Popular 'Club Drug' Tied to Brain, Cognitive Changes

Liam Davenport

October 11, 2018

BARCELONA, Spain — The recreational drug gamma-hydroxybutyrate (GHB) appears to cause functional brain changes, particularly in individuals who have experienced multiple GHB-related comas.

Investigators at the Academic Medical Center, Amsterdam, the Netherlands, note that this novel finding challenges the widely held assumption that the drug, which is also known as "G" or "liquid ecstasy," is safe.

Study investigator Filipa Raposo Pereira, a PhD student in psychiatry, told Medscape Medical News it is important that users understand there is no safe way to take GHB and no safe dose.

She said the narrow window between the desired high and overdose varies from person to person, making it difficult to control.

The findings were presented here at the 31st European College of Neuropsychopharmacology (ECNP) Congress.

Growing Use

A central nervous system depressant, GHB is used extensively in clubs and at private house parties. It produces an initial feeling of euphoria but can also cause sleepiness, and users easily slip into a coma, commonly known as a "G-nap."

Coinvestigator Guido A. van Wingen, PhD, also from the Academic Medical Center, noted that although many users do not experience coma, many see the G-nap as part of the experience.

"They have this erroneous idea that it's safe, because generally, you wake up from these periods of sedation...with no apparent side effects," he told Medscape Medical News.

"So they continue, sometimes even continue with the party and taking other drugs, and they have different erratic behaviors but no apparent residual side effects. So, for them, the drug is still a safe drug," he added.

Some regular users have experienced more than 50 such GHB-induced comas, which often could be scored 3 or higher on the Glasgow Coma Scale and can require hospital treatment.

GHB is now the fourth most common drug-related cause for emergency department visits in Europe. The consequences on the brain are unknown. Despite this, recreational users still consider the drug to be safe when taken at correct doses.

To investigate the impact of GHB and particularly GHB-induced comas on activity in the amygdala and hippocampus and functional connectivity in the affective network, the investigators studied 81 male individuals.

These included 27 users who had never experienced a GHB coma, 27 users who had experienced more than four comas, and 27 polydrug users who had never used GHB and who served as control persons.

Participants completed the Depression, Anxiety and Stress Scale and the Dutch version of the Adult Reading Test.

Depression, Anxiety, Memory Loss

In addition, participants completed an emotion discrimination in faces task while undergoing functional MRI of the whole brain, the hippocampus, and the amygdala.

The results showed that for individuals who had experienced multiple GHB-induced comas, verbal IQ was reduced and there was a 63% increase in stress and a 23% increase in anxiety, compared with other GHB users and control participants.

GHB users who had experienced comas also were found to have undergone alterations in long-term memory.

The emotion discrimination task showed that individuals who had experienced GHB-induced comas were found to have a decrease in activity in the hippocampus, an increase in functional connectivity between the hippocampus and the left fusiform gyrus, and a cluster on the left temporal-parietal-occipital junction compared to the two other groups combined.

When comparing GHB users who had not experienced coma and nonusers, the investigators found that in the group that had not experienced GHB coma, there was a decrease in functional connectivity between the hippocampus and the amygdala compared to nonusers.

In addition to increasing numbers of emergency department admissions, an increasing number of individuals are seeking treatment for dependence.

The researchers note that this suggests that awareness campaigns directed at recreational GHB users are warranted to highlight the lasting adverse effects of GHB, despite the absence of immediate apparent side effects.

Users Beware

Commenting on the study, David Nutt, MD, PhD, Edmond J. Safra Professor of Neuropsychopharmacology at Imperial College London, the United Kingdom, and former president of the ECNP, said "recreational users should be made aware of these findings.

"When GHB is used in a regulated fashion as a medicine — for example, for narcolepsy — there doesn't appear to be a similar risk, so patients on this medicine should not worry," he said.

This research was funded and supported by the Ministry of Health of the Netherlands. The investigators and Dr Nutt have disclosed no relevant financial relationships.

31st European College of Neuropsychopharmacology (ECNP) Congress. Abstract P.718, presented October 8, 2018.

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