Addiction - IMPORTANT: GHB/GBL Addiction & Withdrawal

[malsat]

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.

SWIM is educated and has personal experience with this.

Reputation Comments on this post:

	useful & informative. welcome!
	baller
	Nice post
	Good info on harm reduction!
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	Great posts, thanks for sharing your knowledge and for responding further with links and answers to other questions. You...
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[malsat]

I should also mention that prolonged use of GBL can produce a condition known as metabolic acidosis http://en.wikipedia.org/wiki/Metabolic_acidosis

This is best treated by a medical professional, but possibly taking a few teaspoons of sodium bicarbonate (baking soda) or an electrolyte solution (used to treat diahhoea) every day could help.

G has apparantly been shown to deplete B vitamins, so you should supplement these if using or addicted to G.

[MrG]

Hi malsat and welcome to the forum.

I am always interested to hear new information related to GHB and GBL however, whilst your post may contain valid facts, we tend to operate a "show me the money" policy around here in that anybody who is proposing a theory behind issues associated with a substance need to back it up with verifiable proof.

Can you provide links to research papers that support your post?

This is not to say that we call bs on every new post, but it is important to understand that we can only move forward in developing a greater understanding of the topic in question if we can trust the reliability of the information being offered.

There have been a number of posts concerning what exactly the mechanism behind the "rebound" is and, certainly, the idea of it actually being a type of withdrawal has been put forward but we have yet to find published papers supporting this.

Plus your post about bad G withdrawals does not differentiate between GHB and GBL, something that we know to be a factor in terms of the extent of withdrawal complications.

[malsat]

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/conten...00003/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/cgi/co...ull/283/3/1214

Glutamate excitotoxicity in ethanol withdrawal:
http://www.springerlink.com/content/p71034530wk35611/

Acute ethanol inhibits excitotoxicity:
http://www.blackwell-synergy.com/doi...urnalCode=acer

Acute G inhibits excitotoxicity:
http://www.sciencedirect.com/science...57f27a8e7f49a6

Reputation Comments on this post:

You really know your stuff... keep up the good, informative posts!

[MrG]

Originally Posted by malsat

Acute G inhibits excitotoxicity:

Thanks for the references, much needed.

In that G use inhibits excitotoxicity but it's cessation induces excitotoxicity (is that right?) what is the situation with regards to non-chronic G use (e.g. pharmacological use as opposed to 24/7 dosing).

I find it hard to believe that a substance which can be used 365 days a year (night time only) by narcoleptic patients suffering from cataplexy can be quit with no withdrawal or addiction issues of note yet, if I am to understand you correctly, you are stating that in this instance as well there is an issue regarding excitotoxicity.

Is that what you are saying?

Reputation Comments on this post:

Rep for consistant good posting BUT loved this. Let's fight for the truth NOT US 'Druggy' bullsheeet.

[malsat]

With regard to a pattern of daily single or double doses, to be honest, I'm uncertain as to whether excitotoxicity is something to be concerned about. I'm taking it as a given that there is some degree of GABA-B downregulation and glutamate upregulation following a single dose, but as to whether or not that's significant enough to induce excitotoxicity I honestly don't know, and even if we were to assume that there was some neurotoxicity from this pattern of use, no doubt it would take many years before it was manifested in peripheral neuropathy, cognitive deficits or more serious neurodegenerative disorders like Parkinson's/Alzheimers. It's been speculated that these diseases may be caused by chronic mild excitotoxicity from one cause or another.

Even heavy drinkers take years to develop symptoms of neurological damage. I don't know if this part of society is more heavily affected by Parkinsons etc. than the rest of society.

When I'm in a position to do so, I'd like to conduct some research into this issue and determine if single or double doses do increase suseptibility to excitotoxicity, or maybe an epidemiological study of long term prescribed oxybate users and moderate recreational users to see if they have any problems.

Personally I'm more concerned about the damage done when people try to withdraw from heavy G addictions. I have heard from SWIM that the withdrawal syndrome feels extremely toxic (well, I guess one could hardly expect it to feel as if it's enhacing one's vitality) and that symtoms of peripheral neuropathy (nerve damage in the extremeties) do develop - a tingling/burning/pins and needles sensation in the fingers is what SWIM experienced, in addition to reduced sensation (although SWIM already has some reduced sensation as a result of other issues). According to SWIM, the tingling subsided with time, but sensation does not appear to be fully normal.

Reputation Comments on this post:

v. valuable information on G withdrawal, thank you very much

[braggy]

Originally Posted by malsat

. According to SWIM, the tingling subsided with time, but sensation does not appear to be fully normal.

Any idea how long? Swim, of all places, has been at work this whole week, and his constant scratching and rubbing may look a little strange

[braggy]

Can anybody at all shed some light onto what they would recommend for the daily intake of these vitamins/minerals as talked about above?

Swim's read alot of people saying that there is a massive drain of B vits when on G and would love to know if more people have any information on this.

Swim went cold turkey on Monday off a 4-5 month 24/7 cylce and it really punished him. But looking and feeling alot better come Friday.

Swim though would love to stock up on all those goodies to get him feeling better again, as without access to benzos and the like, its a bit of a struggle with the mind but he's getting there.

Ive heard people talk about Vitamin B Complex, Zinc and Magnesium

Is there anything else thats good? Swim is already taking vit c..

Swim isnt a totally numpty and can follow a basic RDI guide but is there any benefit in taking over this amount to compensate for what may have been lost or will this do more harm than good?

Cheers

[malsat]

Must apologise for the mess of the above post; I'm quite sleep deprived.

Hopefully the references provided are sufficient to satisfy your desire for proof of GABA-B activity and excitotoxicity, and I believe the second reference is enough to establish that the sudden waking syndrome is not merely a consequence of 'stored dopamine release'; here we have a tapestry of different processes respoinsible for this stimulation: GABA-B downregulation, glutamate upregulation, increased glutamate firing as a result of GHB receptor stimulation as the concentration of G declines. Partly a direct effect of the drug, partly mild withdrawal symptom as the drug leaves the body.

Again, apologies for the mess, hopefully tomorrow I'll be more clear headed and can provide references for anything else you're doubtful of.

Reputation Comments on this post:

excellent work

[malsat]

Taking an 'ultra b-vitamin' complex couldn't hurt in the short term (for a week or two as you're withdrawing). B Vitamins are water soluble so even in high doses the excess will just pass out through your body. Vitamin B6 can be neurotoxic in high doses (over 200mg for a period of months). Best to supplement while you're addicted and in WD's, and it can't hurt to supplement at RDA levels when you're clean too!

The zinc and magnesium supplementation is really just to prevent deficiency during withdrawals. If you were deficient in either of these during WD's the neurotoxicity could be worse. I'd say supplement 2-3 the RDA - that's what SWIM did during his own withdrawals. There's no health risk at these levels, but taking 2-3 times the RDA of magnesium might give you loose bowels so reduce dosage if this happens.

Taking antioxidant supplements could help too as oxidative damage plays a role in excitotoxicity. Vitamin C is good but you should take A and E too as they all work together. The best way to get antioxidants is fruit and veg though.

That should help prevent damage during the WD's. Once you're clean try and excercise and eat plenty of fruit+veg. SWIM found the first couple weeks after getting clean ain't much fun unfortunately But things get back to normal in time. Good luck!

[braggy]

Originally Posted by malsat

That should help prevent damage during the WD's. Once you're clean try and excercise and eat plenty of fruit+veg. SWIM found the first couple weeks after getting clean ain't much fun unfortunately But things get back to normal in time. Good luck!

Thanks for that, words I needed to hear

Your advice has been fantastic. thankyou very much.

[lesbos]

VERY nice work Malsat. I'm sure that will help many, either by helping them manage withdrawal, or preventing users slipping into 24/7 in the first place.

If only it were made a 'Sticky'...

@braggy- i'm not certain but any of the antihistamines mentioned in Malsat's first post should help with the itching. Non-drowsy antihistamines may help but without the added benefits.

[English_T]

Personally, swim used ghb for 4 months daily at quite large doses felt fine and when stopped didn't have any problems at all but that's me. I know there's a hell of a lot of US 'research' out there which is funded by persons involved/in support of the 'drug war' and whose research is so biased that it is worthless. Just look at Global warming - you get two sets of results provided one supporting the fact that global warming is happening another which doesn't, all depends who is behind the research - Greenpeace or Industry. However, there are some nice bits of info that are produced on behalf of Pharmaceutical Companies and their medicines, which all have to go through years of thorough independent testing before being released, Xyrem being one of those. The higher doses in this 'review' by the National Health Service are much higher than a recreational dose:

[Lehendakari]

Good Harm reduction info. Most reports I've read of GHB withdrawal involve 24/7 use and there are some horrible stories out there. GHB has short half life so I guess ocassional use don't make much down-up regulation of any receptor even if used daily.

Benzos wouldn't work much for w/ as they bind GABA-A if I'm not mistaken, But SWIM likes to dose a bit of a benzo after GHB wears off as he sees it supresses that "wired" effect GHB has once in the comedown.

Mixing such powerful downers as GHB and benzos is not a good idea but SWIM finds this combo perfect. SWIM has PENTY of experience with both drugs.

He also observed benzos and GHB don't have cross-tolerance with each other.

[Whit]

Just like to thank you for taking your time to post your input on this

Dedicated!

[xsyn]

What kind of cycles are we looking at for withdrawal? SWIM has often used 24/2 then break 24/2 and cycled like that. On some occasions it's been 24/7 break 24/2. SWIM is Currently on a 24/1 break, with a 8/1 break prior to that, and looking to shortly grab a dose to get 4 hours good sleep downtime.

Suggestions?

[braggy]

..Also like to say a big thanks to everyone who has been posting in this forum. I'm now a few weeks off 24/7 gbl dosing and feel fantastic. That sh*t is evil and all I have to say is listen to the advice of the peeps here and convert to ghb or stay clear if you just cant help yourself like me.

big props to everyone. thanks.

braggy

[Zaprenz]

Good write up Malsat

Do you have any information on pregabalin being used clinically for GHB withdrawal? SWIM has read some bits on using gabapentin but wasn't aware they had tested pregabalin clinically yet?


Also SWIM would agree with downregulation of GABA(b) receptors & other GABAergic systems being one of the key components of GHB addiction/withdrawal (which would lead to increased glutaminergic transmission) and agree's the addiction is not just pyschological. (and in fact v.serious)

However SWIM doesn't think it is as simple to remove dopamine from the equation in withdrawals(or use). GABA/Glutamate systems are heavily associated (via downstream or more complicated mechanisms) with dopamine in specific parts of the brain. So even if one can isolate the decreased inhibitory GABAergic transmission or increased glutamate transmission (which may well have excitotoxic properties) - that in itself is going to likely alter dopamine levels considerably (in quite different ways depending on area of brain).

There seems to be a lot of dispute in the literature on the precise involvement of dopamine and the precise mechanism of GHB tolerance/withdrawal (how much is attributed to downregulation of GABA receptors). As well as differences in GBL tolerance/withdrawal but SWIM would still predict dopamine plays a key role in the withdrawal syndrome (whether via downstream effects, hypodopaminergic tolerance or some other complicated mechanism). This might not be the SOLE reason for G addiction/tolerance & withdrawal but SWIM would still predict it plays an important part in some aspects of G withdrawal.


Regardless of the precise mechanism though, tolerance & addiction most certainly occurs and can be very serious and the above is good advice. SWIM would definately agree that anyone going through serious withdrawal should not be afraid to seek proper medical advice. Even if they don't know entirely how to treat withdrawal (and prevent excitotoxicity) they are good at keeping people alive.

[xsyn]

Well just so you guys know, I took a 2 day knock. With use of GABA, 5-htp, melatonin, valerian root and gabatropin to sleep it wasn't too harsh. I've had much worse, and now have been completely G free for 5 days. Sleeping lightly, and sleeping well. Body still responds sketchily to stimulants, and occasionally tingles. All in all, everything seems cool.

[English_T]

Man, there's sooooooo much bullshit about GHB it's insane - SWIM never had ANY withdrawl whatsoever, no a twitch after months of twice daily use. SWIM HAS also been a h addict in the past and suffered 'proper withdrawl' many, many times.

I am going to try and dig into this subject to see how all this crap came about, I suspect, it's part of the US Drug War propaganda but who knows - it seems some people believe they suffer withdrawl or is that placebo type effect?

This from a guy who took for two years:

As for GHB/Xyrem being addictive, it is definitely NOT addictive when taken as prescribed by a sleep specialist. I was a participant in one of the clinical trials a few years ago. After almost two years on Xyrem, the doctor had me stop “cold turkey;” and there were no cravings or withdrawal symptoms whatsoever. As for GHB users passing out and dying, this again is from abusing GHB. If someone takes as much GHB as they desire for a good “high;” then of course they're flirting with death. Here's some more food for thought. Ask any doctor who is a “SLEEP SPECIALIST;” and he or she will likely tell you what a godsend this drug is for narcoleptics. But ask any other doctor about GHB and they'll probably freak out and agree with everything on your website. Sleep specialists are far more knowledgeable about GHB than other doctors. They not only know its potential pitfalls but also know about its medicinal benefits for narcoleptics. But thank you for at least addressing the medical use of GHB for narcoleptics. I was glad to see that you did.

It may be that in totally high doses, at daily, regular, hourly intervals may cause addiction of some sort BUT i'd really like to see some proper evidence on this rather than biased info or bits and pieces from 'someone I once knew'.

Personal experience is good and would make very interesting reading, as would non-biased professional research.

AND let us NOT be confused by the term 'date-rape-drug' which is bandied around and which commonly referred to ROHYPNOL and NOT GHB. Rohypnol is tasteless and could be effective as a heavy sedative (as would valium), GHB is very salty and a dose that would be enough to spike a drink would be horribly salty and definitely noticed unless that person was totally f'cked anyway...

[Pondlife]

SWIM's experiences support what English_T is saying. He has used GHB (and some GBL as well) in moderate doses (2 or 3 grams of GHB in an evening) on many occasions. He has never had any problems on the GHB, nor has he ever experienced withdrawal symptoms.

He's also passed the "take it or leave it" test many times - typically due to a change of plan which involves driving or drinking alcohol. He has never even been tempted to stay at home with the G rather than go to the pub/party or drive to an event. He's got a small supply of G which sometimes goes untouched for weeks. How often would that happen with cigs, heroin or cocaine?

He's never felt shitty the next day. In that respect, he finds it similar to light alcohol use, and much better than a night on the ale. He's never dosed 24/7 though. As many people have said, this seems to be the main thing to avoid with G.

[Alfa]

Are you saying that GBL and GHB are the same when it comes to withdrawals? You post does not distinguish between the two.

[Zaprenz]

English_T the evidence SWIY is giving is for GHB (As the salt).

A considerable number of people are dosing GBL rather than GHB. The pharmacokinetics & pharmacodynamics are not equivalent so any evidence for Xyrem simply doesn't apply [as much as people would like them to be equivalent]. Also Xyrem is given in a clinical setting where dosing is forcefully restricted to a limited amount prescribed in one go by a doctor, it was also a big struggle getting it approved so they are not going to let serious addiction (where patients continue increasing the dose) occur.

i'd really like to see some proper evidence on this rather than biased info or bits and pieces from 'someone I once knew'.

So what SWIY is saying is instead everyone should assume safety and expect not to have any withdrawal symptoms from SWIYs following anecdotal statement:

I never had ANY withdrawl whatsoever, no a twitch after months of twice daily use. I have also been a heroin addict and suffered 'proper withdrawl' many, many times.

SWIM would welcome further non-biased scientific information on addiction/withdrawal also but expecting everyone to go by that one anecdotal experience yet complaining about unbiased "bits and pieces" is just hypocritical.

Also note twice daily use of GHB (the salt) is most definately not equivalent to 24/7 dosing of GBL (I.e 2/4ml per hour all day for months which is what many users have reported & experienced)

SWIM does agree the government is yet again to blame for demonising the drug (and possibly confusing or creating mistrust in the science) as well as GBL(in replacement of GHB) further confusing the topic but one should not then go on to conclude that serious addiction and withdrawal is not possible.

[Pondlife]

Originally Posted by Alfa

Are you saying that GBL and GHB are the same when it comes to withdrawals? You post does not distinguish between the two.

To clarify, almost all of this was with GHB as the sodium salt. However, a few times GBL was used when he hadn't got around to performing the conversion.

There were no noticeable withdrawal or hangover-like effects with either, although he has far more data points with sodium GHB.

[MrG]

SWIM can report the same as far as GHB is concerned. There is absolutely no withdrawal or fiending and, like above, many many times the "take it or leave it test" passes with flying colours.

In fact, in response to Malsat's original post, SWIM stopped using GHB during the week while he did some more research on it's safety without *any* issues whatsoever.

He tells me though that, as is sometimes the case when GHB users haven't had time to make up a batch, following a night on stimulants where he has dosed over a period of 10+hours with GBL, he has felt a little rough the next day, something that does not happen with GHB.

As I have said many times before, the problems come with 24/7 dosing and to get into this state a user would need to consciously allow themselves to dose continuously. It would appear that a number of victims of 24/7 dosing stem from those who use it to control anxiety and panic-attacks and therefore are more likely to find themselves redosing, but this is not the GHB compelling them to do so, this is the fear of their anxiety and panic-attacks that pushes them.