Carolien Zeetsen

120 Discussion This study investigated cognitive impairment in patients with GUD, and its relationship with GHB use patterns and relapse in GHB use after detoxification. Using the MoCA, a substantial number of patients with GUD screened positive for cognitive impairment before detoxification (56.3%). Cognition improved after detoxification with still about one third screening positive for impairment (30.6%). The cognitive domain showing the strongest impairment was memory. No correlation was found between cognitive impairment and the number of comas, GHB use patterns, or severity of GUD. Cognitive impairment before detoxification, particularly on the subscale memory, was associated with relapse between detoxification and follow–up. In the current sample, more than half of the included patients had an indication for cognitive impairment during admittance, with a mean MoCA–TS of 24.2. A recent study observed similar to slightly better MoCA scores in patients with substance use disorders including alcohol, cannabis, stimulant and opioids (MoCA–TS: 25.3, 26.3, 25.9, and 24.7 respectively; Bruijnen, Dijkstra, et al., 2019). Though no direct comparison between these two samples can be made, this does raise the question whether the observed cognitive impairments in patients with GUD are specific for excessive GHB use, or related to (indirect) negative effects of substances of abuse on cognitive performance in general. Furthermore, it is important to note that most patients with primary GUD have poly–substance use problems, often stimulants (Dijkstra et al., 2017; Beurmanjer et al., 2019), making it difficult to differentiate between effects of GHB and other substances. Patients showed a trend towards improvement in MoCA–TS and a significant decrease in scoring below the cut–off between T1 and T2, indicating that cognitive functioning partially recovered during detoxification. This is in line with studies in SUD patients using other sedatives, including alcohol (Wobrock et al., 2009) and benzodiazepines (Ros–Cucurull et al., 2018), who also show improvement of cognitive functioning during abstinence. It is important to note that patients in the current study were only abstinent of GHB for approximately three weeks when T2 was administered. Therefore, further improvement with prolonged abstinence is expected. Literature on alcohol has for instance shown that cognitive function can improve up to after six weeks to over a year of abstinence (Walvoort et al., 2013). Future studies should further investigate recovery of cognitive impairment in patients with GUD with long–term abstinence. Patients with GUD scored particularly low on the domain memory, also when compared to studies in patients with other SUD (Bruijnen, Dijkstra, et al., 2019). Since GHB receptors are predominantly expressed in the hippocampus, this observation might reflect the direct