Regular recreational users of GHB who never had a GHB-induced coma show higher impulsivity and macrostructural and microstructural brain alterations when compared to polydrug users who never used GHB. The criteria considered in this study were a result of self-reported parameters and urine tests.
The overall inclusion criteria were age between 18 and 40 years , native Dutch speaker, and male gender since the majority of GHB users are males 4 , 5 , 9.
Abstinence from recreational drugs for at least 24 h preceding the initiation of this study was required from all of the participants. The overall exclusion criteria were a history of epilepsy, general anesthesia within the 2 years preceding the study, a contra-indication for functional magnetic resonance imaging fMRI scanning e. The study procedures were explained prior to the assessments and written consent was obtained from the participants.
The data herein presented were part of a study assessing the effects of chronic GHB use and GHB-induced comas in the human brain. It entailed a urine test, self-reporting questionnaires i. In this report, we will only present data on impulsivity and brain structure. Other findings have been presented elsewhere 9 — The Dutch version of the adult reading test was used to assess premorbid intellectual functioning, considered a proxy for intelligence quotient IQ Individual differences in impulsivity were assessed with the self-reported BIS 34 , This scale consists of six first-order factors attention, cognitive instability, motor, perseverance, self-control, and cognitive complexity , each comprising three to seven items presented in random order.
Each item is scored from 1 to 4, from never to always feeling a certain way, respectively The scores of all items are then summed up per factor, where higher scores indicate higher impulsivity levels and lower scores indicate lower impulsivity levels If not normally distributed, the data were transformed in order to obtain a normal distribution or were evaluated with non-parametric tests Tables 1 and 2.
All of the groups were tested for differences in co-use of alcohol, nicotine, cannabis, cocaine, stimulants amphetamines, khat, methylphenidate , ecstasy, ketamine, and sedatives benzodiazepines.
This was performed by assessing the self-reported measures of drug use considered in the MATE questionnaire and represented here by a computed variable of total exposure to each substance i. The study groups were assessed for differences in impulsivity BIS subscale; Table 1 Diffusion-weighted and structural images were collected with a 3.
T1-weighted structural images sagittal acquisition; voxel size: 1. Diffusion-weighted images were acquired in 32 isotropic directions in order to test white matter abnormalities. Each image consisted of 48 transverse slices TE: 92 ms; voxel size: 2.
Prior to preprocessing, the origin was manually set to the anterior commissure. T1-weighted images were segmented into gray matter, white matter, and cerebral spinal fluid after bias-field correction to remove non-uniformities in intensity, normalized into Montreal Neurologic Institute MNI space, and smoothed using a Gaussian kernel of 8 mm at full-width half-maximum.
In addition, total intracranial volume TIV was estimated to correct for differences in total brain size. A voxel-based analysis of gray and white matter images thresholded at a tissue probability of 0.
Since the differences between the groups were found in IQ and exposure to cocaine, stimulants, ecstasy, and sedatives, these were introduced as nuisance covariates in a general linear model IQ as linear variable; co-exposure to the four substances as dummy variables. The number of variables representing co-exposure to other drugs in which group differences were observed was adapted to the sample size considered for each neuroimaging method of analysis.
TIV was used to correct for differences in brain volume across subjects Pre-processing consisted in eddy-current correction of potential distortions induced by gradient coils and head motion artefacts, individual non-brain tissue removal with the brain extraction tool, estimation of the diffusion tensor model at each voxel with the DTIFit tool, generating fractional anisotropy FA; degree of diffusion directionality , mean diffusivity MD; average diffusivity rate , axial diffusivity AD; diffusion rate along the main axis of the tensor , and radial diffusivity RD; diffusion rate transverse to the main axis of the tensor scalars 23 — 25 , The diffusion tensor was then assessed for voxel-wise microstructural differences in white matter, at whole-brain with TBSS, or at three a priori defined ROI tracts with streamline tractography analysis.
All FA skeletonized data were submitted to voxel-wise statistical analyses. IQ, exposure to cocaine, stimulants, ecstasy, and sedatives were introduced as nuisance covariates as described previously.
The same analysis was repeated for MD, AD, and RD scalars by projecting the aligned individual images of each participant into the created mean FA skeleton map. Tractography was performed on the ILF, the IFOF, and the UF based on their involvement in impulse control and proximity to regions where functional alterations were associated with recreational GHB use 9 — 11 , 19 , 23 , 24 , Integrity differences in these tracts were assessed with streamline tractography using the TrackVis software v0.
For compatibility reasons, data were transformed from nifti to dtk format, and the tensor orientation was flipped around the z-axis diffusion toolkit; v0. An exclusion ROI was hand-drawn when needed for undesirable streamline elimination. No-GHB group. Such differences were considered in our neuroimaging analysis by introducing them as nuisance covariates. Finally, the GHB-Coma group showed lower attention and self-control and higher cognitive instability than the other two groups.
No differences in the brain macrostructure nor in tractography were found. When testing for the effect of GHB use per se, no significant differences were observed. These differences in the sample number were considered throughout the analysis of demographic and clinical data and values were adjusted whenever necessary.
However, in Table 1 and Table 2 , the data presented concerns the totality of the study sample. The figure represents the sagittal, coronal, and axial brain planes of white matter skeleton in green , with representations of increased fractional anisotropy of the body of the corpus callosum and decreased mean diffusivity of the forceps minor in the GHB-coma group, when compared with the GHB-no coma group and the No-GHB group in red.
In a post hoc analysis, we assessed whether group differences in impulsivity were associated with macrostructure or microstructure DTI indices from TBSS or tractography analyses data by using a group-by-impulsivity interaction controlled for IQ, cocaine, other stimulants, ecstasy, sedatives, and TIV 19 , 22 , No interaction effect was observed between gray matter and impulsivity. Table 4 List of the white matter tracts resulting from a group-by-impulsivity interaction analysis according to different neuroimaging techniques, i.
Figure 2 Group by impulsivity interaction analysis between white matter volume macrostructure and self-control. The figure represents the sagittal, coronal, and axial brain representations of a white matter region in the superior longitudinal fasciculus, shown to strongly interact with the self-control levels of the GHB-coma group when compared to the GHB-no coma group and the no GHB groups.
Figure 3 Group by impulsivity interaction analysis between white matter integrity microstructure and selfcontrol. The figure represents sagittal, coronal, and axial brain representations of the body of the corpus callosum and the uncinate fasciculus, shown to strongly interact with the self-control levels of the GHB-coma group when compared to the GHB-no coma group and the no GHB group.
In green, representation of the white matter skeleton; in red, regions where interaction was different between groups. GHB-induced comas seem to be associated with anatomical differences exclusively in the white matter at a microstructural level.
Furthermore, the GHB-Coma group reported higher impulsivity than the other two groups, which strongly interacted with the FA of the left corpus callosum body and the left UF microstructurally and macrostructurally with the left SLF. No morphological brain differences were associated with GHB use per se, indicating that the structural brain abnormalities were primarily related to GHB-induced comas.
In contradiction of our first hypothesis, increased FA and decreased MD are general indicators of white matter integrity. This suggests that the anatomical alterations observed might have been present already before the occurrence of GHB-induced comas and represent a risk factor for the onset and development of heavy chronic use of GHB 22 , 26 , 42 , However, a similar directionality in FA and MD has been associated with different acute and subacute unconscious periods hours to weeks as a consequence of cytotoxic edema cellular swelling linked to hypoxia that results from factors such as myelin injuries 42 — In alcohol use disorders another GABAergic drug of abuse , the same directionality has also been suggested to be a result of myelin dysregulation, which was correlated with severity of alcohol drinking Together these findings suggest that both or either the number of GHB-induced comas or the heavy doses taken chronically by the GHB-Coma group contribute to the anatomical alterations observed.
Nevertheless, only AD or RD are sensitive biomarkers to the axonal or myelin nature of white matter alterations respectively and these parameters were not associated with GHB-induced comas 42 — Thus, the myelin nature of the observed white matter abnormalities remains hypothetical.
Furthermore, the CC and the forceps minor branch of the CC are tracts responsible for inter-hemispheric communication. Disruption in their integrity has been linked to deficits in affect dysregulation, associative memory, goal-directed behavior, or impulse control 48 — Interestingly, parts of these fasciculi parallel functional connectivity pathways where alterations were previously associated with the GHB-Coma group while performing similar cognitive processes, suggesting that the alterations found might represent a structural correlate to such functional deficits 9 — In contrast to these TBSS findings, no alterations in white matter integrity were found with tractography.
However, TBSS assesses local integrity, whereas tractography assesses mean integrity along the entire tract, suggesting that in the GHB-Coma group, microstructural differences in white matter only occur at a more local level 19 , 26 , 51 , Moreover, transient unconsciousness is mostly associated with subtle injuries often observed only in white matter, of which relatively crude methods such as structural MRI lack the sensitivity to detect 23 , 25 , 26 , 53 , This was also the case in this study where no macrostructural differences in gray or white matter were observed between the groups.
Lastly, since impulsivity is a common comorbidity of substance use disorders particularly of alcohol use dependence and a lasting effect of transient unconsciousness, we decided to compare the level of impulse control between the groups 19 , 21 — 26 , 29 , In the mentioned conditions, gray and white matter alterations have been observed in regions linked to inhibitory control 19 , 21 — 26 , 29 , Here, although no alterations were observed in gray matter, we found a strong interaction in the GHB-Coma group between self-control and the SLF macrostructurally and with the FA of the CC and the UF microstructurally , tracts that are highly implicated in impulse control.
Furthermore, considering the structural alterations observed in the CC of the GHB-Coma group, it is reasonable to assume the involvement of this brain region in self-control. The interaction between the CC and lower self-control in the GHB-Coma group might thus be a neural correlate of the increased impulsivity in this group. Nevertheless, no data are available of the period prior to this study. Hence, this cross-sectional study cannot distinguish between impulsivity as a consequence of heavy GHB use or repeated GHB-induced comas and impulsivity as a risk factor for heavy GHB use.
However, the cross-sectional nature of this study does not allow us to establish a causal link. A dose that makes one person feel euphoric can make another person sick. Moreover, there are some reports that GHB can cause dependence. Treatment of GHB overdoses is difficult because it is difficult for emergency room doctors to detect the drug.
Possible symptoms of GHB use: Dizziness Vomiting Seizures Coma Drowsiness GHB was first developed as a general anesthetic, but because it did not work very well to prevent pain, its use as an anesthetic declined. The observation that GHB may cause the release of growth hormone led some people, especially athletes and body-builders, to take it because they thought it would increase muscle development.
It is now classified as an illegal substance. Research is being conducted to investigate the use of GHB in the treatment of the sleep disorder called narcolepsy. GHB has been grouped with other drugs in the "date-rape drug" category such as Rohypnol , because it can be slipped easily into a drink and given to an unsuspecting victim, who often does not remember being assaulted. GHB is especially dangerous when combined with alcohol. Some of the greatest concentrations of GHB are found in the substantia nigra, thalamus and hypothalamus.
When GHB is ingested by a user, it affects several different neurotransmitter systems in the brain: GHB can increase acetylcholine levels. GHB can increase serotonin levels. GHB can reduce dopamine activity, especially in the basal ganglia. This action is probably the result of the inhibition of the release of dopamine from synaptic terminals.
Some studies show that GHB first inhibits the release of dopamine, then causes the release of dopamine. If someone you are with overdoses, or has an adverse reaction while using GHB, dial triple zero to call an ambulance immediately.
A quick response can save the person's life. Don't delay getting help because you think you or your friend might get into trouble. Ambulance officers are not obliged to call the police.
Stay with the person until the ambulance arrives and tell the ambulance officers as much as you can about what drugs were taken, how long ago and any pre-existing medical conditions the person may have. Treatment options for drug addiction include detoxification, individual counselling and group therapy. See your doctor for information and referral, or contact an alcohol and other drug service in your area.
This page has been produced in consultation with and approved by:. Asking for help when you first suspect you have an alcohol or drug problem is important. If you think you have an addiction, speak to your local doctor or phone DirectLine.
The size of a standard drink can vary according to the type of alcohol. Amphetamines are psychostimulant drugs that speed up the workings of the brain. Prolonged misuse of steroids can cause liver damage and severe mood swings.
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Skip to main content. Home Drugs. Actions for this page Listen Print. Summary Read the full fact sheet. On this page. GHB comes in a few forms including: a colourless, odourless, bitter or salty-tasting liquid — sold in small bottles or vials a coloured liquid crystals or powder this is less common. In moderate amounts, GHB can produce feelings of: relaxation drowsiness sociability euphoria lack of inhibition an increased urge for sex heightened sensitivity to touch.
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