GHB Flashcards
background and history, neural mechanisms, chronic use, adverse effects and legal issues (17 cards)
what is GHB?
gamma hydroxybutyrate
closely related to GABA (gamma-aminobutyric) - inhibitory neurotransmitter
chemists were trying to design GAB analogues as CNS depressant (new sedatives or anaesthetics)
used clinically to treat cataplexy (sudden loss of muscle control experienced by narcoleptics)
initially sold commercially in US health food shops as nutritional supplement for body builders - to reduce fat and increase muscle - but reported adverse effects then resulted in ban
one of two most common date rape drugs along with Rohypnol
not a newly discovered designer drug
biologically synthesised from GABA (amino acid that is structurally similar to GHB)
generally effects of GHB felt within 15 minutes and last for around 3-4 hours
how is GHB related to human metabolism?
natural product of human metabolism
carbohydrate found in abundance in our diet
animal meat, wine and small citrus fruits contain GHB
what are the behavioural effects?
relaxation
drowsiness
sociability
euphoria
lack of inhibition
increased sex drive
heightened sensitivity to touch dizziness
vomiting
tremors
tunnel vision
loss of coordination (ataxia)
confusion, irritation and agitation
hallucinations
blackouts and memory lapses
seizures
coma
respiratory arrest (stopping breathing) and death
what are the forms of GHB?
colourless, odourless, bitter or salty-tasting liquid sold in small bottles or vials
blue coloured liquid
crystals or powder (less common)
what neurotransmitters are involved in GHB action?
dopamine associated with most drugs and leads to reinforcement - targets mesolimbic pathway and induces a sense of reward through dopamine release, becoming reinforcing
GHB more associated with GABA - inhibitory neurotransmitter, explains some of behavioural effects (sense of relaxation, drowsiness)
toluene binges in rats lead to increased GABA several days after exposure in key cortical areas (hippocampus, prefrontal cortex, ventromedial striatum) - regions associated with recognised roles in behavioural flexibility and decision-making
what are the effects of GABA3 and GHB receptors?
both affect dopamine release
GABA3 = inhibit
GHB = excite
what are the two main hypotheses for GHB action?
GHB mediates pre and post-synaptic GABA release
GHB effects are mediated by a specific GHB receptor
what is the hypothesis that GHB mediates pre and post synaptic GABA release?
evidence from animal studies show that some of effects of GHB can be mitigated by GABA receptor antagonists
some research also suggests GHB can act as a GABA receptor antagonist but has a relatively low affinity for these receptor sites
what is the hypothesis that GHB effects are mediated by a specific GHB receptor?
there are specific GABA receptor sites for this substance
highest density of receptors tends to found in the hippocampus and cerebral cortex
these receptors would respond to both naturally produced GHB and chemically produced GHB so excess of this substance could cause “high” and potentially reinforcing effects
why is GHB addictive?
dopamine is substrate of normal reward systems and is common factor across broad spectrum of addictive drugs
mesolimbic pathway implicated in natural reward and drug abuse (dopamine pathway responsible for rewards, motivation and emotions)
gave anaesthetised rats toluene and measured firing in VTA - neurons increased in firing rate and then decreased again within minutes of toluene exposure whilst others were also inhibited
what was Funada et al’s (1992) study into the addictiveness of GHB?
study conducted on mice where mice are placed in two connected chambers
toluene distributed in one of two chambers
mice showed preference for toluene chambers than non-toluene chamber where before administration of the substance they showed no preference for either chamber
if given DA antagonist, no longer show preference
what is the effect of chronic GHB use?
literature has relatively little information regarding long-term impacts of GHB usage
few surveys have been conducted
some evidence of long-term neurological damage
can lead to severe memory problems, heart disease, hallucinations, extreme anxiety, breathing problems
some evidence from rats that long term exposure can lead to neurological damage, affecting the “grasping” reflex as well as alteration in working and spatial memories
what are the adverse effects of GHB use?
participants were significantly slower on behavioural tasks than other addicted groups and healthy controls
particularly bad at visuospatial, executive function and memory tasks
showed significant decreases in activation of the frontal lobe, central area, temporal lobe, parietal lobe and occipital lobe compared to healthy individuals
how does tolerance develop in GHB users?
informal reports from users suggest that they may increase the dosage up to sometimes every 2-4 hours all day and night
what are the symptoms of withdrawal?
insomnia
anxiety
tremors
at high doses - hallucinations, delirium, extreme agitation, psychosis
little actually known about this
withdrawal symptoms appear to be similar to those from other CNS depressants (alcohol, sedatives and hypnotics)
symptoms usually resolve themselves within two weeks
what are the legal issues?
club drug
GHB used like ecstasy and ketamine has gained notoriety for use as “date rape” drug
what are the clinical applications of GHB for narcolepsy?
EDS is most common symptom seen in narcolepsy - persistent sleepiness, sudden “sleep attacks” despite getting enough sleep at night
cataplexy - extreme and sudden muscle weakness and loss of control while awake, in severe cases person may collapse
systematic review and meta-analysis found GHB was effective in treating EDS and cataplexy, though the medication was also not well tolerated
