Brain damage due to GHB-induced coma in 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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Psychopharmacol 27: 625-38, 2007.
2. Camacho A, Matthews SC, Dimsdale JE. Use of GHB compounds by HIV-positive
individuals. Am J Addict 13: 120-7,
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college students. Am J Drug
Alcohol Abuse 31, 6001-607. 2005.
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Australian household survey. Int J Drug
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gamma-hydroxybutyrate (GHB)-related
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of 505 consecutive emergency department
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gamma-hydroxybutyrate (GHB)-related incidents
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features of gamma-hydroxybutyrate and
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Dep 81, 323-326. 2006.
11. Miotto K, Darakjian J, Basch J, Murray S, Zogg J, Rawson R.
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and withdrawal. Am J Addict 10, 232-241. 2001.
12. Munir VL, Hutton JE, Harney JP, Buykx P, Weiland TJ, Dent AW.
Gamma-hydroxybutyrate: a 30 month emergency
department review. Emerg Med Australas 20: 521-30, 2008.
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subjective experiences of
gammahydroxybutyrate (GHB). Drug Alcohol Depend 92, 286-290. 2008.
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Ketelaars A. The Netherlands Drug
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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,
structural and functional brain scans.

The study will take place at the AMC in Amsterdam. The MRI scans that will be
made while the subject is in the MRI scanner will be done by an experienced
researcher. The study will take 2,5 hour for each test subject including 1 hour
in the MRI scanner and including filling in several questionnaires.

For the patient groups (group 1 and 2) applies: the test subject will be picked
up by car and brought back by car to the clinic where he resides by the
researchers.