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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., (© 2021. Crown.)

Background: With widespread moves toward legalization of cannabis, increasing numbers of people with multiple sclerosis (pwMS) are using the drug. Emerging MS-related data show that cannabis can cause or exacerbate cognitive dysfunction., Objective: To understand why people with MS continue using cannabis despite adverse cognitive consequences. It was hypothesized that lack of awareness, a component of metacognition, could explain this decision, in part., Method: Forty pwMS who smoked cannabis almost daily were assigned by odd-even case number selection to either a cannabis continuation (CC) or cannabis withdrawal (CW) group. Both groups were followed for 28 days. All participants completed, at baseline and day 28, the brief repeatable battery of neuropsychological tests (BRNB) in MS for measures of processing speed, memory and executive function; Modified fatigue impact scale (mFIS) for self-report indices of cognitive functioning., Results: No significant baseline differences between the groups on the BRNB and mFIS. At day 28, significant improvement within group was seen on all measures of the BRNB, but only in the CW group (p = .0001 for all indices). A repeat measure ANOVA did not find any significant group (CC vs. CW) × time (baseline and day 28) interactions for the self-report cognitive measures on the mFIS. Cannabis abstainers did report less ability to function away from home. All 19 participants in the CW group reverted to using cannabis on study completion despite being informed individually of their cognitive improvement., Conclusions and Relevance: The inability of pwMS to accurately appraise their memory and executive function can help explain, in part, why they continue to smoke cannabis despite objective evidence of the deleterious cognitive side effects of this behavior., (© 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

To assess whether symptoms of depression change when people with multiple sclerosis (pwMS) discontinue cannabis use, 40 cognitively impaired pwMS who smoked cannabis almost daily were randomly assigned to either a cannabis continuation (CC) or cannabis withdrawal (CW) group. Both groups were followed for 28 days. All participants completed the Hospital Anxiety and Depression Scale. At day 28 the 11-nor-9-carboxy-Δ 9 -tetrahydro-cannabinol (THCCOOH)/creatinine ratio in the CW group declined to zero ( p  = 0.0001), but remained unchanged in the CC group ( p  = 0.709). Depression scores in those pwMS who were using cannabis to manage their depression remained statistically unchanged in the CC group, but declined in the CW group ( p  = 0.006). Despite pwMS using cannabis to help their mood, depression improved significantly off the drug. Our finding provides a cautionary note in relation to cannabis use in pwMS, at least with respect to depression.

• Heavy cannabis use among individuals with MS appears to obscure cognitive sex differences. • Once off the drug, females showed greater improvements in learning and memory, consistent with what is known in the literature. • Cannabis use, particularly among males with MS, may contribute to cognitive decline and exacerbate symptoms. • Cannabis containing THC may have detrimental effects on individuals with MS. Previous studies have investigated the influence of cannabis on cognition among people with MS (pwMS), yet the influence of sex in the context of cannabis use remains unexplored. We aim to fill this gap by investigating cannabis-sex related differences in verbal learning, memory and processing speed in association with fMRI (resting state, and task-based) metrics. Our sample consisted of 19 long-term, frequent cannabis users (8 males, 11 females). Assessments were conducted at baseline and after 28 days of cannabis abstinence. The tests included measures of verbal memory (Selective Reminding Test (SRT)), working memory (n-back), information processing speed (Symbol Digit Modalities Test (SDMT)) and the resting state DMN. To evaluate the effects of cannabis abstinence, we performed a group x time interaction analysis using repeated measures ANCOVA. This analysis controlled for several covariates, including the level of disability (EDSS), baseline cannabis THC metabolite levels, and cannabis withdrawal symptoms. By controlling for these variables, we aimed to isolate the impact of cannabis abstinence on cognitive performance over time. Statistical significance was set at p < 0.05. There were no baseline cognitive differences between the sexes. After 28 days of cannabis abstinence, females performed better on the Selective Reminding Test (SRT) (p = 0.04), with a large effect size (η ² = 0.286). The mean correct response improved over time for females, but there was no statistically significant group x time interaction on the Symbol Digit Modalities Test (SDMT) and the n-back task. Resting state default mode network data showed overall increased activation in females relative to males at day 28, which meshed with lower brain activation during task-based fMRI paradigms. Cannabis negated sex-based cognitive differences. Functional MRI task-based paradigms revealed less cerebral activation in females compared to males, which was associated with comparable or better cognitive performance in females, particularly after cannabis abstinence. [ABSTRACT FROM AUTHOR]

Cognitive dysfunction affects 40-80% of patients with multiple sclerosis. Smoking cannabis may add to these deficits. It is unclear whether coming off cannabis results in cognitive improvement. To address this question, 40 patients with multiple sclerosis who started using cannabis after the onset of multiple sclerosis and who used it for at least 4 days a week over many years were divided by odd-even number selection into two groups: cannabis continuation and cannabis withdrawal. Assessments took place at baseline and after 28 days and included serial versions of the Brief Repeatable Neuropsychological Battery for multiple sclerosis containing tests of verbal and visual memory, processing speed and executive function; structural and functional MRI, the latter entailing a compatible version of the Symbol Digit Modalities Test; urine for cannabinoid metabolites to detect compliance with abstinence. Only those participants deemed globally impaired at baseline (failure on at least two cognitive domains) were enrolled. The results revealed that the two groups were well matched demographically and neurologically. One subject was removed from the withdrawal group because of failed abstinence. Urine analysis revealed the cannabinoid consumed was predominantly tetrahydrocannabinol (THC). There were no baseline between group cognitive differences, but by Day 28 the withdrawal group performed significantly better on every cognitive index (P < 0.0001 for all). Significant within group differences were present for every test over time, but only in the abstinent group (P < 0.0001 for all tests). There were no between group baseline or Day 28 differences in structural MRI indices (global atrophy, total T1 and T2 lesion volume). At index assessment the two groups had a similar performance on the functional MRI-compatible Symbol Digit Modalities Test and there were no group differences in brain activation. However, by Day 28, the withdrawal group completed more trials correctly (P < 0.012) and had a faster reaction time (P < 0.002), associated with significantly increased activation in brain regions known to be associated with performance of the test (bilateral inferior frontal gyri, caudate and declive/cerebellum, P < 0.001 for all regions). These results reveal that patients with multiple sclerosis who are frequent, long-term cannabis users can show significant improvements in memory, processing speed and executive function after 28 days of drug abstinence. The absence of similar improvements in a matched multiple sclerosis group that remained on cannabis shows that beneficial cognitive change after stopping cannabis is not solely attributable to the effects of practice. [ABSTRACT FROM AUTHOR]

To assess whether symptoms of depression change when people with multiple sclerosis (pwMS) discontinue cannabis use, 40 cognitively impaired pwMS who smoked cannabis almost daily were randomly assigned to either a cannabis continuation (CC) or cannabis withdrawal (CW) group. Both groups were followed for 28 days. All participants completed the Hospital Anxiety and Depression Scale. At day 28 the 11-nor-9-carboxy-Δ9-tetrahydro-cannabinol (THCCOOH)/creatinine ratio in the CW group declined to zero (p = 0.0001), but remained unchanged in the CC group (p = 0.709). Depression scores in those pwMS who were using cannabis to manage their depression remained statistically unchanged in the CC group, but declined in the CW group (p = 0.006). Despite pwMS using cannabis to help their mood, depression improved significantly off the drug. Our finding provides a cautionary note in relation to cannabis use in pwMS, at least with respect to depression. [ABSTRACT FROM AUTHOR]

Background: Cannabis use disorders (CUD) are common in schizophrenia (~25%) compared to the general population (~3%). Tetrahydrocannabinol (THC), the principal psychoactive component in cannabis is fat-soluble, resulting in an extended period for cannabinoid elimination. While detection of cannabinoids in urine is indicative of prior cannabis exposure, time of last use is difficult to verify sustained abstinence for extended periods (e.g., 28-days) in chronic cannabis users. Therefore, we evaluated the utility of a sustained cannabis abstinence paradigm in patients with schizophrenia and non-psychiatric controls.Methods: Cannabis dependent patients (n=19) and controls (n=20) underwent 28-days of monitored cannabis abstinence facilitated with contingency management. Urine samples were taken twice weekly. Abstinence was evaluated using 1) Self-report; 2) Qualitative biochemical confirmation using MEDTOX; and 3) in a subset of participants (schizophrenia, n=13; controls, n=13) gas chromatography-mass spectrometry (GC-MS) was performed to obtain quantitative creatinine-normalized carboxy-THC (THC-COOH) metabolite levels <20ng/mL). Subjective assessments were used to assess behavioral correlates of cannabis abstinence and further supported time-dependent abstinence trajectories.Results: Abstinence rates of 42.1% (8/19) in patients and 55% (11/19) in controls (p=0.53) were observed. Increased cannabis withdrawal symptoms in both patients and controls supported abstinence.Discussion: Our results suggest a feasible method for identification of short-term cannabis abstinence in individuals with schizophrenia at rates comparable to controls. Monitoring sustained abstinence may have implications for potential interventions for CUDs in schizophrenia. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]