Marijuana (MJ) remains the most widely abused illicit substance in the United States, and in recent years, a decline in perceived risk of MJ use has been accompanied by a simultaneous increase in rates of use among adolescents. In the current study, we hypothesized that chronic MJ smokers would perform cognitive tasks, specifically those that require executive function more poorly than control subjects, and that individuals who started smoking MJ regularly prior to age 16 (early onset) would have more difficulty than those who started after age 16 (late onset). Thirty-four chronic, heavy MJ smokers separated into early and late onset groups and 28 non-MJ smoking controls completed a battery of neurocognitive measures. As hypothesized, MJ smokers performed more poorly than controls on several measures of executive function. Age of onset analyses revealed that these between-group differences were largely attributed to the early onset group, who were also shown to smoke twice as often and nearly three times as much MJ per week relative to the late onset smokers. Age of onset, frequency and magnitude of MJ use were all shown to impact cognitive performance. Findings suggest that earlier MJ onset is related to poorer cognitive function and increased frequency and magnitude of MJ use relative to later MJ onset. Exposure to MJ during a period of neurodevelopmental vulnerability, such as adolescence, may result in altered brain development and enduring neuropsychological changes.

RationaleMarijuana (MJ) use continues to rise, and as the perceived risk of using MJ approaches an all-time historic low, initiation of MJ use is occurring at even younger ages. As adolescence is a critical period of neuromaturation, teens and emerging adults are at greater risk for experiencing the negative effects of MJ on the brain. In particular, MJ use has been shown to be associated with alterations in frontal white matter microstructure, which may be related to reports of increased levels of impulsivity in this population.ObjectivesThe aim of this study was to examine the relationship between age of onset of MJ use, white matter microstructure, and reported impulsivity in chronic, heavy MJ smokers.MethodsTwenty-five MJ smokers and 18 healthy controls underwent diffusion tensor imaging and completed the Barratt Impulsiveness Scale. MJ smokers were also divided into early onset (regular use prior to age 16) and late onset (age 16 or later) groups in order to clarify the impact of age of onset of MJ use on these variables.ResultsMJ smokers exhibited significantly reduced fractional anisotropy (FA) relative to controls, as well as higher levels of impulsivity. Earlier MJ onset was also associated with lower levels of FA. Interestingly, within the early onset group, higher impulsivity scores were correlated with lower FA, a relationship that was not observed in the late onset smokers.ConclusionsMJ use is associated with white matter development and reported impulsivity, particularly in early onset smokers.

Difficulties in the ability to successfully inhibit impulsive behaviors have been reported in marijuana (MJ) smokers, yet few studies have made direct comparisons between early (prior to age 16) and late (age 16 or later) onset MJ smokers, specifically during behavioral inhibition tasks. The current study utilized the Multi-Source Interference Task (MSIT) during functional magnetic resonance imaging (fMRI) in chronic, heavy MJ smokers and healthy non-MJ smoking controls which revealed a more focal pattern of anterior cingulate activity in controls relative to smokers. Early onset smokers had more focal activation but tended to make more errors of commission relative to late onset smokers, suggesting a possible neural adaptation despite difficulty with behavioral inhibition. Further investigation is warranted, as early exposure to MJ may result in reorganization of critical brain regions.

Marijuana (MJ) use is on the rise, particularly among teens and emerging adults. This poses serious public health concern, given the potential deleterious effects of MJ on the developing brain. We examined 50 chronic MJ smokers divided into early onset (regular MJ use prior to age 16; n = 24) and late onset (age 16 or later; n = 26), and 34 healthy control participants (HCs). All completed a modified Stroop Color Word Test during fMRI. Results demonstrated that MJ smokers exhibited significantly poorer performance on the interference subtest of the Stroop, as well as altered patterns of activation in the cingulate cortex relative to HCs. Further, early onset MJ smokers exhibited significantly poorer performance relative to both HCs and late onset smokers. Additionally, earlier age of MJ onset as well as increased frequency and magnitude (grams/week) of MJ use were predictive of poorer Stroop performance. fMRI results revealed that while late onset smokers demonstrated a more similar pattern of activation to the control group, a different pattern was evident in the early onset group. These findings underscore the importance of assessing age of onset and patterns of MJ use and support the need for widespread education and intervention efforts among youth.

Currently, 25 states and Washington DC have enacted full medical marijuana (MMJ) programs while 18 states allow limited access to MMJ products. Limited access states permit low (or zero) tetrahydrocannabinol (THC) and high cannabidiol (CBD) products to treat specified conditions such as uncontrolled epilepsy. Although MMJ products are derived from the same plant species as recreational MJ, they are often selected for their unique cannabinoid constituents and ratios, not typically sought by recreational users, which may impact neurocognitive outcomes. To date, few studies have investigated the potential impact of MMJ use on cognitive performance, despite a well-documented association between recreational marijuana (MJ) use and executive dysfunction. The current study assessed the impact of 3 months of MMJ treatment on executive function, exploring whether MMJ patients would experience improvement in cognitive functioning, perhaps related to primary symptom alleviation. As part of a larger longitudinal study, 24 patients certified for MMJ use completed baseline executive function assessments and 11 of these so far have returned for their first follow-up visit 3 months after initiating treatment. Results suggest that in general, MMJ patients experienced some improvement on measures of executive functioning, including the Stroop Color Word Test and Trail Making Test, mostly reflected as increased speed in completing tasks without a loss of accuracy. On self-report questionnaires, patients also indicated moderate improvements in clinical state, including reduced sleep disturbance, decreased symptoms of depression, attenuated impulsivity, and positive changes in some aspects of quality of life. Additionally, patients reported a notable decrease in their use of conventional pharmaceutical agents from baseline, with opiate use declining more than 42%. While intriguing, these findings are preliminary and warrant further investigation at additional time points and in larger sample sizes. Given the likelihood of increased MMJ use across the country, it is imperative to determine the potential impact of short- and long-term treatment on cognitive performance as well as the efficacy of MMJ treatment itself.

The vast majority of states have enacted full or partial medical marijuana (MMJ) programs, causing the number of patients seeking certification for MMJ use to increase dramatically in recent years. Despite increased use of MMJ across the nation, no studies thus far have examined the specific impact of MMJ on cognitive function and related brain activation. In the present study, MMJ patients seeking treatment for a variety of documented medical conditions were assessed prior to initiating MMJ treatment and after 3 months of treatment as part of a larger longitudinal study. In order to examine the effect of MMJ treatment on task-related brain activation, MMJ patients completed the Multi-Source Interference Test (MSIT) while undergoing functional magnetic resonance imaging (fMRI). We also collected data regarding conventional medication use, clinical state, and health-related measures at each visit. Following 3 months of treatment, MMJ patients demonstrated improved task performance accompanied by changes in brain activation patterns within the cingulate cortex and frontal regions. Interestingly, after MMJ treatment, brain activation patterns appeared more similar to those exhibited by healthy controls from previous studies than at pre-treatment, suggestive of a potential normalization of brain function relative to baseline. These findings suggest that MMJ use may result in different effects relative to recreational marijuana (MJ) use, as recreational consumers have been shown to exhibit decrements in task performance accompanied by altered brain activation. Moreover, patients in the current study also reported improvements in clinical state and health-related measures as well as notable decreases in prescription medication use, particularly opioids and benzodiapezines after 3 months of treatment. Further research is needed to clarify the specific neurobiologic impact, clinical efficacy, and unique effects of MMJ for a range of indications and how it compares to recreational MJ use.

The neurobiologic effects of cannabis, commonly referred to as 'marijuana' (MJ), have been studied for decades. The impact of recreational MJ use on cognition and measures of brain function and structure is outlined, and variables influencing study results are discussed, including age of the consumer, patterns of MJ use, variations in MJ potency, and the presence of additional cannabinoids. Although evidence suggests that chronic, heavy recreational MJ use is related to cognitive decrements and neural changes, particularly when use begins in adolescence, findings from studies of recreational MJ users may not be applicable to medical marijuana (MMJ) patients given differences in demographic variables, product selection, and reasons for use. Although additional research is needed to fully understand the impact of MJ and individual cannabinoids on the brain, current findings are beginning to inform public policy, including considerations for age limits, potential limits for some cannabinoids, and guidelines for use. However, barriers continue to impede researchers' ability to conduct studies that will guide policy change and provide vital information to consumers and patients regarding best practices and safest methods for use. The need for information is critical, as legalization of MJ for medical and recreational use is increasingly widespread.

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