Adolescent developments in limbic structures and the endogenous cannabinoid system suggest that teenagers may be more vulnerable to the negative consequences of marijuana use. This study examined the relationships between amygdala volume and internalizing symptoms in teenaged chronic marijuana users. Participants were 35 marijuana users and 47 controls ages 16–19 years. Exclusions included psychiatric (e.g., mood and anxiety) or neurologic disorders. Substance use, internalizing (anxiety/depression) symptoms and brain scans were collected after 28 days of monitored abstinence. Reliable raters manually traced amygdala and intracranial volumes on high-resolution magnetic resonance images. Female marijuana users had larger right amygdala volumes and more internalizing symptoms than female controls, after covarying head size, alcohol, nicotine and other substance use (p<0.05), while male users had similar volumes as male controls. For female controls and males, worse mood/anxiety was linked to smaller right amygdala volume (p<0.05), whereas more internalizing problems was associated with bigger right amygdala in female marijuana users. Gender interactions may reflect marijuana-related interruptions to sex-specific neuromaturational processes and staging. Subtle amygdala development abnormalities may underlie particular vulnerabilities to sub-diagnostic depression and anxiety in teenage female marijuana users.

Background-Alcohol and other substance use disorders (AUD/SUD) are common among youth and often continue into adulthood; therefore, the neurocognitive effects of substance use are of great concern. Because neuromaturation continues into young adulthood, youth with AUD/SUD may be at risk for lasting cognitive decrements. This study prospectively examines neuropsychological functioning over 10 years as a function of AUD/SUD history and outcomes.

Previous studies have suggested neural disruption and reorganization in adult marijuana users. However, it remains unclear whether these effects persist in adolescents after 28 days of abstinence and, if they do, what Performance x Brain Response interactions occur. Adolescent marijuana users (n=17) and controls (n=17) aged 16-18 years were recruited from local schools. Functional magnetic resonance imaging data were collected after 28 days' monitored abstinence as participants performed a spatial working memory task. Marijuana users show Performance x Brain Response interactions in the bilateral temporal lobes, left anterior cingulate, left parahippocampal gyrus, and right thalamus (clusters >/=1358 microl; p<.05), although groups do not differ on behavioral measures of task performance. Marijuana users show differences in brain response to a spatial working memory task despite adequate performance, suggesting a different approach to the task via altered neural pathways.

Introduction The Mediterranean and Dietary Approaches to Stop Hypertension diets have been associated with lower dementia risk. We evaluated dietary inflammatory potential in relation to mild cognitive impairment (MCI)/dementia risk. Methods Baseline food frequency questionnaires from n = 7085 women (aged 65–79 years) were used to calculate Dietary Inflammatory Index (DII) scores that were categorized into four groups. Cognitive function was evaluated annually, and MCI and all-cause dementia cases were adjudicated centrally. Mixed effect models evaluated cognitive decline on over time; Cox models evaluated the risk of MCI or dementia across DII groups. Results Over an average of 9.7 years, there were 1081 incident cases of cognitive impairment. Higher DII scores were associated with greater cognitive decline and earlier onset of cognitive impairment. Adjusted hazard ratios (HRs) comparing lower (anti-inflammatory; group 1 referent) DII scores to the higher scores were group 2-HR: 1.01 (0.86–1.20); group 3-HR: 0.99 (0.82–1.18); and group 4-HR: 1.27 (1.06–1.52). Conclusions Diets with the highest pro-inflammatory potential were associated with higher risk of MCI or dementia.

Introduction Medical cannabis is increasingly being used for a variety of health conditions as more states implement legislation permitting medical use of cannabis. Little is known about medical cannabis use patterns and motives among adults across the lifespan. Methods The present study examined data collected at a medical cannabis dispensary in San Francisco, California. Participants included 217 medical cannabis patients who were grouped into age-defined cohorts (younger: 18–30, middle-aged: 31–50, and older: 51–72). The age groups were compared on several measures of cannabis use, motives and medical conditions using one-way ANOVAs, chi-square tests and linear regression analyses. Results All three age groups had similar frequency of cannabis use over the past month; however, the quantity of cannabis used and rates of problematic cannabis use were higher among younger users relative to middle-aged and older adults. The association between age and problematic cannabis use was moderated by age of regular use initiation such that earlier age of regular cannabis use onset was associated with more problematic use in the younger users, but not among older users. Middle-aged adults were more likely to report using medical cannabis for insomnia, while older adults were more likely to use medical cannabis for chronic medical problems such as cancer, glaucoma and HIV/AIDS. Younger participants reported cannabis use when bored at a greater rate than middle-aged and older adults. Conclusions Findings suggest that there is an age-related risk for problematic cannabis use among medical cannabis users, such that younger users should be monitored for cannabis use patterns that may lead to deleterious consequences.

Importance Although chronic relapse is a characteristic of addiction to stimulants, conventional measures (eg, clinical, demographic, and self-report) do not robustly identify which individuals are most vulnerable to relapse. Objectives To test whether drug cues are associated with increased mesolimbic neural activity in patients undergoing treatment for stimulant use disorder and whether this activity is associated with risk for subsequent relapse. Design, Setting, and Participants This prospective cohort study of 76 participants included a control group for baseline group comparisons. Veteran patients (n = 36) with stimulant use disorders were recruited from a 28-day residential treatment program at the Veterans Affairs Palo Alto Health Care System. Healthy controls (n = 40) were recruited from the surrounding community. Baseline data were collected between September 21, 2015, and January 26, 2018, from patients and healthy controls using functional magnetic resonance imaging during a performance of a reward cue task. Patients’ stimulant use was subsequently assessed after treatment discharge (at approximately 1, 3, and 6 months) to assess relapse outcomes. Main Outcomes and Measures Primary measures included neural responses to drug and food cues in estimated mesolimbic volumes of interest, including the medial prefrontal cortex, nucleus accumbens (NAcc), and ventral tegmental area. The primary outcome variable was relapse (defined as any stimulant use), assessed both dichotomously (3 months after discharge) and continuously (days to relapse). Brain activity measures were contrasted between groups to validate neural measures of drug cue reactivity, which were then used to estimate relapse outcomes of patients. Results Relative to controls (n = 40; 16 women and 24 men; mean [SD] age, 32.0 [11.6] years), patients (n = 36; 2 women and 34 men; mean [SD] age, 43.4 [13.3] years) showed increased mesolimbic activity in response to drug cues (medial prefrontal cortex, t 74 = 2.90, P = .005, Cohen d = 0.66; NAcc, t 74 = 2.39, P = .02, Cohen d = 0.54; and ventral tegmental area, t 74 = 4.04, P < .001, Cohen d = 0.92). In patients, increased drug cue response in the NAcc (but not other volumes of interest) was associated with time to relapse months later (Cox proportional hazards regression hazard ratio, 2.30; 95% CI, 1.40-3.79). After controlling for age, NAcc response to drug cues classified relapsers (12 patients; 1 woman and 11 men; mean [SD] age, 49.3 [14.1] years) and abstainers (21 patients; 1 woman and 20 men; mean [SD] age, 39.3 [12.3] years) at 3 months with 75.8% classification accuracy. Model com...

Attenuated response in the anterior insula after alcohol intake may explain some of the decreased interoceptive awareness described during intoxication.

Background A low level of response (LR) to alcohol is an important endophenotype associated with an increased risk for alcoholism. However, little is known about how neural functioning may differ between individuals with low and high LRs to alcohol. This study examined whether LR group effects on neural activity varied as a function of acute alcohol consumption. Methods 30 matched high- and low-LR pairs (N=60 healthy young adults) were recruited from the University of California, San Diego and administered a structured diagnostic interview and laboratory alcohol challenge followed by two fMRI sessions under placebo and alcohol conditions, in randomized order. Task performance and BOLD response contrast to high relative to low working memory load in an event-related visual working memory (VWM) task was examined across 120 fMRI sessions. Results Both LR groups performed similarly on the VWM task across conditions. A significant LR group by condition interaction effect was observed in inferior frontal and cingulate regions, such that alcohol attenuated the LR group differences found under placebo (p<.05). The LR group by condition effect remained even after controlling for cerebral blood flow, age, and typical drinking quantity. Conclusions Alcohol had differential effects on brain activation for low and high LR individuals within frontal and cingulate regions. These findings represent an additional step in the search for physiological correlates of a low LR, and identify brain regions that may be associated with the low LR response.