Gamma-Hydroxybutyrate Increases Resting-State Limbic Perfusion and Body and Emotion Awareness in Humans

Abstract

Gamma-hydroxybutyrate (GHB) is a GHB-/GABA-B receptor agonist inducing a broad spectrum of subjective effects including euphoria, disinhibition, and enhanced vitality. It is used as treatment for neuropsychiatric disorders including narcolepsy and alcohol withdrawal, but is also a drug of abuse. Non-medical users report enhancement of body and emotion awareness during intoxication. However, the neuronal underpinnings of such awareness alterations under GHB are unknown so far. The assessment of regional cerebral blood flow (rCBF) by pharmacological magnetic resonance imaging (phMRI) enables the elucidation of drug-induced functional brain alterations. Thus, we assessed the effects of GHB (35 mg/kg p.o.) in 17 healthy males on rCBF and subjective drug effects, using a placebo-controlled, double-blind, randomized, cross-over design employing arterial spin labeling phMRI. Compared to placebo, GHB increased subjective ratings for body and emotion awareness, and for dizziness (p<0.01-0.001, Bonferroni-corrected). A whole-brain analysis showed increased rCBF in the bilateral anterior cingulate cortex (ACC) and the right anterior insula under GHB (p<0.05, cluster-corrected). ACC and insula rCBF are correlated with relaxation, and body and emotion awareness (p<0.05-0.001, uncorrected). Interaction analyses revealed that GHB-induced increase of body awareness was accompanied by increased rCBF in ACC, whereas relaxation under GHB was accompanied by elevated rCBF in right anterior insula (p<0.05, uncorrected). In conclusion, enhancement of emotion and body awareness, and increased perfusion of insula and ACC bears implications both for the properties of GHB as a drug of abuse as well as for its putative personalized potential for specific therapeutic indications in affective disorders.

Influence of Gamma-Hydroxybutyric Acid-Use and Gamma-Hydroxybutyric Acid-Induced Coma on Affect and the Affective Network

“…In controlled doses, GHB is known to decrease stress, social anxiety, and to induce a state of relaxation and sociability [7,8,11]. However, when taken regularly even at small controlled therapeutic doses, GHB might induce de- GHB, gamma-hydroxybutyric acid.…”

“…These emergency attendances predominantly resulting from GHB-induced comas, are paralleled by growing DOI: 10.1159/000497381 numbers of users seeking treatment for GHB dependence [3][4][5][6]. Recreational GHB-use is known to elicit sociability and emotional awareness, and acute GHB exposure has been linked to altered brain activity of regions related to emotion processing [1,7,8]. However, the long-term effects of regular GHB-use and GHB-induced comas on the affective network have not yet been assessed.…”

Prohedonic properties of gamma‐hydroxybutyrate are associated with changes in limbic resting‐state functional connectivity

“…Additionally, a psychophysiological interaction analysis revealed increased task‐related functional connectivity between NAcc and ventromedial prefrontal cortex (vmPFC) during processing of erotic pictures under GHB, the condition in which subjective sexual arousal was highest (Bosch, Havranek, et al, ). In a second analysis of the same sample, GHB increased body and emotion awareness and regional cerebral blood flow (rCBF) in limbic areas such as the rAI and the bilateral ACC, which correlated with each other (Bosch, Esposito, et al, ). Moreover, a further resting‐state functional connectivity (rsFC) analysis of these data showed that GHB increases salience network rsFC to the default mode network and dorsomedial prefrontal cortex (dmPFC) and from there reciprocally to the salience network (rIA) and to the central executive network (right middle frontal gyrus [MFG]).…”

“…in 20 healthy male participants. Due to the variety of used methods, produced results and covered topics, the investigation is described across four papers, focusing on task‐related brain reactivity towards sexual stimulation (Bosch, Havranek et al, ), whole‐brain resting‐state cerebral perfusion and body and emotion awareness (Bosch, Esposito et al, ), whole‐brain resting‐state functional connectivity and vigilance effects (sedation and stimulation; Bosch et al, ), as well as a seed‐based analysis of the two most important GHB‐related brain areas (right anterior insula [rAI] and anterior cingulate cortex (ACC) and prohedonic effects (euphoria and sexual arousal), which we present here. We found that under influence of the drug, even sexually neutral pictures elicited sexual arousal and activated the bilateral nucleus accumbens (NAcc) and right ACC (Bosch, Havranek, et al, ).…”

“…To further explore the relationship between the neuronal signature on these structures and the prohedonic effects of the drug, we assessed hedonic subjective effects of GHB (35 mg/kg p.o.) including euphoria and sexual arousal (together with the typical side effect nausea), and the rsFC of the above mentioned rAI‐ and ACC‐seeding points (Bosch, Esposito, et al, ) in a sample of 19 healthy male subjects that has been used for previous analyses (Bosch et al, ; Bosch, Esposito, et al, ). Similarities to the previous publications are the same study and sample.…”