Carolien Zeetsen

111 CHAPTER Cognitive i mpairments in patients with GUD predict relapse 6 Introduction Gamma–hydroxybutyrate (GHB) is a GHB and GABA B receptor agonist and an increasingly popular party drug, mainly due to its euphoric, sociability and sexually stimulating effects (Sumnall et al., 2008; Brennan & van Hout, 2014; Whelan et al., 2014; Bosch et al., 2015; Bosch et al., 2017; European Monitoring Centre for Drugs and Drug Addiction, 2017). However, GHB use is also associated with frequent overdoses, comas (Kamal et al., 2017; Beurmanjer et al., 2019), hospital admissions (Dijkstra et al., 2017; Grund et al., 2018), and a risk of physical dependence (Nicholson & Balster, 2001; van Noorden et al., 2016; Dijkstra et al., 2017). In line with DSM–5 criteria for SUD (APA, 2013) physical GHB dependence is commonly part of GHB use disorder (GUD), with a pattern of continued use despite negative consequences, craving for GHB and loss of control over GHB intake (Kamal et al., 2017). Patients with GUD generally show high drop–out and relapse rates, up to 50% – 60% relapse within three months after detoxification (Dijkstra et al., 2017; van Noorden et al., 2017; Beurmanjer et al., 2019). The readmission rate of patients with GUD is twice as high as seen in patients with alcohol or cannabis use disorder (van Noorden et al., 2017). It is unknown why relapse rates are higher among patients with GUD compared to other SUD. It has been suggested that the prosocial effects of GHB with few noticeable downsides could play a part in the high relapse rates (Bosch et al., 2015; Beurmanjer et al., 2019). Other suggested explanations are the high levels of anxiety in patients with GUD (Beurmanjer et al., 2019), similar to for example patients with alcohol use disorder (Schellekens et al., 2015). Another aspect that might be particularly relevant in the context of relapse in patients with GUD is cognitive impairment. In general, cognitive impairment has been associated with relapse in several SUD, e.g. alcohol (Czapla et al., 2015), cocaine (Verdejo–García et al., 2014) and opioids (Ma et al., 2019). While research on cognitive impairment in GUD is limited, several studies suggest negative effects of GHB on cognition. For instance, a double blind, placebo controlled study with healthy volunteers showed that GHB intoxication temporarily impaired working– and episodic memory, in a dose dependent manner (Carter et al., 2009). Recent studies also suggest that GHB–induced comas are associated with (verbal) memory impairments in patients with GUD. In this cross–sectional study GHB– induced comas were also associated with alterations in long–term memory networks and lower hippocampus/lingual gyrus activity while performing memory tasks (Raposo Pereira et al., 2018a; Raposo Pereira et al., 2018b).