Receptor up and down regulation

[Mind-Expansion]

Hey guys,

With the following graphic I wanted to demonstrate the neuroadaptations of your body after administering a drug with regards to receptor up and downregulation.

Let's assume this drug is an amphetamine. Amphetamines exert their effects on dopamine receptors, which increase feelings of pleasure and motivation. They also exert their effects on adrenoreceptors, which increase feelings of alertness and energy. If you have never taken amphetamines before, your dopamine and adrenoreceptors are at baseline. Even if you only take the smallest dose of an amphetamine now, your body will be flooded with dopamine and adrenaline. And you'll be high as fuck. Unfortunately, your body doesn't care if that's good or bad. It senses an excess of dopamine and adrenaline, and as a result, it will downregulate its receptors. So after your high is over, you won't be feeling the way you felt before. You feel worse. You may even have enough dopamine in your system, but with a lack of receptors, the available dopamine can't fullil its job and you feel like shit. But thanks to homeostasis, your body also senses a lack of dopamine receptors in relation to the available dopamine, and as a result, it will upregulate its receptors again and after a while you will be back at baseline.

I also want to add that receptor downregulation is not the only cause of an unpleasurable comedown. In the case of amphetamines, your body also increases dopamine transporters (in order to get rid of excess dopamine) and decreases an enzyme called Tyrosinhydroxylase to prevent further synthesis of L-Dopa. Your body is an increadible adaptation machine and it has a lot if tricks to defend itself from the exposure of such potent chemicals.

 

[Tzcatlipoca]

OP you seem to believe that regulation means receptor expression. I have come to correct this. Norepinephrine and Dopamine play similar and equivalent roles in the way Amphetamines make you feel. Receptor down-regulation does not mean less receptors are expressed by your DNA. Amphetamines and active metabolites occupy available receptors, and are disposed of by homeostatic enzymes that regulate waste excretion. In your example, you've failed to mention peak duration-plateau length and the difference between comedown and rebound.
Welcome to Bluelight,
Tez

 

[Mind-Expansion]

Receptor down-regulation does not mean less receptors are expressed by your DNA.

But?

you've failed to mention peak duration-plateau length and the difference between comedown and rebound.

Could you please explain that in more detail? Thanks!

 

[Birdy-Num-Num]

OP , Really interesting and thanks for the illustration and explanation albeit it's on a very basic level.

Tzcat, thanks also.

question : if you're recovering from 10 year opiate addiction, and now 5 months clean, how long before your dopamine receptors / norephrine receptors recover and will it ever reach baseline? What can help recovery of these receptors .

Also, what about non-addictive non-drug supplements like Mucuna ( produces L-dopa), DLPA, tyrosine, NAC, 5htp (tryptophan) that all impact on serotonin, dopamine, norephrine receptors and affect regulation. . Short term, they're OK and help recovery, but what are your views on prolonged use (over 3 months ) ? Can they be dangerous .

thanks in advance ������

 

[Tzcatlipoca]

Birdy-Num-Num;
IMO NAC works as an opioid/benzo antagonist, at least put me into wd and made me very anxious. Good for getting clean tho. L-dopa, tyrosine, 5htp are endogenous neurotransmitter supplements and they are actually healthy to take on a regular basis.

Best,
Tez

 

[sekio]

question : if you're recovering from 10 year opiate addiction, and now 5 months clean, how long before your dopamine receptors / norephrine receptors recover and will it ever reach baseline?

If you're recovering from opioid use then it's the mu/delta/nociceptin receptors that need to normalize, not norepinephrine/dopamine (which are more relevant for stimulant abuse). Generally speaking it depends on lifestyle factors, if you don't get enough aerobic exercise/dietary protein it will take a long time. Also how frequently you relapse... more relapses = worse.

 

[doxylamine]

L-dopa, tyrosine, 5htp are endogenous neurotransmitter supplements and they are actually healthy to take on a regular basis

Tyrosine is fine (I haven't read anything to suggest otherwise) but I would definitely steer clear of taking L-DOPA unless you have Parkinson's - it's a pretty serious drug and can result in serious side effects, even for those who need it. As for 5-HTP, I wouldn't bother as a significant majority of the resulting serotonin will be produced peripherally and with that there is suspected potential for cardiac valvulopathy due to excessive agonism at the 5-HT2B receptor (well, all peripheral 5-HT receptors but it is 5-HT2B that is relevant to CV). The marginal benefits do not outweigh the potential risks for either L-DOPA or 5-HTP in my opinion.

I'd really just recommend eating more protein than taking any of these, to be honest.

 

[Birdy-Num-Num]

Doxy,

I'm taking mucuna bean extract ( not l-dopa,) though I see your point. Cheers

Sekio,

thanks for that. My issue is that i am many months clean (thanks to Ibogaine flood) , but lacking energy and motivation. Hence, taking those supplements. I am physically fit and do lots of exercise and my diet is very good also with decent protein.

can you suggest supplementation for mu / delta / nociceptin recovery?

cheers

 

[Birdy-Num-Num]

Tzcat, I confess, I am confused that NAC would cause w/d. You saying that after recovering fully, then it can be harmful.

i thought it was safe to take as it's effectively an Amino Acid (600mg a day) .

 

[headdrawer]

Receptor down-regulation does not mean less receptors are expressed by your DNA.

Yes it does.

Norepinephrine and Dopamine play similar and equivalent roles in the way Amphetamines make you feel.

This is also false; even a slightly different mechanism of action on the exact same neurotransmitter can make major differences in discriminative stimuli, so two different ones are definitely not equivalent. Separating conscious experience into components is challenging, but roughly speaking, NE will contribute to general arousal (wheeeeeee!), while DA will increase reward salience/approach incentive (I'm going to start five new projects with all this wheeeeee! I have right now!).

In your example, you've failed to mention peak duration-plateau length and the difference between comedown and rebound.

The first has nothing to do with the current topic, and on the second point you're wrong. Not knowing is fine, but aggressively 'correcting' people with your own misinformation is not cool.

OP, I like your graphic

 

[Seppi]

Yes it does.



This is also false; even a slightly different mechanism of action on the exact same neurotransmitter can make major differences in discriminative stimuli, so two different ones are definitely not equivalent. Separating conscious experience into components is challenging, but roughly speaking, NE will contribute to general arousal (wheeeeeee!), while DA will increase reward salience/approach incentive (I'm going to start five new projects with all this wheeeeee! I have right now!).

Re: what headdrawer said.