GHB is a drug currently making the rounds and is sometimes referred to as “liquid ecstasy.”

GHB. Better Health Channel. October 19, 2018.

Although it’s unlike ecstasy on a molecular basis, many of the effects are the same, and it can leave the recreational user in a stupor. Serious adverse effects include coma, which can lead to brain damage.

 

Although not recognized as a formal disorder, GHB use disorder (GUD) has been discussed in the literature.

 

What is GHB?

The short-chain fatty acid gamma-hydroxybutyrate (GHB) derives from the inhibitory neurotransmitter gamma-aminobutyric acid (GABA).

Once across the blood brain barrier, it exerts GABA-ergic activity in the central nervous system. It connects with GHB receptors and GABA-B receptors, as well as GABA-A receptors. GHB receptors are mainly found in the hippocampus, cortex, thalamus, and amygdala.

 

History of GHB

Its current medical uses include narcolepsy. GHB has become a popular recreational drug in the past 10 years for its euphoric, relaxing, and sexually stimulating effects.

In the US, Australia, UK, and the Netherlands, the use of GHB, and its precursors gamma-butyrolactone (GBL) and 1,4-butanediol, is emerging as a public health issue. Among adults in the US (and The Netherlands), 0.1% to 1.3% use GHB, with the rate being even higher among partiers.

In a systematic review, Dutch researchers identified three main sub-populations as being of particularly high risk for GHB misuse: (1) recreational GHB users who don’t experience adverse effects, (2) recreational users with adverse effects, and (3) users who are dependent on GHB.

Dijkstra BAG, Beurmanjer H, Goudriaan AE, et al. Unity in diversity: a systematic review on the GHB using population. Int J Drug Policy. 2021;94:103230.

These groups overlap in gender, age, and comorbid substance use, but use about the same amount of GHB each time.

 

The authors found that GHB’s often used by experienced drug users along with other substances, with dose and frequency related to comorbidity, dependency, and coma. Non-recreational users could be at greatest risk for dependency, although the transition from recreational to dependent user needs to be elucidated.

 

GHB use disorder

Other, negative side effects include drowsiness, impaired movement, impaired speech, and amnesia.

More serious effects include agitation, respiratory collapse, and loss of consciousness. Risk of overdose is increased when GHB is used together  with other drugs such as alcohol.

Although misuse of GHB as a disorder is not formally recognized by the DSM-5, individuals who misuse GHB usually meet general criteria for substance use disorder (SUD). In the literature, this specific form of SUD is referred to as GHB use disorder, or GUD. The severity of SUD can be characterized as mild, moderate, or severe.

GHB withdrawal is concerning, and there’s a high risk for agitated delirium and epileptic seizures.

 

Risk of brain damage

Comas caused by GHB use could lead to brain damage, according to the results of a neuroimaging study published in Frontiers in Psychiatry. The study involved 27 GHB users who had had 4 or more GHB-induced comas (GHB-Coma), 27 GHB users without GHB-induced comas (GHB-NoComa), and 27 polydrug users who had never used GHB (No-GHB).

Pereira FR, McMaster MTB, Schellekens A, et al. Effects of recreational GHB use and multiple GHB-induced comas on brain structure and impulsivity. Front Psychiatry. 2020;11:166.

 

The authors wrote that multiple GHB-induced comas are related to microstructural alterations at the level of the corpus callosum, in areas tied to goal-directed behavior, associative memory, and affect regulation.

Such changes could serve as the structural basis for the brain activity differences that the GHB-Coma group exhibited while processing such cognitive control functions. This group also noted low self-control, which involved regions of the brain entailing impulse regulation.

Studies such as this one, which help to better define the neurobiological substrates of comorbid impulsivity, are invaluable toward developing interventions that target alterations to brain structure.

The study investigators assert that chronic use of GHB in high doses “represents a serious risk for brain impairment.”

Maximum treatments are warranted, such as relapse prevention using a combination of psychotherapy (eg, motivational enhancement therapy or cognitive behavioral therapy) and pharmacotherapy (eg, baclofen).

It’s important to integrate these findings into current drug awareness campaigns to change common misconceptions among chronic users that GHB use is safe.

 

Treatment for withdrawal

GHB withdrawal is potentially lethal, and symptoms don’t always abate with benzodiazepine. Nevertheless, high-dose benzodiazepines are the selected first-line treatment, possibly based on physicians’ familiarity with titrated use of benzodiazepine for alcohol withdrawal.

It is currently being used by some GHB users to self-manage withdrawal symptoms.

In a study of grey literature on the topic, UK researchers attested to their own anecdotal clinical experiences with using baclofen as a treatment for withdrawal.

Floyd CN, Wood DM, Dargan PI. Baclofen in gamma-hydroxybutyrate withdrawal: patterns of use and online availability. Eur J Clin Pharmacol. 2018;74(3):349–356.

 

“Despite the clinical experience of our centre in which we have successfully treated dozens of patients with GHB/GBL withdrawal with baclofen,” stated the authors, “there is little published data with regard to the use of baclofen to manage GHB withdrawal.”

“The case reports we identified suggested clinical utility with an acceptable safety profile, but it is not possible to draw definitive conclusions in the absence of randomised controlled trials. Furthermore, despite its described use in both inpatient and outpatient settings, there remains a potential risk of significant harm in baclofen overdose."

Sometimes outpatient treatment for GHB withdrawal won’t cut it. In a case study published in Addiction Medicine, a 47-year-old man with GUD required inpatient hospitalization after multiple failed attempts at outpatient treatment.

von Theobald L, Rousselet M, Cholet J, et al. Inpatient gamma-hydroxybutyrate detoxification: a case report describing day-to-day therapeutic management. J Addict Med. 2017;11(3):231–234.

 

GHB withdrawal, which can be severe, is better prevented or attenuated by daily medical monitoring and adjustment of treatment dosage.

“Failure of outpatient detoxification should be included in the indication criteria in the guidelines for inpatient detoxification," the researchers added.

As for prevention, the authors suggested that to prevent exposure to the drug, physicians should prescribe GHB only when medically indicated and absolutely necessary. They also encouraged governments to outlaw GHB and its derivatives.