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Brain and cognitive changes found after regular GHB use

GHB-induced coma linked to negative effects on long-term memory, working memory, IQ and stress

Louise Prime

Tuesday, 09 October 2018

People who regularly use the party drug gamma-hydroxybutyrate (GHB) suffer brain changes, and having had GHB-induced coma is particularly associated with lower IQ and altered brain processes during verbal long-term memory and working memory, scientists have shown. They have called for recreational users to be made aware of these findings, as most people do not realise that there might be any negative effects of GHB, also known as G or liquid ecstasy.

The researchers said in their presentation* at the 31st annual congress of the European College of Neuropsychopharmacology, in Barcelona this week, that GHB – a central nervous system depressant – is used extensively in clubs and elsewhere because it produces an initial feeling of euphoria. However, they added, GHB is the third most common drug-related cause of emergency attendance in Europe, and “it is not unusual that regular GHB users have experienced more than 50 GHB-induced comas”. Despite this, they noted, little is known about the effects of GHB use and GHB-induced comas on affect regulation in humans. So, supported and funded by the Ministry of Health of The Netherlands, they investigated.

They recruited 27 GHB users who had experienced at least four GHB-induced comas (GHB-Coma group), 27 GHB users who never had a GHB-induced coma (GHB-NoComa) and 27 polydrug users who never used GHB (No-GHB). Participants completed self-report questionnaires to assess negative affect (anxiety, depression and stress), and performed an emotional face-matching task during functional magnetic resonance imaging (fMRI) known to probe amygdala and hippocampus activity. They also completed an adult reading test (as a proxy for IQ).

Even in the GHB-NoComa group, the researchers found alterations in identification of negative emotions, with “decreased functional connectivity of the hippocampus with the amygdala in comparison with the No-GHB group”.

In the GHB-Coma group, they reported lower IQ (despite similar educational level), and altered brain processes during verbal long-term memory and working memory. They said: “The GHB-Coma group reported higher levels of stress and anxiety, showed a decrease in hippocampus activity and an increase in functional connectivity between the hippocampus and the left fusiform gyrus and a cluster located on the left temporal-parietal-occipital junction with three peak regions on the angular gyrus, the middle occipital gyrus and on the middle temporal gyrus when compared with the two other groups.” They added that further analysis showed that their findings could not be attributed to group differences in the use of drugs other than GHB.

They noted study limitations such as its inclusion of only men, and they acknowledged that it could not show causation. But they concluded: “These results suggest that GHB use is not without risk. Society is faced with increasing numbers of emergency attendances related to GHB overdose and individuals seeking treatment for GHB dependence. 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.”

In an independent comment, Professor David Nutt of Imperial College, London said: “This research is interesting and recreational users should be made aware of these findings. They probably reflect periods of hypoxia due to excessive GHB concentrations in brain. 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.”


*Conference Abstract P718: Raposa Pereira F, McMaster MTB, Polderman N, et al. The influence of GHB-use and GHB-induced coma on affect and the affective network. Poster presentation, Monday 8 October, 1630-1830, 31st ECNP Congress - Barcelona 2018.

NB: This work also includes research from the peer-reviewed papers: Adverse effects of GHB-induced coma on long-term memory and related brain function, Filipa Raposo Pereira, et al, (published in Drug and Alcohol Dependence, Sept 2018) https://doi.org/10.1016/j.drugalcdep.2018.05.019 and Effect of GHB-use and GHB-induced comas on dorsolateral prefrontal cortex functioning in humans, Filipa Raposo Pereira, et al (published in Neuroimage:Clinical, Sept 2018) https://doi.org/10.1016/j.nicl.2018.09.022.

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