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Causes of rapidly increasing/rigid benzo tolerance at a neurological level

Tranced

Bluelight Crew
Joined
Mar 25, 2003
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Background:
2008: I used to take alprazolam recreationally at parties. I'd take 2mg bars in the same way my friends would take MDMA pills, because I get an atypical reaction to alprazolam - in that it fills me with energy and excitement, and I don't feel groggy or tired. Anyway, I lost my job (credit crunch) and started taking them daily for a week or so at a time, and had a couple of seizures because I didn't know about withdrawal and couldn't pinpoint what was going on.

2014: I was very depressed and my ex-girlfriend had just broke up with me. Etizolam was legal, cheap and widely available in the UK and I started using it with a friend of mine on a very regular basis over the course of 3-4 months. Because alprazolam/etizolam (and other benzos) don't make me tired, and I'm generally pretty sensible, I can take excessive amounts without knocking myself out or ending up in jail/having pissed off all my family and friends/etc. I was concerned about addiction so managed to do some quick tapers and avoid seizures, discontinuing use three days after NYE of that year; and by that point my benzo tolerance had noticeably increased.

To give an example of my tolerance by this point, it would increase exponentially, no matter the benzo. I could buy a strip of 14x 10mg (legit NHS) diazepam and I would need say 40mg to have any kind of effect. If I was to redose within say 24-48 hours, I would need to double up and take 80mg. Any less would quite simply not do anything, even when the initial effects had long worn off. If I wanted to redose again, I would be getting into silly amounts (and often did). By the end of the strip the doses were completely inactive. It would take between 48-72 hours for my tolerance to reduce by roughly half.

March last year (2016) : .. and etizolam was being made illegal in the UK. Vendors were desperate to get rid of their Etizolam stocks, and I'd been buying the odd few strips of tablets with my friend over the past few weeks. It was a few days before the ban and my friend had started buying grams of powder and diluting with PG. He recommended that we take advantage of a sale in which we would could buy 4 grams at 50% discount, and get another two free. We would have a lifetime supply! :\ So next thing you know, we have 3000mg of Etizolam each, i.e 3000 doses.

Well I'm sure you can all imagine exactly what happened. My use went through the window, as did my tolerance. I am not dicksizing, and I can't think of much worse to brag about than the extent of your benzo powder habit. My tolerance increased exponentially and reached seriously ridiculous amounts. I won't get into details, but just think of a likely, high number and stick another 0 on the end. At this point I had switched to alprazolam powder because I had made my way through the initial three grams in a matter of weeks, bought more, and then found alprazolam powder easier and cheaper to acquire.

At my peak dose I started getting brain zaps whilst on benzos (!?). Obviously this is very dangerous territory, and let it serve as a warning to others. That dose felt toxic, and benzo brain zaps = seizures. This should clearly not ordinarily happen whilst you're actively on them! Yes, I was very foolish, and this is the serious danger of RC benzo powders - so avoid at all costs! Just to clarify, 1-2mg of these powders (measured accurately in PG or ethanol) would have my friends fighting to stay awake, so they were definitely relatively pure.

After that peak dose I realised I needed to rapidly taper down, so I did so - by waiting 48-72 hours and reducing my dose by a small amount. This whole episode lasted a few months and involved many seizures. After a long diazepam from an NHS doctor I actually came out of things feeling better than when I started taking (less depression/anxiety).

I don't think I need to echo how dangerous this all was, and the damage it could have done to my health. I don't desire scorn or a stern telling off; what I want to know is the likely reason for a strange neurological quirk.

The Strange Neurological quirk:

Every now and then I still take a benzo, but I'll just buy a few at a time, and I don't encounter problems. However, I've noticed a very strange thing, and I'd like to know if anybody could give me the pharmacological/neurological reason for what is happening.

If I take a benzo, say 20mg diazepam, then the effect might only last for about 1-2 hours max. Once it lasted for 40 minutes[/] before I was suddenly back to baseline (this was when I was still tapering, although on very low amounts so may have been a factor.

However, if I take say 20mg and feel I need a bit more 30 minutes later, I quite simply can not redose unless I take a very high amount (double and then some). You would expect that if I take 20mg diazepam, then take another 20-40mg 30 minutes later, then I would feel the effects of 40-60mg. But I don't, I just never feel the redose and this simply adds to my tolerance. And sometimes it wears straight off. As noted earlier, my tolerance will reduce by roughly half every 48-72 hours.

Clearly my tolerance sort of instantly accrues back to at least over double, but I'm just interested to know if there is a known medical explanation for this? Wat is going on at a neurological level, and what has happened inside my brain?

Apologies for the long read, and hopefully this fits for the forum guidelines. If anybody can add any insight, I'm just interested to learn more. Cheers!
 
Hey there Tranced,

First I'd like to say that supposedly researchers have done EEGs on people while they are having "brain zaps" (I'm assuming this was in the context of SSRI withdrawal) and supposedly there was no evidence of epileptiform activity, their brain waves showed no signs of epilepsy. What we do know is that the brain zaps appear to be a phenomenon of the peripheral cranial nerves, rather than a phenomenon of the brain itself. This is why they tend to occur with eye/head/neck movements.

However, I'm sure that GABA drugs add a different slant to this, and in that context I would caution others to be concerned of an impending seizure if they experience brain zaps on benzos/during benzo withdrawal.


As for the rapid tolerance, GABA receptors can undergo various changes in response to stimulation by drugs like benzos. Phosphorylation of GABA receptors (a phosphoryl group coupling onto the receptor, typically decreasing the strength of the receptor) can occur pretty fast and reduce the efficacy of the benzo, its possible that plays a big role in this rapid tolerance. The GABA receptors could then be dephosphorylated over the next 48-72 hours.

As far as the chronic tolerance goes, there are also various compensations downstream of the cell that the GABA receptor is on, an upregulation of the downstream activity that the benzo normally inhibits, if you will. I can explain this better if need be. There are also long term changes in the GABA receptors that appear to play a role in long term tolerance. The GABA receptor is made up of different components/subunits, and altered subunit composition plays some role in long term benzo tolerance.

Any questions are welcome,
CY
 
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