Harmen Beurmanjer

51 Cognitive Impairments in Patients with GUD 4 Background 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 (Addiction, 2019; Bosch et al., 2015, 2017; Sumnall et al., 2008). However, GHB use is also associated with frequent overdoses, comas (Beurmanjer et al., 2019), hospital admissions (Dijkstra et al., 2017), and a risk of physical dependence (Kamal et al., 2017). In line with DSM-5 criteria for substance use disorder (SUD) (American Psychiatric Association. & American Psychiatric Association. DSM-5 Task Force, 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 (Beurmanjer et al., 2019). Patients with GUD generally show high drop-out and relapse rates, up to 50-60% within three months after detoxification (Beurmanjer, Kamal, de Jong, Dijkstra, & Schellekens, 2018; M. S. van Noorden et al., 2017). The reenrolment rate of patients with GUD is twice as high as seen in patients with alcohol or cannabis use disorder(M. S. 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 (Beurmanjer et al., 2019; Bosch et al., 2015). 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 SUDs, e.g. alcohol (Czapla et al., 2016), cocaine (Turner, LaRowe, Horner, Herron, & Malcolm, 2009) and opioids (Ma, Mei, Wang, Liu, & Zhou, 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, Griffiths, & Mintzer, 2009). Recent studies also suggest that GHB-induced comas are associated with (verbal) memory impairments in patients with GUD (F., 2017; Raposo Pereira, McMaster, Polderman, de Vries, et al.; Raposo Pereira, McMaster, Polderman, DAT de Vries, et al., 2018). Moreover, 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, McMaster, Polderman, de Vries, et al., 2018). GHB-induced comas are common in patients with GUD, with 84% having experienced GHB-induced comas at least once, and often even on a daily basis (Beurmanjer et al., 2019; Dijkstra et al., 2017). Therefore, cognitive impairment might result from repeated comas due to excessive GHB use, and can potentially be an important factor in the high relapse