GHB neurotoxicity, brain damage due to GHB-induced coma in recreational GHB users

GHB has originally been developed as an anaesthetic drug, but is since the
1990s regularly used as a recreational drug
(8). GHB increases feelings of euphoria, relaxation, sociability and sexuality
(13). Users of GHB are generally young
adults (18-30 years) who use the drug in clubs, dance parties or after parties
(15,16). In addition, GHB use is also spread
among other groups, such as bi- or homosexual men (2) and college students (3).
In 2009 in The Netherlands, lifetime
prevalence of GHB use was 1.3%, whereas last month use was 0.2%, indicating low
GHB use continuation (14).
The initial stimulant-like effects of GHB are followed by sedation, but there
is a narrow dose-response margin between
subjective GHB effects and those related to overdose (1). Symptoms of GHB
intoxication include drowsiness, sleep,
confusion, convulsions, collapse, hypostatic pneumonia and coma with
respiratory depression. Symptoms of GHB
intoxication usually resolve within 4 to 8 hours. It is not known whether
experiencing a GHB induced coma leads to
residual long-term harm.
By 2009, 1200 cases of GHB related emergency visits to Dutch general hospitals
were reported (6-fold higher compared to 2003) and the majority of these
emergencies were caused by GHB-induced coma (4). Several other emergency
department (ED) case studies have also reported GHB as one of the major reasons
for drug overdosing and drug-related ED presentations (6,7,9,10,12,16,18) and
72% of GHB-intoxicated patients scored * 12 on the Glasgow Coma Scale (GCS) (7).
GHB is generally considered by users as safe and non-toxic, although it has a
lethal potential and GHB might be addictive. One of the problems (and a
hallmark) of a GHB induced coma is that victims awake next morning within 5
seconds from deep coma to full consciousness without any complaints
(headache/hangover), which gives the user the feeling that a GHB coma has no
residual adverse effects (16). This also explains why the same users experience
more than one coma. There are indications that many GHB users experience a GHB
overdose/coma during their lives (10). In a survey among GHB users in the USA,
66% of 42 users reported loss of consciousness once or multiple times during
GHB use (11). Similar figures were found in a cross-sectional survey of 76
Australian GHB users where 40 subjects (53%) had experienced a GHB overdose and
a third had done so more than three times (5). A Swiss study reported that in a
period of three years, 7 out of 48 patients with GHB coma (15%) were presented
two, three or even six times to the emergency department (10).
In conclusion, GHB intoxication is an emerging problem in different countries,
including The Netherlands, and this is caused mainly by lacking awareness of
the effects of overdose and co-ingestion with other drugs. The objective of
this investigation is to determine whether GHB intoxication/coma might lead to
neurotoxicity (structural brain damage). Because GHB acts as a general
anaesthetic, it is anticipated that cognitive and memory disturbances occur in
GHB users who have experienced one or more coma*s (10).

References
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individuals. Am J Addict 13: 120-7, 2004.
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college students. Am J Drug Alcohol Abuse 31, 6001-607. 2005.
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Addictive disorders affect a steady proportion of the population, and result in
significant negative personal consequences (e.g. loss of jobs, psychosocial
problems) and costs to society (absence from work due to hangover, treatment
costs). GHB is becoming more popular and an increasing number of GHB users is
presented at emergency departments of general hospitals. The search for
vulnerability factors and potential adverse effects of GHB use is therefore
highly relevant. The current literature on neurobiological indicators of brain
damage by GHB use or GHB coma is very small. However, the adverse effects of
similar sedating drugs (general anaesthetics, ketamine and alcohol) on memory
and other
cognitions have been described in the scientific literature.
The detection of severe adverse side effects of GHB overdosing (those leading
to coma) might be helpful to readjust the false belief among GHB users that GHB
is a safe drug. The current study will provide better knowledge on the
neurobiological risk indicators of recreational GHB use. This may result in a
wider awareness among GHB users and drug policy makers about the health risks
of GHB use. If confirmed that GHB is neurotoxic, this observation can be used
in objective counselling (information campaign*s) of recreational GHB users and
the general public to explain that GHB is not an innocent drug.

The main hypothesis to be tested is that one or more comas (*going out*) due to
GHB overdosing is a prominent risk factor of neurotoxic damage in distinct
brain areas.
Specific research questions are:
a) Does exposure to high doses of GHB, known to induce coma result in
structural brain damage according to MRI based images (DTI)?
b) Is the effect of GHB comas dose-dependent i.e. do multiple experienced comas
result in more damage than a single experienced coma according to MRI based
images (DTI)?
c) Does exposure to high doses of GHB, known to induce coma, impair memory and
other cognitions as assessed via validated psychological tests and MRI based
images (DTI)?
d) Do the MRI findings match with psychological assessments of memory and other
cognitions?
e) What are the clinical and socio-demographic characteristics of GHB users who
repeatedly *go out*?

Open study using structured interviews, cognitive tasks, questionnaires and
DTI-scanning of brain.

1. inclusion (various locations of hospitality industry).
2. group session about user profile. Location: (preferentially) Bonger
Institute.
3. * day to fill in the questionnaires, and evaluate cognitive and memory
function plus scanning (maximal 60 min. in the scanner).
Location: UvA Psychology, Roeterseiland. Subjects perform tasks inside and
outside de scanner.
It is possible that contact moment 1 and 2 are combined.