Effects of High-Potency Cannabis on Psychomotor Performance in Frequent Cannabis Users.

Background: Recently increased access to cannabis products in the United States has been associated with increased rates of driving after cannabis use. Although numerous studies indicate that cannabis impairs psychomotor and neurocognitive functions that can affect driving ability, the determination of cannabis-impaired driving risk is complicated by the extent to which frequent cannabis users develop tolerance to THC's subjective, cognitive, and psychomotor effects, and by the fact that there is no validated behavioral or biological marker of recent cannabis use or cannabis-related impairment. This study examined the psychomotor impairment-related effects experienced by frequent cannabis users in Colorado after naturalistic consumption of smoked cannabis, both immediately and 1 h postuse. Results were then validated in a smaller replication sample from Washington state. Methods: In the primary Colorado study, participants (n=70) used the DRUID® mobile app, a brief measure of psychomotor and cognitive domains that are sensitive to the effects of cannabis. First, participants used DRUID to establish a sober baseline impairment score. During a second appointment, they used DRUID at three time points: preuse, immediately after acutely using cannabis, and 1 h postuse. In the Washington replication sample, participants (n=39) used DRUID before acute cannabis consumption and then every half hour for 2.5 h. Results: In both studies, peak DRUID impairment effects were seen immediately after cannabis use, with recovery of performance at 1 h postuse. Specifically, significant quadratic effects of time emerged for both studies (Colorado study: (ß=-0.935, SE=0.204, p<0.001); Washington study: ß=3.0299, SE=1.3085, p<0.01). Domain-specific effects were tested in the larger Colorado study and were observed for reaction time within a complex divided attention task and a postural-stability balance task. Conclusions: These findings demonstrate that psychomotor impairment emerges immediately after acute cannabis use even in regular users, but decreases significantly 1 h postuse. These results underscore the potential utility of the DRUID app for assessing acute cannabis-related psychomotor impairment. Further research is needed to explore whether the DRUID app and/or the specific psychomotor functions it assesses might serve as a tool for measuring cannabis-related driving impairment. Clinical trials registration number for the Colorado Study: NCT03522103.

Investigating sex differences in acute intoxication and verbal memory errors after ad libitum cannabis concentrate use.

BACKGROUND: An innovative naturalistic at-home administration procedure was used to investigate sex differences in subjective drug effects and verbal memory errors after ad libitum use of high potency state legal market Δ9-tetrahydrocannabinol (THC) concentrate. METHODS: Regular concentrate users were randomly assigned to ad libitum administration of one of two cannabis concentrate products (70 % or 90 % THC) that they purchased from a dispensary. 65 participants (N = 34 men, N = 31 women) were assessed in a mobile pharmacology lab before, immediately after, and 1 -h after ad libitum concentrate use. Plasma cannabinoids (THC, 11-OH-THC, CBD), subjective drug effects, and verbal memory errors were assessed at all three time points. RESULTS: Although men and women exhibited similar plasma 11-OH-THC levels across time (p = .10), sex differences were found in plasma THC and CBD after legal market concentrate use, with men displaying significantly higher levels of plasma THC and CBD immediately after cannabis concentrate use (plasma THC [ng/mL]: Mmen = 489.88, Mwomen = 135.08, p < .001; plasma CBD [ng/mL]: Mmen = 1.14, Mwomen = 0.53, p = .04). Despite this, sex differences in subjective effects and verbal memory errors did not emerge, although women reported a steeper decrease in drug liking after use (p = .04). CONCLUSION: These data provide the first look at sex differences after acute naturalistic cannabis concentrate use, and suggest much higher THC exposure in men versus women, but similar acute drug and impairment effects across the sexes. Further studies are needed to determine the mechanisms (e.g. tolerance, cannabinoid metabolism, smoking topography) behind these findings.

Cannabis use and sleep: Expectations, outcomes, and the role of age.

STUDY OBJECTIVES: Determine relationship between cannabis use with 1) expectations of cannabis being a sleep aid, 2) subjective sleep outcomes, and 3) the influence of age on these relationships. METHODS: In 152 moderate cannabis users with a wide age range (67% female, mean age = 31.45, SD = 12.96, age range = 21-70; mean days of cannabis use in prior two weeks = 5.54, SD = 5.25) we examined the influence of cannabis use history and behaviors on expectations of cannabis being a sleep aid and sleep outcomes via the Pittsburgh Sleep Quality Index (PSQI). Moderation analysis examined the role of age in the relationship between cannabis use and sleep outcomes. RESULTS: Endorsing current cannabis use and more days of cannabis use were associated with increased expectations that cannabis use improves sleep (all ß > 0.03, p < 0.04). Frequency of recent use and reported average THC or CBD concentration were largely not associated with sleep outcomes. However, endorsing current cannabis use was associated with worse subjective sleep quality (ß = 1.34, p = 0.02) and increased frequency of consuming edibles was associated with worse subjective sleep efficiency (ß = 0.03, p = 0.04), lower sleep duration (ß = 0.03, p = 0.01), and higher global PSQI scores (worse overall sleep) (ß = 0.10, p = 0.01). Additionally, age had a moderating influence on the relationship between increased self-reported concentration of CBD and both better sleep duration and sleep quality (both p < 0.03). While the main effects of cannabis use on sleep outcomes did not survive multiple comparisons correction test (all p adj > 0.34), the adjusted p values for the main effects of cannabis behaviors/history on expectations of cannabis as a sleep aid (p adj = 0.07-0.09) and the main effects of CBD concentration on sleep duration (p adj = 0.08), as well as the interaction terms of CBD and age for that model (p adj = 0.07), were trending. CONCLUSION: Cannabis users have increased expectations of cannabis being a sleep aid, but few associations existed between cannabis use and sleep outcomes. The two exceptions were endorsing any cannabis use and frequency of edible use. Additionally, age may be an important moderator of the potential positive influence CBD concentration can have on sleep.

Exploring cannabis concentrates on the legal market: User profiles, product strength, and health-related outcomes.

BACKGROUND: Concentrated cannabis products are increasingly available and used, particularly in states with legal cannabis, but little is known about the profiles and characteristics of concentrate users. We aimed to characterize user profiles of cannabis users living in states with legal medical or recreational cannabis who reported using concentrates to those who do not use concentrates. METHODS: An anonymous online survey was advertised in California, Colorado, Nevada, Oregon, and Washington. We compared respondents who endorsed frequent concentrate use (FC; N = 67) (i.e. 4 days/week) with cannabis users who never use concentrates (NC; N = 64), and with those who smoke/vaporize cannabis flower frequently but never or very rarely use concentrates (FF; N = 60), on measures related to cannabis use patterns and cannabinoid product strength, other substance use, and occupational functioning and health. RESULTS: FC endorsed more symptoms of cannabis use disorder as compared to non-concentrate users (p < 0.05), but were similar to FF and NC on other health and occupational outcomes. FC also differed from FF and NC in that they tended to use cannabis that was higher in THC (p < 0.0005), even when using non-concentrated forms of cannabis (p < 0.005). Over half of FC users reported typically using concentrates of at least 80% THC, and 21% endorsed use of (non-concentrated) dry cannabis flower containing at least 30% THC. CONCLUSIONS: Concentrate users endorsed higher symptoms of cannabis use disorder and use higher strength cannabis even when using non-concentrated forms. Frequent use of concentrates may be associated with additional risks over and above frequent use of flower forms.

Within-Family Effects of Smoking during Pregnancy on ADHD: the Importance of Phenotype.

We sought to test within- and between- family associations of smoking during pregnancy (SDP) and attention deficit-hyperactivity disorder (ADHD) symptoms using a structured interview based on the conventional Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) symptoms and the Strengths and Weaknesses of ADHD-Symptoms and Normal-Behavior (SWAN) scale, which is a population based measure that grew out of the notion that an ADHD diagnosis exists on the extreme end of a continuum of normative behaviors and includes both above- and below- average performance on attention and activity. We used a sibling-comparison approach in a sample of 173 families including siblings aged 7-16 years (52% male) drawn from the state of Missouri, USA, wherein mothers smoked during one pregnancy but not the other. There was a within-family effect of smoking during pregnancy on SWAN hyperactivity/impulsivity and SWAN total ADHD behaviors. The associations between SDP and DSM-IV-based ADHD symptom dimensions as well as SWAN inattention were explained by familial confounds. These findings suggest that SDP exerts a potentially causal effect on increased ADHD hyperactive/impulsive behaviors and that this SDP effect is best captured when hyperactivity/impulsivity is assessed more normatively across the population, rather than specifically assessing problematic behaviors via DSM symptoms. Thus, any potentially causal effect of SDP on ADHD symptom dimensions may be restricted to hyperactive/impulsive behaviors rather than inattention, and normative, non-DSM-IV based behavioral measures may provide a more sensitive test of mechanisms of SDP-ADHD symptom associations, particularly in non-clinical samples.

Alpha-2 adrenergic receptors and attention-deficit/hyperactivity disorder.

Pharmacologic management of attention-deficit/hyperactivity disorder (ADHD) has expanded beyond stimulant medications to include alpha-2 adrenergic agonists. These agents exert their actions through presynaptic stimulation and likely involve facilitation of dopamine and noradrenaline neurotransmission, both of which are thought to play critical roles in the pathophysiology of ADHD. Furthermore, frontostriatal dysfunction giving rise to neuropsychological weaknesses has been well-established in patients with ADHD and may explain how alpha-2 agents exert their beneficial effects. In the following review, we consider relevant neurobiological underpinnings of ADHD with respect to why alpha-2 agents may be effective in treating this condition. We also review new formulations of alpha-2 agonists, emerging data on their use in ADHD, and implications for clinical practice. Integrating knowledge of pathophysiologic mechanisms and mechanisms of drug action may inform our medication choices and facilitate treatment of ADHD and related disorders.