Craving and withdrawal symptoms were highest during the first week of the protocol and decreases were observed within the first two weeks of abstinence. We speculate slight increases on these scales toward the end of the protocol are related to anticipation of reinitiation of marijuana use. Follow-up interviews were not conducted past 28-days; therefore, plans for reinitiation of use is speculative, but is consistent with research showing poor longer-term efficacy for abstinence-based CM protocols with adolescents . It remains unclear as to whether depression or substance use presents first, if these conditions simultaneously emerge, or both are associated with extraneous clinical factors . Our preliminary data suggest that marijuana users experiencing subsyndromal depression symptoms at the start of a monitored abstinence period may experience a reduction in those symptoms. The average percent reduction in BDI-II scores relative to baseline for the MJ group was above the minimal clinically significant difference cutoff , which suggests clinically important improvements were observed in some individuals. Sleep difficulties often correspond with depression symptoms . Participants in our study reported fairly minimal sleep difficulties ; however, perceived sleep quality and perceived disturbance no longer differed compared to controls by day 28 of the protocol. This change is notable as perception of general sleep quality is associated with enhanced likelihood for quit success compared to reported sleep duration and efficiency . Abstinence may influence perception of sleep quality,grow vertical despite continued differences in quantity of sleep reported after several weeks of abstinence.
Significant changes on the expectancies sub-scales relaxation and tension reduction and global negative impairment were encouraging, as marijuana users reported less expectation that marijuana helps reduce tension and anxiety and increased perception of global negative consequences by the end of the protocol; those who initiated regular use at a later age reported greater change in these expectancy scales. Expectancies and coping motives may mediate substance use severity in high-risk youth . We also observed differences in reward sensitivity and impulsivity during later time points that were linked to recency of marijuana use. As expected, the marijuana users scored higher on the Barratt Impulsiveness Scale attention domain, as impulsivity traits are likely to impact vulnerability to substance misuse . Conversely, the controls showed higher scores on approach system sub-scales , suggesting controls may be more responsive to reward and reward cues compared to the marijuana users in this investigation; although the degree to which high BAS score predict problematic substance use outcomes may be moderated by high-order cognitive functioning abilities , and the BAS/BIS imbalance . Our BAS findings are similar to work conducted by Wright and colleagues , in which they also found decreased behavioral approach scores in marijuana users ages 18–25. The authors suggest depressive symptoms may underlie decreased BAS scores , although depression symptoms in the users was not statistically different from controls at the time of measurement in our protocol . BAS scales are suggested to represent many difference facets of impulsivity.
While increased BAS sensitivity is linked to substance use in adults and adolescents ; research suggests that higher BAS scores may be linked to lifetime experimentation versus repeated problematic use . Our findings of low BAS scores in our users and lack of group differences on BIS scores may underlie neurocognitive vulnerabilities, marijuana related changes in dopaminergic pathways, and/or a premature neurodevelopmental changes in reward sensitivity for substance users moving beyond experimentation . Limitations include the small sample size and limited Type I error control, reliance on self-report measures, and lack of follow-up beyond the 28-day monitored abstinence period. Marijuana users also reported alcohol use ; therefore changes may be influenced by alcohol use patterns. Further, the sample size is small and multiple comparison corrections were not stringent, therefore replication is important. We cannot rule out regression to the mean as a possible explanation for changes observed without randomization and multiple measurements of each construct assessed. Each impulsivity instrument was administered once, and therefore, we could not examine change over time for this construct. Our non-clinical sample is also predominately male, Caucasian, and from higher-income households; therefore, generalizability may be limited. Studies using randomized controlled trial designs will allow inferences to be made about the efficacy of CM protocols. We observed notable changes in depression symptoms, sleep quality, and self-reported marijuana use expectancies following participation in a 28-day monitored abstinence protocol. Many individuals use marijuana to cope with various degrees of depression, anxiety, and sleep problems and therefore the potential medical application of marijuana for treatment of mental health symptoms continues to be explored despite mixed findings , however this study supports the extant adolescent research literature that consistently shows marijuana use during neurodevelopment likely has a deleterious impact on neural health and emotional functioning .
Future work in our laboratory will continue to explore treatment approaches that target substance misuse and substance-related processes and treatment barriers in the context of neurodevelopmental vulnerabilities and the neurobiology of addiction. Two reviewers independently screened all titles and abstracts. We included observational studies and interventional studies that were published in English and involved participants older than 12 years who had at least 30 days of lifetime marijuana use. This cutoff was chosen to ensure meaningful marijuana exposure. We excluded studies reporting only outcomes after short-term exposure in a laboratory setting and those including fewer than 10 marijuana users. Our search was augmented by author and reference tracking to identify additional articles. The same 2 investigators independently reviewed the full text of all titles and abstracts that passed the initial screen, and disagreements were resolved by discussion or by a third reviewer . Interrater reliability on 80 randomly selected abstracts for the 2 primary reviewers was excellent . For each included study, 4 reviewers independently extracted data on all outcomes, which were categorized as symptoms, obstructive lung disease, pulmonary function, or other respiratory outcomes. They also extracted data on design , study population, participant age, exposure route, average marijuana use, percentage of marijuana-only users, confounders , exposure duration, funding source, and baseline variables. Risk of bias in individual studies was assessed independently by 4 reviewers at both study and outcome levels using either the Cochrane Risk of Bias Tool for outcomes in trial studies or the Newcastle-Ottawa Scale for outcomes in observational studies . We rated studies as having low ROB if they had robust assessment and adjustment for tobacco use, had sufficient follow-up for outcomes to occur, provided detail on exposure assignment ,vertical grow systems and quantified marijuana use. Meta-analyses were done separately for prospective cohort and cross-sectional studies if each design had 2 or more studies with low or moderate ROB. In the symptoms category, we collected data on marijuana users and nonusers for the following 4 specific symptoms: cough, sputum production, wheezing, and dyspnea. For binary outcomes , we extracted risk ratios or calculated them when adequate data were provided. For continuous outcomes , we extracted means and SDs for marijuana smokers and nonsmokers and calculated mean differences with 95% CIs. When several studies examined the same cohort we included only data from the study with the longest follow-up for each outcome.
We present a narrative synthesis of data for which pooled analysis was not possible. We pooled data using a random-effects model. We used the Paule–Mandel method to estimate τ 2 and the Knapp–Hartung method to adjust for small sample sizes. Statistical analysis was done using R software , version 3.3.3. Heterogeneity was evaluated using forest plots and the I 2 statistic; I 2 values of 25%, 50%, and 75% were considered evidence of low, moderate, and high heterogeneity, respectively . Three reviewers discussed the overall strength of evidence for each outcome and graded it as insufficient, low, moderate, or high on the basis of methods outlined by the Agency for Healthcare Research and Quality .Initial searches across databases identified 1265 abstracts; we selected 927 for further evaluation and 70 of those for full-text review. We identified 3 additional articles by reference tracking, yielding 73 potentially relevant articles, of which 22 met inclusion criteria. Of these, 3 were rated as having high ROB . Supplement Tables 2 to 4 list all articles meeting inclusion criteria; studies with sufficient data for meta analysis are referenced in Figures 2 and 3. We included 22 studies . Methods of quantifying marijuana use varied . Across all outcomes and studies, 1255 participants had more than 10 joint-years of exposure and 756 marijuana only smokers had more than 20 joint-years of exposure. We identified 13 distinct outcomes , of which 5 had sufficient supporting data in 2 or more studies and could be pooled in a meta-analysis. Two prospective observational studies and 2 cross sectional studies described other respiratory outcomes . The 2 prospective studies followed participants over 8 years. Current marijuana use was associated with more outpatient visits for respiratory illnesses and respiratory problems , with no increased risk for hospital admission . The high-ROB study was limited by inadequate adjustment for key confounders and lack of reporting on the nature of respiratory problems. The 2 cross-sectional studies examined the effect of methacholine challenge on airway reactivity among marijuana users compared with nonusers and found no difference . Because of increasing social acceptance and widespread use, understanding the health effects of smoking marijuana is important. Our review suggests that use is associated with cough, sputum production, and wheezing. Evidence on the association between daily use and obstructive lung disease and impaired pulmonary function testing is insufficient. An English-language MEDLINE search returned 3 other reviews that examined short- and long-term effects of smoking marijuana. A 2007 systematic review noted an association between marijuana use and respiratory symptoms and outlined the need for more data on marijuana’s association with pulmonary function. Two more recent studies also noted an association with increased respiratory symptoms, including cough, sputum production, and wheezing, but reported conflicting data on the association between long term marijuana smoking and changes in pulmonary function. Our study confirmed these findings and built on the existing literature by assessing risk of bias, pooling data where feasible, and providing a clear picture of the gaps in evidence by rating the strength of the overall evidence. Its smoke contains particulate matter and compounds that induce oxidative stress and inflammation in the lung . Data comparing endobronchial biopsies from marijuana users versus nonusers support the clinical relevance of this type of effect from marijuana smoke exposure. Findings among marijuana users are consistent with chronic airway inflammation and epithelial injury, including basal cell hyperplasia, goblet cell hyperplasia, and subepithelial inflammation, suggesting a mechanistic link between long-term marijuana use and respiratory symptoms. Although our review found no relationship between marijuana use and impairment in spirometric indices, these data should be interpreted with caution because low-strength evidence suggests increased airway resistance with marijuana use, which can precede changes in lung function. Further, exposure in the included studies may have been insufficient to alter pulmonary function test results. Studies of long-term tobacco use suggest that changes to FEV1, become measurable only after 5 to 10 pack-years of smoking . Our review included 243 marijuana users with exposure greater than 20 joint-years across all prospective evaluations of lung function. These low exposure levels limit our ability to draw conclusions about the effect of daily marijuana use. Because obstructive lung disease develops in only about a third of long-term tobacco smokers , is usually not identified until after age 35 or 40 years, and increases in prevalence with age, large cohorts with middle-aged to older populations of heavier marijuana users may be necessary to identify effects on lung function and obstructive lung disease. On the other hand, given the psychoactive effects of tetrahydrocannabinol and its effect on overall function , few users may have heavy enough exposure to cause significant changes in pulmonary function testing. In other words, marijuana’s effect on lung function may not be among its most important health outcomes in the long term. Our review has important limitations. We excluded articles not published in English; thus, we may have overlooked relevant studies. Study populations were young, and marijuana exposure was limited in most prospective studies. Most studies inadequately assessed exposure, and some did not report effect size or details on exposure; this prevented meta analysis for several outcomes.