Cognitive performance in a placebo-controlled pharmacotherapy trial for youth with marijuana dependence
Introduction
Marijuana is the most widely used illicit substance among adolescents. In 2013, Monitoring the Future data indicated daily marijuana use in 1.1% of 8th graders, 4.0% of 10th graders, and 6.5% of 12th graders (Johnston, O'Malley, Miech, Bachman, & Schulenberg, 2014). There is growing evidence that heavy marijuana use during adolescence, a time of dynamic brain development, may impact cognition (Randolph, Turull, Margolis, & Tau, 2013). In adults with persistent marijuana use that started during adolescence, Meier et al. found a decline in intelligence quotient (IQ), with impairments evident in executive functioning and processing speed (Meier, Caspi, Ambler, et al., 2012).
Cognitive performance is multifaceted, and results of studies of marijuana's effects on cognitive performance are mixed. There appear to be certain neuropsychological constructs or domains that are influenced by marijuana use. A recent review of the relevant literature by Randolph et al. (2013) concluded that attention, processing speed, verbal declarative memory, and cognitive control are affected by heavy marijuana use in adolescents. In contrast, language, visual declarative memory, perceptual reasoning, inhibition, and planning did not appear to be consistently affected by marijuana (Randolph et al., 2013).
The literature in this area may often appear contradictory. For example, attention is complex and can be divided into subcategories (complex attention, sustained attention, etc.); some studies have very small sample sizes and methodologies as well as populations studied often differ drastically. Additionally, tests used to examine the same domain or construct can be different across studies. Abdullaev and colleagues found that on tests requiring executive attention (attention required when conflicting information is presented), adolescents who used marijuana performed worse than controls (Abdullaev, Posner, Nunnally, & Dishion, 2010). Hanson et al., concluded that while impairments in verbal memory among cannabis users improve to the level of controls within 3 weeks of abstinence, deficits in attention remain within this same time frame (specifically accuracy in tasks that require attention) (Hanson et al., 2010). Fried and colleagues did not find a significant difference in tests of attention among groups of marijuana users (heavy and light) and controls whereas they did find significant differences in other domains (overall IQ, processing speed, immediate memory, and delayed memory). Interestingly, the negative impact of marijuana on the cognitive domains that were affected resolved at 3 months of sustained abstinence. The sample in this study consisted of individuals exposed to drugs in utero and so must be interpreted with that in mind (Fried, Watkinson, & Gray, 2005).
The purpose of the current study was to evaluate potential changes in cognitive task performance among adolescents enrolled in a randomized, placebo-controlled trial of N-acetylcysteine (NAC) added to brief weekly cessation counseling and contingency management for marijuana cessation (Gray et al., 2012). To our knowledge, there are no previous studies that examine cognitive performance within the framework of a placebo-controlled pharmacotherapy treatment trial for cannabis dependence in adolescents. We hypothesized that cognitive performance would improve with marijuana cessation, and that longer periods of abstinence would predict greater improvements in cognitive performance. Participants were cannabis-dependent upon study enrollment, allowing for assessment of possible improvements in cognition with abstinence among a group of relatively heavy marijuana users seeking treatment.
Section snippets
Participants
Participants were 78 treatment-seeking adolescents, ages 15–21, who met DSM-IV criteria for cannabis dependence, enrolled in the parent trial, and completed a baseline cognitive task performance battery at the treatment initiation visit and at least one additional time point (4 and/or 8 weeks after treatment initiation). Participants ages 18 and above provided informed consent. For participants under age 18, the legal guardian provided informed consent and participant provided assent. The
Results
Baseline demographic and clinical characteristics were examined for the cohort as well as across week 4 abstinence categories (Table 1). At baseline, the mean age of the study cohort was 18.8 ± 1.5 years; 52 (66.7%) of the cohort were male and 71 (91.0%) were Caucasian. There were no significant differences in age, gender or race between those who attained abstinence at week 4 and those who were not abstinent. Participants who were enrolled in school were more likely to attain abstinence at week 4
Discussion
Cognitive performance in certain domains, namely verbal memory and psychomotor speed, as measured by the CNS Vital Signs battery, was significantly better in those with abstinence when compared to those who were not abstinent. Results suggest an improvement in these cognitive performance domains with abstinence from marijuana. The component most impacted by cessation of marijuana in our study appeared to be verbal memory. This is consistent with some of the previous literature. Data on verbal
Conclusions
These results suggest that, in adolescents, cognition, especially certain components of cognition such as verbal memory, may improve within weeks of marijuana cessation. While there are limitations to our study, it is notable that objective verbal memory improvement can be seen and measured in a relatively short time after cessation. Understanding the impact of cessation of marijuana on cognitive performance over time requires further data from more longitudinal studies.
Role of Funding Source
This work was funded by the NIDA-AACAP Resident Research Award. The primary trial was funded by the National Institute on Drug Abuse grant R01DA026777 (PI: Gray). Administrative and technical support was made possible by the National Center for Research Resources grant UL 1RR029882.
Contributors
Amanda Roten composed the first draft of the manuscript, including the introduction, methods (except statstical methods), discussion, and conclusion sections. Nathaniel Baker composed the statistical methods section as well as the results section. He provided statistical analysis. Dr. Kevin Gray was the primary investigator for the parent study. All authors contributed to and approved the final manuscript.
Conflict of interest
Dr. Gray has received funding for unrelated research from Merck, Inc., and Supernus Pharmaceuticals. Dr. Roten and Mr. Baker report no potential conflicts of interest.
Acknowledgments
The authors would additionally like to thank Alan Boyd for his assistance with furthering our understanding of the assessments used in this study.
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