Mary Kathryn Dahlgren

Age of onset of marijuana use and executive function.

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 this study, the authors 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 3 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.

Why so impulsive? White matter alterations are associated with impulsivity in chronic marijuana smokers.

Difficulty monitoring and inhibiting impulsive behaviors has been reported in marijuana (MJ) smokers; neuroimaging studies, which examined frontal systems in chronic MJ smokers, have reported alterations during inhibitory tasks. Diffusion tensor imaging (DTI) provides a quantitative estimate of white matter integrity at the microstructural level. We applied DTI, clinical ratings, and impulsivity measures to explore the hypotheses that chronic, heavy MJ smokers would demonstrate alterations in white matter microstructure and a different association between white matter measures and impulsivity relative to nonsmoking control subjects (NS). Fractional anisotropy (FA), a measure of directional coherence, and trace, a measure of overall diffusivity, were calculated for 6 locations including bilateral frontal regions in 15 chronic MJ smokers and 15 NS. Subjects completed clinical rating scales, including the Barratt Impulsivity Scale (BIS). Analyses revealed significant reductions in left frontal FA in MJ smokers relative to NS and significantly higher levels of trace in the right genu. MJ smokers also had significantly higher BIS total and motor subscale scores relative to NS, which were positively correlated with left frontal FA values. Finally, age of onset of MJ use was positively correlated with frontal FA values and inversely related to trace. These data represent the first report of significant alterations in frontal white matter tracts associated with measures of impulsivity in chronic MJ smokers. Early MJ use may result in reduced FA and increased diffusivity, which may be associated with increased impulsivity, and ultimately contribute to the initiation of MJ use or the inability to discontinue use.

Worth the wait: effects of age of onset of marijuana use on white matter and impulsivity

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.

Age of onset of marijuana use impacts inhibitory processing.

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.

The impact of initiation: Early onset marijuana smokers demonstrate altered Stroop performance and brain activation ☆

Highlights • MJ smokers exhibited poorer performance and altered activation on the Stroop.• MJ smokers reported significantly higher impulsivity than control subjects.• Poorer performance and neural alterations were primarily related to early MJ onset.• Early onset smokers reported higher levels of MJ use than late onset smokers.• Earlier MJ onset and increased MJ use predicted poorer Stroop performance.

Neuroimaging predictors of treatment response in anxiety disorders

Although several psychological and pharmacological treatment options are available for anxiety disorders, not all patients respond well to each option. Furthermore, given the relatively long duration of adequate treatment trials, finding a good treatment fit can take many months or longer. Thus, both clinicians and patients would benefit from the identification of objective pre-treatment measures that predict which patients will best respond to a given treatment. Recent studies have begun to use biological measures to help predict symptomatic change after treatment in anxiety disorders. In this review, we summarize studies that have used structural and functional neuroimaging measures to predict treatment response in obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), generalized anxiety disorder (GAD), and social anxiety disorder (SAD). We note the limitations of the current studies and offer suggestions for future research. Although the literature is currently small, we conclude that pre-treatment neuroimaging measures do appear to predict treatment response in anxiety disorders, and future research will be needed to determine the relative predictive power of neuroimaging measures as compared to clinical and demographic measures.

Splendor in the Grass? A Pilot Study Assessing the Impact of Medical Marijuana on Executive Function

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.

Altered affective processing in bipolar disorder: an fMRI study.

BACKGROUND Previous studies have reported that patients with bipolar disorder (BPD) exhibit altered emotional processing and regulation. However, results remain largely inconsistent across studies. The aim of the current study was to further examine affective processing in patients with bipolar disorder. METHODS Twenty-three patients diagnosed with BPD (Type I) and 18 healthy matched controls completed a backward-masked affect paradigm while undergoing functional magnetic resonance imaging. Participants also completed a computerized, overt task of facial emotional discrimination after scanning. RESULTS Results demonstrated altered affective processing of happy and fearful stimuli in bipolar participants in the amygdala, anterior cingulate cortex (ACC), and dorsolateral prefrontal cortex (DLPFC) relative to controls. BPD participants also displayed significant deficits in identifying fearful facial affect. LIMITATIONS This study has a moderate sample size, and the patients with BPD were significantly older than the healthy control participants; this did not appear to impact results, and although statistically significant, it is not likely biologically significant. CONCLUSIONS These findings may have implications for patients with BPD, as altered affective processing could result in deficits in reading social cues.

The Grass Might Be Greener: Medical Marijuana Patients Exhibit Altered Brain Activity and Improved Executive Function after 3 Months of Treatment

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.

Citicoline Treatment Improves Measures of Impulsivity and Task Performance in Chronic Marijuana Smokers: A Pilot BOLD fMRI Study

Objective Citicoline is an endogenous nucleotide that has historically been used to treat stroke, traumatic brain injury, and cognitive dysfunction. Research has also shown that citicoline treatment is associated with improved cognitive performance in substance-abusing populations. We hypothesized that marijuana (MJ) smokers who received citicoline would demonstrate improvement in cognitive performance as well as increased neural efficiency during tasks of cognitive control relative to those who received placebo. Method The current study tested this hypothesis by examining the effects of citicoline in treatment-seeking chronic MJ smokers. In an 8-week double-blind, placebo-controlled study, 19 MJ smokers were randomly assigned via a double-blind procedure to the citicoline (8 Males, 2 Females) or placebo group (9 Males, 0 Females). All participants completed fMRI scanning at baseline and after 8 weeks of treatment during two cognitive measures of inhibitory processing, the Multi Source Interference Test (MSIT) and Stroop Color Word Test, and also completed the Barratt Impulsiveness Scale (BIS-11), a self-report measure of impulsivity. Results Following the 8 week trial, MJ smokers treated with citicoline demonstrated significantly lower levels of behavioral impulsivity, improved task accuracy on both the MSIT and Stroop tasks, and exhibited significantly different patterns of brain activation relative to baseline levels and relative to those who received placebo. Conclusions Findings suggest that citicoline may facilitate the treatment of MJ use disorders by improving the cognitive skills necessary to fully engage in comprehensive treatment programs.