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In what order does Benzodiazepine withdrawal develop? desensitization/internalisation

M

Memantine

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May 16, 2015
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I am on 60mg Temazepam per week at the moment. I have noticed that over the last two months the effect of my dosage slightly decreased which makes me think that I have developed mild tolerance.

However, when I am completely sober I do not get any withdrawal effects at all. My (sober) sleep has not gotten any worse since I started with Temazepam and the same goes for my average anxiety level.

Therefore I wonder what is the cause of my tolerance. Is it just desensitization to the Benzodiazepine receptor binding site at this stage?

Does the GABA-A receptor internalisation and Glutamate receptor upregulation only develop in more severe cases of Benzodiazepine tolerance leading to a withdrawal syndrome?
 
To keep it simple, it seems that you have developed some tolerance. But no physical dependence. I suggest you keep it that way :)

I´ll leave the neuroscience to someone else.
 
The kindling effect (I think there is a good wiki page on kindling) is very important regarding benzo withdrawal. The idea is essentially when you withdraw repeatedly (even extremely minor withdrawals) that eventually the glutamate rebound gets stronger and stronger, so something that has come out of the kindling effect research (if I recall correctly) is that sporadic use is actually worse than constant use because with constant use there is no chance for real glutamate rebound.

With long term benzo use altered GABA receptors might be playing a role in tolerance (my textbook by prestigious authors says this, I have yet to find a source though), but the receptors should remain sensitive to endogenous GABA. So it's possible to gain tolerance specifically to benzos without necessarily tolerance to endogenous GABA.

Careful with benzos long term. Kindling is probably something that you really want to avoid.
 
When does this kindling effect start, is it in relation to the severity of tolerance and withdrawal or will every single use of a benzo worsen things even with no history of GABA withdrawal, eventually leading to permanent disequilibrium or such?

seemingly occurs with opioids and even serotonergics, withdrawals getting worse with each incidence and more or less independent of how much or how long the recent usage has been. Do not know about stims/dopaminergics but maybe this applies generally to all xenobiotical psychoactives?

Do you know about the mechanisms behind kindling? Any possibility to reverse this, as time doesn't seem to help?
 
I would bet that you would see kindling every single withdrawal but at first it would not be noticeable. But it would be proportional to the withdrawal severity. If you stayed on benzos consistently and plasma levels didn't fluctuate I imagine kindling would be minimal.

I imagine that long term potentiation is the driving force behind the glutamate strengthening. The brain is akin to a muscle in the "use it or lose it" sense, the glutamate that sees a lot of use gets very strong.

I would postulate that many people who have long term problems from chronic benzo abuse really have a glutamate excess problem rather than a GABA deficiency problem.
 
That is a scary theory :(

Do you think I will fuck my brain with 60mg Temazepam once a week? And no other GABAergic substances?

I really like it because it allows me to be worry free and sociable for atleast one time a week :/
 
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