GHB: To many users, a ‘wonder drug’
Introduced in 1960 as an anesthetic, gamma-hydroxybutyrate (GHB) has become a notorious recreational drug. It is often called the “date rape drug” because of its intoxicating sedative effects.
Users have viewed GHB as a dietary supplement that can also enhance athletic and sexual performance, relieve depression, and induce sleep. Weightlifters have used GHB to quickly build muscle while avoiding side effects associated with anabolic steroids.
As more products containing GHB were introduced, many serious adverse events—including seizure, respiratory depression, and profound decreases in consciousness—were identified with its use and misuse. Although the Food and Drug Administration banned over-the-counter sales of GHB in 1990,1 the agent is still widely available on the black market and over the Internet.
GHB also is marketed through its chemical precursors, specifically GBL and 1,4-butanediol. These precursors are rapidly and systemically converted to the active GHB product. GBL is hydrolyzed by a peripheral lactonase, and 1,4-butanediol is processed by alcohol dehydrogenase and aldehyde dehydrogenase—the enzymes involved in ethanol degradation.1
A tiny increase in GHB dose can dramatically increase the symptoms and risk of overdose.4 GHB’s effects are also variable: A 1-teaspoon dose can produce the desired “high” one time and an overdose the next.
GHB and ethanol share a common mechanism of action.5 At pharmacologic doses, GHB appears to act in part through effects on the structurally related GABA neurotransmitter or its receptors.
Not surprisingly, a withdrawal syndrome characterized by delirium and autonomic instability ensues after GHB use is abruptly stopped. By functioning as indirect GABA agonists and ultimately evoking inhibitory neurotransmission, benzodiazepines and most barbiturates may alleviate GHB withdrawal symptoms.4 Thiamine is added to prevent Wernicke-Korsakoff syndrome, as is seen in alcohol withdrawal.5
GHB withdrawal. Symptoms are divided into three phases:
• Phase 1 (acute, first 24 hours). Presenting symptoms include anxiety, restlessness, insomnia, tremor, diaphoresis, tachycardia, and hypertension. Nausea and vomiting are variable but can be unrelenting.
While symptoms vary in severity, most prominent are agitation, restlessness, and insomnia. Some patients do not sleep for days after their last dose, and diffuse body tremors prevent them from sitting or lying still. Tachycardia and hypertension are hard to evaluate at this phase because patients present at different stages of withdrawal. Initial blood pressure readings as high as 240/130 mm Hg and heart rates of 120 bpm have been reported, however.
• Phase 2 (days 2 through 6). Worsening autonomic symptoms, progressive GI symptoms, and overall worsening of the withdrawal mark this tumultuous period. Patients usually present at this point—in acute distress and no longer able to self-treat.
Confusion, delirium, and florid psychosis characterize this phase. Mr. R’s paranoid delusions and hallucinations are the most common form of psychosis seen in GHB withdrawal.5 In some cases, the psychosis impairs social, occupational, and other functioning.
Table 1
Comparison of sedative-hypnotic withdrawal syndromes
| Substance | Onset | Duration of severe symptoms | Autonomic instability* | Neurologic/psychiatric symptoms | Mortality | Major mechanism inducing withdrawal state‡ |
|---|---|---|---|---|---|---|
| GHB | <6 hours | 5 to 12 days | Mild | Severe | <1% | Loss of GHB, GABAA, and GABAB-mediated inhibition |
| Benzodiazepines | 1 to 3 days | 5 to 9 days | Moderate | Moderate | 1% | Loss of GABAA-mediated inhibition |
| Baclofen | 12 to 96 hours | 8 days | Moderate | Severe | None reported | Loss of GABAB-mediated inhibition |
| Ethanol | <6 hours | 10 to 14 days | Severe | Moderate to severe | 5% to 15% | Loss of GABAA-mediated inhibition; disinhibition of NMDA receptors |
| NMDA: N-methyl D-aspartate. | ||||||
| GHB: Gamma-hydroxybutyrate | ||||||
| *Marked by tachycardia, fever, hypertension, and/or diaphoresis. | ||||||
| ‡All withdrawal states involve multifactorial processes. | ||||||
| Source: Reference 5 | ||||||
Underlying or concurrent causes of delirium must be ruled out. Patients at this stage often require physical restraint or immediate sedation to prevent injury and dangerous complications, including hyperthermia and rhabdomyolysis. Benzodiazepines are often used in high doses1 for sedation. IV hydration and antiemetics are also treatment mainstays. Atypical antipsychotics are added ASAP to control the paranoia.
• Phase 3 (days 7 through 13). Symptoms usually resolve at this stage. The delirium most often clears first, followed by restored autonomic stability and GI rest. While decreased sleep and periods of psychosis persist, agitation is less severe. The patient is discharged on average after 11 days.
Intense outpatient follow-up should include individual psychotherapy, substance abuse counseling, and drug therapy. Highly addictive medications should be avoided because of the patient’s substance abuse history.
Did Mr. R accurately report the amount of GBL he had taken? How should GBL and GHB blood levels be measured, given the agents’ rapid absorption rates?
The authors’ observations
As with most drugs of abuse, high doses over time contribute to severe GHB withdrawal syndrome. GHB doses taken before withdrawal are up to 10 times greater than those taken in typical recreational use.5
However, quantifying GHB levels with standard urine drug screens is nearly impossible because: