St. John's Wort: PSSD Eliminated, Anhedonia Gone, Emotions Online!

[PeskyPeater]

Front Pharmacol. 2022; 13: 925879.
Published online 2022 Jun 16. doi: 10.3389/fphar.2022.925879
PMCID: PMC9243434
PMID: 35784746

"In contrast, administration of the selective agonist SA4503 or fluvoxamine (with a high affinity for Sigma-1 receptor) for 2 weeks caused a decrease in the immobilization time of CaMKIV−/− mice in the FST and the tail suspension test (TST), while those effects were abolished by preliminary treatment with the sigma-1 receptor antagonist NE-100 (Moriguchi et al., 2015). The abovementioned evidence indicates that a significant role of sigma-1 receptors in regulating Ca2+-dependent mechanisms of antidepressant action may not only be related to extracellular Ca2+ influx but also to intracellular Ca2+ homeostasis (Urani et al., 2002; Choi et al., 2022).

Sigma-1 Receptors Regulate Excitatory and Inhibitory Balance
The classic “monoamine hypothesis” underlies the development of most clinical antidepressants that primarily exert their effects by enhancing the function of monoamine transmitters (Li, 2020). The translocation property of sigma-1 receptors allows them to modulate proteins directly not only at the ER-mitochondrion interface but also at the membrane where many ion channels, receptors and kinases are found, rendering sigma-1 receptors a unique inter-organelle signaling modulator in living tissues, including the CNS that we focused on (Su et al., 2010). In recent years, an increasing body of evidence suggests that sigma-1 receptors directly interact with proteins at neuronal cell membranes (more information is reviewed in (Ryskamp et al., 2019)) and enhance neurotransmission (Bermack and Debonnel, 2001; Bermack and Debonnel, 2005; Sambo et al., 2017; Sambo et al., 2018). The active roles of sigma-1 receptors in the regulation of neurotransmission, including the glutamatergic, GABAergic, serotonergic, dopaminergic (Sambo et al., 2018) and noradrenergic systems (Dhir A. and Kulkarni SK., 2008), is well documented. Those neurotransmission systems may form the basis for the dynamic balance of E/I neural networks in the brain. Especially, sigma-1 receptors have been reported to regulate presynaptic glutamate release and modulate NMDA receptor activity via direct PPI associations (Kourrich, 2017). Furthermore, sigma-1 receptor activation can also lead to alterations in NMDA receptors that upregulate and traffic to the plasma membrane thus further modulating neuronal intrinsic excitability (Pabba et al., 2014). In addition, Mtchedlishvil et al. found that pregnenolone and a selective sigma-1 receptor agonist (SKF-10047) inhibit the GABA-dependent inhibitory postsynaptic currents in rat hippocampal cell cultures (Mtchedlishvili and Kapur, 2003). We therefore suggest that sigma-1 receptors may regulate the E/I balance in direct or indirect manners. Importantly, there is abundant evidence that the medial prefrontal cortex (mPFC) or the hippocampus rely on the dynamic balance between E/I neurotransmitters for various advanced functions, such as emotion regulation and expression, as well as cognitive functions. Those two neurotransmitters achieve a dynamic balance to maintain normal physiological function under normal circumstances (Ferguson and Gao, 2018). Preclinical studies have shown that chronic stress can lead to decreased E/I neurotransmitter transmission in the mPFC (Fee et al., 2017). Consistent with this, a recent study found that chronic stress can lead to decreased glutamate and GABA neurotransmitter transmission in rat mPFC (Fee et al., 2017; Duman et al., 2019). In this context, GABAergic and glutamatergic neurotransmission may be almost rebalanced but the synapses remain impaired, thus the E/I rebalance may be at a low level. However, we recently found in our laboratory that regulation of the E/I rebalance in the mPFC may be an important mechanism and rate-limiting step in the efficacy of antidepressant effects (Yin et al., 2021).

The glutamatergic and GABAergic as well as serotonergic systems are heavily implicated in antidepressant actions. In this section, we mainly focused on the possible mechanisms by which sigma-1 receptors exert their antidepressant effects through the regulation of E/I balance by theseneurotransmitter systems.

 

[TheCedar1]

hold your horses dear fella. Hypericin is a sigma-1 agonist it can take 2 weeks until good effects are felt

Then how come Lokzo and the others got results within days of taking remotiv?

 

[TheCedar1]

Front Pharmacol. 2022; 13: 925879.
Published online 2022 Jun 16. doi: 10.3389/fphar.2022.925879
PMCID: PMC9243434
PMID: 35784746

I'm not the most smartest man in this world, could you simplify this for me please?

 

[PeskyPeater]

Then how come Lokzo and the others got results within days of taking remotiv?

Every brain is wired somewhat differently and for some SSRI were the cause of PSSD and others certain herbals...

 

[TheCedar1]

Every brain is wired somewhat differently and for some SSRI were the cause of PSSD and others certain herbals...

Yeah, but for me and Lokzo amongst others on this thread, our cause was because of KSM 66, I know for a fact I haven't touched any SSRIs in my life, so I don't understand here man

 

[PeskyPeater]

@TheCedar1

There is the posibility that your batch of Remotiv is old and the hypericin has been degraded. It breakdown after 6 months of storage.

 

[TheCedar1]

@TheCedar1

There is the posibility that your batch of Remotiv is old and the hypericin has been degraded. It breakdown after 6 months of storage.

Impossible as according to the package, it expires in 2024, or is there a separate expiry date I'm not aware of? The company, Ewopharma, stated that once the product reached its expiry date, its rendered ineffective, mine is until 2024.

 

[PeskyPeater]

Impossible as according to the package, it expires in 2024, or is there a separate expiry date I'm not aware of? The company, Ewopharma, stated that once the product reached its expiry date, its rendered ineffective, mine is until 2024.

okay. then the product is not the problem. Do you take progesterone by the way, or some other things that affect steroids?

 

[TheCedar1]

okay. then the product is not the problem. Do you take progesterone by the way, or some other things that affect steroids?

I used to take andractim months ago, but I had already recovered my natty test levels and haven't touched anything since.

Does weight and height influence its effectiveness?

 

[PeskyPeater]

I used to take andractim months ago, but I had already recovered my natty test levels and haven't touched anything since.

Does weight and height influence its effectiveness?

oke. should be good now. I asked bc steroids could have effects on the same pat of the mitochondria as hypericin that affects stereiogenesis.
no, not so much I think. I think you should give it some more time. And go jogging and some concentric exercise to increase your mitochondria

 

[TheCedar1]

oke. should be good now. I asked bc steroids could have effects on the same pat of the mitochondria as hypericin that affects stereiogenesis.
no, not so much I think. I think you should give it some more time. And go jogging and some concentric exercise to increase your mitochondria

Alright then, I will give this a few more weeks, thank you for helping me mate

 

[PeskyPeater]

Alright then, I will give this a few more weeks, thank you for helping me mate

Sure, you're welcome. Looking forward to your progression. Good luck!

I'm actually trialing SJW again myself since yesterday. I have somewhat improved the weak orgasms from PSSD, but i'm still missing that sweet warm cognitive euphoria and I feel off in general, not quite my old self. So I'm with you man, fingers crossed. Let's go

 

[TheCedar1]

Sure, you're welcome. Looking forward to your progression. Good luck!

I'm actually trialing SJW again myself since yesterday. I have somewhat improved the weak orgasms from PSSD, but i'm still missing that sweet warm cognitive euphoria and I feel off in general, not quite my old self. So I'm with you man, fingers crossed. Let's go

I will pray that you recover mate, we're in this together brother, we will defeat this disease

 

[Cooper]

"Entranced by the music. Tickles and goosebumps are back."

Until recent years I always was able to go like that, day after day. Feeling everything to the maximum. I was able to even rewatch a movie 5 times and still laugh about something in the movie.
Sometimes I was watching shows and laughing a good 10minutes without stopping and my belly was hurting. Not each day, but often.

But such ultra high spirits has it's drawbacks, people will lie like the is no tomorrow to you if they figure you are high spirits and do not say anything back.
Not to mention how many fake promises you get that way. Being less high spirits will get you pretty much no promises in nothing and no disappointment.
No regrets here about that type of feeling not being no more, only that I realized many people wanted to be around me and after years I realized no one was doing anything I asked them to do and pretty much all kind of low responsibility people flocked aro

My story:
In 2016, I used dosed Ashwagandha KSM-66. I can’t exactly remember how much, but I remember one specific time after dosing this WAVE of numbness come over me and this VERY dramatic change of headspace. I almost felt like I didn’t care about anything at all. Zero anxiety, zero anticipation for things, just existence, not actually alive. This then lead onto a completely NUMBED orgasm that night, and I was like, hmmmm that was very weird, I should be able to bounce out of this.

Other compounds have definitely worsened me over time:
-Berberine.
-Zinc supplements.
-ALCAR.
-Rhodiola.
-L-Theanine.

SO I waited…. And waited, and waited. Still nothing. 4 years later, still searching for answers, and I had found answers along the way, for sure.

The first one was homeopathic phosphorus 30C. This brought ALL my emotions back online, and made me feel again, it was incredible. I remember hearing birds tweeting near my window, and appreciating this sound and it almost tickling me. Then, I also remember getting that emotional response to music again.
After this, I decided to dabble with Cyproheptadine.
This is unlike many other drugs. In fact, its never something I actively looked forward to taking. Instead, I actually looked forward to what it does following its use.
Eg. How I feel on the withdrawal of the drug.
It makes me feel so fearless and numb on the drug, as in, I can’t feel any emotions, and my appetite goes through the roof. My energy in the gym is ***t on cypro, I feel weak and miserable. No motivation, no life, no vigor, just blah - existence. During this grim days, after using cypro over 25 times in the past 7 months - I know that the rebound is ALWAYS worth it.
This rebound comes EVERY SINGLE TIME…. 4 days AFTER a single 1mg dose. That is, if I take it on a sunday night at 5pm, I will feel like ***t for 3 days and then on day, I get this REBOUND, where my PSSD disappears and this last for a few days on. HOW?!?!?!?

But never did I ever think that there would be a drug that is to be used to RECALIBRATE the brain over time, to recover from this enduring PSSD. It feels like it reconnects that cosy/soft spot of the brain that is required to FEEL music, to feel hot water on skin, to be cosy on the couch, imagine living a life where you can no longer even enjoy relaxing, or having a hot bath, because there’s no emotional response to it, there’s no depth. This is what PSSD has been for me.
But, when the cypro wears off, you feel your YOUNG self re-emerging and all of a sudden FEELINGS come back.
My logic and verbal fluency improve on cypro.

It definitely has its side effects.
Ravenous appetite, minor headaches in the mornings, grogginess/sleepiness (This wears off after repeated use). Eventually, it leaves you feeling resilient and adaptable. Less triggered, much more in control and in tune with your mind, there’s no scatter feeling, you feel clear and hear your own voice, however, your background mind chatter is completely gone when conversing with other people.
Cypro definitely makes me feel clinically depressed the morning after using it. I feel like it sucks ALL the life out of me.
Stop thinking about the future. I find myself way more PRESENT on cypro.
But after realising that every single time that I kept getting bumped out of these windows and then having to RELY on cypro to bounce me back out 4 days after dosing was just too much for me to handle. So I QUIT. I told my dad to take the box away from me.

ENTERING: St. John’s Wort Ze 117 Extract - *The final frontier* - March 19, 2020.
I remember first dosing, not really noticing much at all. In fact, the second day, I actually thought my symptoms were getting worse. I almost quit.

But then, I had something very scary and exciting happen to my brain.

I remember I was half-dreaming one night, and having this grim-reaper looking like entity, standing in front of me. I was a little scared, but he came over to me and really hurt me, did something to my head, but then afterwards I remember laughing and saying thank you, I remember feeling like he had taken away something that was stuck inside me, and then I was free again, a liberating moment.

Anyway, this was then followed by the start of the “random flashbacks of emotions”. This was the first sign that something significant was changing, for the better. Day 4-5 all orgasm feeling and erection feelings were excellent. Morning woods and sexual dreams came back too.

Day 6 on St John's Wort extract (Ze 117) - LOW in hyperforin:
ALL my PSSD symptoms have reversed.... Complete sensation back, feeling, anhedonia disappeared, I have a thrill for life, excitatory response and RANDOM Flashbacks and emotions.


Keep in mind that in the past I had used Perika SJW brand, but this did not help me at all, in fact, I felt hyper-paranoid and anxious and even more numbed on this particular extract.


This is copying what CYPRO does to me on the rebound... But I feel much better using SJW Ze 117 low in hyperforin instead of relying on diabetic cyproheptadine just to feel good. And I feel like this SJW will lead to permanent effects if I stick with it for long enough.

SEXUALITY/PSSD
My refractory period has gone down significantly, I have erotic dreams again and I can have a massive climax and pleasure again. Stronger ‘gasms. Quicker reload. I get erections just staring at hot girls easily, like a 14 year old again.

This is also what I have noticed from St. John's Wort Extract (Positive effects started on day 3, and got WORSE initially):
-Flashbacks and waves of emotions like when I was a child. This was robbed from me, almost as if I had been SSRI'd.
-I started crying at night about my past soccer childhood career that ended… This was an AMAZING feeling, being able to FEEL the pain of crying…. Crying was difficult for me prior to this.
-Hurt feelings when something bad happens, that little stab to the heart feeling is back.
-Difficulty working at a fast pace, because I am emotional or feeling my thoughts which is interrupting my flow state. Usually when I'm numb, I can work insanely quick and find myself in a flow state a lot. This is harder when I am alive again.
-Thrill and excitatory response is back, the suspense feeling is back, I can FEEL a movie or music.
-Less altruistic and more focused on how I can SATISFY myself, more addictive prone, more inclined to take risks.
-More distracted.
-Startle response back.
-Entranced by the music. Tickles and goosebumps are back.
-Emotional flashbacks to when I was younger playing video games at Tato’s.
-Slightly more unusual behaviours and less stable, but more emotional, way more emotional, the emotional depth has come back online fully. That thrill and excitatory response has come back and is like a feeling in the chest that is just there and tickling
-Little bit slower and worsened verbal fluency, but this is because I am now more HEIGHTENED and thrill is back!!!
-Flashbacks to sitting down at primary school for MOVIES in the halls, where we used to sit down and feel that thrill of sitting next to hot girls…. that little excitation of being in , where we used to have assembly’s and I used to get excited if a hot girl sat near me!!!
-Anticipation for the BELL to go, in class, waiting for break, the excitation and thrill to go outside and SHOW off.
-Hyper alert and vigilant.
-Hesitation before speaking, that little thrill is back.

I feel like a re-emergence of my OLD personality is back. I must say though, there were definitely advantages to being NUMB though, but this is a story for another time.


After 4 days of using SJW you have reached steady state dose in plasma and then you could lower the dose maybe against the anxiety. I went from 900 to 600mg to 300mg a day, taking half capsules 2x day. And for me caffeine made me aggressive and anxious, I think because SJW is also an adenosine antagonist like caffeine is and can more easily deplete the dopamine stores. SJW should shift the Serotonin/dopamine balance towards Dopamine. I felt it in my behavior I became more dopamine dominant. Also had high euphoria in the evenings but with lowered focus. But chill.

Here’s some other reports online about SJW helping with anhedonia/PSSD:
“[February 27] I went to the pharmacy immediately and bought SJW 900 mg tablets. I’ve taken them for five days now, and wow… just WOW!

My morning wood is very strong and I get very intense erotic dreams now. At first I was a little afraid, because I read that SJW works like SSRI. But it does not. There are no sexual side effects, except the positive ones. I am a little dizzy, though. Today I had the most intense orgasm since I got PSSD four years ago. I will definitely continue the treatment. I must say, that I already made some progress over the years, but I constantly had to force myself to masturbate. Now I am horny again. There is still much room for improvement, but I made the first step into the door. And this is still the fifth day, where SJW is supposed to fully kick in after 2 – 3 weeks.”


“The first two days I also had the impression that the symptoms got worse a bit. I almost quit to be honest. Then it got better and better. Today is the sixth day and I get strange flashes of emotions I haven’t felt for years. I even forgot about them. This only lasts about a second or two, but it gives me hope, that there is some rewiring going on in my brain. I even had an erotic dream again. The whole four years I had do deal with PSSD I got five erotic dreams in total, which I can remember. Three of them happened this week. ”


“Today is the 10th day of my SJW treatment. My penis was a bit more numb today than the previous days and the orgasm wasn’t very great too. I rose my dose from 900 mg to 1350 mg yesterday, though. Maybe my nervous system has to adjust to the new dosage first. Overall feeling is pretty good. I still get these emotion-flashes which remind me that my capability of having positive emotions hasn’t died yet. Playing computer games is a little bit fun too. I used to be a hardcore-gamer before I got PSSD. When my emotions got numb, I stopped playing. Windows where my condition becomes a little better have occured prior to my SJW treatment, but now they seem to be more often and more intense, but I am far away from being cured.”


“The SSRI-like symptoms are compensated by the effects on dopamine and other neurotransmitters to some extend, I think. To my surprise I had an almost acceptable orgasm yesterday – with an enjoyable buildup. I don’t notice any withdrawal symptoms so far. I think I just quit taking normal doses, before the stuff can make any permanent mess with my receptors. Maybe I should try the OP method and take small doses several times a week, because I am convinced now that this drug has beneficial effects on PSSD.”


“My sexuality has further improved, by the way. Buildup was very good today, the orgasm was longer and more enjoyable and I even noticed a significant increase in semen amount. As a bonus I got a very strong anxiolytic and antidepressive, pleasant effect. I feel good and the reward system functions better. Played Hearthstone yesterday and it was an exciting blast! I must add that I was very anhedonic before I tried SJW (minus the windows). The at first experienced negative sexual side effects have completely faded away. It takes a little bit longer until I cum, but that is a good thing in my case!”


“I would recommend a brand that has the whole bandwidth of active components. I am on “Laif 900″. I live in Germany, don’t know whether it is available in foreign countries, but you can order it via the internet, I guess.”


“As I wrote, SJW impacted my sexuality negatively too. But that faded away. I think it is pretty expectable that an imbalanced system gets initially imbalanced even more when it gets repaired. Antidepressents cure depressions but worsen the symptoms at the beginning of the treatment. Teeth surgery elevates pain before it lessens it in the long run. Antipsychotics can make psychosis worse before it gets better. There is rarely a cure which heals you in an instant without temporary side effects.


But everyone is different. It could very well be that SJW worsens your symptoms in the long run and doesn’t help you at all. You must know for yourself if you take that risk. I am glad that I did. But 1000 mg as the initial dose is very brave. I started with 450 mg which triggered an uncomfortable panic attack.”


“This is the best thing that happened to me in a long time! I thank the OP so much, you are my hero man! :) Also thanks to Ghost for encouraging me to give it another try!”


“UPDATE: I can’t believe what is happening! Seriously!


I WANT things! My anticipatory anhedonia has completely vanished.This is an absolute milestone. Even in my best windows I was too anhedonic to really want something emotionally. It is just still a very general feeling. I don’t want specific things, I just feel I want something, lol. I think I have to learn to deal with this emotion again, but I am SO happy that my reward system has awoken. :)

Sexuality has also further improved. I get a boner now by just thinking about sex. A not very strong one though, but my morning erections are extraordinary strong. I think this is all because the 5HT1A and 5HT2A receptors have upregulated. They both trigger dopamine release. SSRI are known for downregulating them which can result in anhedonia, memory problems and sexual side effects. It all makes sense now to me.


EDIT: I rose the dose to 900 mg daily yesterday, because I have adapted to the side effects, and I like the feeling the herb gives me so much that I want to try normal treatment dosage. Maybe this has accelerated the improvement of my reward system.”


“Update: I found out that the anti-anhedonic effects of SJW get elevated a lot when I drink coffee. SJW agonizes adenosine whereas caffeine antagonizes it. Two cups of green tea give me a dopmaninergic buzz that lasts several hours, most likely because of the l-theanine/caffeine combination.”

Did your penile sensitivity etc. also came back to normal? Orgasms?

 

[TheCedar1]

Sure, you're welcome. Looking forward to your progression. Good luck!

I'm actually trialing SJW again myself since yesterday. I have somewhat improved the weak orgasms from PSSD, but i'm still missing that sweet warm cognitive euphoria and I feel off in general, not quite my old self. So I'm with you man, fingers crossed. Let's go

Hey man,
Do you think levothyroxine could cause 5ht1a desensitisation, since thyroid tends to do that?

 

[PeskyPeater]

Hey man,
Do you think levothyroxine could cause 5ht1a desensitisation, since thyroid tends to do that?

If you mean that study done on rats with t3 and imipramine, then I don;t think its an issue for humans. the converted rat dosage to humans is 2.7mcg per kilogram of bw that is 200mcg of t3. source

 

[MCurtone]

@Lokzo Did you continue to see the benefits from Remotiv SJW? Please let me know, I've been suffering with this plus PFS since 2016. I took copious amounts of KSM66 as well for 6-12 months, mega dosing it.

Emotions - little to none
Feel robotic
Brain fog that comes and goes
Low dopamine
Anhedonic
Libido that comes and goes

 

[Jayvee]

Can anyone here tell me, if ZE 117 was to down regulate beta-adrenoceptor, would that result in less active noradrenaline in the system or would it mean more noradrenaline and therefore stress?

 

[Prosper127]

orld/people. I'm also more positive and generally happier. Libido is als

@Lokzo Did you continue to see the benefits from Remotiv SJW? Please let me know, I've been suffering with this plus PFS since 2016. I took copious amounts of KSM66 as well for 6-12 months, mega dosing it.

Emotions - little to none
Feel robotic
Brain fog that comes and goes
Low dopamine
Anhedonic
Libido that comes and goes

Hi MCurton, saw one of your old posts on GHB to raise Allo, are you aware that haidut provides an allo liquid supplement ?

AlloP - Liquid Allopregnanolone For Lab/R&D

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[Bozidar]

Hi guys.
Yesterday, I stumbled upon this thread.
Today, I went to drugstore, bought the st John's wort. Tomorrow I will try it.
Switzerland, its over the counter, but its expensive. 30 franks for 30 pills 500mg.
I have high hopes for this to work.