Cannabis use has been linked to impairments in neuropsychological functioning across a large and continually expanding body of research. Yet insight into underlying causal relations remains limited due to the historically cross-sectional nature of studies in this area. Recently, however, studies have begun to use more informative design strategies to delineate these associations. The aim of this article is to provide a critical evaluation and review of research that uses longitudinal designs to examine the link between cannabis use and neuropsychological functioning. In summarizing the primary findings across these studies, this review suggests that cannabis use leads to neuropsychological decline. However, across most studies, these associations were modest, were present only for the group with the heaviest cannabis use, and were often attenuated (or no longer significant) after controlling for potential confounding variables. Future studies with neuropsychological data before and after initiation of cannabis use, along with careful measurement and control of "shared risk factors" between cannabis use and poorer neuropsychological outcomes, are needed to better understand who, and under what conditions, is most vulnerable to cannabis-associated neuropsychological decline. (JINS, 2017, 23, 893-902)

Background Urea cycle disorders are caused by dysfunction in any of the six enzymes and two transport proteins involved in urea biosynthesis. Our study focuses on Ornithine Transcarbamylase deficiency (OTCD), an X-linked disorder that results in a dysfunctional mitochondrial enzyme, which prevents the synthesis of citrulline from carbamoyl phosphate and ornithine. This enzyme deficiency can lead to hyperammonemic episodes and severe cerebral edema. The objective of this study was to use a cognitive battery to expose the cognitive deficits in asymptomatic carriers of OTCD. Materials and Methods In total, 81 participants were recruited as part of a larger urea cycle disorder imaging consortium study. There were 25 symptomatic participants (18 female, 7 male, 25.6 years ± 12.72 years), 20 asymptomatic participants (20 female, 0 male, 37.6 years ± 15.19 years), and 36 healthy control participants (21 female, 15 male, 29.8 years ± 13.39 years). All participants gave informed consent to participate and were then given neurocognitive batteries with standard scores and T scores recorded. Results When stratified by symptomatic participant, asymptomatic carrier, and control, the results showed significant differences in measures of executive function (e.g. CTMT and Stroop) and motor ability (Purdue Assembly) between all groups tested. Simple attention, academic measures, language and non-verbal motor abilities showed no significant differences between asymptomatic carriers and control participants, however, there were significant differences between symptomatic and control participant performance in these measures. Conclusions In our study, asymptomatic carriers of OTCD showed no significant differences in cognitive function compared to control participants until they were cognitively challenged with fine motor tasks, measures of executive function, and measures of cognitive flexibility. This suggests that cognitive dysfunction is best measurable in asymptomatic carriers after they are cognitively challenged.

Reduced motivation is often noted as a consequence of cannabis use. However, prior studies examining this association have suboptimally operationalized motivation and have yielded mixed findings. This review discusses motivation and the closely related construct of reward sensitivity. We summarize the available literature examining associations between motivation and cannabis use, addressing the following questions: (a) Is there evidence for decreased motivation among cannabis users? (b) Is there evidence that lack of motivation among cannabis users is specific to their use of cannabis (rather than to use of other addictive drugs)? and (c) Is there evidence suggesting a causal relationship between cannabis use and motivation? Using PubMed, PsycINFO, and WebofScience, we conducted a literature search of studies examining nonacute effects of cannabis use on motivation, apathy, amotivation, effort, and reward sensitivity in humans. This search yielded 22 studies, which were reviewed in detail. We conclude that, although cross-sectional evidence of a cannabis-specific effect on motivation is equivocal, there is partial support from longitudinal studies for a causal link between cannabis use and reduced motivation. Additionally, we propose that reward sensitivity and motivation represent distinct yet related constructs and that reductions in one may not always lead to reductions in the other. Future work should longitudinally examine associations between cannabis use, motivation, and reward sensitivity; carefully define and operationalize these constructs; and control for the influence of potential confounding factors. (PsycINFO Database Record

The urea cycle is the primary nitrogen-disposal pathway in humans. It requires the coordinated function of six enzymes and two mitochondrial transporters to catalyze the conversion of a molecule of ammonia, the α-nitrogen of aspartate, and bicarbonate into urea. Whereas ammonia is toxic, urea is relatively inert, soluble in water, and readily excreted by the kidney in the urine. Accumulation of ammonia and other toxic intermediates of the cycle lead to predominantly neurologic sequelae. The disorders may present at any age from the neonatal period to adulthood, with the more severely affected patients presenting earlier in life. Patients are at risk for metabolic decompensation throughout life, often triggered by illness, fasting, surgery and postoperative states, peripartum, stress, and increased exogenous protein load. Here the authors address neurologic presentations of ornithine transcarbamylase deficiency in detail, the most common of the urea cycle disorders, neuropathology, neurophysiology, and our studies in neuroimaging. Special attention to late-onset presentations is given.

Objective: As the perceived risk of cannabis use continues to decline among youths and access continues to increase, it becomes more important to synthesize the rapidly growing literature on the effects of cannabis on neurocognition. Hundreds of studies examining associations between cannabis use and neurocognitive functioning have been published in recent decades. However, results often differ across individual studies, particularly when sample sizes are small. Metaanalytic methods help to make sense of this literature and have been increasingly applied to studies on cannabis use and neurocognition.Methods: A systematic literature search using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted to identify peer-reviewed metaanalyses of neurocognitive or functional neuroimaging data that examined associations between cannabis use and non-acute effects on neurocognitive functioning (n = 8).Results: Current findings suggest that regular healthy cannabis users, regardless of age, display poorer neurocognitive functioning relative to nonusers of small to medium effect sizes across many neurocognitive domains, as well as functional brain alterations when compared to non-users. Adverse effects are not uniform across neurocognitive domains and evidence for adolescent-onset users having poorer neurocognitive outcomes remains equivocal based on these studies. However, less is known about cannabis effects on neurocognition among clinical samples, as findings from specific clinical samples revealed mixed results.Conclusions: Meta-analyses have played an important role in helping to grasp the totality of results from a large body of literature on cannabis effects on neurocognition, yet more research (particularly large-scale longitudinal studies) is needed to identify critical periods or patterns of use that are more likely to result in negative outcomes.