γ-Hydroxybutyric Acid: Pharmacokinetics, Pharmacodynamics, and Toxicology.

Gamma-hydroxybutyrate (GHB) is a short-chain fatty acid present endogenously in the brain and used therapeutically for the treatment of narcolepsy, as sodium oxybate, and for alcohol abuse/withdrawal. GHB is better known however as a drug of abuse and is commonly referred to as the "date-rape drug"; current use in popular culture includes recreational "chemsex," due to its properties of euphoria, loss of inhibition, amnesia, and drowsiness. Due to the steep concentration-effect curve for GHB, overdoses occur commonly and symptoms include sedation, respiratory depression, coma, and death. GHB binds to both GHB and GABAB receptors in the brain, with pharmacological/toxicological effects mainly due to GABAB agonist effects. The pharmacokinetics of GHB are complex and include nonlinear absorption, metabolism, tissue uptake, and renal elimination processes. GHB is a substrate for monocarboxylate transporters, including both sodium-dependent transporters (SMCT1, 2; SLC5A8; SLC5A12) and proton-dependent transporters (MCT1-4; SLC16A1, 7, 8, and 3), which represent significant determinants of absorption, renal reabsorption, and brain and tissue uptake. This review will provide current information of the pharmacology, therapeutic effects, and pharmacokinetics/pharmacodynamics of GHB, as well as therapeutic strategies for the treatment of overdoses. Graphical abstract.

Pociones sexuales. Relación entre alcohol, drogas y sexo / Sex potions. Relationships between alcohol, drugs and sex

A lo largo de la historia, el consumo de drogas y de alcohol ha estado íntimamente ligado a la conducta sexual. A pesar de ello, sin embargo, casi todos los esfuerzos por mejorar la salud sexual y reducir los niveles de consumo de drogas y alcohol se ocupan de ambos problemas como si fueran independientes. Con una disponibilidad potencialmente mayor que nunca de sustancias que tienen efectos relacionados con el sexo, analizar los vínculos entre sexo y consumo de drogas se ha convertido en un factor crítico para tratar ambos problemas. En el presente estudio nos ocupamos de las relaciones entre alcohol, drogas y conducta sexual, incluyendo el consumo de afrodisíacos y facilitadores sexuales, de cómo las sustancias están cada vez más vinculadas a la violencia sexual, y de cómo el propio sexo puede ser un medio para obtener drogas. Analizamos cómo aquellos que consumen drogas y alcohol son sexualmente más activos, tienen más posibilidades de practicar un sexo poco seguro y, por ese motivo, mayor riesgo de enfermedades de transmisión sexual o de embarazos no deseados. Vemos cómo los servicios de asistencia para el consumo de drogas y la salud sexual pueden beneficiarse de un acercamiento entre ambos problemas. Finalmente, en el área de la prevención, estudiamos cómo los servicios de salud sexual pueden utilizar las imágenes relacionadas con la droga para dirigirse a quienes corren el riesgo de contraer enfermedades de transmisión sexual, y cómo esas iniciativas cada vez mayores en la prevención de drogas deben desafiar la imagen sexual de muchas substancias a fin de reducir su atractivo (AU)

Throughout history drug and alcohol use has been intimately linked with sexual behaviour. Despite this however most attempts to improve sexual health and reduce levels of drug and alcohol use treat them as separate issues. With the availability of substances that have sex related effects potentially greater than ever, examining the links between sex and substance use has become a critical factor in addressing both issues. Here we discuss the relationships between alcohol, drugs and sexual behaviour, including the use of drugs as aphrodisiacs and sexual facilitators, how substances are increasingly being implicated in sexual assault, and how sex itself can be a means of obtaining drugs. We examine how those who use alcohol and drugs are more sexually active, more likely to practise unsafe sex, and hence at greater risk of sexually transmitted infections and unwanted pregnancy. We consider how treatment services for substance use and sexual health may benefit from an understanding of each other issues. Finally in the area of prevention, we discuss how sexual health services might utilise drug related imagery to target those at risk of sexual transmitted infections and how those developing drug prevention initiatives must challenge the sexual image of many substances in order to reduce their appeal (AU)

Effects of sustained gamma-hydroxybutyrate treatments on spontaneous and evoked firing activity of locus coeruleus norepinephrine neurons.

BACKGROUND: Gamma-hydroxybutyrate is currently used to promote nighttime sleep in the treatment of narcolepsy; however, it is also a drug of abuse ("Liquid Ecstasy") associated with a withdrawal syndrome with anxiety features. Of interest, the activity of locus coeruleus neurons is a reflective index of these above mentioned behavioral states. METHODS: Using in vivo extracellular unitary recordings, sustained administration of gamma-hydroxybutyrate (40 mg/kg/day via minipump implanted subcutaneously) on the spontaneous and sensory-evoked burst firing of locus coeruleus norepinephrine neurons was assessed in rats. RESULTS: A 2-day and 10-day gamma-hydroxybutyrate administration decreased the spontaneous firing activity of locus coeruleus neurons by 52% and 54%, respectively, when compared with controls. A similar degree of attenuation on evoked burst firing of norepinephrine neurons also occurred in these rats (2-day gamma-hydroxybutyrate: 47% and 10-day gamma-hydroxybutyrate: 58%), when compared with controls. In contrast, rats treated with gamma-hydroxybutyrate for 10 days followed by removal of the minipump for 36 hours resulted in a 33% augmentation in spontaneous locus coeruleus activity as compared with controls. Furthermore, a robust 79% increase in burst firing in response to paw-pinch was exhibited in theses rats. CONCLUSIONS: Chronic gamma-hydroxybutyrate treatment inhibits the spontaneous and sensory-evoked burst firing of locus coeruleus norepinephrine neurons, whereas these indices are enhanced during drug withdrawal. The alteration in norepinephrine activity during chronic gamma-hydroxybutyrate administration may contribute to the ability of this agent to induce sleep and regulate narcoleptic episodes. Enhanced norepinephrine activity during withdrawal may be related to symptoms of anxiety on rapid termination of this drug in abusers.