sodium-oxybate and Cognition-Disorders

In several countries, including the Netherlands, the use of GHB seems to be rising. GHB is regarded by recreational users as an innocent drug without any side effects. Recently, the number of patients in treatment due to GHB addiction sharply increased. In addition, various studies report incidents following risky GHB use or GHB overdosing. Other sedative drugs, like ketamine and alcohol have been shown to result in unintended neurotoxic harm at the level of memory and cognitive function. As outlined in the present review, GHB and ketamine have a common mode of action, which suggests that GHB may also lead to similar neurotoxicity as ketamine. GHB overdosing, as well as binge drinking (and high ketamine doses), induce profound coma which is probably neurotoxic for the brain especially in the maturing brain of young adults. It is therefore advocated to investigate possible long-term neurotoxic effects in recreational GHB users e.g. by studying the residual effects on cognition and memory.

Topics: Alcoholism; Anesthetics; Anesthetics, Dissociative; Animals; Central Nervous System Depressants; Cognition Disorders; Coma; Drug Overdose; Ethanol; Glutamic Acid; Humans; Illicit Drugs; Ketamine; Neurotoxicity Syndromes; Oxidative Stress; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders; Succinate-Semialdehyde Dehydrogenase

The use of "club drugs" such as MDMA, ketamine, and GHB appears to have increased in Western countries over the last 20 years, and Australia is no exception to that trend. While levels of use appear to be relatively low in the general population, among users of these drugs a number of adverse health and psychological problems, including dependence, have been reported. MDMA or ecstasy is the third most commonly used illicit drug in Australia, and relatively more information is available on its use in Australia than of drugs such as GHB or ketamine. Although there are no population level data available, levels of ketamine use in the general population appear to be lower than those of MDMA. In addition, the harms reported by recreational users are not excessive and the mortality rate is low. At the individual level, many of those who experiment find the effects aversive and do not persist. The harms that require further investigation are the association between ketamine and unsafe sex and injecting behaviors, the neurotoxic effects, and use in situations where there is a heightened risk of accidental death when the user's cognition is grossly impaired. In contrast, while least is known of the epidemiology of GHB use, there is mounting evidence suggesting significant acute and long-term risks associated with the use of this drug. This suggests an urgent need for international research on the patterns of use, health, and psychosocial consequences of GHB use. In order to address public health issues associated with a range of club drug use, there is a need for research to identify the trends in population prevalence of these drugs. This could be most easily achieved by the inclusion of MDMA, ketamine, and GHB in household surveys that are currently collected routinely in a number of countries.

Topics: Adjuvants, Anesthesia; Adolescent; Adult; Anesthetics, Dissociative; Australia; Cognition Disorders; Female; Hallucinogens; Humans; Ketamine; Male; N-Methyl-3,4-methylenedioxyamphetamine; Prevalence; Recreation; Risk Factors; Risk-Taking; Sexual Behavior; Sodium Oxybate; Substance-Related Disorders

The pharmacologic effects of sodium oxybate (SO) have a number of similarities with those of alcohol. This study evaluated the pharmacodynamic interaction of SMO.IR (a solid immediate release formulation of SO) and alcohol (0.7 (males) or 0.57 (females) g kg(-1) alcohol using 40% vodka).. In a randomized, double-blind, double-dummy, crossover trial, 24 healthy volunteers received randomly a) 2.25 g SMO.IR and placebo alcohol preparation, b) 2.25 g f SMO.IR and alcohol, c) 2.25 g SMO.IR matching placebo and alcohol and d) 2.25 g of SMO.IR matching placebo and placebo alcohol preparation. Objective and subjective cognitive parameters, adverse events and vital signs were assessed before, 15 and 165 min after treatment administration.. Alcohol produced the expected cognitive impairment and the expected subjective sedation rapidly after intake (from 15 min). The objective effects of SMO.IR were much less pronounced than those of alcohol. The reverse was observed for subjective complaints, which were related to lesser stimulation and greater sedation. Nevertheless, 165 min after administration this sedation feeling was less with SMO.IR than with alcohol. There was a significant interaction between SMO.IR and alcohol at 15 min (i.e. increase in alertness and stimulation and decrease in sedation). In addition, an isolated mild decrease in digit vigilance accuracy occurred at 165 min post-dose after the combination. The co-administration of SMO.IR and alcohol was safe and well-tolerated.. SMO.IR and alcohol have distinct adverse effect profiles. The objective effects of SMO.IR are much less marked than those of alcohol. No deleterious interaction was observed.

Topics: Adolescent; Adult; Attention; Cognition Disorders; Cross-Over Studies; Double-Blind Method; Drug Interactions; Drug Liberation; Ethanol; Eye Movements; Female; Healthy Volunteers; Humans; Male; Photic Stimulation; Postural Balance; Sodium Oxybate; Young Adult

In recent years, the abuse of the club drug gamma-hydroxybutyrate (GHB) has become increasingly popular among adolescents. The drug induces euphoria but can also result in sedation, anaesthesia as well as short-term amnesia. In addition, the abuse of GHB causes cognitive impairments and the mechanism by which GHB induces these impairments is not clarified. The present study investigates the impact of GHB treatment on spatial learning and memory using a water maze (WM) test in rats. Furthermore, the behavioural data is combined with an autoradiographic analysis of the GABAB and the IGF-1 receptor systems. The results demonstrate that the animals administered with GHB display an impaired performance in the WM test as compared to controls. In addition, significant alterations in GABAB and IGF-1 receptor density as well as GABAB receptor functionality, were observed in several brain regions associated with cognitive functions e.g. hippocampus. To conclude, our findings suggest that GHB treatment can affect spatial learning and memory, and that this outcome at least to some extent is likely to involve both GABAB and IGF-1 receptors.

Topics: Animals; Autoradiography; Brain; Central Nervous System Agents; Cognition Disorders; Dose-Response Relationship, Drug; Hippocampus; Illicit Drugs; Male; Maze Learning; Neuropsychological Tests; Rats, Sprague-Dawley; Receptor, IGF Type 1; Receptors, GABA-B; Sodium Oxybate; Spatial Memory; Substantia Nigra

Gamma hydroxybutyrate (GHB) was identified in the blood of 13 subjects arrested for impaired driving. GHB concentrations ranged from 26 to 155 mg/L (mean 87 mg/L, median 95 mg/L). In eight cases, GHB was the only drug detected, and signs of impairment were consistent with those of a CNS depressant, including erratic driving (weaving, swerving, ignoring road signs), confusion, incoherent speech, unresponsiveness, lack of balance, unsteady coordination, poor performances on field sobriety tests, and varying states of wakefulness. Given the ability of GHB to induce sleep and unconsciousness, it is evident from these cases that recreational use of the drug has the potential to impair a person's driving ability.

Topics: Adult; Anesthetics, Intravenous; Automobile Driving; Cognition Disorders; Female; Humans; Male; Motor Skills Disorders; Sleep; Sodium Oxybate; Substance-Related Disorders; Unconsciousness