Management and Treatment of Gamma Butyrolactone Withdrawal Syndrome

Abstract

Gamma butyrolactone (GBL) is an increasingly popular drug of abuse that is readily available in most countries, and it is often purchased over the Internet. In addition to the acute hazards of intoxication and overdose, users who are dependent on GBL can also experience severe withdrawal reactions, including hallucinations, agitation, confusion, delusions, delirium, rhabdomyolysis, and seizures. Most of the existing literature suggests the use of a high-dose benzodiazepine as a first-line treatment for GBL withdrawal. However, several cases of resistance to benzodiazepines have been observed, which likely reflect some pharmacological differences between benzodiazepines and GBL. Specifically, the effects of benzodiazepines are primarily mediated by gamma-aminobutyric acid (GABA)-A receptors, while GBL and its analogues act mainly at GABA-B receptors, with possible additional effects via the ionotropic GABA-A receptors. In this regard, recent studies have found that GBL and its analogues possess a high affinity for a specific form of extrasynaptic GABA-A receptors that are strongly activated by barbiturates, such as phenobarbital, but that are insensitive to benzodiazepines. Taken together, these findings suggest that barbiturates could be evaluated as first-choice agents for the treatment of GBL/gamma hydroxybutyrate (GHB) withdrawal instead of benzodiazepines. In support of this view, we describe a clinical case of difficult to manage GBL withdrawal symptoms in a 42-year-old male. We also review the literature on treatment options for GBL/GHB withdrawal, including benzodiazepine-resistant withdrawal.

Presentations to an urban emergency department in Switzerland due to acute γ-hydroxybutyrate toxicity

“…However, benzodiazepines appear to be a therapeutic option in cases of GHB withdrawal symptoms (e.g., anxiety, insomnia, tremor, tachycardia, agitation, delirium, and hallucinations), which may occur after long-term abuse, beginning within 1–6 h after taking the last dose [1]. Barbiturates (e.g., phenobarbital), baclofen, or propofol may also be considered treatments, particularly in cases of benzodiazepine-refractory GHB withdrawal [2, 28–30]. Specifically for non-responsive hallucinations, antipsychotics may also be indicated [30].…”

Delirium in the course of dependence upon gamma-butyrolactone (GBL) - a case report

“…The authors reported among other things, respiratory failure and acute renal failure [4,10,11]. In the management of withdrawal syndromes and delirium in GBLaddicted patients using of benzodiazepines is recommended [1,2,4,5,6,7,9]. In order to control a significant agitation, administration of haloperidol may be helpful [4,5].…”

A Systems Biology Approach for Identifying Hepatotoxicant Groups Based on Similarity in Mechanisms of Action and Chemical Structure

“…The order of the compounds in the table corresponds with the column order in the clustering heatmap (cluster #12), gemfibrozil forms a separate group (cluster #7), and valproic acid is clustered together with a set of other compounds (cluster #13). These compounds include the COX-2-selective, nonsteroidal anti-inflammatory drug nimesulide which is known to affect both GABA neurotransmission and PPARD signaling just like valproic acid [43,54,55] and phenobarbital, which is also an anticonvulsant that interacts with the GABAergic response [56].…”