiles. De nombreux organismes, ainsi que les « Recommandations canadiennes pour l'usage du cannabis à moindre risque ¼, recommandent d'utiliser un vaporisateur au lieu de fumer le cannabis afin d'en réduire les risques pour la santé. Notre commentaire attire l'attention sur les preuves actuelles concernant le potentiel de réduction des méfaits du vapotage du cannabis. L'utilisation d'un vaporisateur de cannabis peut réduire l'émission de monoxyde de carbone, les symptômes respiratoires chroniques et l'exposition à plusieurs toxines tout en produisant des effets subjectifs et une concentration de THC dans le sang semblables à ceux du cannabis fumé, ce qui pourrait réduire les méfaits chez les fumeurs réguliers de cannabis. Par contre, les nouveaux consommateurs de cannabis, peu importe la méthode d'administration du cannabis choisie, peuvent éprouver des effets subjectifs intenses et une détérioration cognitive, ainsi qu'une susceptibilité accrue à la dépendance. Les responsables des politiques devraient donc songer à limiter l'accès des jeunes au cannabis et adopter des stratégies pour réduire la conduite avec facultés affaiblies par cette drogue. Des études futures devraient porter sur les conséquences, pour les fumeurs réguliers de cannabis, de vapoter l'herbe séchée à l'aide d'un vaporisateur au lieu de fumer le cannabis, et sur les effets à long terme du vapotage du cannabis médical, et explorer plus avant l'association entre les lésions pulmonaires associées au vapotage et les liquides à vapoter contenant du THC.

Cannabis, Impaired Driving, and Road Safety: An Overview of Key Questions and Issues.

The road safety impact of cannabis has been a topic of much discussion and debate over the years. These discussions have been revitalized in recent years by initiatives in several jurisdictions to legalize non-medical cannabis. Canada became the second country to legalize non-medical cannabis use in October, 2018, preceded by Uruguay in December 2013. Road safety concerns were key issues in the Canadian government's deliberations on the issue. In this paper, we identify several key questions related to the impact of cannabis on road safety, and provide a consideration of the relevant literature on these questions. These questions cover several perspectives. From an epidemiological perspective, perhaps the central question is whether cannabis use contributes to the chances of being involved in a collision. The answer to this question has evolved in recent years as the ability to conduct the relevant studies has evolved. A related question is the extent to which cannabis plays an important role in road safety, and recent research has made progress in estimating the collisions, injuries, and deaths that may be attributed to cannabis use. Several questions relate to the behavioral and pharmacological effects of cannabis. One central question is whether cannabis affects driving skills in ways that can increase the chances of being involved in a collision. Another important question is whether the effects of the drug on the driving behavior of medical users is similar to, or different from, the effects on non-medical users and whether there are sex differences in the pharmacological and behavioral effects of cannabis. Other important questions are the impact of tolerance to the effects of cannabis on road safety as well as different routes of administration (e.g., edibles, vaped). It remains unclear if there is a dose-response relationship of cannabis to changes in driving. These and other key questions and issues are identified and discussed in this paper.

Preliminary Eye-Tracking Data as a Nonintrusive Marker for Blood Δ-9-Tetrahydrocannabinol Concentration and Drugged Driving.

Background: Cannabis is one of the drugs most often found in drivers involved in serious motor vehicle collisions. Validity and reliability of roadside cannabis detection strategies are questioned. This pilot study aimed to investigate the relationship between eye characteristics and cannabis effects in simulated driving to inform potential development of an alternative detection strategy. Materials and Methods: Multimodal data, including blood samples, eye-tracking recordings, and driving performance data, were acquired from 10 participants during a prolonged single-session driving simulator experiment. The study session included a baseline driving trial before cannabis exposure and seven trials at various times over ∼5 h after exposure. The multidimensional eye-tracking recording from each driving trial for each participant was segmented into nonoverlapping epochs (time windows); 34 features were extracted from each epoch. Blood Δ-9-tetrahydrocannabinol (THC) concentration, standard deviation of lateral position (SDLP), and mean vehicle speed were target variables. The cross-correlation between the temporal profile of each eye-tracking feature and target variable was assessed and a nonlinear regression analysis evaluated temporal trend of features following cannabis exposure. Results: Mean pupil diameter (r=0.81-0.86) and gaze pitch angle standard deviation (r=0.79-0.87) were significantly correlated with blood THC concentration (p<0.01) for all epoch lengths. For driving performance variables, saccade-related features were among those showing the most significant correlation (r=0.61-0.83, p<0.05). Epoch length significantly affected correlations between eye-tracking features and speed (p<0.05), but not SDLP or blood THC concentration (p>0.1). Temporal trend analysis of eye-tracking features after cannabis also showed a significant increasing trend (p<0.01) in saccade-related features, including velocity, scanpath, and duration, as the influence of cannabis decreased by time. A decreasing trend was observed for fixation percentage and mean pupil diameter. Due to the lack of placebo control in this study, these results are considered preliminary. Conclusion: Specific eye characteristics could potentially be used as nonintrusive markers of THC presence and driving-related effects of cannabis. clinicaltrials.gov (NCT03813602).

The influence of conditioned stimuli on [11C]-(+)-PHNO PET binding in tobacco smokers after a one week abstinence.

Stimuli previously paired with drugs of dependence can produce cravings that are associated with increased dopamine (DA) levels in limbic and striatal brain areas. Positron Emission Tomography (PET) imaging with [11C]-(+)-PHNO allows for a sensitive measurement of changes in DA levels. The purpose of the present study was to investigate changes in DA levels, measured with PET imaging with [11C]-(+)-PHNO, in regions of interest in smokers who had maintained abstinence for 7-10 days. Participants (N = 10) underwent two PET scans on separate days, during which they viewed either smoking-related or neutral images, in counterbalanced order. Craving was measured with the 12-item Tobacco Craving Questionnaire (TCQ) and the Questionnaire on Smoking Urges-Brief (QSU-B). Compared to neutral cues, smoking cues did not increase craving. There were no changes in [11C]-(+)-PHNO binding in the cue condition compared to the neutral condition for most regions of interest (ventral pallidum, globus pallidus, limbic striatum, associative striatum, sensorimotor striatum). However, binding potential in the substantia nigra was greater in the smoking-cue condition, indicating decreased synaptic dopamine. There is a potential change of DA level occurring in midbrain following the presentation of smoking-related cues. However, this preliminary finding would need to be validated with a larger sample.

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).

Use of Cannabidiol for the Treatment of Anxiety: A Short Synthesis of Pre-Clinical and Clinical Evidence.

Anxiety disorders have the highest lifetime prevalence of any mental illness worldwide, leading to high societal costs and economic burden. Current pharmacotherapies for anxiety disorders are associated with adverse effects and low efficacy. Cannabidiol (CBD) is a constituent of the Cannabis plant, which has potential therapeutic properties for various indications. After the recent legalization of cannabis, CBD has drawn increased attention as a potential treatment, as the majority of existing data suggest it is safe, well tolerated, has few adverse effects, and demonstrates no potential for abuse or dependence in humans. Pre-clinical research using animal models of innate fear and anxiety-like behaviors have found anxiolytic, antistress, anticompulsive, and panicolytic-like effects of CBD. Preliminary evidence from human trials using both healthy volunteers and individuals with social anxiety disorder, suggests that CBD may have anxiolytic effects. Although these findings are promising, future research is warranted to determine the efficacy of CBD in other anxiety disorders, establish appropriate doses, and determine its long-term efficacy. The majority of pre-clinical and clinical research has been conducted using males only. Among individuals with anxiety disorders, the prevalence rates, symptomology, and treatment response differ between males and females. Thus, future research should focus on this area due to the lack of research in females and the knowledge gap on sex and gender differences in the effectiveness of CBD as a potential treatment for anxiety.

Exploring occupancy of the histamine H3 receptor by pitolisant in humans using PET.

BACKGROUND AND PURPOSE: BF2.649 (pitolisant, Wakix®) is a novel histamine H3 receptor inverse agonist/antagonist recently approved for the treatment of narcolepsy disorder. The objective of the study was to investigate in vivo occupancy of H3 receptors by BF2.649 using PET brain imaging with the H3 receptor antagonist radioligand [11 C]GSK189254. EXPERIMENTAL APPROACH: Six healthy adult participants were scanned with [11 C]GSK189254. Participants underwent a total of two PET scans on separate days, 3 h after oral administration of placebo or after pitolisant hydrochloride (40 mg). [11 C]GSK189254 regional total distribution volumes were estimated in nine brain regions of interest with the two tissue-compartment model with arterial input function using a common VND across the regions. Brain receptor occupancies were calculated with the Lassen plot. KEY RESULTS: Pitolisant, at the dose administered, provided high (84 ± 7%; mean ± SD) occupancy of H3 receptors. The drug was well-tolerated, and participants experienced few adverse events. CONCLUSION AND IMPLICATIONS: The administration of pitolisant (40 mg) produces a high occupancy of H3 receptors and may be a new tool for the treatment of a variety of CNS disorders that are associated with mechanisms involving H3 receptors.

Exploring the role of the Ser9Gly (rs6280) Dopamine D3 receptor polymorphism in nicotine reinforcement and cue-elicited craving.

Preclinical studies show that the dopamine D3 receptor (D3R) is involved in the reinstatement of drug seeking and motivation for drugs of abuse. A D3R gene variant, Ser9Gly (rs6280) has been linked to nicotine dependence, yet the mechanisms underlying its involvement in nicotine dependence is unclear. This study investigated the relationship between the Ser9Gly variant and measures of both nicotine reinforcement and cue-elicited craving. Phenotypes of smoking behaviors were assessed in genetically grouped (Glycine vs. No Glycine carriers) current smokers (n = 104, ≥ 10 cigarettes per day). Laboratory measures included a forced choice session (to measure reinforcement of nicotine containing vs. denicotinized cigarettes), and a cue-reactivity session (to measure smoking cues vs. neutral cues elicited craving). The forced choice procedure revealed that subjective ratings were significantly higher in response to nicotinized compared to denicotinized cigarettes; however the Ser9Gly variant did not influence this effect. By comparison, smoking cues elicited greater craving over time compared to neutral cues, and Glycine carriers of the Ser9Gly D3R variant seem to experience a significant blunted cue-elicited craving effect. Results support D3R involvement in nicotine cue reactivity. However, more research is needed to reveal how this gene variant modulates various aspects of nicotine dependence.