Sudden loss of benzo euphoria, why? NOT tolerance.

[>Marquis<]

Apologies for the length of the post but I though perhaps the following details might be relevant to the question.

From june of last year to the current day I have been in a seesaw addiction process between alcohol, benzo's and GBL. This was due to the fact that I would become dependent on GBL and detox with benzos, only to become so euphoric and uninhibited by the benzos that I would take high doses for around 2 weeks (~100mg diazepam a day, although it began with a month long period wherein I consumed something like 300-350mg alprazolam), run out of benzos, feel okay for a week or so as the diazepam left my system and then enter withdrawals whereupon I would turn to GBL to treat the withdrawals until I could obtain more benzos (2-3 weeks).

This cycle persisted until last december at which point the benzo wd's were so intense that even high dose GBL did not alleviate the paranoia and insomnia (4-5ml would not even get me to sleep, whereas before that anything over 1ml would knock me out). At the time this happened I had though it was due to G tolerance, having been off valium for around 2 weeks. At this point I found 20mg diazepam, took 10mg (while still on the G) and found that my symptoms alleviated somewhat, and another 10mg made me feel normal. This lasted for a little over a day.

Anyway, a week or so later (having taken the odd mg of alprazolam to keep the wd's at bay) I obtained more diazepam but found that I experienced no euphoria. I'm currently off GBL and on a diazepam taper (down to 10mgs) but it still remains that no amount of diazepam makes me euphoric. Higher doses (up to 40mg) will cause cognitive dysfunction and disinhibition but no euphoria.

I was wondering if anyone could explain this, possibly in the light of my on-off GBL and diazepam usage? It's not tolerance; it was a sudden change in my response to diazepam - one day it could get me high, a week later, nothing.

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I deleted and reposted this with a clearer title in the hopes of getting an educated answer from someone.

 

[Hammilton]

You haven't been doing this long, and tolerance is the most reasonable explanation. Actually, AFAICT, the only explanation.

The longer you do this the more you'll become familiar with the drugs effects ('psychological tolerance') but you'll also become physically tolerance. Benzos produce tolerance notoriously fast and take similarly notorious length of time to return to baseline.

Because of your rotation, after <12 months you're just experiencing this now. Be careful though, because it WILL NOT be long before you lose the ability to enjoy benzos at all.

You are really going to screw your life up if you continue this.

 

[>Marquis<]

This is what's so curious about the situation.

I was already quite tolerant before this happened, as evidenced by the powerful withdrawals, and the loss of pleasurable effects was not a gradual process that occurred with use, but a sudden change that occurred while I was experiencing withdawals and on the GBL part of the cycle, so I was wondering if there was something more complex than 'tolerance' that would have caused this, possibly something to do with excitotoxicity or neural plasticity.

And as mentioned in my post I'm currently on a medically supervised diazepam taper and down to 10mg a day and feeling baseline at that, but if I do take more it doesn't matter how much I take, there is no euphoria but the other standard benzo effects are there, cognitive dysfunction, disinhibition etc. I just start to feel very fatigued. I would imagine if it was just tolerance then I would be able to feel euphoria at some point, but no.

So I'm on a taper and I'm not 'continuing this', but sadly I have already messed up a good part of my life thanks to the demon drug GBL.

 

[shibireru]

Are you using opioids?

I read a study not long ago which purported to show that the administration of mu-opioid receptor antagonists diminishes the pleasureful effects of alcohol. That's not to say that it completely blocked the effects of the alcohol, since alcohol is such a dirty drug that achieves its effects through a wide variety of mechanisms. It may be that the benzos are still able to diminish noradrenergic and adrenergic neurotransmission, producing anxiolysis and somnolence, but no longer able to increase opioidergic neurotransmission (note that opioidergic neurotransmission is something of an oxymoron, since mu-opioid receptor agonists probably achieve their effects by decreasing cAMP synthesis and thus the metabolic activity of the cell and frequency of cellular depolarization) to the point of producing noteworthy euphoria.

 

[bignbrown]

I did valium for the first time this weekend, did a bit too much (probably around 40-50mg spread over the weekend), and i forgot about its long half life and you dont need to top up etc, but then i hear about the tolerance, would this mean if i had 15-20mg of valium this saturday with a beer or two, would it not effect me as much? Or does it take longer for the tolerance to kick in?

 

[>Marquis<]

Are you using opioids?

I read a study not long ago which purported to show that the administration of mu-opioid receptor antagonists diminishes the pleasureful effects of alcohol. That's not to say that it completely blocked the effects of the alcohol, since alcohol is such a dirty drug that achieves its effects through a wide variety of mechanisms. It may be that the benzos are still able to diminish noradrenergic and adrenergic neurotransmission, producing anxiolysis and somnolence, but no longer able to increase opioidergic neurotransmission (note that opioidergic neurotransmission is something of an oxymoron, since mu-opioid receptor agonists probably achieve their effects by decreasing cAMP synthesis and thus the metabolic activity of the cell and frequency of cellular depolarization) to the point of producing noteworthy euphoria.

It's quite interesting that you mention opiods. Before I learned of G I went through an opiod phase and spent several months using potent ones; oxy, insnufflated hydromorphone and oral and IV morphine. A wonderful time. This was only for a month or two. A year followed before I began using G, and in that time I had completely lost the ability to enjoy codeine. It wasn't tolerance, I don't believe it was a psychological 'this just isn't as good' effect, it just didn't produce euphoria or any pleasure at all.

During my initial G addiction (October 2007 - January 2008, several months before I entered my heavy GABA agonist addiction in the OP) I began using poppy tea and enjoyed it for several months after I quit the G. Since then I've used codeine often and it produces the same euphoria it did before my experience with potent opiods. I don't know if this could be related to my GABA agonist abuse, but there you go.

 

[>Marquis<]

I have an update on this as well.

A week or so ago I came across some levetiracetam (Keppra, an anticonvulsant) and decided to see if it would help with my diazepam taper. (500mg 2X daily) It did help to attenuate the emotional WD effects somewhat.

The interesting thing, however, is this: I stayed awake all night at one point and took codeine in the late morning. I had an anxiety attack (unrelated to the benzo WD's) and took 10mg diazepam (the codeine had nearly worn off at this point). Shockingly, that wonderful sense of peace and happiness that is benzo euphoria returned, just as it would have been had I taken 10mg diazepam back in October. I took another 500mg keppra and another 10mg diazepam and drifted through the afternoon in total bliss.

A few days ago I attempted to try this again (having been off the keppra for several days) although I had a full night's sleep and no codeine. 500mg keppra followed an hour or so later with 10mg diazepam. There was the slightest alert of benzo euphoria so I took another 5mg diazepam, but it never took off past the point of the alert.

I'd love to understand the biochemistry or psychology of what happened that day that brought my lovely D euphoria back. D and codeine doesn't do it, keppra and D doesn't quite do it and D, codeine and sleep deprivation doesn't do it, but somehow the combination of all four brought it back.

 

[sunyata]

set and setting also play a role in drug euphoria, Hammillton.

 

[Heisenberg]

Try Lyrica.
You'll get the GABA buzz back.

Rest GABA drugs for a year and they'll effect you again

 

[permastoned]

Lyrica is good.

What you don't realise OP is that you can get tolerance to some effects of a drug, e.g. euphoria, which is usually the effect most sensitive to tolerance, whilst still retaining the other effects of the drug. Therefore it is still tolerance.

 

[LabRatNW]

Your body can get used to the cycling of drugs if you do it on a regular enough basis. Whats the time span of a cycle for you? Days? weeks? months?

 

[Heuristic]

Just to put forward an alternative hypothesis:

Your euphoria is really the sudden release of tension and anxiety. As you use benzos regularly, you become accustomed the lack of such tension and anxiety, and so the change in state seems less dramatic.

I'm sure you already know this, but I have to add:

Cycling through abusive use of these drugs will only exacerbate your anxiety problem. You're essentially putting yourself on a drug-controlled roller-coaster, and I'm sure it's becoming quite difficult to discern the difference between anxiety caused by a sudden absence of certain drugs in your system, your baseline anxiety levels, and anxiety caused by actual events in the world which is a signal for you to pay closer attention and take action.

 

[>Marquis<]

Lyrica is good.

What you don't realise OP is that you can get tolerance to some effects of a drug, e.g. euphoria, which is usually the effect most sensitive to tolerance, whilst still retaining the other effects of the drug. Therefore it is still tolerance.

I'm not inclined to believe that. I was under the impression that tolerance developed gradually. In this case I went from euphoria to absence of euphoria in the space of about a week in which I didn't take any valium. Just like that, total loss of the effect. It was so sudden that I initially thought that the batch of tabs I'd just bought were duds.

 

[>Marquis<]

Your body can get used to the cycling of drugs if you do it on a regular enough basis. Whats the time span of a cycle for you? Days? weeks? months?

Back when I was doing it I'd spend about two weeks on GBL, another two weeks on valium, a further week in which the valium left my system and then back onto GBL as the benzo WD's kicked in.

 

[>Marquis<]

Just to put forward an alternative hypothesis:

Your euphoria is really the sudden release of tension and anxiety. As you use benzos regularly, you become accustomed the lack of such tension and anxiety, and so the change in state seems less dramatic.

I'm sure you already know this, but I have to add:

Cycling through abusive use of these drugs will only exacerbate your anxiety problem. You're essentially putting yourself on a drug-controlled roller-coaster, and I'm sure it's becoming quite difficult to discern the difference between anxiety caused by a sudden absence of certain drugs in your system, your baseline anxiety levels, and anxiety caused by actual events in the world which is a signal for you to pay closer attention and take action.

Luckily I'm off the rollercoaster now! I've tapered down to around 2.5mg diazepam a day and will be off it for good in the next week or so :D

Just as a side note that some may find interesting, less than a week ago I began using 0.5-2.5g sodium bromide a day. Some would consider this unwise but desperate times call for desperate measures, and I figured the long half life of bromide would make it very effective if it was successful in aiding my withdrawal. I'm glad to say that the bromide has completely attenuated the emotional WD symptoms of the taper, namely irritability and also insomnia. I've experienced no side effects whatsoever and will discontinue the bromide once I'm finished the diazepam.

 

[robatussin]

lol this guy knows it is his tolerance/cross tolerence but doesn't wanna admit it

 

[>Marquis<]

Yes, you sure hit the nail on the head there robatussin. Thanks for finally convincing me.

Despite the fact that I've been physically dependent on alcohol, alprazolam, diazepam, GBL, hydromorphone, morphine, poppy tea and codeine and despite the fact that I've experienced a gradual loss of euphoria with continued and chronic use of all of these except diazepam I'm unwilling to admit to myself that this exceptional, sudden loss of euphoria is due to tolerance. Oh, what a fool I am for having some curiosity about the mechanism for this unusual development.

 

[>Marquis<]

To give an example of the kind of idea I was looking for - I reccently came across the textbook "Gamma-hydroxybutyrate: Molecular, Functional, and Clinical aspects" which discusses in some detail the biochemistry associated with GHB-induced absence seizures. In this chapter he makes reference to data that "suggest that GHB-induced absence seizures may result in a significant alteration of the alpha4 subunit of the GABA-A R", namely a decrease in alpha4 mRNA in the thalamus.

Although this particular fact is effectively irrelevant to why I suddenly lost effects of diazepam, it provides a framework from which to develop a concept that would explain what happened without reference to the all too simplified idea that it was 'just tolerance' developing.

When this phenomenon occured I was suffering from benzo withdrawals and so was taking relatively large GBL doses in an attempt to stabilise myself; once 1ml had been a recreational dose but now the benzo WD's were so severe that 3ml would not even induce sleep easily (without a GBL tolerance).

Now admittedly I would have been developing a gradual tolerance for the benzo's, hence the WD's, however I do believe that the exceptionally high doses of GBL combined with the diazepam WD's could have created an environment that was able to rapidly alter the extent to which diazepam-friendly BZR subunits were expressed in my brain, thus leading to the sudden, rather than gradual, loss of effects at that time.

 

[cnspiracy314]

Brilliant: Right on the Head.

Just to put forward an alternative hypothesis:

Your euphoria is really the sudden release of tension and anxiety. As you use benzos regularly, you become accustomed the lack of such tension and anxiety, and so the change in state seems less dramatic.

I'm sure you already know this, but I have to add:

Cycling through abusive use of these drugs will only exacerbate your anxiety problem. You're essentially putting yourself on a drug-controlled roller-coaster, and I'm sure it's becoming quite difficult to discern the difference between anxiety caused by a sudden absence of certain drugs in your system, your baseline anxiety levels, and anxiety caused by actual events in the world which is a signal for you to pay closer attention and take action.

I am going to have to agree with every last bit of this. I've only dabbled in opiates and benzos as well as other hard drugs. However, weed, alchohol and I have been pretty good friends for the last ten years (weed by far being the more important of the two). Euphoria is very psychological in nature and I believe is often associated with 'peaks' in any drug experience (despair in valleys and neutral at inflection points). Ever heard the phrase, 'chasing the dragon'? Peaks become increasingly difficult to obtain, especially if you have little to nothing to really feel good about. Have you ever noticed when you were at a peak and realized you had used up your stash, suddenly your in a valley, sometimes without a neutral inbetween?

In other words, you can't simply describe your loss of EUPHORIA!!! in terms of chemicals. Wake up and realize you're chasing the Dragon.

Suggestion from a Hypocrite: Find EUPHOria in accomplishment and use this to 'maintain'. Its a whole lot more rewarding in the sense that accomplishments (other than scoring a bag) lead to a long term sense of self worth (self worth=1000 x simulated euphoria) as well as dollars.

 

[cnspiracy314]

To give an example of the kind of idea I was looking for - I reccently came across the textbook "Gamma-hydroxybutyrate: Molecular, Functional, and Clinical aspects" which discusses in some detail the biochemistry associated with GHB-induced absence seizures. In this chapter he makes reference to data that "suggest that GHB-induced absence seizures may result in a significant alteration of the alpha4 subunit of the GABA-A R", namely a decrease in alpha4 mRNA in the thalamus.

Although this particular fact is effectively irrelevant to why I suddenly lost effects of diazepam, it provides a framework from which to develop a concept that would explain what happened without reference to the all too simplified idea that it was 'just tolerance' developing.

When this phenomenon occured I was suffering from benzo withdrawals and so was taking relatively large GBL doses in an attempt to stabilise myself; once 1ml had been a recreational dose but now the benzo WD's were so severe that 3ml would not even induce sleep easily (without a GBL tolerance).

Now admittedly I would have been developing a gradual tolerance for the benzo's, hence the WD's, however I do believe that the exceptionally high doses of GBL combined with the diazepam WD's could have created an environment that was able to rapidly alter the extent to which diazepam-friendly BZR subunits were expressed in my brain, thus leading to the sudden, rather than gradual, loss of effects at that time.

I guess the unanswered questions here is, "Does chemistry dictate psychology, does psychology dictate chemistry, or is it some unfathomable combination of the two that is vastly complicated with the introduction of ludicrous amounts of distinct psychoactive substances?"

I tend to think its the third. The human brain will always refuse to be painted black and white!