12. G-Hydroxybutyrate (GHB) Overdose and Withdrawal

Mechanism

GHB is a structural precursor of GABA with agonist activity at both GHB receptors and GABA-B receptors (usually at higher doses), rapidly leading to CNS depression. GHB receptors can lead to changes in serotonin, dopamine, opioid and other neurotransmitters in the CNS, which can result in euphoria, but also stimulant effects. 

  • Initially marketed as a dietary supplement for weight loss and body building.
  • Known recreationally as a “club drug” or “date rape drug” for euphoric and sedative effects, respectfully.
  • Liquid GHB is odorless and clear.

Signs and Symptoms

  • Intoxication: most common presentation is abrupt onset sedation and unconsciousness (GCS typically below 8) within 15-45 minutes of ingestion; however, can also have stimulant effects in up to 35% of patients. Rapid recovery usually within a 3-8 hours, sometimes longer. Amnestic effects of GHB ingestion are associated with physical trauma and sexual assault. Other signs include bradycardia, hypotension (less common), mild hypothermia, bradypnea + respiratory acidosis, myoclonus/seizure-like effects, rhabdomyolysis, nausea/vomiting (especially with co-ingestion of alcohol).
  • Withdrawal: occurs with extended use, usually 1-6 hours after use or dose reduction. Initial symptoms include insomnia, cramping, tremor, diaphoresis, and anxiety, which can be followed by severe agitation, paranoia, hallucinations and delirium. Appears similar to alcohol and benzodiazepine withdrawal, though onset/offset is quicker and neuropsychiatric effects can be more prominent. Delirium tremens-like syndrome with autonomic instability can occur (usually within 24 hours) along with hallucinations and seizures. Other complications include hyperthermia and rhabdomyolysis. Symptom course can be unpredictable.

Evaluation

  • History: evaluate for ingestion from friends or witnesses. Check co-ingestions (co-ingestion with alcohol noted in 30% of users). Suspect GHB intoxication in a patient who presents with abrupt onset of coma with rapid recovery within a few hours. If able or upon recovery, screen for physical trauma and/or sexual assault given amnestic effects. Withdrawal should be suspected in any patient with prolonged GHB use and recent cessation or dose-reduction.
  • Laboratory: not routinely available and usually a clinical diagnosis, but can be detected with mass spectrometry (comprehensive toxicology test). Consider other toxicologic testing as co-ingestion is common. Consider HIV and STI testing for any patient with evidence or suspicion of sexual assault. For patients with suspected withdrawal, check CK and BMP.

Management

  • Overdose: protect the airway and provide mechanical ventilation if needed. Management is largely supportive; patients who require intubation often have rapid recovery of mental status and are extubated within a few hours. Try naloxone given high rate of co-ingestion, though not clinically effective for GHB ingestion alone. Patients may require prolonged hospitalization due to delirium.
  • Withdrawal: management is largely supportive. Benzodiazepines are the mainstay of treatment for agitation; may require high doses and even this can be ineffective. If refractory to benzodiazepines, consider barbiturates, baclofen, propofol, or dexmedetomidine. Treat elevated CK with fluids. Treat hyperthermia (see Drug-Induced Hyperthermia section).
    • Haloperidol and other antipsychotics are NOT recommended, as they are both ineffective and can lead to adverse effects of dystonia, neuroleptic malignant syndrome, and lowered seizure threshold.  

Key Points

  • Most patients present with co-ingestion of GHB and other substances.
  • GHB overdose causes severe CNS and respiratory depression, but usually resolves over a few hours.
  • GHB withdrawal is similar to alcohol and benzodiazepine withdrawal and can be refractory to benzodiazepine treatment. Antipsychotics are not recommended.

 

Britt GC and McCantz-Katz Elinore. A brief overview of the clinical pharmacology of ”club drugs.”

McDonough M, Kennedy N, Glasper A, Bearn J. Clinical features and management of gamma-hydroxybutyrate (GHB) withdrawal: a review. Drug Alcohol Depend. 2004;75(1):3‐9.

Poisoning and Drug Overdose, 6th ed. 2012.

Substance Use & Misuse 2005; 40: 1189-1201.