DistyBoi
Bluelighter
- Joined
- Nov 17, 2011
- Messages
- 307
Been researching this recently and figured I would share what I have found out. Its not a strictly a 'new mechanism', more a collection of inferences from various already existing studies that I dont see many people who often discuss GHB/GBL to have much knowledge of.
Now I used to think (like many other people) this was due to a "dopamine rebound" effect, but this thread by df user malsat seems to show its in fact a combination of upregulated glutamate receptors causing excitotoxicity (plus in very high doses apoptosis), and down-regulated GABA-B (see his full post italicised below). There is more going on than simply this, but these two factors seem to be the main points. The former seems to be treatable with phenibut and the latter with benzodiazepines.
Now I have got some GBL here at the moment, and having had a couple of days where I've ended up re-dosing throughout the majority of the day (about 12-15ml in total) I ended up a bit of an anxious mess when it wore off. Today however I was bracing for a similar effect having dosed throughout the day the night before. Then I remembered I had some phenibut, so I took 500mg at the same time as my last dose, then another 500mg when I woke up three hours later. I have to say it worked amazingly, I have got literally no GHB hangover at all! Which has made me wonder how long this can be kept up for, and what the possible health implications of dosing with GHB in the day and using a small dose of phenibut, to block the calcium channels and reduce the glutamate production that gives you that horrible edgy feeling.
Heres his more in detail post, he does provide references to science journals to each point later in the thread, which I will post below it too for those that want to see literature:
Hi, I'm new to the forums. I'm a student of neuroscience (by no means an expert).
Just so you all know, the 'dopamine rebound' theory is incorrect. G is a physically addictive substance, in the classical sense, like heroin or cocaine.
Skip to the end if you don't want to read a lot of sciency stuff, just want help with addiction.
G binds to the GABA-B receptor in the brain. GABA is the main inhibitory neurotransmitter. It reduces neural activity, producing relaxation etc.
G use will cause downregulation of GABA-B receptors from a single use - the brain produces less and less GABA-B receptors plus upregulation of glutamate receptors (more glutamate receptors). Glutamate is the main excitatory neurotransmitter, essentially it increases neural activity. In addition there is a GHB receptor. GHB is present naturally in the brain, where it binds to GHB receptors and produces and excitatory response (increasing stimulation). When you come down from a dose of G, or stop dosing during an addiction, the combination of downregulated GABA-B plus upregulated glutamate receptors (plus the continued stimulation of GHB receptors as one comes down from a dose) produces excessive neural stimulation, hence the sudden waking effect from night-time G use.
In addiction, this produces the withdrawal effects.
'Excitotoxicity' is a condition that can be caused by large amounts of glutamate in the brain. Glutamate binds to its receptors (AMPA, NMDA and kainate) and in excess can cause a large influx of calcium ions into neurons. This calcium influx can cause a process called 'apoptosis', also known as programmed cell death. Essentially, the neurons commit suicide.
It follows from the mechanism of action of G that in withdrawal, excitotoxicity plays a role. Considering this, anyone in a G addiction should seek medical assistance if possible and request gabapentin or pregabalin, two drugs which block calcium channels and reduce glutamate production in the brain. These drugs could prevent the neurotoxicity caused by G withdrawal.
It's likely that some of the withdrawal symptoms are caused by downregulation of other neurotransmitters (acetylcholine most likely, possibly also dopamine).
THE END:
The G withdrawal sweats and high heart rate/blood pressure can be treated with clonidine (clinically). SWIM has found that the sweats can be treated with first generation antihistamines (dramamine, benadryl, also piriton somewhat) which have anticholinergic activity.They can be bought OTC.
Bad G withdrawal will produce paranoid delusions/hallucinations/psychosis, which MUST be treated by medical professionals.
Benzodiazepenes (valium, xanax etc, active at GABA-A) can help with the withdrawals, but should be tapered. If you have a supply and are using them to treat your withdrawals, be aware that you could end up addicted to them, with similar withdrawals to G.
Alcohol can also ease the withdrawals(active at GABA-B also, but doesn't ease all the symptoms, and psychosis will still develop unhindered), but it's unpleasant when you end up having to drink 30-40 units of alcohol (equivalent to 10 LITRES of beer) just to ease the anxiety, then develop a HUGE hangover in a few hours.
Supplementing with zinc and magnesium could help to prevent some of the neurotoxicity.
Taping your dose down over a period of several weeks is the best way to get off it by yourself. DO NOT STOP COLD TURKEY, PEOPLE HAVE DIED THIS WAY.
As I mentioned before, it's VERY likely that withdrawing from G addiction can cause nerve damage (most noticable as a reduction in sensation of the extremities or a tingling/burning/pins and needles sensation in the fingers/toes/face), and as such you should be getting off it under the supervision of a medical professional. Most of them have no idea when G is, much less how to treat it. Try and find some medical info on the net, print it out and show it to them. Mention excitotoxicity and ask to be treated with GABAPENTIN OR PREGABALIN in addition to clonidine and a benzodiazepene tapering program.
References:
Well, it's widely known that neurotransmitter systems will up- and down-regulate receptors in response to insufficient or excessive stimulation in order to mantain homeostasis. G is known to bind to GABA-B so downregulation here is a logical result. Inhibition of glutamate firing would be expected to produce glutamate receptor upregulation. Excessive stimulation of glutamate receptors (which would be expected in a situation in which there has been upregulation of glutamate receptors and an increase in glutamate firing) induces excitotoxicity by calcium ion saturation;
Chronic GBL producing GABA downregulation:
http://www.springerlink.com/content/mj22m213107x5043/
GHB reducing extracellular glutamate levels in millimolar concentrations via GABA-B, increasing extracellular glutamate levels in nanomolar concentrations via GHB receptor stimulation (this means that as a dose of G leaves the system, inhibitory effects via GABA-B are no longer active while there is excitation due to GHB still binding the GHB receptor):
http://www.ingentaconnect.com/content/bsc/jnc/2003/00000087/00000003/art00017
I do not believe there have been any studies done regarding the G withdrawal syndrome and excitotoxicity, but with the similarities between ethanol, benzodiazepene and G withdrawal syndromes and MoA's, it makes sense that excitotoxicity plays a role in G withdrawal. Ethanol and benzo withdrawals HAVE been shown to involve excitotoxicity. Excitotoxicity has been implicated in neuronal death experienced by chronic drinkers, plus it has been postulated the the malaise of a hangover is partly caused by excitotoxicity/minor withdrawal.
Another parallel is that acute ethanol adminisration (probably benzos too, I haven't checked) has been shown to protect against excitotoxicity, as has acute G administration.
Chronic ethanol exposure enhacing NMDA activity+increasing sensitivity to excitotoxicity (note that increased sensitivity was observed after only 2 days):
http://jpet.aspetjournals.org/content/283/3/1214.full
Glutamate excitotoxicity in ethanol withdrawal:
http://www.springerlink.com/content/p71034530wk35611/
Acute ethanol inhibits excitotoxicity:
http://onlinelibrary.wiley.com/doi/...ionid=0712B05956097CBC8F8FEC813794D5E7.d01t02
Acute G inhibits excitotoxicity:
http://www.sciencedirect.com/science/article/pii/S0006899303032529
Now I used to think (like many other people) this was due to a "dopamine rebound" effect, but this thread by df user malsat seems to show its in fact a combination of upregulated glutamate receptors causing excitotoxicity (plus in very high doses apoptosis), and down-regulated GABA-B (see his full post italicised below). There is more going on than simply this, but these two factors seem to be the main points. The former seems to be treatable with phenibut and the latter with benzodiazepines.
Now I have got some GBL here at the moment, and having had a couple of days where I've ended up re-dosing throughout the majority of the day (about 12-15ml in total) I ended up a bit of an anxious mess when it wore off. Today however I was bracing for a similar effect having dosed throughout the day the night before. Then I remembered I had some phenibut, so I took 500mg at the same time as my last dose, then another 500mg when I woke up three hours later. I have to say it worked amazingly, I have got literally no GHB hangover at all! Which has made me wonder how long this can be kept up for, and what the possible health implications of dosing with GHB in the day and using a small dose of phenibut, to block the calcium channels and reduce the glutamate production that gives you that horrible edgy feeling.
Heres his more in detail post, he does provide references to science journals to each point later in the thread, which I will post below it too for those that want to see literature:
Hi, I'm new to the forums. I'm a student of neuroscience (by no means an expert).
Just so you all know, the 'dopamine rebound' theory is incorrect. G is a physically addictive substance, in the classical sense, like heroin or cocaine.
Skip to the end if you don't want to read a lot of sciency stuff, just want help with addiction.
G binds to the GABA-B receptor in the brain. GABA is the main inhibitory neurotransmitter. It reduces neural activity, producing relaxation etc.
G use will cause downregulation of GABA-B receptors from a single use - the brain produces less and less GABA-B receptors plus upregulation of glutamate receptors (more glutamate receptors). Glutamate is the main excitatory neurotransmitter, essentially it increases neural activity. In addition there is a GHB receptor. GHB is present naturally in the brain, where it binds to GHB receptors and produces and excitatory response (increasing stimulation). When you come down from a dose of G, or stop dosing during an addiction, the combination of downregulated GABA-B plus upregulated glutamate receptors (plus the continued stimulation of GHB receptors as one comes down from a dose) produces excessive neural stimulation, hence the sudden waking effect from night-time G use.
In addiction, this produces the withdrawal effects.
'Excitotoxicity' is a condition that can be caused by large amounts of glutamate in the brain. Glutamate binds to its receptors (AMPA, NMDA and kainate) and in excess can cause a large influx of calcium ions into neurons. This calcium influx can cause a process called 'apoptosis', also known as programmed cell death. Essentially, the neurons commit suicide.
It follows from the mechanism of action of G that in withdrawal, excitotoxicity plays a role. Considering this, anyone in a G addiction should seek medical assistance if possible and request gabapentin or pregabalin, two drugs which block calcium channels and reduce glutamate production in the brain. These drugs could prevent the neurotoxicity caused by G withdrawal.
It's likely that some of the withdrawal symptoms are caused by downregulation of other neurotransmitters (acetylcholine most likely, possibly also dopamine).
THE END:
The G withdrawal sweats and high heart rate/blood pressure can be treated with clonidine (clinically). SWIM has found that the sweats can be treated with first generation antihistamines (dramamine, benadryl, also piriton somewhat) which have anticholinergic activity.They can be bought OTC.
Bad G withdrawal will produce paranoid delusions/hallucinations/psychosis, which MUST be treated by medical professionals.
Benzodiazepenes (valium, xanax etc, active at GABA-A) can help with the withdrawals, but should be tapered. If you have a supply and are using them to treat your withdrawals, be aware that you could end up addicted to them, with similar withdrawals to G.
Alcohol can also ease the withdrawals(active at GABA-B also, but doesn't ease all the symptoms, and psychosis will still develop unhindered), but it's unpleasant when you end up having to drink 30-40 units of alcohol (equivalent to 10 LITRES of beer) just to ease the anxiety, then develop a HUGE hangover in a few hours.
Supplementing with zinc and magnesium could help to prevent some of the neurotoxicity.
Taping your dose down over a period of several weeks is the best way to get off it by yourself. DO NOT STOP COLD TURKEY, PEOPLE HAVE DIED THIS WAY.
As I mentioned before, it's VERY likely that withdrawing from G addiction can cause nerve damage (most noticable as a reduction in sensation of the extremities or a tingling/burning/pins and needles sensation in the fingers/toes/face), and as such you should be getting off it under the supervision of a medical professional. Most of them have no idea when G is, much less how to treat it. Try and find some medical info on the net, print it out and show it to them. Mention excitotoxicity and ask to be treated with GABAPENTIN OR PREGABALIN in addition to clonidine and a benzodiazepene tapering program.
References:
Well, it's widely known that neurotransmitter systems will up- and down-regulate receptors in response to insufficient or excessive stimulation in order to mantain homeostasis. G is known to bind to GABA-B so downregulation here is a logical result. Inhibition of glutamate firing would be expected to produce glutamate receptor upregulation. Excessive stimulation of glutamate receptors (which would be expected in a situation in which there has been upregulation of glutamate receptors and an increase in glutamate firing) induces excitotoxicity by calcium ion saturation;
Chronic GBL producing GABA downregulation:
http://www.springerlink.com/content/mj22m213107x5043/
GHB reducing extracellular glutamate levels in millimolar concentrations via GABA-B, increasing extracellular glutamate levels in nanomolar concentrations via GHB receptor stimulation (this means that as a dose of G leaves the system, inhibitory effects via GABA-B are no longer active while there is excitation due to GHB still binding the GHB receptor):
http://www.ingentaconnect.com/content/bsc/jnc/2003/00000087/00000003/art00017
I do not believe there have been any studies done regarding the G withdrawal syndrome and excitotoxicity, but with the similarities between ethanol, benzodiazepene and G withdrawal syndromes and MoA's, it makes sense that excitotoxicity plays a role in G withdrawal. Ethanol and benzo withdrawals HAVE been shown to involve excitotoxicity. Excitotoxicity has been implicated in neuronal death experienced by chronic drinkers, plus it has been postulated the the malaise of a hangover is partly caused by excitotoxicity/minor withdrawal.
Another parallel is that acute ethanol adminisration (probably benzos too, I haven't checked) has been shown to protect against excitotoxicity, as has acute G administration.
Chronic ethanol exposure enhacing NMDA activity+increasing sensitivity to excitotoxicity (note that increased sensitivity was observed after only 2 days):
http://jpet.aspetjournals.org/content/283/3/1214.full
Glutamate excitotoxicity in ethanol withdrawal:
http://www.springerlink.com/content/p71034530wk35611/
Acute ethanol inhibits excitotoxicity:
http://onlinelibrary.wiley.com/doi/...ionid=0712B05956097CBC8F8FEC813794D5E7.d01t02
Acute G inhibits excitotoxicity:
http://www.sciencedirect.com/science/article/pii/S0006899303032529
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