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).

Implementation of Community Health Worker Support for Tobacco Cessation: A Mixed-Methods Study.

Objective: Adults with serious mental illness have high tobacco use disorder rates and underutilization of first-line tobacco cessation pharmacotherapy. In a randomized trial, participants offered community health worker (CHW) support and primary care provider (PCP) education had higher tobacco abstinence rates at two years, partly through increased tobacco cessation pharmacotherapy initiation. This study determined the association between participant-CHW engagement and tobacco abstinence outcomes. Methods: This was a secondary, mixed-methods analysis of 196 participants in the trial's intervention arm. Effects of CHW visit number and duration, CHW co-led smoking cessation group sessions attended, and CHW-attended PCP visit number on tobacco use disorder pharmacotherapy initiation and tobacco abstinence were modeled using logistic regression. Interviews with 12 CHWs, 16 participants, and 17 PCPs were analyzed thematically. Results: Year-two tobacco abstinence was associated with CHW visit number (OR=1.85, 95% CI=[1.29, 2.66]) and duration (OR=1.85, 95% CI=[1.33, 2.58]) and number of groups attended (OR=1.51, 95% CI=[1.00, 2.28]); effects on pharmacotherapy initiation were similar. 1-3 CHW visits per month over two years was optimal for achieving abstinence. Interviews identified engagement facilitators, including CHWs establishing trust, providing goal accountability, skills reinforcement, and assistance overcoming barriers to treatment access and adherence related to social determinants of health and illness factors. Robust training and supervision facilitated CHW effectiveness. Barriers included PCPs' and care teams' limited understanding of the CHW role. Conclusions: Feasible CHW engagement was associated with tobacco abstinence in adults with serious mental illness. CHW implementation may benefit from promoting CHW training and integration within clinical teams.

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.

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.

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).

Effect of a Tobacco Cessation Intervention Incorporating Weight Management for Adults With Serious Mental Illness: A Randomized Clinical Trial.

Importance: Tobacco smoking drives markedly elevated cardiovascular disease risk and preventable death in persons with serious mental illness, and these risks are compounded by the high prevalence of overweight/obesity that smoking cessation can exacerbate. Guideline-concordant combined pharmacotherapy and behavioral smoking cessation treatment improves abstinence but is not routinely offered in community settings, particularly to those not seeking to quit smoking immediately. Objective: To determine the effectiveness of an 18-month pharmacotherapy and behavioral smoking cessation intervention incorporating weight management and support for physical activity in adults with serious mental illness interested in quitting smoking within 1 or 6 months. Design, Setting, and Participants: This was a randomized clinical trial conducted from July 25, 2016, to March 20, 2020, at 4 community health programs. Adults with serious mental illness who smoked tobacco daily were included in the study. Participants were randomly assigned to intervention or control, stratified by willingness to try to quit immediately (within 1 month) or within 6 months. Assessors were masked to group assignment. Interventions: Pharmacotherapy, primarily varenicline, dual-form nicotine replacement, or their combination; tailored individual and group counseling for motivational enhancement; smoking cessation and relapse prevention; weight management counseling; and support for physical activity. Controls received quitline referrals. Main Outcome and Measures: The primary outcome was biochemically validated, 7-day point-prevalence tobacco abstinence at 18 months. Results: Of the 298 individuals screened for study inclusion, 192 enrolled (mean [SD] age, 49.6 [11.7] years; 97 women [50.5%]) and were randomly assigned to intervention (97 [50.5%]) or control (95 [49.5%]) groups. Participants self-identified with the following race and ethnicity categories: 93 Black or African American (48.4%), 6 Hispanic or Latino (3.1%), 90 White (46.9%), and 9 other (4.7%). A total of 82 participants (42.7%) had a schizophrenia spectrum disorder, 62 (32.3%) had bipolar disorder, and 48 (25.0%) had major depressive disorder; 119 participants (62%) reported interest in quitting immediately (within 1 month). Primary outcome data were collected in 183 participants (95.3%). At 18 months, 26.4% of participants (observed count, 27 of 97 [27.8%]) in the intervention group and 5.7% of participants (observed count, 6 of 95 [6.3%]) in the control group achieved abstinence (adjusted odds ratio [OR], 5.9; 95% CI, 2.3-15.4; P < .001). Readiness to quit within 1 month did not statistically significantly modify the intervention's effect on abstinence. The intervention group did not have significantly greater weight gain than the control group (mean weight change difference, 1.6 kg; 95% CI, -1.5 to 4.7 kg). Conclusions and Relevance: Findings of this randomized clinical trial showed that in persons with serious mental illness who are interested in quitting smoking within 6 months, an 18-month intervention with first-line pharmacotherapy and tailored behavioral support for smoking cessation and weight management increased tobacco abstinence without significant weight gain. Trial Registration: ClinicalTrials.gov Identifier: NCT02424188.

Promoting Evidence-Based Tobacco Cessation Treatment in Community Mental Health Clinics: Protocol for a Prepost Intervention Study.

BACKGROUND: Tobacco smoking is highly prevalent among persons with serious mental illness (SMI) and is the largest contributor to premature mortality in this population. Evidence-based smoking cessation therapy with medications and behavioral counseling is effective for persons with SMI, but few receive this treatment. Mental health providers have extensive experience working with clients with SMI and frequent treatment contacts, making them well positioned to deliver smoking cessation treatment. However, few mental health providers feel adequately trained to deliver this treatment, and many providers believe that smokers with SMI are not interested in quitting or have concerns about the safety of smoking cessation pharmacotherapy, despite substantial evidence to the contrary. OBJECTIVE: We present the protocol for the pilot "IMPACT" (Implementing Action for Tobacco Smoking Cessation Treatment) study, which aims to pilot test a multicomponent implementation intervention to increase the delivery of evidence-based tobacco smoking cessation treatment in community mental health clinics. METHODS: We are using a prepost observational design to examine the effects of an implementation intervention designed to improve mental health providers' delivery of the following four evidence-based practices related to smoking cessation treatment: (1) assessment of smoking status, (2) assessment of willingness to quit, (3) behavioral counseling, and (4) pharmacotherapy prescribing. To overcome key barriers related to providers' knowledge and self-efficacy of smoking cessation treatment, the study will leverage implementation strategies including (1) real-time and web-based training for mental health providers about evidence-based smoking cessation treatment and motivational interviewing, including an avatar practice module; (2) a tobacco smoking treatment protocol; (3) expert consultation; (4) coaching; and (5) organizational strategy meetings. We will use surveys and in-depth interviews to assess the implementation intervention's effects on providers' knowledge and self-efficacy, the mechanisms of change targeted by the intervention, as well as providers' perceptions of the acceptability, appropriateness, and feasibility of both the evidence-based practices and implementation strategies. We will use data on care delivery to assess providers' implementation of evidence-based smoking cessation practices. RESULTS: The IMPACT study is being conducted at 5 clinic sites. More than 50 providers have been enrolled, exceeding our recruitment target. The study is ongoing. CONCLUSIONS: In order for persons with SMI to realize the benefits of smoking cessation treatment, it is important for clinicians to implement evidence-based practices successfully. This pilot study will result in a set of training modules, implementation tools, and resources for clinicians working in community mental health clinics to address tobacco smoking with their clients. Trial Registration: ClinicalTrials.gov NCT04796961; https://clinicaltrials.gov/ct2/show/NCT04796961. TRIAL REGISTRATION: ClinicalTrials.gov NCT04796961; https://clinicaltrials.gov/ct2/show/NCT04796961. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/44787.

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.

A randomized controlled trial of varenicline and brief behavioral counseling delivered by lay counselors for adolescent vaping cessation: Study protocol.

Background: Approximately one-fifth of high-school seniors and college students currently vape nicotine. Adolescents express a desire to quit vaping, and case reports have shown promise for e-cigarette tapering with dual behavioral and pharmacologic therapies. However, there are no published clinical trials to date that test these intervention approaches for adolescent nicotine vaping cessation. In this three-arm randomized, placebo-controlled, parallel-group study, we aim to assess the efficacy of varenicline in combination with brief behavioral counseling and texting support on vaping cessation in adolescents dependent on vaped nicotine. Methods: The study will enroll 300 individuals between the ages of 16-25 with daily or near-daily nicotine vaping who reside in the Greater Boston area. Participants will be randomly assigned in a 1:1:1 ratio in blocks of six to one of the three arms: (1) a 12-week course of varenicline titrated to 1 mg bid, brief behavioral counseling delivered by a lay counselor, and an introduction to This is Quitting (TIQ) texting support created by the Truth Initiative; (2) a 12-week course of placebo, brief behavioral counseling, and TIQ; and (3) 12 weeks of enhanced usual care, consisting of advice to quit and an introduction to TIQ. The primary outcome will be biochemically verified continuous vaping abstinence at the end of the treatment (week 12). Secondary outcomes include continuous abstinence at follow-up (week 24), 7-day point prevalence abstinence at weeks 12 and 24, safety and tolerability of varenicline in an adolescent vaping population, as well as change in mood and nicotine withdrawal symptoms across the intervention period. Exploratory outcomes include change in comorbid substance use behaviors and nicotine dependence. Analysis will be intent-to-treat, with multiple imputation sensitivity analyses for participants with missing or incomplete outcome data. Discussion: This is the first study to evaluate varenicline in combination with a novel, brief, lay counselor delivered vaping cessation program for adolescents who vape nicotine. Results will inform clinicians on the effectiveness and acceptability of this promising, but not yet tested intervention.Clinical trial registration: ClinicalTrials.gov, identifier NCT05367492.

Preliminary feasibility of integrating tobacco treatment into SUD peer recovery coaching: a mixed-methods study of peer recovery coaches.

BACKGROUND: Individuals with substance use disorder (SUD) have high prevalence of cigarette smoking and difficulty quitting. Peer recovery coaches (PRCs; individuals with lived SUD experience) facilitate SUD behavior change in recoverees but it is unknown if/how they address tobacco treatment in SUD recovery coaching. We assessed PRC's tobacco-related practices and attitudes about tobacco treatment in SUD recovery. METHODS: The Tobacco use In Peer-recovery Study (TIPS) was a cross-sectional mixed-methods pilot survey (January-March 2022) of the 26 PRCs employed by a Massachusetts-based healthcare system's 12 SUD treatment clinics/programs. PRCs completed a quantitative survey (n = 23/26; 88%) and a telephone-based qualitative interview (n = 20/26; 77%). RESULTS: One-third of PRCs reported current smoking, 50% reported former smoking, and 18% never smoked. Among PRCs, 61% reported accompanying recoverees outdoors to smoke, 26% smoked with recoverees, 17% had provided cigarettes to recoverees, 32% used smoking to help build peer-relationships, and 74% rated smoking as socially acceptable in SUD treatment. PRCs reported regularly talking to recoverees about tobacco treatment (65%), believed they should have a role in helping recoverees quit smoking (52%), and were interested in tobacco treatment training (65%). A majority of both nonsmoking and current smoking PRCs (73% vs. 57%) regularly talked to recoverees about quitting smoking. CONCLUSION: PRCs' attitudes about integrating tobacco treatment into SUD recovery coaching were generally positive and PRCs reported they could have a role in helping recoverees with tobacco treatment. Barriers to integrating tobacco treatment into SUD recovery include use of cigarettes as a peer-recovery tool and high prevalence and social acceptability of smoking in SUD recovery.

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.

A Pragmatic Cluster-Randomized Trial of Provider Education and Community Health Worker Support for Tobacco Cessation.

OBJECTIVE: Individuals with serious mental illness have a high prevalence of tobacco use disorder and related early mortality but underutilize smoking cessation medication. The authors determined whether clinician-delivered education to primary care providers regarding safety, efficacy, and importance of cessation medication (provider education [PE]) alone or combined with community health worker (CHW) support would increase tobacco abstinence in this population, compared with usual care. METHODS: All adult current tobacco smokers receiving psychiatric rehabilitation for serious mental illness through two community agencies in Greater Boston were eligible, regardless of readiness to quit smoking. Primary care clinics were cluster randomized to PE or usual care, with a nested, participant-level randomization to CHW or no CHW in PE-assigned clinics. The primary outcome was blindly assessed, biochemically verified tobacco abstinence at year 2. RESULTS: Overall, 1,010 eligible participants were enrolled. PE was delivered to providers in 53 of 55 assigned clinics; 220 of 336 CHW-assigned participants consented to CHW support. Year 2 abstinence rates were significantly higher among participants assigned to PE+CHW versus usual care (12% vs. 5%; adjusted odds ratio [AOR]=2.40, 95% confidence interval [CI]=1.20-4.79) or PE alone (12% vs. 7%; AOR=1.84, 95% CI=1.04-3.24). No effect of PE alone on abstinence was detected. Compared with participants assigned to usual care, those assigned to PE+CHW had greater odds of varenicline use (OR=2.77, 95% CI=1.61-4.75), which was associated with higher year 2 abstinence (OR=1.97, 95% CI=1.16-3.33). CONCLUSIONS: Combined PE and CHW tobacco cessation support increased tobacco abstinence rates among adults with serious mental illness.

The effects of reduced nicotine content cigarettes on biomarkers of nicotine and toxicant exposure, smoking behavior and psychiatric symptoms in smokers with mood or anxiety disorders: A double-blind randomized trial.

BACKGROUND: The U.S. Food and Drug Administration and the government of New Zealand have proposed a reduction of the nicotine content in cigarettes to very low levels. This study examined the potential effects of this regulation in smokers with affective disorders. METHODS: In a randomized controlled parallel group trial conducted at two sites in the USA (Penn State University, Hershey, PA and Massachusetts General Hospital, Boston, MA) 188 adult smokers with a current (n = 118) or lifetime (n = 70) anxiety or unipolar mood disorder, not planning to quit in the next 6 months, were randomly assigned (1:1) to smoke either Usual Nicotine Content (UNC) (11.6 mg nicotine/cigarette) research cigarettes, or Reduced Nicotine Content (RNC) research cigarettes where the nicotine content per cigarette was progressively reduced to 0.2 mg in five steps over 18 weeks. Participants were then offered the choice to either receive assistance to quit smoking, receive free research cigarettes, or resume using their own cigarette brand during a 12-week follow-up period. Main outcomes were biomarkers of nicotine and toxicant exposure, smoking behavior and dependence and severity of psychiatric symptoms. The pre-registered primary outcome was plasma cotinine. RESULTS: A total of 143 (76.1%) randomized participants completed the randomized phase of the trial, 69 (73.4%) in the RNC group and 74 (78.8%) in the UNC group. After switching to the lowest nicotine content cigarettes, compared to smokers in the UNC group, at the last randomized visit the RNC group had significantly lower plasma cotinine (metabolite of nicotine): difference between groups, -175.7, 95% CI [-218.3, -133.1] ng/ml. Urine NNAL (metabolite of NNK, a lung carcinogen), exhaled carbon-monoxide, cigarette consumption, and cigarette dependence were also significantly lower in the RNC group than the UNC group. No between-group differences were found on a range of other biomarkers (e.g. 8-isoprostanes) or health indicators (e.g. blood pressure), or on 5 different psychiatric questionnaires, including the Kessler K6 measure of psychological distress. At the end of the subsequent 12-week treatment choice phase, those randomized to the RNC group were more likely to have quit smoking, based on initial intent-to-treat sample, n = 188 (18.1% RNC v 4.3% UNC, p = 0.004). CONCLUSION: Reducing nicotine content in cigarettes to very low levels reduces some toxicant exposures and cigarette addiction and increases smoking cessation in smokers with mood and/or anxiety disorders, without worsening mental health. TRIAL REGISTRATION: TRN: NCT01928758, registered August 21, 2013.

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.