How much time will it take for serotonin, GABAB receptors to up/reregulate/reset ?

[Kdem]

In my case, clonazepam taken daily for years.

Let's not start an argument about this, but is known and there is evidence that this drug has an important secondary effect on GABAB and serotonin. I could provide references.

Is anything known about how much time it takes for these receptors to 'reset' (upregulate, downregulate, whatever) back to normal after discontinuation of the drug ?

 

[sekio]

No, there's too many variables to consider, genetics and environment for instance.

 

[Erikmen]

It´s been more than 4 months without methadone or any other opiates and I still feel short of endorphin.
Exercises were making me feel better but now it´s only okay.
Maybe never.

 

[AlphaMethylPhenyl]

I've been off of Focalin for four and half months. I still am sleeping and eating all the time and am depressed. It's gotten better though.

 

[dopamimetic]

The same for SSRIs (venlafaxine being very nasty, but was also much longer on it than on the others I´ve tried) / serotonin. Probably this caused lasting changes to the transporters and/or genetics as I get these infamous brain zaps now associated with anxious, tensed mood and fatigue / restlessness combined after taking anything with SSRI properties for just 2-3 days, sometimes even dosing once is enough... and some years ago I had no problem to use DXM at <150mg daily for (too) long times without anything remarkable. Now it´s a hell of electroshocks through my brain and bed-locking tiredness together with anger at everyone and everything alternating with anxiety and restlessness.

In contrast ceasing methylphenidate is not worth to mention for me. Amphetamine takes up to a week to regenerate but is still much easier. Granted, I never had to dose high on stimulants either. But the venla were just 150mg/d too.

 

[Kdem]

GABAB being more complicated, could any of the atypical antipsychotics that act as serotonin antagonists, SSRIs or other drugs help to 'reset' the serotonin 'receptors' ? Without major downsides ?

Not everybody has ideal genetics, and not everyone is in a 'good' environment.

 

[mb-909]

Atypical antipsychotics block most of your receptors depending on the product. They are powerful mind altering drugs supposed to change your brain chemistry for a long period of time. I took antipsychotics for 7 weeks including tapering off and had a really bad breakdown. Brain zaps, tremors, brain fog and the list goes on and on. If you don't have any psychotic breakdown with possible suidicial thoughts I would stay away from those drugs at all costs. 9 months have passed and I made big strides being able to read, paint and write with ease for the first time in years. It will take some time for your brain to alter and get used to the drugfree state. Stay sober, eat healthy and stay positive. Sometimes the biggest effects on the outcome of once health is a simple placebo effect: Believing.

For my personal interrest I might try a single amphetamine dose to partly undo the effects of the neuroleptic doses I took. I don't know how trustworthy the following study is, because only the excerpt is available, but at least in monkeys positive results were yielded by amphetamine administration:

"Chronic blockade of dopamine D2 receptors, a common mechanism of action for antipsychotic drugs, down-regulates D1 receptors in the prefrontal cortex and, as shown here, produces severe impairments in working memory. These deficits were reversed in monkeys by short-term coadministration of a D1 agonist, ABT 431, and this improvement was sustained for more than a year after cessation of D1 treatment. These findings indicate that pharmacological modulation of the D1 signaling pathway can produce long-lasting changes in functional circuits underlying working memory. Resetting this pathway by brief exposure to the agonist may provide a valuable strategy for therapeutic intervention in schizophrenia and other dopamine dysfunctional states."

- http://www.sciencemag.org/content/287/5460/2020.short

 

[serotonin2A]

Atypical antipsychotics block most of your receptors depending on the product.

That statement really couldn't be further from the truth.

 

[mb-909]

First-generation antipsychotics, known as typical antipsychotics, were discovered in the 1950s. Most second-generation drugs, known as atypical antipsychotics, have been developed more recently, although the first atypical antipsychotic, clozapine, was discovered in the 1950s and introduced clinically in the 1970s. Both generations of medication tend to block receptors in the brain's dopamine pathways, but atypicals tend to act on serotonin receptors as well.

- https://en.wikipedia.org/wiki/Antipsychotic


"Aripiprazole acts as an antagonist/inverse agonist (unless otherwise noted) of the following receptors and transporters:^{[42][43][44][45][46][47][48][49]}

Receptor	Ki (nM)	Efficacy
5-HT1A	5.6	partial agonist
5-HT1B	832
5-HT1D	65.5
5-HT2A	8.7
5-HT2B	0.4
5-HT2C	22.4	partial agonist
5-HT3	628
5-HT5A	1240
5-HT6	642
5-HT7	10	weak partial agonist
D1	1170
D2	1.6	partial agonist
D3	5.4	partial agonist
D4	514	partial agonist
D5	2130
α1A-adrenergic	25.9
α1B-adrenergic	34.4
α2A-adrenergic	74.1
α2B-adrenergic	102
α2C-adrenergic	37.6
β1-adrenergic	141
β2-adrenergic	163
H1	27.9
M1	6780
M2	3510
M3	4680
M4	1520
M5	2330
SERT	1080
NET	2090
DAT	3220	"

- https://en.wikipedia.org/wiki/Aripiprazole


Probably should have said "type" of receptors and in "certain" brain areas, but I would expect that knowledge from anybody.

=> Atypical antipsychotics tend to bind to quiet a lot of different receptor types in different brain areas blocking those pathways.

 

[serotonin2A]

Probably should have said "type" of receptors and in "certain" brain areas, but I would expect that knowledge from anybody.

=> Atypical antipsychotics tend to bind to quiet a lot of different receptor types in different brain areas blocking those pathways.

So we should assume when you write something that you mean something else? Even if you meant monoamine receptors, your statement would still not be correct:

The concentration of aripiprazole in the CNS of patients is approximately 100 nM (based on PET data). At that concentration, aripiprazole would only occupy 19 of the 31 receptors in your table. And only 15 of those receptors would be occupied at a level > 20%. So even if we discount the fact that there are hundreds of other types of receptors in the brain, aripiprazole only interacts with about half of the receptors that you listed.