Demographic and Clinical Characteristics of Regular GHB-Users with and without GHB-Induced Comas

Abstract

Background

Gamma hydroxybutyric acid (GHB) has been used recreationally for nearly three decades and its chronic use is frequently associated with serious adverse events including GHB-intoxication with GHB-induced comas. Moreover, despite its low prevalence, the number of individuals with GHB-use disorders is steadily increasing. However, the risk-factors associated with chronic GHB-use or the development of a GHB-use disorders remain poorly understood. Purpose: This study aims to profile two types of GHB-users, those with and those without GHB-induced comas. Methods: We included 27 GHB users with ≥4 GHB-induced comas (GHB-Coma), 27 GHB users without a coma (GHB-NoComa), and 27 polydrug users who never used GHB (No-GHB). Participants completed self-reported questionnaires in order to assess their demographic and clinical features, and their use profile of GHB and other drugs. Results: The typical GHB user in our sample was young, single, living alone, well-educated, and a student. The GHB-Coma group had lower self-control and reported higher negative affect than the GHB-NoComa group. GHB-Coma participants were heavier GHB users and mostly used GHB alone at home, whereas the GHB-NoComa group mostly used GHB with friends and in nightclubs. Remarkably, the majority of participants were not concerned about potential neurocognitive impairments induced by GHB-intoxication and/or GHB-induced comas. Conclusion: In this assessment, different profiles for recreational users with and without GHB-induced comas were well expressed. Their description contributes to a better understanding of the risk factors associated with recreational GHB-use, GHB-induced coma, and the development of GHB-use disorders.

Keywords:

• GHB
• GHB-induced coma
• sleeping disorders
• demographics
• polydrug use
• negative affect
• impulsivity
• rape drug

Introduction

Gamma hydroxybutyric acid (GHB), together with its precursors gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD), has been used as a recreational drug for nearly three decades (European Monitoring Centre for Drugs and Drug Addiction, 2018; Madah-Amiri et al., 2017; United Nations Office on Drugs and Crime, 2017; Uporova et al., 2018). However, the risk-factors associated with chronic GHB-use or the development of a GHB-use disorder are still poorly understood.

In its recreational form, GHB is mostly known as a “party” drug. In the beginning of the twenty-first century GHB use reached a peak in popularity, when mainstream media attention reported it as a silent rape-facilitating drug that could enhance libido and cause anterograde amnesia (Gonzalez & Nutt, 2005; Miotto et al., 2001; Miró et al., 2017; Varela, 2004). Such a reputation led to the official classification of GHB as an illicit narcotic in many countries, and since then, its lifetime prevalence has remained relatively low and stable (0.1%–13% worldwide) (Bosch et al., 2012; Carter et al., 2009; European Monitoring Centre for Drugs and Drug Addiction, 2018; Kamal, Van Noorden et al., 2016; Uporova et al., 2018; World Health Organization, 2015). However, GHB-overdose often involving profound GHB-induced coma is currently considered the fourth most common drug-related problem at European emergency rooms. Furthermore, the number of GHB-addicted patients seeking detoxification and relapse prevention treatment has been steadily increasing (European Monitoring Centre for Drugs and Drug Addiction, 2018; Madah-Amiri et al., 2017; Public Health England, 2016; United Nations Office on Drugs and Crime, 2017).

This disproportional high risk of intoxication and abuse liability has been associated with the recreational appeal of the drug, which results from an intoxication that wears out quickly and without “hangover,” even from transient profound states of unconsciousness (Barker et al., 2007; Palamar & Halkitis, 2006; Van Sassenbroeck et al., 2007). Such an outcome promotes the generalized view (among regular users and some medical personal) that GHB is not addictive, and that no neurological or cognitive harm is associated with severe intoxication or chronic GHB-use (Barker et al., 2007; Korf et al., 2014; Liechti et al., 2016; Miró et al., 2017; Palamar & Halkitis, 2006).

Moreover, the capacity of GHB to induce a dose-dependent stimulant or sedative effect, adds to its recreational appeal (Korf et al., 2014; Liechti et al., 2016; Miró et al., 2017; Van Sassenbroeck et al., 2007). This dual effect is associated with euphoria, disinhibition, sensory sensibility or sexual arousal at lower doses, evolving into anxiolytic effects, narcotic and sedative properties, and altered states of consciousness, at higher doses (Bosch et al., 2017; Kapitány-Fövény et al., 2015; Korf et al., 2014; Liakoni et al., 2016; Liechti et al., 2016; Miró et al., 2017; Van Sassenbroeck et al., 2001). However, the dose–response window of GHB is extremely narrow and small dose increments can easily lead to overdose associated with vomiting, hypotonia, clonic movement, anterograde amnesia, anxiety, or aggression (Kamal, Van Noorden et al., 2016; Liakoni et al., 2016; Miró et al., 2017; Van Sassenbroeck et al., 2001, 2007; Zvosec et al., 2001). In more severe cases, GHB-overdose can lead to hypotension, bradycardia, GHB-induced coma, and even death (Barker et al., 2007; Kamal, Van Noorden et al., 2016; Liakoni et al., 2016; Miró et al., 2017; Van Sassenbroeck et al., 2007; Zvosec et al., 2001).

GHB-induced coma in particular is considered a hallmark of GHB-intoxication (Kamal, Van Noorden et al., 2016; Liakoni et al., 2016; Metcalf et al., 1966; Van Amsterdam et al., 2016). This is a specific type of coma, which despite being transient and short-lived (1–4 h), often reaches the most critical stage of profound unresponsiveness on the Glasgow Coma Scale (Korf et al., 2014; Liechti et al., 2016; Metcalf et al., 1966; Miró et al., 2017; Van Amsterdam et al., 2016). Remarkably, no immediate side effects follow these comas largely due to the fast metabolism of GHB, known to induce a fast-in/fast-out effect. An effect that is expressed is by an abrupt onset and abrupt recovery from intoxication (Abanades et al., 2006; Brenneisen et al., 2004; Carter et al., 2006; Liechti et al., 2016; Van Sassenbroeck et al., 2001, 2007).

Furthermore, despite commonly perceived as non-addictive, when GHB is used at a chronic level, it has been shown that users can develop tolerance to the drug and severe craving (i.e. urge to use). In turn, this can contribute to intensification of drug use despite negative consequences, a syndrome classified by the DSM-5 as a substance use disorder (SUD), the terminology employed to define abuse or dependence of GHB (Dijkstra et al., 2017; Kamal et al., 2015; Kamal, Van Noorden et al., 2016; van Noorden et al., 2017). Nevertheless, the terminology employed to classify use, abuse, or dependence of GHB remains highly variable. Thus, in this study GHB-users will be categorized as follows: regular users of moderate doses who never had a GHB-induced coma dose: 4–40 mL/day); chronic users of moderate to high doses who had ≥4 GHB-induced comas with or without a DSM-5 GHB use disorder (dose: >40 mL/day, and up to 165 mL/day; around the clock).

When considering the steady increase in the number of individuals with GHB-use disorders, the limited knowledge on the risk-factors associated with chronic GHB-use or the development of a GHB-use disorders is noteworthy. Therefore, in order to characterize the average GHB-user, the main aim of this article is to describe the profiles of two different types of users: GHB users with multiple GHB-induced comas and GHB users who never had a GHB-induced coma. To better profile these groups they will be compared to polydrug users who never used GHB, since GHB is often used in a polydrug fashion.

Methods

Participants

In this descriptive study, 81 participants were recruited through addiction centers in the Netherlands, flyers, internet advertisements, and snowball sampling. Three different groups of participants matched for age and education level were included: 27 GHB users with ≥4 GHB-induced comas (GHB-Coma); 27 GHB users without GHB-induced comas (GHB-NoComa); and 27 polydrug users who never used GHB (No-GHB). Inclusion criteria for all participants were: age between 18 and 40 years; native Dutch speaker; male gender (since most GHB-users are males). Additional inclusion criterion for the GHB-users was the use of GHB ≥25 times in the last 2 years before inclusion in the study. Additional inclusion criterion for the GHB-Coma group was an arbitrary minimum of 4 GHB-induced comas in order to have enough contrast with the GHB-NoComa group. Polydrug use of other recreational drugs was defined as the use of alcohol, nicotine, cannabis, cocaine, other stimulants (amphetamines, khat, methylphenidate), ecstasy, ketamine, and/or sedatives (benzodiazepines). The exclusion criteria for the study were: a history of epilepsy, general anesthesia in the two years before the study; a contra-indication for MRI scanning (e.g. metal objects in the body or head injury); any coma unrelated to GHB use; and currently under treatment for narcolepsy with cataplexy (since treatment may involve the use of medical GHB/sodium oxybate).

After explanation of the study procedure, written informed consent was obtained from all participants prior to initiation of the study. This study was in accordance with the Helsinki Declaration principles (7th revision, 2013), the Medical Research Involving Human Subjects (WMO, 1998), and approved by the Medical Ethics Review Committee of the Academic Medical Centre (Büller et al., 2010; World Medical Association, 2013).

The data presented here are part of a larger study assessing the neurocognitive and neural effects of regular GHB-use and GHB-induced comas in humans. The study consisted of an initial urine test, followed by completing questionnaires related to GHB and other drug use, depression, anxiety, stress, and impulsivity levels. During the subsequent neuroimaging session, structural and functional scans were collected in the following order: structural MRI; resting-state fMRI; long-term memory fMRI: a paired association task; diffusion weighted imaging, working memory (WM) fMRI: an n-back task; and emotion processing fMRI: a face matching task. Finally, outside the scanner, participants performed digitized neuropsychological tests, including verbal memory, spatial memory, intra-extra dimensional set shifting, and probabilistic reversal learning. Here, we only present data on demographic and clinical variables of this sample. Additional analyses of data related to this sample is presented elsewhere (Raposo Pereira et al., 2018a, 2018b; Raposo Pereira, McMaster et al., 2019; Raposo Pereira, Zhutovsky et al., 2019).

Assessments

Premorbid intellectual functioning was assessed with the Dutch version of the Adult reading test as a proxy for premorbid intelligence quotient (IQ) (Schmand et al., 1991).

Alcohol and drug use patterns were assessed with the Measurement in Addiction for Triage and Evaluation questionnaire (MATE 2:1), by collecting information on the frequency of daily use in the preceding month, the months of daily use, and daily dose (Schippers et al., 2011). The pattern of GHB use is not considered in the MATE2:1 and therefore, a specific GHB-questionnaire was created by the Dutch GHB monitoring project in order to assess the characteristics of use of GHB in detail (De Jong & Dijkstra, 2013). In addition, the Desire Thinking Questionnaire (DTQ) was adjusted for GHB in order to measure thinking desire and craving for GHB (Beurmanjer et al., 2016; Caselli & Spada, 2011).

Impulsivity levels were assessed with the Barratt Impulsivity Scale (BIS), using the three impulsivity subscales: attentional impulsivity (8 items), motor impulsivity (11 items), and non-planning impulsivity (11 items) (Patton et al., 1995). Each item was scored on a scale of 1–4 (1 = rarely/never; 2 = occasionally; 3 = often; 4 = almost always/always) (Patton et al., 1995).

Negative affect was assessed with the self-report Depression, Anxiety, and Stress Scale (DASS-21) consisting of three clusters of seven statements each, rated from 0 to 3 (ranging from not applicable to accurately complying with the individual) (Lovibond & Lovibond, 1995). The sum of depression, anxiety, or stress scores is evaluated with their severity on a scale of five levels: normal, mild, moderate, severe, or extremely severe (Lovibond & Lovibond, 1995).

Statistical analysis

Demographic and clinical data were analyzed with the SPSS24 (IBM Software Analytics, New York, USA) software. Normally distributed data were evaluated through Analysis of Variance (ANOVA). If not normally distributed, data were transformed in order to obtain a normal distribution or evaluated with non-parametric tests (Mann–Whitney U-test for two groups or Kruskal–Wallis H-test for more than two groups). Group differences in GHB daily dose (mL/day), years since first use, prevalence of days using GHB on the previous month, months of daily use, and total exposure as defined by years of use × daily dose were analyzed only in the groups with GHB users. With regard to polydrug use (apart from GHB), we defined a final drug exposure variable which was calculated as follows: years of weekly use × daily dose for each recreational drug considered on the MATE:2.1 questionnaire (Table 2). In order to avoid type I errors, we corrected for multiple comparisons using Bonferroni corrections. However, considering the pilot nature of this study and the relatively small sample size, data was Bonferroni corrected only per variable domain: demographics (α = 0.05/5 = 0.01), clinical characteristics (α = 0.05/10 = 0.005), GHB-use characteristics (α = 0.5/4 = 0.0125), drug use other than GHB (α = 0.5/8 = 0.006), and sleep problems (α = 0.05/5 = 0.01).

Results

Eighty-one participants were included in this sample: 27 chronic users of GHB-doses with ≥4 GHB-induced comas (GHB-Coma); 27 regular users of moderate GHB-doses without GHB-induced comas (GHB-NoComa); and 27 polydrug users who never used GHB (No-GHB).

Comparison of the three groups

Table 1 shows that there were no differences between the groups in age (mean = 26.5 years) and education level. However, after correction for multiple comparisons (Bonferroni correction; α = 0.05/5 = 0.01), the GHB-Coma group still showed a trend for lower premorbid IQ (H (2) = 9.22; p = .010), compared with the GHB-NoComa group (p = .003). There were no significant differences between the groups in housing and working situation, or marital status. The majority of GHB users lived independently (42%) or with a flat mate (30%), were students (51%), and single (93%).

Table 1. Demographic and psychological data for the GHB-Coma, GHB-NoComa, and No-GHB group.

	GHB-Coma (N = 27)		GHB-NoComa (N = 27)		No-GHB (N = 27)		Difference
	Mean	SD	Mean	SD	Mean	SD	p*
Demographic data
Age	25.67	5.37	26.22	4.58	27.67	9.26	.733
Marital status	1.04	0.19	1.07	0.27	1.11	0.42	.803
Housing situation	2.41	1.22	1.85	1.13	2.44	1.29	.122
Work situation	3.37	1.33	3.00	1.14	2.85	0.99	.244
Educational level	6.50	1.62	6.84	1.21	6.65	1.38	.756
Clinical data
Premorbid IQ	89.22	10.59	97.63	7.51	93.81	8.04	.010
Attention (attentional)	12.63	2.39	10.96	2.55	12.07	2.53	.053
Cognitive instability (attentional)	7.63	1.96	6.59	2.00	6.07	1.73	.013
Motor (motor)	16.30	3.38	15.07	3.64	15.59	2.12	.181
Perseverance (motor)	7.48	1.70	7.85	1.46	8.04	1.43	.429
Self-control (non-planning)	14.96	2.61	12.59	3.17	12.59	1.95	.002^a^,^b
Cognitive complexity (non-planning)	12.96	2.85	11.15	2.23	11.37	2.29	.041
Depression	11.70	7.80	5.41	5.84	5.56	8.16	.002^a,^b
Anxiety	9.26	7.02	3.35	4.29	3.33	4.11	<.001^a,^b
Stress	14.37	10.06	7.11	5.12	6.96	5.61	.004^a,^b

Notes. Abbreviations: SD = standard deviation.

* Kruskal–Wallis H.

^a Post hoc Mann–Whitney U: GHB-Coma < GHB-NoComa → self-control_p = .001; depression_ p = .002; anxiety p = .001; stress = 0.005.

^b Post hoc Mann–Whitney U: GHB-Coma < GHB-NoGHB → self-control_p = .006; depression_p = .001; anxiety p < .001; stress p = .004.

Table 1 also shows that even after correction for multiple comparisons there were significant differences between the groups in self-control (H (2) = 12.52; p = .002) with lower self-control (higher impulsivity) in the GHB-Coma group compared to the GHB-NoComa group and the No-GHB group (p = .001 and p = .006, respectively). This was also the case for depression, anxiety, and stress levels (H (2) = 13.73, p = .002; H (2) =17.38, p < .001; H (2) = 10.96, p = .004, respectively). And post hoc tests showed that higher levels of depression, anxiety, and stress were reported by the GHB-Coma group when compared with the GHB-NoComa group (p = .002, p = .001, and p = .005, respectively) and the No-GHB group (p = .001, p < .001, and p = .004, respectively).

Table 2 shows that there are significant differences between the groups in the use of drugs other than GHB. The GHB-Coma group was more exposed to nicotine, ecstasy, and other sedatives when compared to the GHB-NoComa group, and more exposed to nicotine, cocaine, other stimulants, and other sedatives compared to the No-GHB group. Moreover, the GHB-NoComa group was more exposed to cocaine and other stimulants than the No-GHB group. However, when corrected for multiple comparisons, only the use of sedatives was higher in the GHB-Coma group when compared to both the GHB-NoComa group and the No-GHB group.

Table 2. Recreational drug exposure (i.e. years of weekly use × daily dose) in the GHB-Coma, GHB-NoComa, and No-GHB groups.

	GHB-Coma (N = 27)		GHB-NoComa (N = 27)		No-GHB (N = 27)		Difference
	Mean	SD	Mean	SD	Mean	SD	p*
Alcohol	10.17	30.21	11.94	23.25	12.00	34.25	.385
Nicotine	115.31	138.18	40.31	61.70	39.60	83.61	.026^a^,^b
Cannabis	4.81	8.71	3.36	5.45	4.00	6.40	.829
Cocaine	1.96	5.12	0.20	0.50	0.03	0.12	.012^b^,^c
Other stimulants	3.36	7.60	0.57	2.15	0.16	0.38	.013^b^,^c
Ecstasy	1.95	4.84	0.09	0.32	0.42	1.36	.028^a
Ketamine	0.16	0.46	0.24	0.91	0.06	0.20	.745
Sedatives	1.52	7.49	0.16	0.80	0.00	0.00	<.001^a^,^b

Notes. Abbreviations. SD = standard deviation.

* Kruskal–Wallis H.

^a Post hoc analysis Mann–Whitney U: GHB-Coma > GHB-NoComa → nicotine, p = .030; ecstasy, p = .0009; other sedatives, p = .005.

^b Post hoc analysis Mann–Whitney U: GHB-Coma > No-GHB → nicotine, p = .015; cocaine, p = .003; other stimulants, p = .009; other sedatives, p < .001.

^c Post hoc analysis Mann–Whitney U: GHB-NoComa > No-GHB → cocaine, p = .037; stimulants, p = .016.

GHB-Coma group vs. GHB-NoComa group

Moreover, the GHB-Coma and the GHB-NoComa group showed clear differences in their GHB-use profile. The GHB-Coma group used GHB in higher daily doses (U = 139, p < .001) and more frequently in the preceding month (U = 229, p = .018) when compared to the GHB-NoComa group (GHB-Coma 50.52 mL/day for ±13 days in the last month; GHB-NoComa 18.56 mL/day for ±3 days in the last month; Table 3).

Table 3. GHB-use profile of the GHB-Coma and the GHB-NoComa groups.

	GHB-Coma (N = 27)		GHB-NoComa (N = 27)		Difference
	Mean	SD	Mean	SD	p^a
Characteristics of GHB-use
°Year start use	2010	3.79	2011	2.04	.675
°Daily dose (mL/day)	50.52	41.88	18.56	10.79	<.001*
°Days of GHB use in preceding month	13.33	13.21	2.85	2.16	.018*
°Hours between dosages	1.66	0.41	1,91	0.39	.063
Sleep patterns
°Used GHB to sleep better	1.37	0.49	1.07	0.27	.009*
°Start having GHB-induced sleeping problems	1.52	0.51	1.11	0.32	.001*
°Need GHB to fall asleep	1.41	0.50	1.07	0.27	.005*
°Need GHB to stay asleep	1.37	0.49	1.04	0.19	.003*
°Sleep better with GHB	1.37	0.49	1.15	0.36	.065

Notes. Abbreviations. SD = standard deviation.

^a Mann–Whitney U.

* p < .05.

Table 4 shows that the most common reason to start using GHB and to use during the last 6 months was euphoria and this was true in both the GHB-Coma (59%) and the GHB-NoComa (85%) group. The GHB-Coma group mostly started to use GHB at a friend’s house (30%) but in the last 6 months used at home (41%), whereas the GHB-NoComa group mostly started and continued to use GHB in clubs and during dance parties (40%). Both groups started and used GHB in the preceding 6 months with friends. However, with time, the GHB-Coma group also started to use GHB alone (44%). Importantly, 52% of the GHB-Coma group started to have sleeping problems, whereas the GHB-NoComa group reported no sleeping problems.

Table 4. Reason and location for the recreational use of GHB.

	GHB-Coma (N = 27)	GHB-NoComa (N = 27)
	n (%)	n (%)
Reason to start using
Forget problems	6 (22.2%)	1 (3.7%)
Euphoria	16 (59.3%)	28 (85.2%)
More confidence	2 (7.4%)
Better sex	1 (3.7%)
Friends use it	1 (3.7%)	1 (3.7%)
Replacement for alcohol		1 (3.7%)
Reason to use last 6 months
Forget problems	10 (37%)	1 (3.7%)
Euphoria	15 (55.6%)	25 (92.6%)
No hangover		1 (3.7%)
More confidence	1 (3.7%)
Friend use it
Counter withdrawal feeling
Location where use started
Home	6 (22.2%)	2 (7.4%)
Friend’s house	8 (29.6%)	6 (22.2%)
Club/disco	4 (14.8%)	8 (29.6%)
Dance party	3 (11.1%)	11 (40.7%)
After party	2 (7.4%)
Street	2 (7.4%)
Everywhere	1 (3.7%)
Location of use last 6 months
Home	11 (40.7%)	2 (7.4%)
Friend’s house	4 (14.8%)	4 (14.8%)
Club/disco	4 (14.8%)	9 (33.3%)
Dance party	1 (3.7%)	11 (40.7%)
After party	2 (7.4%)
Everywhere	4 (14.8%)	1 (3.7%)
How use started
Alone	1 (3.7%)	1 (3.7%)
With friends	24 (88.9%)	26 (96.3%)
With partner	1 (3.7%)
How used last 6 months
Alone	12 (44.4%)	2 (7.4%)
With friends	13 (48.1%)	24 (88.9%)
With partner	1 (3.7%)	1 (3.7%)

Discussion

This study aimed to describe the profile of different GHB-users based on self-reports of demographic and clinical data. More specifically, we looked at differences between chronic users of high GHB-doses with multiple GHB-induced comas (GHB-Coma group) and regular users of moderate GHB-doses who never had a GHB-induced coma (GHB-NoComa group). In our sample, the average GHB user was young, mostly single, living alone, well-educated, and generally a student. However, heavier GHB-users tended to be at sick leave from work.

The GHB-Coma group tend to have a lower premorbid intellectual functioning (IQ) than the GHB-NoComa group. IQ is a determinant factor on the permanent adaptation to continuously changing environments contingent on internal goal representations (e.g. resist GHB-related cues and motivational saliency), and therefore, on cognitive control (Hyman et al., 2006; Koob & Volkow, 2010; Sesack & Grace, 2010; Verdejo-García et al., 2006). Hence, considering the similar level of education between the groups, the tendency for a lower IQ in the GHB-Coma group suggests that this group has a poorer cognitive control, which might be associated with a preexisting vulnerability to resist drug related cues and adopt internal goals of abstinence.

Low self-control has also been considered a risk factor to the development of chronic drug use and SUD, and this was reported by the GHB-Coma group when compared with the GHB-NoComa group (Brady & Sinha, 2005; Koob & Volkow, 2010; Verdejo-García et al., 2006). Higher impulsivity, or lower capacity to control impulses, suggests a propensity to start and develop chronic GHB-use. A consequence of poor inhibitory capacity of drug urges, which prioritizes drug motivational bias (immediate pleasure), and disregards internal goals of abstinence (Koob & Volkow, 2010; Sesack & Grace, 2010; Wise, 2008). One other common risk factor to the onset and development of chronic drug use is negative affect, highly comorbid with regular GHB use (Kamal et al., 2015, 2017; Verdejo-García et al., 2007; Zvosec & Smith, 2005). Accordingly, higher levels of depression, anxiety, and stress were self-reported by the GHB-Coma group when compared to other two groups, and could have contributed to start using the drug (in a self-medication manner to ease preexisting negative emotions). Alternatively, as often seen in chronic substance use, the GHB-Coma group may have developed withdrawal symptoms or may have become depressed in the course of chronic heavy GHB use. Both are features that may have acted as reinforcing factors of GHB-use (Choudhuri et al., 2013; Kamal et al., 2015, 2017; Zvosec & Smith, 2005).

The consumption patterns of GHB greatly differed between groups. The GHB-Coma group used significantly higher doses and during more days in the last month than the GHB-NoComa group. However, it is interesting to note that the doses taken by the GHB-NoComa group and part of the GHB-Coma group were rather similar. Therefore, the occurrence of GHB-induced comas may not be simply a function of very high GHB dosages, but also be related to the frequency of use, higher in the GHB-Coma group. Alternatively, it may be related to the presence of more vulnerable phenotypes that predispose certain users to GHB-induced comas.

Most of these GHB-induced comas occurred by accident, lasting for a period between 1 to 3 h. Moreover, in the heavier GHB-Coma participants most comas occurred at home, while in the less heavy users, comas mostly happened in the house of friends. Remarkably, participants did not seem to worry about these transient but deep comas, with more than half reporting indifference for potential lasting effects. However, GHB-induced comas have been compared to a state of pharmacological-induced unconsciousness (anesthesia), which – when not accompanied by oxygen support – can lead to oxidative stress and functional (cognitive) and structural brain alterations (Barker et al., 2007; Nayak et al., 2006; Palamar & Halkitis, 2006; Perouansky & Hemmings, 2009; Snyder et al., 2017).

It is reported in the literature that GHB is often co-used with other drugs (Gonzalez & Nutt, 2005; Kamal, Dijkstra et al., 2016; Korf et al., 2014; Liakoni et al., 2016; Miró et al., 2017). In the current study this was also the case, and the GHB-Coma group used more nicotine, ecstasy, and sedatives than the GHB-NoComa group. Yet, after correcting for multiple comparisons, only the use of sedatives (benzodiazepines) remained significantly higher in the GHB-Coma group. It is important to notice that this group also reported the highest frequency of sleep disturbances, which in part might have resulted from a synergistic effect between benzodiazepines and GHB (central nervous system depressants). However, evidence has shown that the occurrence of sleeping problems is one of the most reported withdrawal effects of chronic GHB use and may persist even after abstinence. (Bosch et al., 2012; Brunt et al., 2013; Kamal et al., 2016a; Kapoor et al., 2013). In line with this evidence, sleep disturbances were mostly reported by the GHB-Coma group. Though, the literature has also demonstrated that a sub-group of regular GHB-users initiate or increase the use of GHB with the intent to control irregular sleep, as self-medication (Bosch et al., 2012; Brunt et al., 2013; Kamal et al., 2016a; Kapoor et al., 2013). However, the causal nature and the direction of these effects cannot be defined in the current cross-sectional study.

The main reason to start the use of GHB were the euphoric effects induced by the drug and both the GHB-Coma and GHB-NoComa participants started its use with this intent and continued to do so for at least six months. Though, while the two groups started to use GHB with friends, the GHB-NoComa group continued to use with friends, in clubs, and during festivals, whereas the GHB-Coma group started to use on their own, at home, or private environments. Such is consistent with a previous findings showing that GHB-users with multiple GHB-intoxications were more often home users compared with GHB users with occasional GHB-intoxications (Korf et al., 2014).

This descriptive study illustrates differences and similarities between heavy GHB-users with multiple GHB-induced comas and moderate GHB-users who never had a GHB-induced coma. However, some limitations must be considered. In general, all individuals volunteered to participate in the study and therefore, they may not be representative of the entire population of GHB-users. Another limitation is the inclusion of only males. Although they normally constitute the majority of GHB-users, this does not allow to generalize our findings to female GHB users (Miró et al., 2017). Also, our control group consisted of polydrug users since this is the way in which GHB-users tend to use GHB. However, a polydrug user control group is not representative of the general population and therefore the characteristics of GHB-users in our study could not be compared with the population “norm.” Lastly, neither type I errors (false positive findings) nor type II errors (false negative findings) can be fully excluded. We made Bonferroni corrections per variable domain but not for all variables simultaneously thus reducing but not fully excluding type I errors, whereas type II errors may have occurred due to the relatively small sample size of this study.

In the present sample, a distinct profile was clearly observed for the average chronic user of high GHB-doses with multiple GHB-induced comas and the average regular user of moderate GHB doses who never had a GHB-induced coma. In addition, most of the GHB-users with repeated GHB-induced comas reported no immediate side effects and consequently believe on the absence of risk associated with the use of GHB. Their perception of the expected “experience” and the lack of concerns about future problems related to GHB-use and/or GHB-induced comas are important to be considered by policy makers and health professionals. Therefore, these findings may contribute to the formulation of tailored campaigns to prevent excessive GHB use. This can be achieved by highlighting the fact that despite no side effects are immediately apparent, the regular use of GHB with GHB-induced comas can leave persistent sequelae on memory and emotion processing, and alter brain structure. These campaigns should also address individuals with higher propensity to negative affect, since this may be a vulnerable phenotype to heavier use. However, most importantly, they should stress the risk of using GHB with other sedatives and emphasize the life threatening risk of passing out alone at home (often the case). Lastly, these campaigns should address the impact of regular GHB-use on sleeping patterns, and stress the risks inherent to the use of GHB as self-medication for sleeping problems. Nevertheless, further studies are needed to gain a better insight into the type and severity of physical harm associated to chronic GHB use and repeated GHB-induced comas.

Disclosure statement

No potential conflict of interest statement is reported by the authors.