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Why does GHB have such strong effects?

Renz Envy

Renz Envy

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Joined
Sep 29, 2010
Messages
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During even a low-end overdose there is virtually nothing a person can do to avoid passing out.

I know this will probably not be an easy answer, but why does GHB "knock out" users so effectively?

Another question:
I sort of doubt the legitimacy of this, and certainly do not wish to try it, but
Why is the recreational dose so close to overdose, yet miles away from a lethal dose? I find it hard to convince people this is true, as GHB has a nasty way of landing individuals in the hospital.



I am trying to educate myself fully on the effects so that I may understand the dangers of long-term moderate GHB use.
 
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GHB binds to two kinds of receptors: the GABA-B receptor and the so called GHB receptor. The sedation is caused by GABA-B binding, and a GABA-B antagonist completely prevents the hypnotic effect of GHB, see http://www.ncbi.nlm.nih.gov/pubmed/11689189 . Another GABA-B agonist is the antispasmodic drug baclofen, which also has a narrow 'therapeutic window'.

The euphoric effects are probably caused by binding to the GHB receptor, which unlike GABA-B is excitatory. A selective GHB agonist (there are some, but not tested on humans) would probably cause an euphoric effect without sedation...
 
So I understand that it begins as a GHB receptor agonist and is more partial to GABA-B with higher doses?
 
polymath said:
A selective GHB agonist (there are some, but not tested on humans) would probably cause an euphoric effect without sedation...
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I have pondered their existence.

I also wonder if this would lead to an increase in heart rate and blood pressure or decrease.

Edit: The reason I ask this question is because GHB seems to have a very broad spectrum of effects on the body. Its narcotic effects(Of which I was previously well aware of) seem to be only the tip of the iceberg.

I am curious if anyone has an article or a very in depth study of its individual effects.
 
A friend and I were discussing the subjective qualities of GHB as different than other GABAergics. We agreed that it seemed to, though impairing motor function, make ones thinking seem "clear headed" and give one a sense of perceptive clarity even while with realization that one's movements were slowed and compromised. Such seemed to be in a more precisely "frameable" manner than with say alcohol. Perhaps at the proper dosage the GHB receptor is a nootropic of sorts.
 
A selective GHB agonist would cause neurotoxicity. It's when the GABA B agonist levels of GHB drop to low to prevent the neurotoxicity that it occurs. I think the reason there aren't any compounds out there for human consumption that are purely GHB agonist is that they would probably give you a seizure.
 
Nexus298 said:
A selective GHB agonist would cause neurotoxicity. It's when the GABA B agonist levels of GHB drop to low to prevent the neurotoxicity that it occurs.
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Has excitotoxicity truly been confirmed in humans undergoing unmediated GHBr agonism? How might it act or be mediated in conjunction with the glutamatergic system? Are there any known studies, perhaps with NMDA-agonism/antagonism, of its relation to affect glutamatergic processes?
 
We can only speculate about the effects of selective GHB agonists... AFAIK they haven't even been tested on animals.

There have been some experiments where GHB was administered with a GABA-B antagonist like SCH-50911, though, and this blocked the sedative/hypnotic effects but not all other behavioral effects.

High doses of caffeine cause seizures, too...
 
The title of this thread sounds like it deserves a punch-line but I cannot think of one.

I have witnessed a number of clinical presentations of GHB or GHB suspected (prodrugs) overdoses. Due to the alarmingly profound unresponsive states thatGHB produces (albeit often transient and without sequela), friends/family are understandably quick to call for EMS (or drag a frat-brother to admittance). In some cases, within the time of receipt and transit by EMS to intake, the patients were effectively ambulatory. This is not license to abuse the drug without regard of consequence, just an observation.
 
Nagelfar said:
A friend and I were discussing the subjective qualities of GHB as different than other GABAergics. We agreed that it seemed to, though impairing motor function, make ones thinking seem "clear headed" and give one a sense of perceptive clarity even while with realization that one's movements were slowed and compromised. Such seemed to be in a more precisely "frameable" manner than with say alcohol. Perhaps at the proper dosage the GHB receptor is a nootropic of sorts.
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The glutamate release by the GHB agonism is cognitive enhancing indeed.
 
Amisulpiride wich is a GHB agonist improves cognitive function in shizophrenic patients.
 
^ Amisulpride is a pharmacological pipe bomb. It hits a wide range of receptors, and I don't think we can attribute its cognitive enhancing or antipsychotic effects to its GHB agonist activity. Not with any degree of certainty, anyway.
 
negrogesic said:
(or drag a frat-brother to admittance)
Click to expand...

Sorry to stereotype, but wouldn't an overdose on the part of a frat brother often involve alcohol? The situation with benzodiazapines is similar: acute overdose of benzodiazapines taken alone is only potentially fatal with very high doses, but in combination with other gabanergic drugs, the threshold of toxicity is far lower.

ebola
 
Alcyone said:
^ Amisulpride is a pharmacological pipe bomb. It hits a wide range of receptors, and I don't think we can attribute its cognitive enhancing or antipsychotic effects to its GHB agonist activity. Not with any degree of certainty, anyway.
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Other ap's do what it does; the special thing is the GHB agonism and suprisingly the only ap working really well against negatives; what supports this is that all glutamate modulaters added to ap's help the negatives.
 
MeDieViL said:
Other ap's do what it does; the special thing is the GHB agonism and suprisingly the only ap working really well against negatives; what supports this is that all glutamate modulaters added to ap's help the negatives.
Click to expand...
You may very well be right, and I'm not in any position to disagree with you anyway. I guess what I'm trying to say is; given the intrisic complexity of psychotic disorders coupled with the broad-spectrum pharmacological profile of amisulpride and other antipsychotics (not to mention the frequent use of combination therapy), it is extremely difficult to pinpoint which particular drug-receptor interaction is causing one specific response (whether it be a beneficial or an adverse effect).

Isn't ziprasidone generally considered equivalent to amisulpride in treating 'negative' symptoms of psychosis? There are also case reports on aripiprazole producing cognitive enhancement in schizophrenia. Ziprasidone and aripiprazole both have even 'dirtier' pharmacological profiles than amisulpride, but to the best of my knowledge they don't hit the GHB receptor.

Could you rule out antagonism of presynaptic D2 and D3 autoreceptors as a cause of cognitive enhancement in psychotic patients? (not a rhetorical juestion, just interested in your insights)
 
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For the last question; absolutely as the doses used block those receptors.

All antipsychotics cause cognitive enhancement in shizophrenia but its very mild; ami is the only one that also helps anhedonia and social anxiety just like clozapine wich is also very glutaminergic.

Zyprexa is also a 5HT7 antagonist however doesnt work for anhedonia; the 5HT7 antagonism wich they share also aid glutaminergic function.
 
Renz Envy said:
During even a low-end overdose there is virtually nothing a person can do to avoid passing out.

I know this will probably not be an easy answer, but why does GHB "knock out" users so effectively?


Another question:
I sort of doubt the legitimacy of this, and certainly do not wish to try it, but
Why is the recreational dose so close to overdose, yet miles away from a lethal dose? I find it hard to convince people this is true, as GHB has a nasty way of landing individuals in the hospital.



I am trying to educate myself fully on the effects so that I may understand the dangers of long-term moderate GHB use.
Click to expand...
I always thought it was how much it would peak. It takes G 2 hours to hit you or knock you out. Some people dose too soon before that period which is where the lethal dosing comes in.
 
Hospitals and ER do not even know how to handle GHB cross overs. At least none here do. Theyll give you narcan on spot though and put you in respitory breathing shits. I found that out the hard way. GHB is just not a toy drug. Its medicine.
 
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