Intoxication with GHB/GBL: characteristics and trends from ambulance-attended overdoses

Intoxication is a frequent cause of calls to emergency medical services (EMS) in Norway, with most of these poisonings being self-inflicted [1–3]. Primarily these cases involve alcohol and opioids, particularly heroin [4, 5]. However, in recent years, Scandinavia has experienced overdoses due to so-called “club drugs” (gamma-hydroxybuturate (GHB) and gamma-butyrolactone (GBL)) [6–9].

Gamma-hydroxybutyrate is found naturally occurring in many tissues of the body, and is closely related to the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) [10]. The sodium salt of gamma-hydroxybutyric acid is called gamma-hydroxybuturate (GHB). It is likely that GHB has its own GHB receptor, and when in high doses works to activate GABA B receptors, including dopamine release in the brain [11, 12]. GABA-B receptors are likely activated both in the pre- and post-synapses, which may explain many of the different effects of GHB intoxication [13].

The drug was originally developed in the 1960s in an attempt to create a GABA analog that would cross the blood-brain barrier [11]. When the compound proved to have strong sedative properties, it was then considered for its use as an anesthetic agent. Given the narrow therapeutic interval, combined with large individual differences in tolerance, today the drug has a very limited medicinal use [14, 15]. The calming and euphoric effects of GHB in low doses (20–30 mg/kg) have given the drug the nickname “liquid ecstasy” [16]. Since the drug is both inexpensive and easy to ingest, it has been popular as a “party drug.”

The oral absorption of GHB is relatively fast, with peak concentrations in plasma after 20–45 min, and half-life of 20–30 min [17]. At higher doses (> 50 mg/kg), the hypnotic effects are more prominent, and at doses >60 mg/kg coma, convulsions, and respiratory depression can occur [16]. The clinical hallmark of GHB poisoning is rapid onset of coma, with respiratory depression, hypoventilation and bradycardia [11–13]. Combination with alcohol potentiates these effects, especially respiratory depression and hypotension [10, 18].

GHB is a metabolic precursor to gamma-butyrolactone (GBL) and 1.4-butanediol (1.4 BD). GBL is used in the chemical industry, and is relatively easily acquired via the internet. Therefore, it has been imported to Norway in large quantities, predominately from Eastern Europe (personal communication, Hordaland Police District). The drug may be either “cooked” into GHB by the addition of caustic soda, or ingested directly, since after oral ingestion the substance is rapidly converted to GHB [19]. GBL appears to be more potent than GHB, as animal studies have shown that the substance at equimolar oral doses gave both a faster and longer-lasting effect than GHB, as well as a higher peak plasma concentration [20, 21]. Increasing occurrences of fatal poisonings and deaths in which GBL was probably involved, as well as more international focus on this drug was the reason that also GBL was classified as a narcotic and therefore prohibited in Norway in March 2010 [22].

The intoxicating effects of GHB are well known, and it has been reported to be involved in varying rates of fatal poisonings [8, 23, 24]. In Norway, opioids are most commonly taken parenterally and are significantly more costly, lending to a lower threshold to try the innocent appearing “soda caps” with GHB. GHB is often used recreationally as a party drug, with typical users viewing the drug as relatively non-toxic and harmless, comparable to alcohol [25].

Ambulance records have been used to investigate epidemiological trends for a variety of issues [26–28]. Population level monitoring of GHB use is limited [29], and the indirect information provided by ambulance records can provide a current overview of GHB overdoses in the city. This information can give insight into distinct user groups and patterns of use, which can in turn be used to monitor and guide treatment and prevention interventions. Further, an investigation into temporal patterns may shed light on what role the GBL restriction had on overdoses. Therefore, the aims of this study were to investigate characteristics and temporal trends of GHB/GBL ambulance attended overdoses in Bergen from 2009 to 2015.

Fatal poisoning from drug overdoses is frequent in Scandinavia [9, 31], as in many cities. Although alcohol and opioids account for the majority of the substances reported for these events, in recent years GHB/GBL overdoses have also been a significant concern. Through this epidemiological analysis of ambulance trends, characteristics about the GHB/GBL patients and the circumstances surrounding their overdoses were explored. In general, these patients were male, in their mid-20s, and found unconscious at the scene. The temporal patterns suggest party use, being most frequent during late-night and weekends.

The characteristics and incidences of these GHB/GBL overdoses, when compared with opioid overdoses show notable differences. The GHB/GBL victims are younger than opioid overdose victims, and are hospitalized more often [32]. This age difference is consistent with what others have found, demonstrating a younger demographic [1, 7, 23, 33]. Gender distribution was similar to opioid overdoses [32, 34], with an approximate 70% to 30% male to female ratio. Further, seasonal differences between opioid overdoses and GHB/GBL overdoses were observed. Others have reported a summer peak for opioid overdoses [32], however this study found June to be the month with the lowest incidence of GHB/GBL overdoses.

The reported symptoms for a GHB/GBL overdose correspond to findings from other studies [13]. Unconsciousness and reduced consciousness were the most common symptoms, with over 85% of patients being in this group. A small portion (9%) was registered as irritated or agitated, which also corresponds with the findings in other studies [35]. The proportion is probably lower than for other drug-related/poisoning events (for example, with alcohol), since many patients are partially or completely unconscious. Other studies have found alcohol intoxications to include more traumatic injuries [36] and sexual assault [37] than the GHB/GBL patients in this study.

Ambulance attendances for alcohol intoxication showed temporal similarities with GHB/GBL patients. We found a peak in GHB/GBL overdoses during the weekends, similar to alcohol-related road accidents [38] and hospital admissions [39].

Following the ban on GBL in 2010, an eventual decrease in GHB/GBL overdoses was observed beginning in 2012 and continuing through 2015. The incidence shift from 2009 to 2015 shows a significant decrease in GHB/GBL overdoses. In Norway and throughout Europe, increases in the use of ecstasy/MDMA has been observed [31]. While co-consumption of ecstasy and GHB is low [40], polydrug use remains a concern [41]. “Club drug” recreational users have similar user groups, and it is possible that this decreasing GHB trend in Bergen has been influenced by the increasing use of ecstasy/MDMA.

Acute intoxication due to substance use accounts for a significant portion of all acute ambulance call-outs in Bergen during week-ends. Characteristics of overdoses from opioids or GHB/GBL varied in several ways, shedding light on the apparent differences in these distinct patient groups. A focus on this distinct user group can help to guide prevention and outreach efforts, as many may not regularly access low-threshold services. The reduction in GHB/GBL overdoses following the ban on GBL may suggest that prohibition on the use of the drug may have had an effect on the number of overdoses, although this may also be explained by an increase in ecstasy/MDMA use. The review of ambulance records on the prehospital treatment of overdoses can be beneficial in monitoring, preparing, and prevention efforts aimed to benefit this distinct group.