Adolescence is a particularly vulnerable neurodevelopmental period marked by high rates of engagement with risky alcohol use. This review summarizes the cognitive and neural consequences following alcohol use during adolescence from longitudinal design studies in humans and animals. Findings from human adolescent studies suggest that binge drinking and heavy alcohol use is associated with poorer cognitive functioning on a broad range of neuropsychological assessments, including learning, psychomotor speed, attention, executive functioning, and impulsivity. adolescence is memory, visuospatial functioning, Alcohol use during associated with accelerated decreases in gray matter and attenuated increases in white matter volume, and aberrant neural activity during executive functioning, attentional control, and reward sensitivity tasks, when compared to non-drinking adolescents. Animal studies in rodents and nonhuman primates have replicated human findings, and suggest cognitive and neural consequences of adolescent alcohol use may persist into adulthood. Novel rodent studies demonstrate that adolescent alcohol use may increase reward responsiveness of the dopamine system to alcohol later in life, as well as disrupt adolescent neurogenesis, potentially through neuroinflammation, with long-lasting neural and behavioral effects into adulthood. Larger longitudinal human cognitive and neuroimaging studies with more diverse samples are currently underway which will improve understanding of the impact of polysubstance use, as well as the interactive effects of substance use, physical and mental health, and demographic factors on cognition and neurodevelopment.

IMPORTANCE Substance use disorders (SUDs) represent a pressing public health concern. Combined behavioral and pharmacological interventions are considered best practices for addiction. Cognitive behavioral therapy (CBT) is a first-line intervention, yet the superiority of CBT compared with other behavioral treatments when combined with pharmacotherapy remains unclear. An understanding of the effects of combined CBT and pharmacotherapy will inform best-practice guidelines for treatment of SUD. OBJECTIVE To conduct a meta-analysis of the published literature on combined CBT and pharmacotherapy for adult alcohol use disorder (AUD) or other SUDs.

Computerized cognitive bias modification paradigms may have utility in reducing adolescent cannabis use. Future work should consider developing a paradigm that addresses both cannabis and alcohol, as well as alternative computerized approaches for coping with addictive behavior in conjunction with bias modification.

Cannabis-using youth show more activation to cannabis cues than non-cannabis cues in brain regions underlying incentive salience, reward, and visual attention. This task could be useful for future studies examining neural underpinnings of reward processes in adolescent cannabis users.

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Alcohol use disorder (AUD) is a highly prevalent but severely under-treated disorder, with only three widely-approved pharmacotherapies. Given that AUD is a very heterogeneous disorder, it is unlikely that one single medication will be effective for all individuals with an AUD. As such, there is a need to develop new, more effective, and diverse pharmacological treatment options for AUD with the hopes of increasing utilization and improving care. In this qualitative literature review, we discuss the efficacy, mechanism of action, and tolerability of approved, repurposed, and novel pharmacotherapies for the treatment of AUD with a clinical perspective. Pharmacotherapies discussed include: disulfiram, acamprosate, naltrexone, nalmefene, topiramate, gabapentin, varenicline, baclofen, sodium oxybate, aripiprazole, ondansetron, mifepristone, ibudilast, suvorexant, prazosin, doxazosin, N-acetylcysteine, GET73, ASP8062, ABT-436, PF-5190457, and cannabidiol. Overall, many repurposed and novel agents discussed in this review demonstrate clinical effectiveness and promise for the future of AUD treatment. Importantly, these medications also offer potential improvements towards the advancement of precision medicine and personalized treatment for the heterogeneous AUD population. However, there remains a great need to improve access to treatment, increase the menu of approved pharmacological treatments, and de-stigmatize and increase treatment-seeking for AUD.

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Background: Identifying neural characteristics that predict cannabis initiation is important for prevention efforts. The orbitofrontal cortex is critical for reward response and may be vulnerable to substance-induced alterations. Aims: We measured orbitofrontal cortex thickness, surface area, and volume prior to the onset of use to predict cannabis involvement during an average nine-year follow-up. Methods: Adolescents ( n=118) aged 12–15 years completed baseline behavioral assessment and magnetic resonance imaging scans, then were followed up to 13 years with annual substance use interviews. Logistic regression examined baseline (pre-substance use) bilateral medial and lateral orbitofrontal cortex characteristics (volume, surface area, or cortex thickness) as predictors of regular cannabis use by follow-up. Post-hoc multinomial logistic regression assessed whether orbitofrontal cortex characteristics significantly predicted either alcohol use alone or cannabis+alcohol co-use. Brain-behavior relationships were assessed through follow-up correlations of baseline relationships between orbitofrontal cortex and executive functioning, reward responsiveness, and behavioral approach traits. Results: Larger left lateral orbitofrontal cortex volume predicted classification as cannabis user by follow-up ( p=0.025, odds ratio=1.808). Lateral orbitofrontal cortex volume also predicted cannabis+alcohol co-user status ( p=0.008, odds ratio=2.588), but not alcohol only status. Larger lateral orbitofrontal cortex volume positively correlated with greater baseline reward responsiveness ( p=0.030, r=0.348). There were no significant results by surface area or cortex thickness ( ps>0.05). Conclusions: Larger left lateral orbitofrontal cortex measured from ages 12–15 years and prior to initiation of substance use was related to greater reward responsiveness at baseline and predicted classification as a cannabis user and cannabis+alcohol co-user by final follow-up. Larger lateral orbitofrontal cortex volume may represent aberrant orbitofrontal cortex maturation and increasing vulnerability for later substance use.