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. 2021 May 26;10(11):2333.
doi: 10.3390/jcm10112333.

Characterization of the GHB Withdrawal Syndrome

Casper J H Wolf  1   2   3 , Harmen Beurmanjer  3   4 , Boukje A G Dijkstra  3   4 , Alexander C Geerlings  1 , Marcia Spoelder  2 , Judith R Homberg  2 , Arnt F A Schellekens  1   3
Affiliations

Characterization of the GHB Withdrawal Syndrome

Casper J H Wolf et al. J Clin Med. .

Abstract

The gamma-hydroxybutyric acid (GHB) withdrawal syndrome can have a fulminant course, complicated by severe complications such as delirium or seizures. Detoxification by tapering with pharmaceutical GHB is a safe way to manage GHB withdrawal. However, a detailed description of the course of the GHB withdrawal syndrome is currently lacking. This study aimed to (1) describe the course of GHB withdrawal symptoms over time, (2) assess the association between vital signs and withdrawal symptoms, and (3) explore sex differences in GHB withdrawal. In this observational multicenter study, patients with GHB use disorder (n = 285) were tapered off with pharmaceutical GHB. The most reported subjective withdrawal symptoms (SWS) were related to cravings, fatigue, insomnia, sweating and feeling gloomy. The most prevalent objective withdrawal symptoms (OWS) were related to cravings, fatigue, tremors, sweating, and sudden cold/warm feelings. No association between vital signs and SWS/OWS was found. Sex differences were observed in the severity and prevalence of specific withdrawal symptoms. Our results suggest that the GHB withdrawal syndrome under pharmaceutical GHB tapering does not strongly differ from withdrawal syndromes of other sedative drugs. The lack of association between vital signs and other withdrawal symptoms, and the relative stability of vitals over time suggest that vitals are not suitable for withdrawal monitoring. The reported sex differences highlight the importance of a personalized approach in GHB detoxification.

Keywords: GHB; abstinence; addiction; dependence; detoxification; gamma-hydroxybutyric acid; sex differences; treatment; withdrawal.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure A1
Figure A1
Development of vital signs over time in males and females during the first 11 days of GHB tapering. Data presented as mean ± SEM. Error bars are not shown if they are shorter than the size of the symbol. # = main effect of sex, p < 0.05; ### = main effect of time, p < 0.001; #### = main effect of time/sex, p < 0.0001; * = time × sex interaction, p < 0.05.
Figure 1
Figure 1
Flowchart of participants included in the study.
Figure 2
Figure 2
Average relative severity and prevalence of subjective- and objective withdrawal symptoms. (a) Heat map of all 33 SWS over time for the first 11 detoxification days. Symptoms are ranked based on the average severity of the symptom over all days for males and females combined. (b) Heat map of all 34 OWS over time for the first 11 detoxification days. Symptoms are ranked based on the average presence of the symptom over all days for males and females combined.
Figure 2
Figure 2
Average relative severity and prevalence of subjective- and objective withdrawal symptoms. (a) Heat map of all 33 SWS over time for the first 11 detoxification days. Symptoms are ranked based on the average severity of the symptom over all days for males and females combined. (b) Heat map of all 34 OWS over time for the first 11 detoxification days. Symptoms are ranked based on the average presence of the symptom over all days for males and females combined.
Figure 3
Figure 3
Development of vital signs over time during the first 11 days of GHB tapering. Data are presented as the average of all patients measured on the respective days ± SEM (n = 108–263). Error bars may lie under the symbol of the graph. *** = main effect of time p < 0.001; **** = main effect of time p < 0.0001.
Figure 4
Figure 4
Development of subjective- and objective withdrawal symptoms over time in males and females. (a) Development of subjective withdrawal symptoms (SWS) during GHB detoxification, divided by sex. SWS are presented as the average severity of all 33 measured SWS during the day (males n = 74–184, females n = 31–76). (b) Development of objective withdrawal symptoms (OWS) during GHB detoxification, divided by sex. OWS are presented as the average presence of all 34 measured objective withdrawal symptoms during the day (males n = 77–191, females n = 31–72). Data are presented as mean ± SEM. #### = main effect of time p < 0.0001; * = time x sex interaction p < 0.05.
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