Impact of year-long cannabis use for medical symptoms on brain activation during cognitive processes.

Importance: Cannabis is increasingly being used to treat medical symptoms, but the effects of cannabis use on brain function in those using cannabis for these symptoms is not known. Objective: To test whether brain activation during working memory, reward, and inhibitory control tasks, areas of cognition impacted by cannabis, showed increases following one year of cannabis use for medical symptoms. Design: This observational cohort study took place from July 2017 to July 2020 and is reported on in 2024. Setting: Participants were from the greater Boston area. Participants: Participants were recruited as part of a clinical trial based on seeking medical cannabis cards for anxiety, depression, pain, or sleep disorders, and were between 18 and 65 years. Exclusion criteria were daily cannabis use and cannabis use disorder at baseline. Main Outcomes and Measures: Outcomes were whole brain functional activation during tasks involving working memory, reward and inhibitory control at baseline and after one year of cannabis use. Results: Imaging was collected in participants before and one year after obtaining medical cannabis cards; 57 at baseline (38 female [66.7%]; mean [SD] age, 38.0 [14.6] years) at baseline, and 54 at one-year (37 female [68.5%]; mean [SD] age, 38.7 [14.3] years). Imaging was also collected in 32 healthy control participants (22 female [68.8%]; mean [SD] age, 33.8 [11.8] years) at baseline. In all groups and at both time points, functional imaging revealed canonical activations of the probed cognitive processes. No statistically significant difference in brain activation between the two timepoints (baseline and one-year) in those with medical cannabis cards and no association of changes in cannabis use frequency with brain activation were found. Conclusions and Relevance: Findings suggest that adults do not show significant neural effects in the areas of cognition of working memory, reward, and inhibitory control after one year of cannabis use for medical symptoms. The results warrant further studies that probe effects of cannabis at higher doses, with greater frequency, in younger age groups, and with larger, more diverse cohorts.Trial Registration: NCT03224468, https://clinicaltrials.gov/. Key Points: Question:: This study investigated the impact of year-long cannabis use for medical symptoms on brain activation during cognitive processes implicated in cannabis use.Findings:: Functional magnetic resonance imaging during a working memory, reward, and inhibitory control task was collected at baseline and after one year of medical cannabis card ownership. After one year, brain activation did not differ statistically from baseline and was not associated with changes in cannabis use frequency.Meaning:: The absence of activation differences suggests that adults using cannabis for medical conditions may not experience significant neural effects in regards to reward, working memory, or inhibitory control.

Intoxication due to Δ9-tetrahydrocannabinol is characterized by disrupted prefrontal cortex activity.

Neural states of impairment from intoxicating substances, including cannabis, are poorly understood. Cannabinoid 1 receptors, the main target of Δ9-tetrahydrocannabinol (THC), the primary intoxicating cannabinoid in cannabis, are densely localized within prefrontal cortex; therefore, prefrontal brain regions are key locations to examine brain changes that characterize acute intoxication. We conducted a double-blind, randomized, cross-over study in adults, aged 18-55 years, who use cannabis regularly, to determine the effects of acute intoxication on prefrontal cortex resting-state measures, assessed with portable functional near-infrared spectroscopy. Participants received oral THC (10-80 mg, individually dosed to overcome tolerance and achieve acute intoxication) and identical placebo, randomized for order; 185 adults were randomized and 128 completed both study days and had usable data. THC was associated with expected increases in subjective intoxication ratings (ES = 35.30, p < 0.001) and heart rate (ES = 11.15, p = 0.001). THC was associated with decreased correlations and anticorrelations in static resting-state functional connectivity within the prefrontal cortex relative to placebo, with weakest correlations and anticorrelations among those who reported greater severity of intoxication (RSFC between medial PFC-ventromedial PFC and DEQ scores, r = 0.32, p < 0.001; RSFC between bilateral mPFC and DEQ scores, r = -0.28, p = 0.001). Relative to placebo, THC was associated with increased variability (or reduced stability) in dynamic resting-state functional connectivity of the prefrontal cortex at p = 0.001, consistent across a range of window sizes. Finally, using frequency power spectrum analyses, we observed that relative to placebo, THC was associated with widespread reduced spectral power within the prefrontal cortex across the 0.073-0.1 Hz frequency range at p < 0.039. These neural features suggest a disruptive influence of THC on the neural dynamics of the prefrontal cortex and may underlie cognitive impairing effects of THC that are detectable with portable imaging. This study is registered in Clinicaltrials.gov (NCT03655717).

Associations between behavioral and self-reported impulsivity, brain structure, and genetic influences in middle childhood.

Impulsivity undergoes a normative developmental trajectory from childhood to adulthood and is thought to be driven by maturation of brain structure. However, few large-scale studies have assessed associations between impulsivity, brain structure, and genetic susceptibility in children. In 9112 children ages 9-10 from the ABCD study, we explored relationships among impulsivity (UPPS-P impulsive behavior scale; delay discounting), brain structure (cortical thickness (CT), cortical volume (CV), and cortical area (CA)), and polygenic scores for externalizing behavior (PGSEXT). Both higher UPPS-P total scores and more severe delay-discounting had widespread, low-magnitude associations with smaller CA in frontal and temporal regions. No associations were seen between impulsivity and CV or CT. Additionally, higher PGSEXT was associated with both higher UPPS-P scores and with smaller CA and CV in frontal and temporal regions, but in non-overlapping cortical regions, underscoring the complex interplay between genetics and brain structure in influencing impulsivity. These findings indicate that, within large-scale population data, CA is significantly yet weakly associated with each of these impulsivity measures and with polygenic risk for externalizing behaviors, but in distinct brain regions. Future work should longitudinally assess these associations through adolescence, and examine associated functional outcomes, such as future substance use and psychopathology.

Use of Tobacco Products and Suicide Attempts Among Elementary School-Aged Children.

Importance: The use of tobacco products, including e-cigarettes and vaping, has rapidly increased among children. However, despite consistent associations found between smoking cigarettes and suicidal behaviors among adolescents and adults, there are limited data on associations between emerging tobacco products and suicidal behaviors, especially among preadolescent children. Objective: To examine whether the use of tobacco products is associated with nonsuicidal self-injury (NSSI), suicidal ideation (SI), and suicide attempts (SAs) among preadolescent children. Design, Setting, and Participants: This cohort study, conducted from September 1, 2022, to September 5, 2023, included participants in the Adolescent Brain Cognitive Development study, a population-based cohort of 11 868 US children enrolled at 9 and 10 years of age. The cross-sectional investigation focused on 3-year periods starting from the baseline to year 2 of follow-up. Statistical analysis was performed from October 1, 2022, to June 30, 2023. Main Outcomes and Measures: Children's use of tobacco products was assessed based on youth reports, including lifetime experiences of various nicotine-related products, supplemented with hair toxicologic tests. Main outcomes were children's lifetime experiences of NSSI, SI, and SAs, assessed using the K-SADS-5 (Kiddie Schedule for Affective Disorders and Schizophrenia for the DSM-5). Multivariate logistic regression was conducted to examine the associations of the use of tobacco products with NSSI, SI, and SAs among the study participants. Sociodemographic, familial, and children's behavioral, temperamental, and clinical outcomes were adjusted in the analyses. Results: Of 8988 unrelated study participants (median age, 9.8 years [range, 8.9-11.0 years]; 4301 girls [47.9%]), 101 children (1.1%) and 151 children (1.7%) acknowledged lifetime use of tobacco products at baseline and at 18-month follow-up, respectively. After accounting for various suicide risk factors and potential confounders, children reporting use of tobacco products were at a 3 to 5 times increased risk of SAs (baseline: n = 153 [adjusted odds ratio (OR), 4.67; 95% CI, 2.35-9.28; false discovery rate (FDR)-corrected P < .001]; year 1: n = 227 [adjusted OR, 4.25; 95% CI, 2.33-7.74; FDR-corrected P < .001]; and year 2: n = 321 [adjusted OR, 2.85; 95% CI, 1.58-5.13; FDR-corrected P = .001]). Of all facets of impulsivity measures that were significant correlates of use of tobacco products, negative urgency was the only independent risk factor for SAs (adjusted OR, 1.52 [95% CI, 1.31-1.78]; FDR-corrected P < .001). In contrast, children's alcohol, cannabis, and prescription drug use were not associated with SAs. Conclusions and Relevance: This study of US children suggests that the increased risk of SAs, consistently reported for adolescents and adults who smoke cigarettes, extends to a range of emerging tobacco products and manifests among elementary school-aged children. Further investigations are imperative to clarify the underlying mechanisms and to implement effective preventive policies for children.

Substance Use, Suicidal Thoughts, and Psychiatric Comorbidities Among High School Students.

This cross-sectional study evaluates the dose-dependent association between alcohol, cannabis, and nicotine use and psychiatric symptoms among participants in the Substance Use and Risk Factor Survey and the Youth Risk Behavior Survey.

Contingency management is associated with positive changes in attitudes and reductions in cannabis use even after discontinuation of incentives among non-treatment seeking youth.

BACKGROUND: It is important to identify interventions that reduce harm in youth not motivated to change their cannabis use. This study evaluated how short-duration contingency management (CM) impacts cannabis use attitudes and behavior after abstinence incentives are discontinued among non-treatment seeking youth. METHODS: Participants (N=220) were randomized to 4 weeks of abstinence-based CM (CB-Abst; n=126) or monitoring (CB-Mon; n=94). Participants completed self-report and provided biochemical measures of cannabis exposure at baseline, end-of-intervention, and 4-week follow-up. Changes in self-reported cannabis use frequency (days/week; times/week) and biochemically verified creatinine-adjusted 11-nor-9-carboxy-tetrahydrocannabinol concentrations (CN-THCCOOH) were analyzed between groups from baseline to follow-up. In CB-Abst, cannabis use goals at end-of-intervention were described and changes in cannabis use at follow-up were explored by goals and cannabis use disorder (CUD) diagnosis. RESULTS: There was a group by visit interaction on cannabis use (days: beta=0.93, p=0.005; times: beta=0.71, p<0.001; CN-THCCOOH: beta=0.26, p=0.004), with reductions at follow-up detected only in CB-Abst. Following 4 weeks of abstinence, 68.4% of CB-Abst participants wanted to reduce or abstain from cannabis use following completion of CM. Those in CB-Abst who set end-of-intervention reduction goals and were without CUD had greater decreases in cannabis use frequency at follow-up (Goals*time on days/week: beta=-2.27, p<0.001; CUD*time on times/week: beta=0.48, SE=0.24, t=2.01, p=0.048). CONCLUSIONS: Findings support the utility of brief incentivized abstinence for generating motivation to reduce cannabis use and behavior change even after incentives end. This study supports CM as a potentially viable harm reduction strategy for those not yet ready to quit.

The Developmental Timing but Not Magnitude of Adolescent Risk-Taking Propensity Is Consistent Across Social, Environmental, and Psychological Factors.

PURPOSE: Risk-taking is thought to peak during adolescence, but most prior studies have relied on small convenience samples lacking participant diversity. This study tested the generalizability of adolescent self-reported risk-taking propensity across a comprehensive set of participant-level social, environmental, and psychological factors. METHODS: Data (N = 1,005,421) from the National Survey on Drug Use and Health were used to test the developmental timing and magnitude of risk-taking propensity and its link to alcohol and cannabis use across 19 subgroups defined via sex, race/ethnicity, socioeconomic status, population density, religious affiliation, and mental health. RESULTS: The developmental timing of a lifespan peak in risk-taking propensity during adolescence (15-18 years old) generalized across nearly all levels of social, environmental, and psychological factors, whereas the magnitude of this peak widely varied. Nearly all adolescents with regular substance use reported higher levels of risk-taking propensity. DISCUSSION: Results support a broad generalizability of adolescence as the peak lifespan period of self-reported risk-taking but emphasize the importance of participant-level factors in determining the specific magnitude of reported risk-taking.

Assessing changes in sleep across four weeks among adolescents randomized to incentivized cannabis abstinence.

BACKGROUND: Withdrawal from cannabis use is associated with sleep disturbances, often leading to resumption of use. Less is known about the impact of abstinence on sleep in adolescence, a developmental window associated with high rates of sleep disturbance. This study investigated effects of sustained abstinence on self-reported sleep quality and disturbance in adolescents reporting frequent cannabis use. METHODS: Non-treatment seeking adolescents, recruited from school screening surveys and the community, with frequent cannabis use (MAge=17.8, SDAge=1.7, 47% female, 45% non-white) were randomized to four weeks of biochemically-verified abstinence, motivated via contingency management (CB-Abst, n=53), or monitoring without an abstinence requirement (CB-Mon, n=63). A mixed-effects model was used to predict change in Pittsburgh Sleep Quality Index (PSQI) scores. RESULTS: Participants in CB-Abst reported higher overall PSQI scores than those in CB-Mon (M=1.06, p=0.01) indicating worse sleep during the four-week trial. Sleep disruptions in CB-Abst increased during Week 1 of abstinence (d=0.34, p=0.04), decreased during Week 2 (d=0.36, p=0.04), and remained constant for the rest of the trial. At Week 4, sleep was comparable to baseline levels for those in CB-Abst (p=0.87). Withdrawal-associated sleep disruption in the CB-Abst group was circumscribed to increases in sleep latency (b=0.35; p=0.05). CONCLUSIONS: Cannabis abstinence in adolescents was associated with transient delayed onset of sleep initiation falling asleep during the first week of abstinence. Findings highlight withdrawal-associated changes in sleep latency as an intervention target for supporting adolescents attempting abstinence. Future research should use objective measures of sleep and focus on elucidating mechanisms underlying sleep disturbances with cannabis use and withdrawal.

Resting state network connectivity is associated with cognitive flexibility performance in youth in the Adolescent Brain Cognitive Development Study.

Cognitive flexibility is an executive functioning skill that develops in childhood, and when impaired, has transdiagnostic implications for psychiatric disorders. To identify how intrinsic neural architecture at rest is linked to cognitive flexibility performance, we used the data-driven method of independent component analysis (ICA) to investigate resting state networks (RSNs) and their whole-brain connectivity associated with levels of cognitive flexibility performance in children. We hypothesized differences by cognitive flexibility performance in RSN connectivity strength in cortico-striatal circuitry, which would manifest via the executive control network, right and left frontoparietal networks (FPN), salience network, default mode network (DMN), and basal ganglia network. We selected participants from the Adolescent Brain Cognitive Development (ABCD) Study who scored at the 25th, ("CF-Low"), 50th ("CF-Average"), or 75th percentiles ("CF-High") on a cognitive flexibility task, were early to middle puberty, and did not exhibit significant psychopathology (n = 967, 47.9% female; ages 9-10). We conducted whole-brain ICA, identifying 14 well-characterized RSNs. Groups differed in connectivity strength in the right FPN, anterior DMN, and posterior DMN. Planned comparisons indicated CF-High had stronger connectivity between right FPN and supplementary motor/anterior cingulate than CF-Low. CF-High had more anti-correlated connectivity between anterior DMN and precuneus than CF-Average. CF-Low had stronger connectivity between posterior DMN and supplementary motor/anterior cingulate than CF-Average. Post-hoc correlations with reaction time by trial type demonstrated significant associations with connectivity. In sum, our results suggest childhood cognitive flexibility performance is associated with DMN and FPN connectivity strength at rest, and that there may be optimal levels of connectivity associated with task performance that vary by network.

Pain catastrophizing is associated with reduced neural response to monetary reward.

Introduction: Pain catastrophizing, a measure of an individual's negative emotional and cognitive appraisals of pain, has been included as a key treatment target in many psychological interventions for pain. However, the neural correlates of pain catastrophizing have been understudied. Prior neuroimaging evidence suggests that adults with pain show altered reward processing throughout the mesocorticolimbic reward circuitry. Methods: In this study, we tested the association between Pain Catastrophizing Scale (PCS) scores and neural activation to the Monetary Incentive Delay (MID) reward neuroimaging task in 94 adults reporting a range of pain, insomnia, and mood symptoms. Results: Results indicated that PCS score but not pain intensity was significantly associated with blunted activation in the caudate and putamen in response to feedback of successful vs. unsuccessful trials on the MID task. Mediation analyses indicated that PCS score fully mediated the relationship between depression symptoms and reward activation. Discussion: These findings provide evidence that pain catastrophizing is independently associated with altered striatal function apart from depression symptoms and pain intensity. Thus, in individuals experiencing pain and/or co- morbid conditions, reward dysfunction is directly related to pain catastrophizing.

Longitudinal Associations Between Cannabis Use and Cognitive Impairment in a Clinical Sample of Middle-Aged Adults Using Cannabis for Medical Symptoms.

Introduction: Cannabis use to alleviate medical symptoms is increasing in middle-aged and older adults. Cognitive impairment associated with cannabis use may be especially detrimental to these understudied age groups. We hypothesized that among middle-aged and older adults who used cannabis for 12 months, frequent (≥3 days/week) compared with nonfrequent (≤2 days/week) use will be associated with cognitive impairment. Materials and Methods: We performed secondary analysis on data from a clinical trial of cannabis use for medical symptoms. Participants (n=62) were ≥45 years, and completed a baseline and at least one postbaseline visit. Cognitive domains were assessed through the Cambridge Neuropsychological Test Automated Battery. Cannabis use was assessed prospectively through daily smartphone diaries. Frequency of cannabis use was a binary predictor in a mixed-effects logistic regression model predicting cognitive impairment adjusted for baseline cognitive functioning. Results: At baseline, participants were primarily nonfrequent cannabis users; however, in all other time periods, most participants were frequent users (range: 55-58%). Cognitive outcomes did not differ between frequent and nonfrequent cannabis users. However, in sensitivity analyses, respondents with problematic cannabis use scored significantly worse on one cognitive domain compared to those without problematic cannabis use. Conclusions: In a clinical sample of adults aged ≥45 years, no longitudinal associations were found between cannabis use and cognitive functioning. However, a few significant associations were observed between problematic use and cognitive functioning. Further research is needed to assess the impact of cannabis use on adults, particularly those aged ≥65 years, and to investigate potential subtler influences of cannabis use on cognition. ClinicalTrials.gov ID: NCT03224468.

The Cannabis Effects Expectancy Questionnaire-Medical (CEEQ-M): Preliminary psychometric properties and longitudinal validation within a clinical trial.

The use of cannabis for medical symptoms is increasing despite limited evidence for its efficacy. Expectancies-prior beliefs about a substance or medicine-can modulate use patterns and effects of medicines on target symptoms. To our knowledge, cannabis expectancies have not been studied for their predictive value for symptom relief. The 21-item Cannabis Effects Expectancy Questionnaire-Medical (CEEQ-M) is the first longitudinally validated measure of expectancies for cannabis used for medical symptoms. The questionnaire was developed for a randomized clinical trial of the effect of state cannabis registration (SCR) card ownership on symptoms of pain, insomnia, anxiety, and depression in adults (N = 269 across six questionnaire administrations). Item-level analyses (n = 188) demonstrated between-person stability of expectancies and no aggregate, within-person expectancy changes 3 months after individuals gained access to SCR cards. Exploratory factor analysis (n = 269) indicated a two-factor structure. Confirmatory factor analysis at a later timepoint (n = 193) demonstrated good fit and scalar invariance of the measurement model. Cross-lagged panel models across 3 and 12 months (n = 187 and 161, respectively) indicated that CEEQ-M-measured expectancies did not predict changes in self-reported cannabis use; symptoms of pain, insomnia, anxiety, and depression; and well-being. However, greater baseline cannabis use predicted more positive expectancy changes. The findings suggest that the CEEQ-M is psychometrically sound. Future work should clarify at what timescales cannabis expectancies have predictive value and how cannabis expectancies for medical symptoms are maintained and diverge from other substance use expectancies. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Genetic patterning for child psychopathology is distinct from that for adults and implicates fetal cerebellar development.

Childhood psychiatric symptoms are often diffuse but can coalesce into discrete mental illnesses during late adolescence. We leveraged polygenic scores (PGSs) to parse genomic risk for childhood symptoms and to uncover related neurodevelopmental mechanisms with transcriptomic and neuroimaging data. In independent samples (Adolescent Brain Cognitive Development, Generation R) a narrow cross-disorder neurodevelopmental PGS, reflecting risk for attention deficit hyperactivity disorder, autism, depression and Tourette syndrome, predicted psychiatric symptoms through early adolescence with greater sensitivity than broad cross-disorder PGSs reflecting shared risk across eight psychiatric disorders, the disorder-specific PGS individually or two other narrow cross-disorder (Compulsive, Mood-Psychotic) scores. Neurodevelopmental PGS-associated genes were preferentially expressed in the cerebellum, where their expression peaked prenatally. Further, lower gray matter volumes in cerebellum and functionally coupled cortical regions associated with psychiatric symptoms in mid-childhood. These findings demonstrate that the genetic underpinnings of pediatric psychiatric symptoms differ from those of adult illness, and implicate fetal cerebellar developmental processes that endure through childhood.

Cannabis use for medical symptoms: Patterns over the first year of use.

BACKGROUND: As greater numbers of states in the United States and countries in the world continue to legalize cannabis for medical use, it has become increasingly important to assess patterns of cannabis use in individuals using cannabis for medical symptoms over time. A public health concern is that, like recreational cannabis, some individuals using cannabis for medical reasons may develop detrimental patterns of use, leading to the development of a cannabis use disorder (CUD). METHODS: In a 9-month longitudinal cohort study following a 12-week randomized, waitlist-controlled trial in 149 adults who used cannabis to alleviate insomnia, pain, depressed mood, or anxiety (RCT: NCT03224468), we assessed whether patterns of cannabis use for the 9 months following the RCT were associated with the development of CUD. RESULTS: We identified five unique trajectories of use; 31 participants (21%) had low stable or no use, 50 (34%) had medium stable use, 19 (13%) had high stable use, 26 (17%) showed de-escalating and 23 (15%) showed escalating use over 9 months following the RCT. Of 149 participants enrolled, 19 (13%) met diagnostic criteria for CUD at 12 months. Only the escalating cannabis use pattern predicted significantly higher rates of CUD compared to the low or no use category (OR = 4.29, 95% CI = 1.21 to 10.87, p = 0.02). CONCLUSIONS: These data indicate that most individuals using cannabis for medical symptoms have a stable pattern of use over the first year. Escalation of use may be a detrimental pattern that warrants further concern.

Development of cannabis use disorder in medical cannabis users: A 9-month follow-up of a randomized clinical trial testing effects of medical cannabis card ownership.

Background: Evidence for long-term effectiveness of commercial cannabis products used to treat medical symptoms is inconsistent, despite increasingly widespread use. Objective: To prospectively evaluate the effects of using cannabis on self-reported symptoms of pain, insomnia, anxiety, depression, and cannabis use disorder (CUD) after 12 months of use. Methods: This observational cohort study describes outcomes over 9 months following a 12-week randomized, waitlist-controlled trial (RCT: NCT03224468) in which adults (N = 163) who wished to use cannabis to alleviate insomnia, pain, depression, or anxiety symptoms were randomly assigned to obtain a medical marijuana card immediately (immediate card acquisition group) or to delay obtaining a card for 12 weeks delay (delayed card acquisition group). During the 9-month post-randomization period, all participants could use cannabis as they wished and choose their cannabis products, doses, and frequency of use. Insomnia, pain, depression, anxiety, and CUD symptoms were assessed over the 9-month post-randomization period. Results: After 12 months of using cannabis for medical symptoms, 11.7% of all participants (n = 19), and 17.1% of those using cannabis daily or near-daily (n = 6) developed CUD. Frequency of cannabis use was positively correlated with pain severity and number of CUD symptoms, but not significantly associated with severity of self-reported insomnia, depression, or anxiety symptoms. Depression scores improved throughout the 9 months in all participants, regardless of cannabis use frequency. Conclusions: Frequency of cannabis use was not associated with improved pain, anxiety, or depression symptoms but was associated with new-onset cannabis use disorder in a significant minority of participants. Daily or near-daily cannabis use appears to have little benefit for these symptoms after 12 months of use.

Cannabis use and sleep quality in daily life: An electronic daily diary study of adults starting cannabis for health concerns.

BACKGROUND: Real world patterns of cannabis use for health concerns are highly variable and rarely overseen by a physician. Pragmatic effectiveness studies with electronic daily diaries that capture person-specific patterns of cannabis use and health symptoms may help clarify risks and benefits. METHODS: As part of a larger, randomized trial (NCT03224468), adults (N = 181) seeking cannabis for insomnia, pain, or anxiety or depressive symptoms were randomized to obtain a medical cannabis card immediately (MCC) or a waitlist control (WLC) and completed 12-weeks of daily web-based surveys on cannabis use and sleep, pain, and depressive symptoms. RESULTS: Completion rates of daily surveys were moderate to high (median completed: 72 out of 90 days). Daily reports of cannabis use were consistent with monthly interview assessments and urinalysis. The MCC group increased cannabis use frequency in the 12 weeks following randomization, while WLC did not. Among the MCC group, self-reported sleep quality was significantly higher on cannabis use days, compared to nonuse days. The MCC group displayed long-term sleep improvements, consistent with increasing cannabis frequency. No improvements were found for pain or depressive symptoms. CONCLUSION: Cannabis use is associated with same day improvements in self-reported sleep quality, but not pain or depressive symptoms, although sleep improvements occurred in the context of increased frequency of cannabis use, raising the risk for cannabis use disorder. Daily web-based assessments of cannabis appear valid and feasible in adults seeking cannabis for health concerns, providing a flexible, complementary method for future real-world effectiveness studies with expanded and objective measures.

State-Level Recreational Cannabis Legalization Is Not Differentially Associated with Cannabis Risk Perception Among Children: A Multilevel Regression Analysis.

Introduction: As more states pass recreational cannabis laws (RCLs) for adults, there is concern that increasing (and state-sanctioned) cannabis acceptance will result in a reduced perception of risk of harm from cannabis among children. We aimed to discover whether children in states with RCLs had decreased perception of risk from cannabis compared with children in states with illicit cannabis. Methods: We analyzed data from the multisite multistate Adolescent Brain and Cognitive Development Study to determine how the perception of cannabis harm among children (age at baseline: 9-10; N=10,395) changes over time in states with and without RCLs. Using multilevel modeling, we assessed survey responses from children longitudinally across 3 years, adjusting for state-, family-, and participant-level clustering and child-level factors, including demographics (sex, race, and socioeconomic status), religiosity, and trait impulsivity. Results: There was no significant main effect of state RCLs on perceived risk of cannabis use, and no differences in change over time by state RCLs, even after controlling for demographic factors and other risk (e.g., impulsivity) and protective (e.g., religiosity) factors. Conclusions: This analysis indicates that state-level RCLs are not associated with differential perception of cannabis risk among children, even after controlling for demographics, trait impulsivity, and religiosity. Future studies could assess how perception of risk from cannabis changes as children and adolescents continue to mature in states with and without RCLs.