Adolescent marijuana use is linked to poorer neural health and psychological distress symptoms

In addition to high rates of marijuana use, young adults have higher rates of cigarette smoking, binge drinking and heavy alcohol use than any other age group.As marijuana becomes more widely available, it will be imperative to monitor its use along with health risk behaviors. Substance use interventions may also benefit from addressing multiple substances at once. Study limitations include the cross-sectional design; we cannot draw definitive conclusions about causal relationships between variables in our model and marijuana use. Second, the study was conducted with young adults in California and may not generalize to all young adults or to the population as a whole. In addition, urban young adults are notoriously difficult to reach in population surveys and our relatively low response rate reflects this challenge; though robust, the sample may suffer from unidentified non-response bias. Finally, marijuana use was measured using self-report, which could not be validated biologically. Nevertheless, these findings offer new insight into the correlates of marijuana use among young adults. Neural and mental health vulnerabilities and use-related problems play a role in maintenance of problematic marijuana use patterns after initiation of use, barriers and failed attempts to quit or cut back on use,vertical growing racks and consequently, increasing prevalence rates of marijuana use disorders . Focusing efforts on better understanding cannabis-related processes and barriers that may promote use and influence behavioral interventions for adolescent marijuana users is a critical public health concern . Contingency Management is an evidence-based treatment for reducing marijuana use .

Biochemical verification is typically an important aspect of abstinence-based CM. Vouchers are given as positive reinforcement for negative drug screening . Limited work pointedly explores how a monitored abstinence protocol with adolescents simultaneously influences trajectories of sub-syndromal mental health symptoms , sleep disturbance, marijuana use expectancies and consequences, and reward sensitivity in non-treatment seeking marijuana users compared to matched controls . Barriers to treatment success may be associated with cannabis-related problems and processes that can influence emotional processing , cognitive attributions and self efficacy , and risk taking behaviors . We recently examined neural health changes and neural recovery in adolescent marijuana users pre- and post monitored abstinence and found alterations in cortical thickness that continue to persist after 28-days of monitored abstinence, and associations between cortical thickness and lifetime marijuana use and age of marijuana use onset. Findings also suggest resolution of cerebral blood flow differences . Secondary aims of the larger neuroimaging study included characterization of stress and reward-related addiction cycle symptoms in the sample. Gaining a better understanding of how physiological symptoms , mental health symptoms, and cannabis-related factors and barriers may be affected by common behavioral interventions targeting marijuana use may help uncover potential treatment interfering factors for adolescent marijuana users that have clinical implications in preventing or treating problematic use .Therefore, this study aimed to evaluate 1) the influence of 28-days of monitored abstinence on changes in subsyndromal emotional functioning, sleep difficulties, marijuana withdrawal, marijuana craving, marijuana expectancies, and marijuana-related problems, and 2) characterize reward sensitivity and attention impulsivity measured after cessation of marijuana use in a sample of adolescent marijuana users.

Associations between age of marijuana use onset and lifetime marijuana use was also explored. The sample included n=26 marijuana users and n=30 demographically matched controls on age, gender, ethnicity, and family history of substance use disorder, who completed bi-weekly urine toxicology for 4 weeks and repeated administration of self-report instruments assessing emotional functioning and marijuana use symptoms over the 28-day protocol. We hypothesized that following completion of monitored abstinence, marijuana users would report less depression and anxiety symptoms, sleep-related problems, and marijuana-related problems and symptoms by day 28 of the protocol compared to baseline; and minimal group differences would be observed at follow-up. Notably, the marijuana users recruited for the study were not treatment-seekers or experiencing severe levels of mental health distress, despite regular use of marijuana. Adolescents were recruited from local San Diego schools and included 26 marijuana users ≥ 200, past month marijuana use episodes range 1–28, past three-month average marijuana use days range 7–30 and 30 control teens with minimal substance use histories . A district-approved research flyer that described a paid research opportunity at the University of California, San Diego was distributed throughout San Diego high schools. Teens and demographically matched controls were screened for substance use and exclusionary criteria. Ninety-six percent of participants in the MJ group met current Diagnostic and Statistical Manual for Mental Disorder-Fourth Edition cannabis abuse or dependence criteria, while 15% met current alcohol abuse or dependence criteria. Only one individual in the CON group met current abuse criteria for alcohol use, and none of the individuals in the CON group met cannabis abuse/dependence criteria. Comprehensive screening interviews were administered to adolescents and parents/guardians; adolescents provided assent for their own participation and guardians were required to provide consent in accordance with the University of California, San Diego Human Research Protections Program.

Exclusionary criteria included history of a DSM-IV Axis I disorder other than alcohol or cannabis use disorder, use of psychoactive medications, learning disability or mental retardation, neurological condition , or traumatic brain injury with loss of consciousness >2 min; prenatal alcohol or drug exposure; premature birth; left handedness; and non-fluency in English. Participants completed all appointments at the University of California, Department of Psychiatry and asked to refrain from all intoxicants during participation . Self-report measures were administered during the toxicology appointments . Participants were compensated $10 for each successful urine toxicology screen . CON did not test positive for urine marijuana metabolites at baseline or over the course of the study. Participants were not required to be abstinent at the Day 0 appointment, and days since last use of marijuana ranged from 1–18 at Day 0; 80% of MJ reported use within 1–5 days of the Day 0 appointment and 73% tested positive for marijuana metabolites in urine /mL cut-off concentration. Starting at the first toxicology appointment, THCCOOH to creatinine concentration ratios were examined in relation to published data on these ratios determined in marijuana users during sustained monitored abstinence for confirmation of abstinence over the course of 4 weeks. New cannabis use was determined by dividing each THCCOOH normalized to creatinine concentration by the previously collected THCCOOH normalized to creatinine concentration and comparing this ratio to the 95% CI ratio for the time interval between the collections. For example, the 95% limit for the U2/U1 ratio was 1.when the collection interval was ≤ 24 h and 0.91, 0.51, 0.24, and 0.14 for collections ranging from 1–4 days, respectively. A successful urine toxicology screen was determined by determining the time difference between the urine specimens, selecting the correct metabolite ratio for this time frame, and comparing the obtained U2/U1 ratio for the participant to the 95% limit for the specific time difference . Breath alcohol with the Alco-Sensor IV Breathalyzer was also evaluated for all participants at each urine toxicology screen appointment and sobriety from alcohol was confirmed for all participants . Fifty-six individuals finished the 28-day protocol ; 8 of n=26 users reported ≤4 days of cannabis use during the monitored abstinence period; however,vertical grow room design biweekly toxicology screening showed a trend of decreasing THCCOOH/creatinine ratios among all users that completed. Loss to follow-up was relatively small and within the acceptable range for clinical trials ; the four individuals that did not complete the protocol were marijuana users that continued to use during monitored abstinence and failed to complete the final appointments. Those four individuals were not included in the final sample or any statistical analysis presented in this manuscrip.The Customary Drinking and Drug Use Record assessed quantity and frequency of lifetime marijuana, alcohol, cigarette, and other drug use and age of marijuana use onset . The Timeline Follow back quantified self-reported substance use at each visit during the 28-day monitored abstinence protocol . Marijuana symptoms, expectancies, and consequences questionnaires were administered throughout the protocol .

The Marijuana Craving Questionnaire is a 10- item self-report questionnaire -70 that evaluates intention and desire to smoke marijuana, anticipated pleasure, and anticipated relief from negative affect and withdrawal . The Marijuana Withdrawal Discomfort Scale is a 30-item self-report form on which participants rate the severity of withdrawal symptoms to severe over the past 24-hours ; these symptoms change with marijuana use but include experiences related to mood and sleep that CON may also experience. Total MWDS scores range from 0–90. The Marijuana Problem Scale assesses 19 functional problems to serious problem associated with marijuana use and total scores range from 0–38. The Marijuana Effect Expectancy Questionnaire provides a measure of appraisal on six sub-scales , relaxation/tension , social/sexual facilitation , perceptual/cognitive enhancement , global negative effects , and craving/physical effects ; this 48-item instrument asks participants to identify a value between 1 and 5 for each item to identify if a participant expects marijuana-related effects to occur in one or more of these domains . High scores reflect a high level of expectancy on the corresponding sub-scale. The Beck Depression Inventory Second Edition and Spielberger State Trait Anxiety Inventory assessed depressive symptoms and state anxiety . State Trait Anxiety scores were converted to gender-normed T-scores for high-school age boys and girls . The Family History Assessment Module evaluated family history of psychiatric and substance use disorders. The Pittsburgh Sleep Quality Index is a brief self-report measure administered to capture sleep quality via a global summary score. The PSQI contains 18 items and yields seven sub-scales – worse that measure sleep onset latency, efficiency, duration, disturbance, days of dysfunction, overall quality -21; poor sleep quality threshold >5, and sleep medication usage. The Behavioral Inhibition System and Behavioral Approach System scales consist of 24 items that measure avoidance and approach sensitivities reflective of reward sensitivity personality traits. Four response options range from very true to very false for me ; BAS sub-scales include reward responsiveness, fun seeking, and drive. The Barratt Impulsiveness Scale is a 30- item self-report measure administered to assess impulsivity; items are on a 4-point scale and range from rarely to almost/always . Barratt sub-scales examined include cognitive impulsivity , motor impulsivity , and non-planning impulsivity . The Wechsler Abbreviated Scale of Intelligence Vocabulary sub-test was included as an estimate of premorbid intellectual functioning . Parental income and grade point average were collected during a comprehensive clinical interview at baseline. We focused on four secondary a priori analyses for measures in which we observed a change over time. These correlations focused on two key variables 1) cumulative marijuana use , and 2) age of marijuana use onset. These variables show robust associations with neurodevelopmental and mental health functioning outcomes in the research literature and with neural health in this sample in particular . Therefore, the study addressed three key questions: is age of MJ use onset or cumulative MJ use associated with 1) self-reported changes in depression, anxiety, or sleep quality over monitored abstinence, 2) changes in MJ use expectancies, withdrawal, and craving over monitored abstinence, or 3) reward sensitivity and attentional impulsivity. We also examined if change in MJ use expectancies was related to change in emotional distress over monitored abstinence, given the increasing attention to how beliefs about marijuana use may distinctly influence treatment outcomes and use patterns . The current findings expand the literature in several ways including: 1) MJ demonstrated decreased self-reported subsyndromal depression symptoms by week three of monitored abstinence, and greater changes in depression and anxiety symptoms were observed in those reporting more lifetime marijuana use at baseline; 2) group differences in perceptions of sleep quality and sleep disturbance resolved by Day 28, although MJ continued to report less sleep than controls; 3) MJ reported increased expectation of global negative effects and less expectation that marijuana helps reduce tension and anxiety after completing 28-days of abstinence; and 4) MJ reported less incentive sensitivity and more attentional impulsivity compared to controls, measured after self-reported subsyndromal emotional symptoms substantially decreased . Findings also support the extant literature identifying withdrawal and craving symptoms following cessation of use .

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