Addiction biology
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Since the discovery of the endocannabinoid system, a growing body of psychiatric research has emerged focusing on the role of this system in major psychiatric disorders like schizophrenia (SCZ), bipolar disorder (BD), major depression and anxiety disorder. Continuing in the line of earlier epidemiological studies, recent replication studies indicate that frequent cannabis use doubles the risk for psychotic symptoms and SCZ. Further points of clinical research interest are alterations of endocannabinoids and their relation to symptoms as well as postmortem analyses of cannabinoid CB(1) receptor densities in SCZ. ⋯ In addition, prior antipsychotic treatment decreased the numerical density of CB(1) immunoreactive glial cells in bipolar patients. Although the data on the influence of cannabis use on the development of major depression is controversial, cannabinoid compounds could display a new class of medication, as suggested by the antidepressive effects of the fatty acid amino hydrolase inhibitor URB597 in animal models. With numerous open questions and controversial results, further research is required to specify and extend the findings in this area, which provides a promising target for novel pharmacotherapeutic interventions.
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Naltrexone blocks the opioid receptors that modulate the release of dopamine in the brain reward system and therefore blocks the rewarding effects of heroin and alcohol. It is generally assumed that naltrexone leads to reduction of craving, but few studies have been performed to prove this. The purpose of the present study was to examine the effect of the administration of naltrexone on craving level after rapid opioid detoxification induced by naltrexone. ⋯ These results suggest that the use of opioids is associated with increased craving and that abstinence for opioids is associated with less craving, independent of the use of naltrexone. This is in contrast to the general opinion. Because of the naturalistic design of the study, no firm conclusions can be drawn, but the results grounded the needs of an experimental study.
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Selected ion flow tube mass spectrometry (SIFT-MS) has been used to measure simultaneously the concentrations of both carbon disulphide and acetone in exhaled breath following the ingestion of a single dose of disulfiram (Antabuse). Carbon disulphide is a product of the metabolism of disulfiram and is excreted mainly through the lungs. Acetone is a product of normal metabolism and appears in the breath of all individuals. ⋯ Breath carbon disulphide was seen to increase from 15 p.p.b. to 618 p.p.b. over a 28-hour period, in the single individual tested, following ingestion of disulfiram, while acetone levels increased from 300 p.p.b. (normal) to over 4000 p.p.b. (greatly elevated). No such increases were seen in the breath of the control subject over the same period. An obvious positive correlation between breath carbon disulphide and acetone concentrations following disulfiram ingestion is seen and discussed.
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The serotonin transporter (5-HTT) regulates serotonin transmission and modulates behavioral effects of drug of abuse. A polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) yielding a short (S) and long (L) allele has been associated with severity of substance abuse. The aims of the study were to investigate whether 5-HTTLPR genotypes differed in their response to treatment in cocaine- and alcohol-abusing patients. ⋯ Interestingly, individuals with the S allele showed greater severity of alcohol use at admission (F = 4.84, p = 0.03), and the SS genotype showed less improvement in alcohol measures than the LL at follow-up (F = 3.68, p = 0.03), after controlling for baseline variables. While we found no association of the 5-HTTLPR variants with severity of cocaine abuse or any cocaine-related outcome measures, the data suggested that the 5-HTTLPR polymorphism may distinguish responders from non-responders to behavioral treatment in terms of alcohol use. Further investigations are required to determine the role of the 5-HTTLPR polymorphism in influencing treatment - outcome among substance abusers.
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A single exposure of infant rats or mice to ethanol during synaptogenesis (mid to late pregnancy for humans) can cause developing neurons to commit suicide (die by apoptosis) on a massive scale. The neuronal loss demonstrated in recent studies is more severe and much more widely distributed (many brain regions, plus spinal cord and retina) than has been documented in prior animal ethanol studies. By suppressing neuronal activity via NMDA glutamate and GABAA receptors, ethanol disrupts synaptogenesis, thereby activating in developing neurons a programmed signal to commit suicide. These recent findings help clarify important aspects of the fetal alcohol syndrome, and demonstrate the usefulness of an in vivo infant rodent model for studying the neurotoxic effects of ethanol on the developing central nervous system.