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

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

Unread post by Meso »

It has come to my attention that people are trying this regimen without taking precautions into consideration despite the several disclaimers and warnings. Others try it despite having symptoms of low serotonin, ending up with more anxiety and/or depression. I've discussed this with site admins and have decided that I would add a section dedicated to probing and harm-reduction. I'm suffering from a concussion due to an accident last Sunday, so will update this thread after I'm mentally able to.

Disclaimer 1: This regimen is still highly experimental - I don't know how other people would react to it. It poses various risks and it's too dysphoric and too "dirty".

Disclaimer 2: Please don't try this regimen until I confirm or deny permanent improvements to baseline in at least a couple of weeks. Although promising, it's still too early - let's not jump to conclusions. In theory, would work for high-serotonin / low glutamate subtype of PSSD only. Even if you are of this subtype, I don't know how you would react to it, it's too dirty with many mechanisms of actions.

Disclaimer 3: This regimen is very risky and should only be attempted under supervision while having sufficient precautionary measures available. It's your own risk.

In this thread, I will discuss my initial findings related to a curative regimen that I have attempted. For the past couple of months, I've been secretly experimenting with a new 2-drug regimen with the potential of being at least a partial cure - setting a new baseline with permanent improvements. I will type all my findings and what I would expect next, so expect this to be a large thread.

The regimen is: Dextromethorphan hydrobromide (250-300 mg) + Naltrexone (25 mg) for 1 week, followed by gradual tapering off and complete withdrawal by the end of the 2nd week. This regimen, in theory, would work for high-serotonin / low glutamate subtype of PSSD only. I'll discuss the science behind this regimen in-depth, but first:
A- First of all, why all the secrecy?
First reason is, giving false hope (or placebo report) to this community is the most dangerous thing one can do due to the number of people desperate and suicidal because of PSSD. Let me emphasis the "initial finding" and "in-progress" nature of this thread. It's better to wait for another month or two to truly be certain that benefits are indeed permanent. That said, people were getting very curious so I thought I'd write this thread.

Second reason is, this regimen carries so many risks of permanent worsening and even death. I preferred to try it myself first to see if my cure theory holds true and since I can take precautions as needed.

Here are some of the risks:
- Serotonin syndrome: DXM has SRI and serotonin releasing action. This is especially risky since this regimen is for high-serotonin subtype only. Having Cyproheptadine on hand is a must.
- Psychosis: DXM is psychotomimitic. If you are prone to psychosis or bipolar and/or have family members who suffer from psychotic disorders or bipolar disorders, there's a good chance that DXM would trigger that for you - sometimes permanently so. Having an antipsychotic and a benzo on hand is a must.
- Suicide/suicidal ideation: This regimen is extremely dysphoric! You are blocking mu receptors while being very dissociated on a NMDA antagonist. This combination is very risky if you are prone to depression.
- Severe panic attack: Mu opioid receptor antagonism leads to disinhibition of locus coeruleus' NE firing (norepinephrine nucleus).
- Permanent worsening of PSSD: As with every relief or cure attempt of PSSD, sometimes these drugs would lead to the opposite of the desired effect; namely permanent worsening of PSSD. This regimen carries this risk, especially because of its initial pro-serotonergic nature.
- Bromism: In case you decide to take DXM at high doses chronically for some reason, bromide ions would build up in your body (they have a half-life of 12 days). This would lead to toxic bromism. This risk is non-existent if taken for only 2 weeks, but it's worth knowing.
- Other ingredient toxicity: DXM is often mixed with other substances. These can be antihistamines, phenylephrine/pseudoephedrine, anticholinergic agents, and guaifenesin. This can lead to accidental overdose on those substances, which is especially dangerous in case of anticholinergics (Google anticholinergic poisoning).
B- Okay. So what do you mean by saying 'high-serotonin / low glutamate subtype'?
Let me first explain what serotonin negative feedback loop is:

Serotonin firing is tightly controlled by a negative feedback loop involving the main serotonin nucleus in the brain (raphe nuclei).
1- Serotonin transporter (SERT): This makes sure that serotonin is transported from the synaptic space back into the neuron. Low SERT expression would lead to high serotonin symptoms.
2- Presynaptic 5HT-(1A, 1B, 1D) autoreceptors: These put the brakes on serotonin release. 5HT1A is the most prominent.
3- G protein-coupled inwardly-rectifying potassium channels (GIRKs): Simply put, without sensitive GIRK channels, 5HT1A autoreceptors won't work since they depend on GIRK function. Same goes for many other receptors (such as GABA-B receptors which are also GIRK-dependent).
4- Monoamine oxidase A (MAO-A) enzyme: This oxidizes serotonin, rendering it inactive.

If any of these pathways are malfunctioning, you end up with high-serotonin symptoms, which include:
- Blunted affect / flattened affect: Serotonin enhances cortical inhibition of sub-cortical regions, leading to suppressed limbic-cortical feedback.
- Anhedonia/Apathy/Amotivation: Same as above + blunting dopamine and glutamate release.
- Poor cognitive abilities.
- Loss of libido: potentially reducing central AR expression + serotonin in the lateral hypothalamus is very suppressive to the medial preoptic area (mPOA) activity.
- Genital shrinkage: possible effect on peripheral AR expression and vasoconstrictive effects.
- Erectile dysfunction: directly through inhibitory action on spinal reflexes + indirectly through downregulating oxytocin release and NMDA receptors.
- Anogasmia: blunting oxytocin release and sexual excitability.
- Erogenous genital numbness: by affecting brain regions responsible for erogenous sensations (i.e. parietal lobe).

To identify whether your PSSD involves high serotonin, there are several "probing" strategies that can be tried:
- Alcohol hangover: this leads to rebound glutamate firing + transient 5HT1A autoreceptor hypersensitivity. It can give people of this subtype a window of relief.
- MDMA afterglow: MDMA use leads to serotonin depletion, making some people to experience pro-sexual aferglow effect.
- Fenclonine: same as above.
- Baclofen: as a probe, if you don't react to it unless high doses (75+ mg) are taken, this can potentially signal 5HT1A autoreceptors insensitivity and/or desensitized GIRK channel. Both of these are generally caused by high serotonin. Baclofen works on serotonin by indirectly disabling 5HT1A autoreceptor function, causing postsynaptic serotonin release. If autoreceptors or GIRK channels are already desensitized, baclofen won't work.
C- Right. How can this regimen potentially cure PSSD, then? get to the science!

Dextromethorphan HBr:
- GIRK channel antagonist restoring GIRK channel sensitivity after subchronic intake of high doses.
- Bromide ions are inhibitory to serotonin release.
- NMDA receptor antagonism leading to AMPA receptors activation + mu opioid receptors upregulation.
- Nicotinic receptors antagonism leading to rapid upregulation and improvement in limbic response.
- Sigma-1 agonism.

As NMDA receptors are present on GABA interneurons, activation of NMDA receptors leads to inhibition of AMPA receptors. AMPAR activation + neurotrophic effect (BDNF/TrkB) is hypothesized to have a rapid antidepressant effect. The opposite is also true - overexpression or over-activation of NMDA receptors leads to reduced AMPAR/neurotrophy, causing pro-depressive effect. Serotonin generally leads to NMDA downregulation, playing a small part in the antidepressant effect (but ruining NMDAR/cGMP/NO pathway responsible for erectile function).

Subchronic intake of DXM HBr would hopefully do the following:
- Restoration of the serotonin negative feedback loop by correcting GIRK sensitivity.
- Reducing serotonin release (due to bromide ion build up).
- Partial neurotrophic effect that can be potentiated by drugs boosting BDNF and/or upregulating TrkB receptors.
- Re-balacing NMDA/AMPA receptor ratio, leading to better erectile function.

- Mu and kappa opioid receptor antagonism --> upregulation.
- Gonadal hormones boosting effect, leading to increased central and peripheral AR receptor expression.
- Microglia inactivation.
- TLR2/4 inhibition.

There's is a phenomenon called "absolute refractory period" in rats. After a rat becomes sexually exhausted following multiple orgasms, introducing a new receptive female (novel stimulus) doesn't work any more to stimulate the male rat to participate in sexual intercourse.

It was found that this transient-but-complete insensitivity to sexual stimuli occur rapidly after multiple orgasms. Upon further investigation, it was found that orgasms downregulate AR expression in the mPOA - which is the main cause for this phenomenon.

Why use Naltrexone, then?
So, I had the idea "what if we block mu receptors instead? could that potentiatlly lead to downstream upregulation of mPOA AR expression?" which lead to testing of Naltrexone in this regimen in a bid to reverse serotonin's effect on central AR expression - at least partially.

Second reason is re-sensitization of the limbic pathways to the hedonistic response and pleasure by restoring mu receptors' reactivity to transient, phasic endorphine release.

Third reason is restoring both positive and negative emotional spectrum and reactivity. Mu and kappa opioid receptors play a crucial role in emotional sensation. Kappa is more involved in negative emotions - which makes Naltrexone for restoring both positive and negative emotions through sensitization.
D- Interesting. However, what makes you sure that these benefits would "stick" permanently if achieved?
Do not understimate long-term potentiation (LTP). With NMDA receptors inhibited, AMPA receptors activity would be drastically enhanced through increased glutamate release. This can be enough to trigger the "what fires together wires together, as long as there's a burst of dopamine" mechanism. NMDA receptors are also important for LTP and erectile function, so we get a 'during' and 'after' drug effects.

"During" phase: Improved AMPAR, neurotrophic effect and LTP.
"After" phase: Upregulated NMDAR expression, further facilitated LTP, and pro-erectile function.

I already suspect that PSSD is caused in part by the lowered glutamate and blunted HPA reactivity --> leading to long-term depression (LTD) affecting several pathways. It's more plausible to my brain than a frank methylation issue - and can maybe explain why some people get windows of full relief lasting a couple of days occasionally.

I think brain areas responsible for PSSD symptoms are permanently or at least semi-permanently "sleeping" due to LTD. With some AMPAR and neurotophic enhancement, maybe we can trigger potent enough LTP to waken them up and restore the circuits. This requires lowering serotonin + sensitizing GIRK during the extra glutamate phase.

I suspect that the pro-glutamatergic effects of DXM aren't sufficient for LTP and a glutamatergic agent (i.e. Semax) is better added to the regimen. But I wanted to try the 2-drug on their own first to see what benefits stick.

Thread is continued on the following post.
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Re: Cure attempt #2 (in-progress / initial findings)

Unread post by Meso »

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.

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.
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.

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)
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.

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.
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.
[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.
[Update 3]

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.
[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:

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.

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.

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

Unread post by finities infinities »

Awesome post! It says a lot! Your state before PSSD resembles my state before PAWS when I was experiencing sadness, it was a kind of "real" sadness that you really feel into, and you mentioned the beautiful experience of music and the feeling of the atmosphere of the place! I definitely lost it after Carbamazepine PAWS. ( but my REM dreams is opposite- before paws I had no rem dreams but actually my rem sleep is overactive)
DXM is similar to carbamazepine in me- the rebound, withdrawal effect is very bad for me- increase all my Carbamazepine PAWS symptoms to enormous and suicidal.
You mentioned about light and sound sensitivity, yes! This is my main symptoms, that I have been struggling with since carbamazepine withdrawal. Thank you for mentioning this because I forgot to mention it in my thread!
That is why I stopped listening to music, I'm quite over-conditioned by aversion, I am still hypersensitive to sound, which seems to me unbearable noise.
That's how I wonder that your pattern sounds familiar. It reminded me a little of 2017 when I did it, by accident the same, only in the stronger version withdrawing carbamazepine, just as all my mental disorders that I did not feel for many years returned and the same after the withdrawal of carbamazepine I had a sudden erection enhancement. Before carbamazepine PAWS my libido was much higher but my erection function was weaker.
So, my healing regimen would have to include something that goes in the opposite direction, apart from libido (it's zero and I have cold contracted genital, blood vessels).
Last edited by finities infinities on Fri Oct 25, 2019 2:18 pm, edited 2 times in total.
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Re: Cure attempt #2 (in-progress / initial findings)

Unread post by naiverat »

Praise Lord Meso
Fluoxetine Jan. '16 - Aug. 16'. Low libido, weak erections, CNS dysfunction, anhedonia

Windows on the following: Inositol, choline, NAC + Histidine, MSM, SJW, L-Arginine, Sildenafil, Naltrexone, boron
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Re: Cure attempt #2 (in-progress / initial findings)

Unread post by i.hope »

Thanks for giving us hope! this is life-changing news to me because your background is very similar to mine and I think I have the same subtype of PSSD

How were you able to source DXM ? is it available online ? or did you extract it from other meds that contains it ? or did you just take high doses of meds that contain it?
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Re: Cure attempt #2 (in-progress / initial findings)

Unread post by mrstaircase »

You can buy it as a cough medicine in the netherlands/belgium.
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Re: Cure attempt #2 (in-progress / initial findings)

Unread post by TalkingAnt »

Exciting results!

Is it required that DXM and naltrexone are ran at the same time?

I wonder what the minimum effective doses of these two are, as I imagine the side effects of these drugs will make it difficult to last even a few days on this regimen for many of us.

I happen to have both DXM and naltrexone on hand, but I might need to come off of rasagiline before trying this. Also, this regimen will probably make me feel terrible and exacerbate insomnia, so I'm not committing to trying anything yet.
finities infinities
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Re: Cure attempt #2 (in-progress / initial findings)

Unread post by finities infinities »

I think about what you wrote all the time and try to imagine your thoughts before and after therapy. When did you have thoughts similar to what I wrote in my thread? After therapy, did you start thinking about existential topics, e.g. can the earth's resources or combination of haircuts, clothes shapes, human faces, tree shapes run out? Have you become more analytical or rational or more magical, optimist, wishful?
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Re: Cure attempt #2 (in-progress / initial findings)

Unread post by Meso »

Hey fellow sufferers!
I've added a "post-regimen updates section" to the 2nd OP after the "conclusion". This is to keep it all in one place for new-comers, so people won't have to read through so many pages of posts to find the updates, in case this threads gets too large.

Consider it a log for monitoring my post-regimen "drug-free" new baseline and getting there. I've decided to be completely drug-free for at least 2 weeks in order to really gauge my new baseline after the NMDA-rebound withdrawal syndrome.

I'll also quote it so you don't have to return to page 1 in the future if you are already keeping an eye on this thread:
Mesolimbo wrote: 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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Re: Cure attempt #2 (in-progress / initial findings)

Unread post by lukejimmy »

Does your PSSD involve deralization/depersonalization and has DXM ndma antagonist withdrawal produced a rebound effect?
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