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1.  Sleep Architecture in Adolescent Marijuana and Alcohol Users during Acute and Extended Abstinence 
Addictive behaviors  2009;34(11):976-979.
This study examined sleep changes following cessation of marijuana and alcohol use during late adolescence. Twenty-nine heavy marijuana and alcohol users and 20 matched controls were studied during a 28-day monitored abstinence period. Sleep as examined as a function of prior substance use during Nights 1–2 and Nights 27–28. On Night 2, percent Rapid Eye Movement sleep was predicted by past month alcohol use, whereas percent Slow Wave Sleep was predicted by marijuana intake. By Night 28, neither alcohol no marijuana use predicted any sleep architecture measure. However, on Night 28, indices of period limb movements (PLMs) in sleep were predicted by marijuana and alcohol intake. Results indicate that in adolescents: (1) cessation of heavy marijuana and alcohol use may influence sleep; (2) most sleep abnormalities abate within several weeks of abstinence; and (3) PLMs may increase following abstinence.
doi:10.1016/j.addbeh.2009.05.011
PMCID: PMC2727851  PMID: 19505769
Polysomnography; Adolescence; Alcohol; Marijuana; Withdrawal; Sleep
2.  Spatial Working Memory Performance and fMRI Activation Interactions in Abstinent Adolescent Marijuana Users 
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 × 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 × Brain Response interactions in the bilateral temporal lobes, left anterior cingulate, left parahippocampal gyrus, and right thalamus (clusters ≥ 1358 μl; 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.
doi:10.1037/0893-164X.21.4.478
PMCID: PMC2373252  PMID: 18072830
marijuana; cannabis; adolescence; spatial working memory; functional magnetic resonance imaging
3.  Acute Ethanol Effects on Brain Activation in Low- and High-Level Responders to Alcohol 
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.
doi:10.1111/j.1530-0277.2010.01193.x
PMCID: PMC3774836  PMID: 20477775
Level of response; fMRI; visual working memory; cerebral blood flow
4.  Gender effects on amygdala morphometry in adolescent marijuana users 
Behavioural brain research  2011;224(1):128-134.
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.
doi:10.1016/j.bbr.2011.05.031
PMCID: PMC3139567  PMID: 21664935
Adolescence; Anxiety; Depression; Development; Gender; Marijuana; Structural MRI
5.  Alcohol Attenuates Activation in the Bilateral Anterior Insula during an Emotional Processing Task: A Pilot Study † 
Aims: Alcohol acutely reduces agitation and is widely used in social situations, but the neural substrates of emotion processing during its intoxication are not well understood. We examine whether alcohol's social stress dampening effect may be via reduced activity in the cortical systems that subserve awareness of bodily sensations, and are associated with affective distress. Methods: Blood oxygen level-dependent activation was measured through 24 functional magnetic resonance imaging sessions in 12 healthy volunteers during an emotional face-processing task following ingestion of a moderate dose of alcohol and a placebo beverage. Results: Results revealed that bilateral anterior insula response to emotional faces was significantly attenuated following consumption of alcohol, when compared with placebo (clusters >1472 μl; corrected P < 0.05). Conclusion: Attenuated response in the anterior insula after alcohol intake may explain some of the decreased interoceptive awareness described during intoxication.
doi:10.1093/alcalc/agr066
PMCID: PMC3201697  PMID: 21665869
6.  Impact of Adolescent Alcohol and Drug Use on Neuropsychological Functioning in Young Adulthood: 10-Year Outcomes 
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.
Methods
The 51 participants consisted of 18 youth with persisting AUD/SUD, 19 youth with remitted AUD/SUD, and 14 community youth with no AUD/SUD history followed over 10 years (ages 16 to 27 on average) with neuropsychological testing and substance use interviews on 8 occasions. Neuropsychological performance from baseline to 10-year follow-up was compared between the three groups.
Results
Despite scoring higher than controls at intake, both AUD/SUD groups showed a relative decline in visuospatial construction at 10-year follow-up (p=.001). Regressions showed that alcohol use (β=−.33, p < .01) and drug withdrawal symptoms (β=−.31, p<.05) over follow-up were predictive of year 10 visuospatial function. Alcohol use also predicted verbal learning and memory (β=−.28, p<.05), while stimulant use predicted visual learning and memory function (β=−.33, p=.01). More recent substance use was associated with poorer executive function (β=.28, p<.05).
Discussion
These findings confirm prior studies suggesting that heavy, chronic alcohol and other substance use persisting from adolescence to young adulthood may produce cognitive disadvantages, primarily in visuospatial and memory abilities. Youth who chronically consume heavy quantities of alcohol and/or experience drug withdrawal symptoms may be particularly at risk for cognitive deterioration by young adulthood.
doi:10.1080/1067828X.2011.555272
PMCID: PMC3083020  PMID: 21532924
adolescence; young adulthood; alcohol; substance use disorders; withdrawal; neurocognition; memory; visuospatial function; executive function

Results 1-6 (6)