Alcohol abuse and alcohol depen

Abstract Alcoholism results from an interplay between genetic and environmental factors, and is linked to brain defects and associated cognitive, emotional, and behavioral impairments. A confluence of findings from neuroimaging, physiological, neuropathological, and neuropsychological studies of alcoholics indicate that the frontal lobes, limbic system, and cerebellum are particularly vulnerable to damage and dysfunction. An integrative approach employing a variety of neuroscientific technologies is essential for recognizing the interconnectivity of the different functional systems affected by alcoholism. In that way, relevant experimental techniques can be applied to assist in determining the degree to which abstinence and treatment contribute to the reversal of atrophy and dysfunction. Keywords Alcoholism . Frontal lobes . Limbic system . Cerebellum . Right hemisphere Alcoholic beverages contain ethanol, a psychoactive drug with relaxant and euphoric effects, consumed by people throughout the world. In general, the effects of alcohol intoxication follow a biphasic time course as the initial feelings of relaxation and exuberance give way to hangover, exhaustion, and depression, or vomiting and loss of consciousness in cases of higher doses (Nagoshi and Wilson 1989). Criteria for classifying someone as an alcoholic vary Risky drinking patterns for men are defined as consuming more than 14 drinks per week, or more than four drinks in a single day at least once a month; for women, the limits are more than seven drinks per week and three drinks per da

Using the Neuroadaptagen KB200z to Ameliorate Terrifying, Lucid Nightmares in RDS Patients: the Role of Enhanced, Brain-Reward, Functional Connectivity and Dopaminergic Homeostasis.

BACKGROUND: Lucid Dreams are a form of dream life, during which the dreamer may be aware that he/she is dreaming, can stop/re-start the dreams, depending on the pleasantness or unpleasant nature of the dream, and experiences the dream as if he/she were fully awake. Depending on their content, they may be pleasant, un-pleasant or terrifying, at least in the context of patients, who also exhibit characteristics of Reward Deficiency Syndrome (RDS) and Posttraumatic Stress Disorder (PTSD). CASE SERIES: We present eight clinical cases, with known substance abuse, childhood abuse and diagnosed PTSD/RDS. The administration of a putative dopamine agonist, KB200Z, was associated with the elimination of unpleasant and/or terrifying, lucid dreams in 87.5% of the cases presented, whereas one very heavy cocaine abuser showed a minimal response. These results required the continuous use of this nutraceutical. The lucid dreams themselves were distinguishable from typical, PTSD nightmares insofar as their content did not appear to reflect a symbolic rendition of an originally-experienced, historical trauma. Each of the cases was diagnosed with a form of RDS, i.e., ADHD, ADD, and/or Tourette's syndrome. They all also suffered from some form of Post-Traumatic-Stress-Disorder (PTSD) and other psychiatric diagnoses as well. CONCLUSION: The reduction or elimination of terrifying Lucid Dreams seemed to be dependent on KB220Z, whereby voluntary stopping of the agent results in reinstatement of the terrifying non-pleasant nature of the dreams. Following more required research on a much larger population we anticipate confirmation of these seemingly interesting observations. If these results in a small number of patients are indeed confirmed we may have found a frontline solution to a very perplexing and complicated symptom known as lucid dreams

Frontal brain dysfunction in alcoholism with and without antisocial personality disorder

Alcoholism and antisocial personality disorder (ASPD) often are comorbid conditions. Alcoholics, as well as nonalcoholic individuals with ASPD, exhibit behaviors associated with prefrontal brain dysfunction such as increased impulsivity and emotional dysregulation. These behaviors can influence drinking motives and patterns of consumption. Because few studies have investigated the combined association between ASPD and alcoholism on neuropsychological functioning, this study examined the influence of ASPD symptoms and alcoholism on tests sensitive to frontal brain deficits. The participants were 345 men and women. Of them, 144 were abstinent alcoholics (66 with ASPD symptoms), and 201 were nonalcoholic control participants (24 with ASPD symptoms). Performances among the groups were examined with Trails A and B tests, the Wisconsin Card Sorting Test, the Controlled Oral Word Association Test, the Ruff Figural Fluency Test, and Performance subtests of the Wechsler Adult Intelligence Scale. Measures of affect also were obtained. Multiple regression analyses showed that alcoholism, specific drinking variables (amount and duration of heavy drinking), and ASPD were significant predictors of frontal system and affective abnormalities. These effects were different for men and women. The findings suggested that the combination of alcoholism and ASPD leads to greater deficits than the sum of each

Zonisamide, Topiramate, and Levetiracetam: Efficacy and Neuropsychological Effects in Alcohol Use Disorders

Abstract The anticonvulsant topiramate not only decreases ethanol consumption in alcohol dependence (AD) but also may produce several adverse events including cognitive impairment. Zonisamide is a structurally related anticonvulsant that is a promising agent for the treatment of AD and may have greater tolerability than topiramate. This study evaluated the effects of zonisamide (400 mg/d) on alcohol consumption and its neurotoxic effects in subjects with AD. A double-blind placebo-controlled clinical trial was conducted using 2 comparator anticonvulsant drugs, topiramate (300 mg/d) and levetiracetam (2000 mg/d), which does not impair cognition. Study medications were administered for 14 weeks, including a 2-week taper period. Medication adherence was facilitated using Brief Behavioral Compliance Enhancement Treatment. The neurotoxicity of the study drugs was assessed using neuropsychological tests and the AB-Neurotoxicity Scale. Compared with placebo, both zonisamide and topiramate produced significant reductions in the drinks consumed per day, percent days drinking, and percent days heavy drinking. Only the percent days heavy drinking was significantly decreased in the levetiracetam group. The topiramate cell was the only group that had a significant increase on the mental slowing subscale of the Neurotoxicity Scale compared with placebo at study weeks 11 and 12. Topiramate and zonisamide both produced modest reductions in verbal fluency and working memory. These findings indicate that zonisamide may have efficacy in the treatment of AD, with effect sizes similar to topiramate. Both of these drugs produced similar patterns of cognitive impairment, although only the topiramate group reported significant increases in mental slowing

Activation instead of blocking mesolimbic dopaminergic reward circuitry is a preferred modality in the long term treatment of reward deficiency syndrome (RDS): a commentary

BACKGROUND AND HYPOTHESIS. Based on neurochemical and genetic evidence, we suggest that both prevention and treatment of multiple addictions, such as dependence to alcohol, nicotine and glucose, should involve a biphasic approach. Thus, acute treatment should consist of preferential blocking of postsynaptic Nucleus Accumbens (NAc) dopamine receptors (D1-D5), whereas long term activation of the mesolimbic dopaminergic system should involve activation and/or release of Dopamine (DA) at the NAc site. Failure to do so will result in abnormal mood, behavior and potential suicide ideation. Individuals possessing a paucity of serotonergic and/or dopaminergic receptors, and an increased rate of synaptic DA catabolism due to high catabolic genotype of the COMT gene, are predisposed to self-medicating any substance or behavior that will activate DA release, including alcohol, opiates, psychostimulants, nicotine, gambling, sex, and even excessive internet gaming. Acute utilization of these substances and/or stimulatory behaviors induces a feeling of well being. Unfortunately, sustained and prolonged abuse leads to a toxic" pseudo feeling" of well being resulting in tolerance and disease or discomfort. Thus, a reduced number of DA receptors, due to carrying the DRD2 A1 allelic genotype, results in excessive craving behavior; whereas a normal or sufficient amount of DA receptors results in low craving behavior. In terms of preventing substance abuse, one goal would be to induce a proliferation of DA D2 receptors in genetically prone individuals. While in vivo experiments using a typical D2 receptor agonist induce down regulation, experiments in vitro have shown that constant stimulation of the DA receptor system via a known D2 agonist results in significant proliferation of D2 receptors in spite of genetic antecedents. In essence, D2 receptor stimulation signals negative feedback mechanisms in the mesolimbic system to induce mRNA expression causing proliferation of D2 receptors. PROPOSAL AND CONCLUSION. The authors propose that D2 receptor stimulation can be accomplished via the use of Synapatmine™, a natural but therapeutic nutraceutical formulation that potentially induces DA release, causing the same induction of D2-directed mRNA and thus proliferation of D2 receptors in the human. This proliferation of D2 receptors in turn will induce the attenuation of craving behavior. In fact as mentioned earlier, this model has been proven in research showing DNA-directed compensatory overexpression (a form of gene therapy) of the DRD2 receptors, resulting in a significant reduction in alcohol craving behavior in alcohol preferring rodents. Utilizing natural dopaminergic repletion therapy to promote long term dopaminergic activation will ultimately lead to a common, safe and effective modality to treat Reward Deficiency Syndrome (RDS) behaviors including Substance Use Disorders (SUD), Attention Deficit Hyperactivity Disorder (ADHD), Obesity and other reward deficient aberrant behaviors. This concept is further supported by the more comprehensive understanding of the role of dopamine in the NAc as a "wanting" messenger in the meso-limbic DA system.LifeGen, Inc.; Electronic Waveform Lab; Huntington Beach and Path Research Foundatio

An Automated Mobile Game-based Screening Tool for Patients with Alcohol Dependence

Traditional methods for screening and diagnosis of alcohol dependence are typically administered by trained clinicians in medical settings and often rely on interview responses. These self-reports can be unintentionally or deliberately false, and misleading answers can, in turn, lead to inaccurate assessment and diagnosis. In this study, we examine the use of user-game interaction patterns on mobile games to develop an automated diagnostic and screening tool for alcohol-dependent patients. Our approach relies on the capture of interaction patterns during gameplay, while potential patients engage with popular mobile games on smartphones. The captured signals include gameplay performance, touch gestures, and device motion, with the intention of identifying patients with alcohol dependence. We evaluate the classification performance of various supervised learning algorithms on data collected from 40 patients and 40 age-matched healthy adults. The results show that patients with alcohol dependence can be automatically identified accurately using the ensemble of touch, device motion, and gameplay performance features on 3-minute samples (accuracy=0.95, sensitivity=0.95, and specificity=0.95). The present findings provide strong evidence suggesting the potential use of user-game interaction metrics on existing mobile games as discriminant features for developing an implicit measure to identify alcohol dependence conditions. In addition to supporting healthcare professionals in clinical decision-making, the game-based self-screening method could be used as a novel strategy to promote alcohol dependence screening, especially outside of clinical settings