Downregulation And Upregulation Puns

So.... I came across this semi-ancient article from 2013.

Basically, the dude interviewed in the article does not recommend MMJ for PTSD due anandamine receptor downregulation... is the receptor downregulation with anandamine plastic? In other words, is the downregulation permanent or malleable and so can it change to upregulation? It does appear like the lack of anandamine is the key neurobiological marker with PTSD based on the information that I've read... though the dude interviewed there also seems to have personal interest for the medical development of his own treatment. Is anyone aware of what is the name of the medication they are developing? I would be interested to do some research on this topic...

My question here is pretty simple. And let's assume that oral GABA does make it's way across the BBB in some amount for further simplicity. I take GABA in doses ranging from 750mg to 2250mg and definitely notice an effect. I feel decreased anxiety and an increased ability to focus away from intrusive thoughts. However, knowing how sensitive the brain is to tinkering with GABA (and mine in particular), I do not take it every day. My question is this: could supplementing pure GABA downregulate GABA receptors or GABA production similar to how abusing benzos or phenibut can lead to withdrawal symptoms? I would prefer not to experiment on my own because I am currently in intensive therapy and am on my third week of fluoxetine and would not like to have any particularly bad days due to fucking around with my GABA system. Thanks in advance!

I get several acne breakouts the morning after fapping so I think it must be something hormonal. I never get acne until I ejaculated recently.

Another bad thing is the mood swings and unexplainable sadness that is at worst the day after fapping. However this goes often away by the 48 hour mark. It won't return until I relapse again.

After some time has passed after fapping, I suddenly start to feel emotional, feel motivated and just feel better about everything. I turn more optimistic. It got to be something hormonal.

Hello,

Mugwort acts as a GABA antagonist, though still promotes relaxation. Does anyone know how this exactly works?

One would think that antagonizing GABA would result in wakefulness and anti-fatigue, which is also one of Mugworts main effects.

Though the real question is: If Mugwort acts as a GABA antagonist, will long-term usage result in the upregulation of GABA?

I'd love to give more on Mugwort, I actually made a small paper on this unique and mystical herb but I can't share my knowledge this morning as I have already left the dream world and am on my way to work!

Have a good day/night everyone!

Best regards,

Waddling Psycho

I had made a post here about a week ago about my depression-like symptoms, anhedonia, and ADHD-like symptoms all appearing by accidentally quitting caffeine. While that may have definitely played a role, resuming caffeine intake has helped me in the "now" greatly. It does elevate my mood, clear the fog, help motivate me and stay focused, much like a mid-day "reboot" of my mind, but my outlook on things has not been altered.

I completely missed another aspect of my life that changed. I moved. Provoked by the change in environment I began taking melatonin nightly at a dose of 3mg. A year or so later I realized .3mcg is optimal for sleep so I began splitting the 3mg tablets, 1.5mg was about the lowest I could manage which is still too much but would have to do. In any case, I was using at least 1.5mg for about 2 years straight. My longest break was 2 weeks which probably was not enough time to see any improvement.

Now, starting therapy, I am a beacon of depression and ADHD and I have discovered today melatonin is anti-dopaminergic. Causing issues that would mimick symptoms of both.

Studies involved (IIRC one includes an interesting case where they proved this action by giving it to someone with Parkinson's, which is caused by a loss of dopamine, creating even more severe symptoms temporarily)

https://www.ncbi.nlm.nih.gov/pubmed/12043836

https://www.ncbi.nlm.nih.gov/pubmed/15301928

https://www.ncbi.nlm.nih.gov/pubmed/8221133

https://www.ncbi.nlm.nih.gov/pubmed/7127086

Various sources, claiming a boost in dopamine and serotonin?

I of course plan to stop taking it, but this had me thinking... Why wasn't the brains response to upregulate dopamine in my chronic melatonin usage? Why is there other anecdotal evidence (threads below) that the mood change persists for as long as you take it? Could someone with more knowledge explain this to me? Could it be that upregulating dopamine is often counter-intuitive (many health conditions related to dopamine hyper sensitivity) so the brain does not do it?

*Side note: I have read before that dopamine upregulation is a dangerous risk of microdosing stims and is often permanent. I don't know if this is unique to stimu

Could someone explain? Maybe I’m not seeing things clearly here. I’m desensitized from porn.

NMDA receptor upregulation: molecular studies in cultured mouse cortical neurons after chronic antagonist exposure

Tl;dr: Question in the title + how likely would this be to happen? (I presume dependent on dose/frequency and timespan the drug was taken).

I could only find this paper which supports the idea that prolonged exposure to an NMDAr antagonist causes upregulation of NMDAr receptors.

The experiment was done on mice though so I don't know if it translates to humans too. If, hypothetically speaking it does, would it be possible for the increase in NMDAr receptors to cause excitotoxicity (once the agent is suddenly withdrawn)? And how likely would this occur?

NMDA induced neurotoxicity seems to be a very complex topic. I've read up about it for a while, but still can't wrap my head around it. It seems that the scientific community isn't 100% sure about all the underlying mechanisms either.

What particularly interests me is excitotoxicity in humans. Since it seems like Olney's Lesions only occur in mice, but not in humans, I'd love to know what the effects on humans are besides perhaps schizophrenogenic effects and cognitive decline.

Hey y'all, I've been struggling with some bad anhedonia aka lack of enjoyment from anything since being dependent on phenibut at moderate doses for a couple months and getting PAWS (post acute withdrawal symptom) since getting off it.

I'm considering getting some salvia right now because what I've read a lot about kappa opioid receptors being upregulated during periods of drug withdrawal and/or intense stress/trauma seems to align with the events I went thru and now symptoms I'm dealing with.

I know that salvia is a highly potent kappa opioid agonist so my plan is to do my best to restore my kappa opioid receptors back to normal by regularly using salvia in responsible, reasonable doses to downregulate them. I understand that the actual high/trip may be unpleasant and am completely prepared for that given that the afterglow is supposed to have the exact opposite effects, with a much increased hedonic tone.

However, I'm a little worried that salvia could actually worsen things because I've read several people talking about things how they didn't feel joy for a month afterwards, their anhedonia got much worse, they felt depersonalized, all kinds of stuff I really want to avoid. I know dose can be a big factor but some of these experiences were from reasonable, sub breakthrough dosages.

Is salvia more likely to help or hurt me? I know that people emphasize that smoking a high potency extract is very different from quidding the leaves and slowly getting used to the plant. I plan to really respect this stuff in terms of the dose and be immensely careful with set, setting, and sitters if necessary.

Also, is smoking a low potency extract or quidding (dried leaves, I don't have access to fresh) better to maximize the long last antidepressant salvia afterglow? It seems like this study (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2721268/) is saying that lower doses work better, which would make me think that quidding would be better since smoking seems to be so powerful.

I'm basing that on a part I came across on the bottom of the study where it says "Thus, it appears that salvinorin A, given acutely, at very low doses, produced antidepressant-like effects whereas, when repeatedly administered at high doses, it is pro-depressant." I could definitely be misinterpreting it though, and would love more insight into exactly how to best salvia, if at all, off purposes.

Thanks in advance y'all! I'm also considering LSD microdosing for my situation, it worked well

I'm not particularly scientifically literate but a brief perusal of this text seems to conclude exactly that. Can anyone concur? Thanks in advance.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3432916/

https://preview.redd.it/y4hb1cxj54a41.png?width=635&format=png&auto=webp&s=f6f6718e436b976dd3dbc7000eba0b7020b4b1e5

I was musing today about medication tolerance and have been wondering if there is a limit to the amount of dopamine downregulation that happens when taking these drugs long-term. From my limited understanding, medications increase the amount of dopamine available in certain parts of the brain (which is beneficial), yet the brain eventually fights back via downregulation.

Now, is there a limit to the amount of downregulating the brain can do? Will my current dose of Vyvanse eventually lead to a pre-medication state of dopamine availability, therefore requiring a continued increase in dose?

If someone could clarify that would be great!

https://chemrxiv.org/articles/7-Hydroxymitragynine_is_an_Active_Metabolite_of_Mitragynine_and_a_Key_Mediator_of_its_Analgesic_Effects/7692710

This is just one link I've found but I've read numerous things indicating that the cause for some people to lose the positive aspects of kratom is due to the Upregulation of the CYP3A liver enzymes which are responsible for metabolizing the kratom.

Now my main question is, will time or anything resolve this?

Hello,

I’m currently going through benzo withdrawal.

There’s the popular view that it’s Gabba receptors that need to be unregulated in order for the person to recover and take time

However the flip side argument is the increase of NMDA receptors are what causes the symptoms and the glutamate storm.

And anything taken to block the glutamate will backfire in the long term as the NMDA will up regulate over time.

Has anything ever been shown to down regulate NMDA receptors permanently.

Anymore information about this problem would be much appreciated.

So.... I came across this semi-ancient article from 2013... as of being someone with PTSD and who smokes weed, this topic interests me. Basically, the dude interviewed in the article does not recommend MMJ for PTSD due anandamine receptor downregulation... is the receptor downregulation with anandamine plastic? In other words, is the downregulation permanent or malleable and so can change to upregulation? It does appear like the lack of anandamine is the key neurobiological marker with PTSD... though the dude interviewed there also seems to have personal interest for the medical development of his own treatment. Also, is anyone aware of what is the name of the medication they are developing?