Cure attempt #2 (in-progress / initial findings)

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Jaxx
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Re: Cure attempt #2 (in-progress / initial findings)

Unread post by Jaxx »

Meso wrote:[Update 6]
15-12-2019 (Day-Month-Year)


This is the final update on the DXM/nalt trial. It's been so long since last update and emotional/hedonistic improvements never returned. Sexual improvements still remain, though.

Symptoms:
Libido: 9/10
Erections: 7/10
Orgasms: 10/10
Hedonistic response: 3/10
Emotional response: 1/10
Cognition: 3/10

This means that DXM/nalt worked to centrally upregulate AR and restore some negative feedback loop on serotonin, but the effects are moderate and don't target peripheral AR. I still have peripheral issues such as loss of muscle mass, hair problems, high-pitch voice, and mild ED, etc.

I'm now trialing another regimen that targets all central and peripheral AR/ER issue as well as the shortcomings of this previous trial (including cognitive symptoms). I'll keep the details secret and I retain the right to report the regimen here or abstain from doing so, regardless of the outcome.

I'm keeping the details secret this time around since many people have shown impulsiveness and irresponsible behavior with the DXM/nalt trial. For example people trying it without any precautionary measures, some trying mega high doses of DXM without having high serotonin (no probing + against my advice), and even some trying it after quitting SRIs for less than 1 month!
i thought the resensitising of girk channels was the key mechanism of dxm/nalt, you think the ar effect were perhaps more important?
Also, you mentioned feeling more energy in the beginning, did this effect maintain (pre-concussion)
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Meso
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Re: Cure attempt #2 (in-progress / initial findings)

Unread post by Meso »

Jaxx wrote: i thought the resensitising of girk channels was the key mechanism of dxm/nalt, you think the ar effect were perhaps more important?
Also, you mentioned feeling more energy in the beginning, did this effect maintain (pre-concussion)
Both are important. The regimen has lowered central serotonin as evident by reversal of anorgasmia and re-introduction of pre-PSSD premature ejaculation.

Lowering serotonin and upregulating AR expression weren't enough to restore the emotional/hedonistic responses. As per the new research review findings, the improvements in blunted affect and anhedonia (as well as anxiety) could be mediated through a compensatory mGluR5 upregulation in relation to NMDA antagonism. Ketamine, which isn't a GIRK antagonist, can also restored the emotional response - which means it's not GIRK-related. These improvements would then be temporary since NMDA receptors end up being upregulated and mGluR5 downregulated again.

A good question here is: what has caused mGluR1/5 to be hypoactive in PSSD? why is there a PFC dysfunction in PSSD? the answer could be ER-alpha to beta imbalance.
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garycooper
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Re: Cure attempt #2 (in-progress / initial findings)

Unread post by garycooper »

I was wondering if anybody else has tried this, and made any progress. This is by far the most successful trial to address sexual symptoms, using deduction and theory, that I've seen.

I agree that getting NALT and DXM is not easy for everyone, and I assume it's why not many people have ultimately tried this.
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Re: Cure attempt #2 (in-progress / initial findings)

Unread post by AUserIUsedToKnow »

The trial doesn't work, as most of what this website has to offer.
I'm reading to many errors and mistakes, but I dont have the time right now to pinpoint every single of them.
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Meso
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Re: Cure attempt #2 (in-progress / initial findings)

Unread post by Meso »

AUserIUsedToKnow wrote: Wed Sep 15, 2021 1:22 am The trial doesn't work, as most of what this website has to offer.
I'm reading to many errors and mistakes, but I dont have the time right now to pinpoint every single of them.
You haven't tried it yourself so stop talking out of your ass. If you think this forum is useless then why are you here wasting everybody's time? If you want to be a waste of breath keep trolling and I'd be happy to ban you. :roll:

On topic, I personally know two people who were brave enough to trial this regimen and they got better.
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Re: Cure attempt #2 (in-progress / initial findings)

Unread post by Extremaduro »

Does that also reverse medication induced akathisia? Or is it a complete different story?
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Re: Cure attempt #2 (in-progress / initial findings)

Unread post by MisterCharlie »

Meso wrote: Wed Sep 15, 2021 7:49 am
AUserIUsedToKnow wrote: Wed Sep 15, 2021 1:22 am The trial doesn't work, as most of what this website has to offer.
I'm reading to many errors and mistakes, but I dont have the time right now to pinpoint every single of them.
You haven't tried it yourself so stop talking out of your ass. If you think this forum is useless then why are you here wasting everybody's time? If you want to be a waste of breath keep trolling and I'd be happy to ban you. :roll:

On topic, I personally know two people who were brave enough to trial this regimen and they got better.
I actually love your science (impresses me and gives me hope) and your cures/cure attempt Posts and I tried this one. Couldn't stay on it as long as you and never could tolerate the 200mg dose DXM. Couldn't tell how much better I got afterwards, maybe 5% to 10%, but it was a reasonable chance to take to improve. Tried reboxetine before as it is also a girk antagonist but I didnt notice much in the short term.

If I could life forever on just the benefits of ropinirole, I would do it, greatly increased libido, erections and genital sensitivity but serious, dangerous, eye and chest pain side effects. I have tried other things like seroquel to block dopamine receptors to upregulate them (starting from lose dose and increasing gradually), gotten more sexual feelings, more energy, and more morning erections. Loved your idea with baclofen (ACTH release, GR downregulation, glutamate rebound), which also agonizes gaba B and therefore (I think) downregulates inhibitory GABA B in the long term and thereby increase erections. Saw an article that Gaba A down regulation increases non contact erections which I have close to 0 of, so I am looking into something that I can trial for that after finding a drug that helps downregulate the amygdala (fear, threat assessment center of the brain) and greatly decreased my stress levels.

Tried large doses of L-histidine, re the nitric oxide stack post, viewtopic.php?t=4628&hilit=nitritic+oxide&start=110 and about two weeks after starting I think it causes zinc depletion which I think then causes serotonin and gaba depletion. I felt miserable as hell but was having an orgasm or two a day no problem. No sure if there is more to research there.

I can take a big dose of fasoracetam and one to two days later get massive, frequent, and powerful erections for awhile (doesnt effect penis sensitivity). But Im still trying to figure out why, maybe you know. Aniracetam strongly upregulates AMPA receptors, which might be helpful to us. I'm constantly trying things and researching. For example: Sodium valproate, lithium orotate, sodium butyrate, and/or hydralazine to demethylate RNA changes by drugs/antidepressants to pre PSSD settings- but I don't hear about other people's experiences or any success stories re demethylation. Havent really seen a source where I could buy that drug (fenclonine or something) thats good for serotonin depletion, but I would try it in a heart beat.

Only tried baclofen from this trial: https://www.pssdforum.org/viewtopic.php?f=20&t=2863 but Im curious if you would recemmend trialing the other drugs from that specific trial other than metformin (which seems awesome to try regardless, anti ageing benefits for example)

I highly encourage you to ignore the large number of subversives on this website and continue your good work with the rest of us who are staying active with trials and research- to help ourselves and others reclaim our dignity and destiny.
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Re: Cure attempt #2 (in-progress / initial findings)

Unread post by Gonzo »

Meso wrote: Fri Oct 25, 2019 12:20 pm Details of the experiments
This DXM/Naltrexone cure attempt is broken down into 2 seperate parts:
First part, I tried high dose DXM for just a couple of days. This is followed by 2 months intake of low dose DXM (20-30 mg) and Naltrexone (10 mg).

Second part, I tried high dose DXM (250-300 mg) + Naltrexone (25 mg) for 1 week straight, followed by 1 week of tapering down both drugs.

The DXM I managed to acquire had an antihistamine in it (chlorpheniramine maleate). I also managed to acquire one that had guaifenesin in it without any antihistamine. Keep this in mind as you read my experiment, as an antihistamine effect was present during the first part.

My baseline as compared to pre-PSSD (without any drugs in system:
* 40% overall cognitive functions. (very poor memory, focus, and attention)
* 25% erectile quality. (+ some genital shrinkage)
* 25% genital sensitivity. (frank + erogenous numbness)
* 10% libido. (near-complete chemical castration)
* 10% emotional reactivity (flattened affect).
* 10% hedonistic/pleasure capacity (severe anhedonia).

I had tried dozens upon dozens of drugs and supplements to alleviate these symptoms in vain before coming up with the symptomatic relief regimen.

Background:
I used to suffer from major depressive disorder (MDD), generalized anxiety disorder (GAD) and social anxiety disorder (SA) before PSSD. I was also overly-emotional, getting immense euphoria from music, and I was hypersexual with immense libido. This made me prone to premature ejaculation, but my refractory period was mere minutes, so it didn't matter. I also have REM sleep behavior disorder (RBD) 8 years before PSSD.

Suffice to say, with the post-PSSD baseline I'm a shadow of what I used to be pre-PSSD. Although these pre-PSSD psychiatric disorders were very disabling to my life, at least I enjoyed my time at home listening to music/playing games. I was also the top of the class at university with a couple of professors promising a career in education and post-grad (teaching assistant). After PSSD, everything was ruined - even the small things I was really good at/enjoyed.

PSSD made me feel pretty much dead inside and more disabled overall. This lead to heavy suicidal ideation until I came up with a symptomatic relief regimen. Although I was mostly functional on it, it was so expensive for me. This lead me to attempt a cure with Vortioxetine - it worsened my condition and pushed my PSSD subtype into higher extracellular serotonin. I became extremely tolerant to Baclofen, and the regimen was no longer as effective. This lead me to this 2nd cure attempt.
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First part report:
The first thing I noticed after taking high dose DXM/Naltrexone for 3 days was feeling severe dissociation, dysphoria, and general emotional/physical numbness during their effect.

For some reason, my erectile function was completely restored even while high on this dissociative. It was better than 20 mg Vardenafil. In retrospect, I don't know what caused the pro-erectile effect. My DXM contained an antihistamine, sure, but I tried a DXM/guaifenesin formulation (second part of experiment) and never experienced this pro-erectile effect. I've recently re-tried the antihistamine-containing DXM formulation and that didn't affect my erectile function at all. It remains a big mystery.

After the drugs were out of my system, I had experienced complete reversal of blunted/flattened affect. I was able to laugh and cry again, I was able to experience the full emotional spectrum - but mostly negative emotions because MDD/GAD were back in full-force!

It was very overwhelming, so I decided to take lower doses instead (20-30 mg DXM + 10 mg Naltrexone). I knew this dose wasn't enough to restore LTP/serotonin negative feedback loop but I had to try it any way.

After a month on this, libido had improved significantly - and my reaction to visual stimuli was very strong. Wet dreams were also back with sexual undertones often occurring in dreams. I felt my hypothalamus is finally starting to develop a "thirst" for sexual relief.

After another month on these low doses, emotional reactivity was partially restored (to a tolerable level) and libido was skyrocketing. I enjoyed music immensely. My hedonistic capacity had increased but it was mainly emotionally-mediated. I became more sociable and enjoyed spending time with people. However, my enjoyment of other activities were reduced. I thought this might be due to the antihistamine (antihistamines always made me anhedonic).

Alas, these low doses were not enough to trigger permanent benefits. As soon as the drugs were complete out of my system, my symptoms crept back on. I knew I needed higher doses to recover the negative feedback loop on serotonin. Which leads us to the second part of the experiment.

Taking low does DXM daily (as in a symptomatic relief) is also out of the question, since it's an SRI and it has a significant memory-weakening effect.

My REM sleep behavior disorder (RBD) has been worsening ever since taking this regimen.

So, to recap (temporary improvements):
* 30% overall cognitive functions. (even worse memory)
* 90% erectile quality.
* 90% genital sensitivity.
* 90% libido (intense craving for sexual stimuli).
* 100% emotional reactivity.
* 50% hedonistic/pleasure capacity.

After a day without the regimen, those improvements begin to fade noticeably.

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Second part report:
Taking high dose DXM (250-300 mg) + Naltrexone (25 mg) for 2 weeks proved to be extremely dysphoric, but I decided to just bite the bullet and push through. For this second part, I managed to find a DXM formulation that only contained guaifenesin. (No more antihistamine)

When the drugs are partially out of my system, I notice immense lust and strong reaction looking at the female body - very, very mesmerizing. Wet dreams are almost a daily thing now. Sexual stimuli are very exciting, to the point of instinct taking over, this leads to premature ejaculation (I had this even before PSSD so it's okay).

Refractory period is relatively short (60 minutes), although this makes PE problematic. These are all signs of lower serotonin.

Emotions are very pronounced, with nostalgia and euphoria listening to music. Very close to pre-PSSD emotions and libido-wise. Able to laugh and cry without a problem. Feeling more associated with the worldly events around me.

For some reason though, the pro-erectile effect is reduced after switching to the DXM-gaufenesin formulation the past week. I'm tapering down using the DXM- antihistamine formulation in a bid to restore the full potential of the pro-erectile effect (possibly in vain).

This is my tapering schedule for the past few days:
Friday: 200 mg DXM + 20 mg Naltrexone.
Sunday: 150 mg DXM + 15 mg Naltrexone.
Monday: 100 mg DXM + 10 mg Naltrexone.
Tuesday: 50 mg DXM + 5 mg Naltrexone.
Wednesday: None.

There is some NMDAR-mediated withdrawal symptoms that feel similar to mild benzo withdrawal (severe irritability, blunted affect, anhedonia, sound/light intolerance)

This makes this Friday my 3rd completely drug-free day. All benefits are so far steady and stable with no sign of abating. In fact, I fapped 8 times counting today and yesterday to test whether fapping would affect benefits negatively - it doesn't.

MDD/GAD/SA are back, but I've been adapting a little to them. REM sleep behavior disorder (RBD) had been worsening before stabilizing a bit, recently. Sleep is slightly more refreshing and I no longer experience excessive daytime sleepiness.

To recap (hopefully permanent improvements / new baseline):
* 40% overall cognitive functions. (now that DXM is out of my system, cognition should improve a bit)
* 50% erectile quality. (for some reason took a dive ever since switching to the gaufenesin formulation)
* 90% genital sensitivity. (very sensitive, very pleasurable = premature ejaculation)
* 90% libido (intense craving for sexual stimuli and relief).
* 75% emotional reactivity. (+ MDD/GAD/SA, most likely affected by NMDAR-mediated withdrawal)
* 40% hedonistic/pleasure capacity. (NMDAR-mediated withdrawal affecting this)
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Final thoughts on the regimen + insights:
I have a feeling that this time around, I managed to restore the serotonin negative feedback loop significantly. This is evident by the sexual and limbic excitation (over-excitation sometimes), immense pleasure and premature ejaculation as well as ability to experience anxiety and depression again.

That said, this is only the 3rd day being drug-free. In 7 more days, if the benefits remain, it should be a more tangible proof. If I retain these improvements for the next month or two without abating, then it's a solid proof.

Before vs after this regimen:
* 40%40% overall cognitive functions.
* 25%50% erectile quality.
* 25%90% genital sensitivity.
* 10%90% libido.
* 10%75% emotional reactivity.
* 10%40% hedonistic/pleasure capacity.

New insights:
- I've always thought that low NMDA receptor function leads to blunted affect. This experiment makes it clear that both too-high and too-low NMDAR activation result in blunted affect.
- Oxytocin, mu and kappa opioid receptors are very important for emotional reactivity and feeling the "mood" of a place, movie, or a song.
- Since NMDA receptors are responsible for mu receptor downregulation, lowering NMDA expression would improve the phasic mu receptor response (orgasms, emotions, etc).
- Neither this regimen nor the antihistamine were the reason for the transiently improved erectile function. It's a mystery.
- Prolonged or intense stimulation of mu receptors leads to downregulation of AR expression in the mPOA → absolute refractory period.
- If the sexual symptoms of PSSD are mediated through high serotonin, the emotional symptoms are within the domain of NMDA/mu receptors' control.
- Cognitive symptoms in PSSD might respond to glutamatergics and neurotrophy.

Future directions:
1- After withdrawal syndrome, I expect this baseline to continue improving significantly.
2- I should wait for at least a week to confirm whether these benefits are permanent/semi-permanent. 1-2 months would be very sufficient.
3- I should capitalize on DXM's neurotrophy by adding 1500 mg Metformin (to upregulate TrkB and boost BDNF)
4- I should look more into erectile function and why it had improved drastically during the first 2 months.
5- There can be a couple more variation to the regimen which are relatively safer (i.e. Fenclonine + Naltrexone)
6- Sleep is more refreshing, but I think with reducing neuroinflammation and increasing neurotrophy, sleep will be even more refreshing.

Conclusion:
This regimen is still highly experimental - I don't know how other people would react to it. For the risks it poses, I think if there's a permanent 50-75% baseline improvement it would be worth it. Otherwise, it's too dysphoric and too risky. Just a matter of time now.
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Post-regimen updates section

[Update 1]
27-10-2019 (5th day after last doses)


NMDAR-mediated withdrawal syndrome is still evident but it's getting better. It feels akin to a mild benzo withdrawal.
Symptoms I currently experience:
- Anhedonia/amotivation
- Blunted affect (but still far better than PSSD baseline)
- Irritability
- Light and sound intolerability
- Memory problems

Sexuality-wise, benefits are neither fading nor being counteracted by the NMDAR rebound. Just the emotional/hedonistic ones are to a certain degree.

I hope this NMDA rebound won't reverse the pro-emotional and pro-hedonistic benefits I've gained from AMPA activation while on this regimen. I'll keep it clean though, so I'm not going to take i.e. memantine. I'll just wait it out.
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[Update 2]
31-10-2019 (9th day after last doses)


The NMDA-rebound withdrawal state has essentially passed. Because of this NMDA rebound, I have largely lost the emotional and hedonistic improvements I'd seen. Sure, I'm doing better than before this trial, but I'm really aiming for 100% recovery of at least the emotional response.

For this, I have decided to take DXM/Nalt for 3 days and then withdraw again but this time use Mematine during the withdrawal, in order to prevent NMDAR-mediated relapse.

I think I also discovered why I lost the erectile improvements of DXM/Nalt. Yesterday, I took 10 mg Vardenafil, which restored my erectile function as expected. However, what's unexpected is that erectile quality hasn't decreased 24 hours later. I still experience drastic improvements.

This makes me believe that DXM/Nalt have restored my erectile function for 2 months but then I experienced low NO level (diet low on NO donors). Vardenafil simply letting NO to accumulate for a while. I expect that supplementing L-Arginine is all I need now.

As for sexual improvements as a whole, they still persist to this day. High libido and genital sensitivity.
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[Update 3]
7-11-2019


This is my first day after the 3-day DXM/Nalt reintroduction.

First thing I noticed while on DXM is that I'm completely tolerant to its dissociative effect. Which means my NMDA receptors are still quite upregulated. After taking DXM for 3 days, I notice that emotional improvements haven't returned and I feel very irritable. I half-expected this, since emotional/hedonistic improvements were related to NMDA antagonism from the Dextrorphan (DXM's metabolite), which is a more potent NMDA antagonist.

This means that I'll have to wait until NMDA receptors return to baseline level. But at least I know that NMDAR overactivity is the root cause of my blunted affect and anhedonia. After NMDA receptors are back to baseline, I'll have to figure out a way to downregulate them even further. I'm contemplating chronic intake of d-aspartic acid in a week to speed up their return to baseline.

How to downregulate NMDA receptors below baseline is beyond me. I know that dopamine receptors regulate NMDA receptors and vice-versa, but I'll need to read more studies on how NMDA receptors are fundamentally regulated.

Sexual improvements are still present.
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[Update 4]
14-11-2019 (Day-Month-Year)


Right. So it's been a while and I have good news and bad news.

NMDAR signaling is starting to reach a stable baseline. I'm noticing more emotions and hedonistic response returning, but i still need to focus on downregulating NMDAR beyond baseline. For this, the best solution is TrkB receptor upregulation + BDNF boosting - as this can downregulate NMDAR.

Cognitive symptoms are currently the worst. Without Rasagiline + Donepezil, I experience intense brainfog and aberrantly prolonged sleep inertia. My long-term and short-term memory are senile-like mild dementia. Since I'm looking into a permanent cure for my PSSD instead of symptomatic relief, it doesn't make sense returning to these drugs. The best solution is, therefore, TrkB receptor upregulation + BDNF boosting to restore limbic integrity, boost hippocampal neurogenesis, upregulate dopamine receptors, and improve glutamate firing.

The only drugs/supplements I know of that can upregulate TrkB receptors to a significant degree are Metformin, Schisandra, Semax, and Genistein. Other things are weak (i.e. Forskolin and niacin). For TrkB receptor upregulation and BDNF boosting, I'll take:
- 500 mg Metformin. (+ Ubiquinol and cyano-B12, since Metformin can lower those)
- 500 mg Schisandra.

I won't start taking these right away since they are expensive and I can't buy them at the moment. I didn't even buy l-cirulline yet. (currently in the middle of moving out, and that costs too much). Schisandra can be replaced by N-Acetyl-Semax, but I have no access to it (won't pass through customs).

What about sexual function?
I have been having sex on a daily basis - sometimes twice a day. But I'm noticing that my refractory period is getting longer and longer each time. Orgasm-mediated mu activity is probably reversing some of the AR upregulation that took place in the mPOA - especially since my orgasms are much more intense than pre-PSSD = much more robust mu activity.

Don't be alarmed though, this worsening is mild and likely transient. Probably I just need to skip sex for a couple of days. I still crave the female body form and find it mesmerizing to look at. So it's not that bad. I wish I can return to pre-PSSD level where refractory period was only 10 minutes, though. I've also noticed that on days I have 2 orgasms, the following day I wake up with no morning wood.

This means that my AR signaling has recovered a lot but it's still not at an optimal level. Too many orgasms without taking any break might be enough to reverse some of the permanent sexual benefits. I'm currently researching ways to boost AR signaling with excellent leads (you can find more info on my Discord server: https://discord.gg/Mej6ct9).

New baseline (so far):
Libido: 9/10
Erections: 9/10
Orgasms: 12/10 (Better than pre-PSSD)
Hedonistic response: 4/10
Emotional response: 4/10
Cognition: 3/10

I doubt that it would improve further than this without NMDAR downregulation and TrkB receptor upregulation.

Random tidbits:
Speaking of emotions/hedonistic response, I have to say I noticed that when I'm enjoying music, I feel perfectly content listening to it that I have no desire for watching a TV series or playing a game. It's a little strange.

GAD is also no where to be found despite of the mild improvement in emotional response. I still have diarrhea and IBS so I guess it isn't related to GAD after all.

Dreams are extremely vivid and deep. Almost daily wet-dreams or sex-themed dreams, but overall having very bizarre themes. It's like tripping while asleep.

That's all for this update.

[Update 5]
19-11-2019 (Day-Month-Year)


I caught a cold yesterday and couldn't sleep. Too much histamine was making me feel worse, since histamine potentiates NMDA receptors.

I had to take something for sleep, so I went for 50 mg Lamotrigine. Woke up feeling extremely good mood-wise. I can feel sunshine and the 'atmosphere' of the room/house and places I go. I react well to music and hedonistic response is completely recovered. It's the closest I've felt to pre-PSSD ever.

Symptoms:
Libido: 9/10
Erections: 9/10
Orgasms: 10/10
Hedonistic response: 10/10
Emotional response: 7/10
Cognition: 3/10

This is making me very hopeful - a complete reversal is just a matter of lowering tonic glutamate firing. Hopefully Schisandra and Metformin can achieve this as well as restore cognitive functions. Too much/little NMDA receptors activation are not good for cognition.

Emotional response has improved a bit, but it's not fully back. My entire body feels very sensitive to touch and I don't crave being around any one. Probably the illness, though.

[Update 6]
15-12-2019 (Day-Month-Year)


This is the final update on the DXM/nalt trial. It's been so long since last update and emotional/hedonistic improvements never returned. Sexual improvements still remain, though.

Symptoms:
Libido: 7/10
Erections: 7/10
Orgasms: 10/10
Hedonistic response: 3/10
Emotional response: 1/10
Cognition: 3/10

This means that DXM/nalt worked to centrally upregulate AR and restore some negative feedback loop on serotonin, but the effects are moderate and don't target peripheral AR. I still have peripheral issues such as loss of muscle mass, hair problems, high-pitch voice, and mild ED, etc.

I'm now trialing another regimen that targets all central and peripheral AR/ER issue as well as the shortcomings of this previous trial (including cognitive symptoms). I'll keep the details secret and I retain the right to report the regimen here or abstain from doing so, regardless of the outcome.

I'm keeping the details secret this time around since many people have shown impulsiveness and irresponsible behavior with the DXM/nalt trial. For example people trying it without any precautionary measures, some trying mega high doses of DXM without having high serotonin (no probing + against my advice), and even some trying it after quitting SRIs for less than 1 month!
Dude, chlorpheniramine is actually an SSRI, I wonder how you don't know that if you are supposed to be a pssd expert who treats pssd suffers. And you even reports improvements? Sorry this is no sense.
chlorpheniramine caused me a permanent crash.
It's an old post but i can't skip it
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