Enabling endpoint development for interventional clinical trials in individuals with Angelman syndrome: a prospective, longitudinal, observational clinical study (FREESIAS).

Background: Angelman syndrome (AS) is a rare neurodevelopmental disorder characterized by the absence of a functional UBE3A gene, which causes developmental, behavioral, and medical challenges. While currently untreatable, comprehensive data could help identify appropriate endpoints assessing meaningful improvements in clinical trials. Herein are reported the results from the FREESIAS study assessing the feasibility and utility of in-clinic and at-home measures of key AS symptoms.

Neuropsychological performance in young adults with cannabis use disorder.

Background And Aims: Cannabis is a commonly used recreational drug in young adults. The worldwide prevalence in 18- to 25-year-olds is approximately 35%. Significant differences in cognitive performance have been reported previously for groups of cannabis users.

Extemporaneous preparation strategy for early phase clinical studies.

Extemporaneous preparations (EPs) of investigational drugs, which are compounded at the clinical study site by a pharmacist, are being increasingly used in early phase clinical studies to accelerate the development of new medicines. The successful application of EP strategies in clinical studies requires 'fit-for-purpose' formulation design and preparation processes, as well as administration procedures that are safe, flexible, cost-effective, and simple to adapt by a compounding pharmacist at the clinical site. DNS-7801 is a weakly basic investigational compound that exhibits a higher aqueous solubility at lower pH with its solubility dropping off precipitously with increase in pH.

A proof-of-concept randomized controlled study of gabapentin: effects on cannabis use, withdrawal and executive function deficits in cannabis-dependent adults.

There are no FDA-approved pharmacotherapies for cannabis dependence. Cannabis is the most widely used illicit drug in the world, and patients seeking treatment for primary cannabis dependence represent 25% of all substance use admissions. We conducted a phase IIa proof-of-concept pilot study to examine the safety and efficacy of a calcium channel/GABA modulating drug, gabapentin, for the treatment of cannabis dependence.

Effects of chronic, heavy cannabis use on executive functions.

This case describes the clinical course of a cannabis-dependent individual entering a 12-week abstinence-based research program. The case illustrates the effects of chronic, heavy cannabis use on executive functions at three time points: 1) 24 hours of abstinence; 2) 4 weeks of abstinence; and 3) 12 weeks of abstinence. It is followed by discussions by two clinical psychologists and a psychiatrist.

An evidence based review of acute and long-term effects of cannabis use on executive cognitive functions.

Cannabis use has been shown to impair cognitive functions on a number of levels-from basic motor coordination to more complex executive function tasks, such as the ability to plan, organize, solve problems, make decisions, remember, and control emotions and behavior. These deficits differ in severity depending on the quantity, recency, age of onset and duration of marijuana use. Understanding how cannabis use impairs executive function is important.

Chronic alcohol consumption impairs visuo-spatial associative memory in periadolescent rhesus monkeys.

Unlabelled: Alcohol abuse in the adult is often preceded by high alcohol consumption during adolescence. Profound changes in brain structure and function occur during this developmental period, therefore alcohol may impact essential cognitive skill development during the formal educational years. The objective of this study was to determine if chronic oral alcohol intake slows acquisition and performance of cognitive tasks in male adolescent rhesus monkeys.

Long-lasting reduction in hippocampal neurogenesis by alcohol consumption in adolescent nonhuman primates.

Binge alcohol consumption in adolescents is increasing, and studies in animal models show that adolescence is a period of high vulnerability to brain insults. The purpose of the present study was to determine the deleterious effects of binge alcohol on hippocampal neurogenesis in adolescent nonhuman primates. Heavy binge alcohol consumption over 11 mo dramatically and persistently decreased hippocampal proliferation and neurogenesis.

Acamprosate in the treatment of alcohol dependence: clinical and economic considerations.

Acamprosate has been commercially available in the USA since 2004 to treat alcohol dependence. Its safety and efficacy have been demonstrated in a number of clinical trials worldwide, which overall have shown significant improvements in abstinence compared with placebo. As with all alcoholism pharmacotherapies, acamprosate is used in conjunction with psychosocial interventions.

Robust and stable drinking behavior following long-term oral alcohol intake in rhesus macaques.

Face validity in animal models of alcohol abuse and dependence is often at odds with robust demonstrations of ethanol-seeking. This study determined the relative influence of ethanol and a flavorant in maintaining ethanol intake in a nonhuman primate model of "cocktail" drinking. Four-year-old male monkeys were maintained on a 6% ethanol/6% Tang solution made available in daily (M-F) 1-h sessions.

Oral administration of (+/-)3,4-methylenedioxymethamphetamine and (+)methamphetamine alters temperature and activity in rhesus macaques.

Rationale: Emergency Department visits and fatalities in which (+/-)3,4-methylenedioxymethamphetamine (MDMA) or (+)methamphetamine (METH) are involved frequently feature unregulated hyperthermia. MDMA and METH significantly elevate body temperature in multiple laboratory species and, most importantly, can also produce unregulated and threatening hyperthermia in nonhuman primates. A majority of prior animal studies have administered drugs by injection whereas human consumption of "Ecstasy" is typically oral, an important difference in route of administration which may complicate the translation of animal data to the human condition.

Impact of ambient temperature on hyperthermia induced by (+/-)3,4-methylenedioxymethamphetamine in rhesus macaques.

The ambient temperature (T(A)) under which rodents are exposed to (+/-)3,4-methylenedioxymethamphetamine (MDMA) affects the direction and magnitude of the body temperature response, and the degree of hypo/hyperthermia generated in subjects can modify the severity of lasting brain changes in 'neurotoxicity' models. The thermoregulatory effects of MDMA have not been well described in non-human primates and it is unknown if T(A) has the potential to affect acute hyperthermia and therefore other lasting consequences of MDMA. The objective of this study was to determine if the temperature alteration produced by MDMA in nonhuman primates depends on T(A) as it does in rats and mice.

Differential contributions of dopaminergic D1- and D2-like receptors to cognitive function in rhesus monkeys.

Rationale: Dopaminergic neurotransmission is critically involved in many aspects of complex behavior and cognition beyond reward/reinforcement and motor function. Mental and behavioral disorders associated with major disruptions of dopamine neurotransmission, including schizophrenia, attention deficit/hyperactivity disorder, Parkinson's disease, Huntington's disease, and substance abuse produce constellations of neuropsychological deficits in learning, memory, and attention in addition to other defining symptoms.

Objective: To delineate the role dopaminergic D1- and D2-like receptor subtypes play in complex brain functions.

Hyperthermia induced by 3,4-methylenedioxymethamphetamine in unrestrained rhesus monkeys.

Background: Exposure to (+/-)3,4-methylenedioxymethamphetamine ((+/-)MDMA) results in lasting reductions of many markers for serotonin terminals in a range of species. In rodents, the severity of insult depends in large part on the generation of hyperthermia in the subject. (+/-)MDMA can produce either hyperthermia or hypothermia in rodents depending on the ambient temperature and these effects may be limited to the S(+) enantiomer.

A retrospective review of the neuropsychological test performance of physicians referred for medical infractions.

Physician-related errors are rising, resulting in an increase in disciplinary actions by licensing medical authorities. It has been previously reported that cognitive impairment may be responsible for 63% of all physician-related medical adverse events. In this paper we examine neuropsychological testing results from 148 physicians referred for assessment by the California Medical Board (CMB) for various infractions.