I Will Be Taking Cyproheptadine's Younger Brother - Pizotifen

[Lokzo]

As many of you would know by now... I am the guy who gets a SPECTACULAR rebound effect from Cyproheptadine.

This is what happens:

Now, what I need help with is developing THEORIES, as to WHY CYPRO WORKS.

But it doesn't work when we dose it acutely.

In fact, a single dose of cyproheptadine (<1mg), will cause the following effects:
-Horrible libido.
-Fatigue.
-Ravenous appetite.
-Incredible digestion.
-Numbing of all my emotions.
-Zero Anxiety
-Amazing sleep.


BUT...... It's the REBOUND of cypro.... That CURES me of PSSD.

DAY 4 and 5 AFTER using 1mg of cypro, there's this incredible SNAPBACK effect....

Orgasm returns, no more blunted libido, everything amazing.


But WHY....

What is happening 4 days after Cypro?

I need help understanding how to replicate these effects.

So I will be testing the 5-HT2A Antagonism theory by using Pizotifen.

Has anyone had any experience with this drug?

 

[PeskyPeater]

Goodday!

5HT2 and -3 activation is involved in sexual dysfunction. link

Cyproheptadine blocks strongly the 5HT2 link

Seems to me it's bc when antagonizing (or agonizing) the 5HT2 system it will downregulate, reducing the inhibition on dopamine. This makes you feel better for a while. But im not quite sure why this is only temporary effect. As 5HT1 affects 5HT2 expression, which is affected by taking ashwagandha I suppose increasing expression of the 5HT1 could help.

Functional regulation of 5-HT2A​

The functional regulation of 5-HT2A involves desensitization and re-sensitization, which differentiates 5-HT2A from conventional GCPRs (e.g. the B2 adrenergic receptor) and prevents overstimulation1. At the molecular level, desensitization and re-sensitization of the receptor is controlled via clathrin-mediated receptor internalization and recycling1. This dynamin-dependent internalization can be triggered by antagonists or agonists of the receptor and exists to allow recuperation of signaling competence1. Long-term use of 5-HT2A antagonists has been shown to downregulate 5-HT2A expression1 and, while the mechanism of this "paradoxical regulation" is unknown, it is likely due to functional regulation. Everything we know about the 5-HT2A (serotonin) receptor

5-HT2A and schizophrenia​

There is evidence that abnormalities in 5-HT2A play a significant role in the pathology and treatment of schizophrenia2, a psychological disorder characterized by psychosis. Because the receptor modulates dopamine release in the cortex and striatum1, changes in 5-HT2A function are thought to be responsible for the motor and cognitive defects observed in the disease. ...

 

[Lokzo]

Goodday!

5HT2 and -3 activation is involved in sexual dysfunction. link

Cyproheptadine blocks strongly the 5HT2 link

Seems to me it's bc when antagonizing (or agonizing) the 5HT2 system it will downregulate, reducing the inhibition on dopamine. This makes you feel better for a while. But im not quite sure why this is only temporary effect. As 5HT1 affects 5HT2 expression, which is affected by taking ashwagandha I suppose increasing expression of the 5HT1 could help.

Thanks for your input.

Bear in mind that these symptoms really began when I first used Ashwagandha many years ago.

I’m also trying to uncover if Pizotifen is a 5-HT1A antagonist as well?

 

[PeskyPeater]

Pizotifen (BC-105) is a potent 5-HT2 receptor antagonist, with a high affinity for 5-HT1C binding site[1]. Pizotifen is an antidepresent 5-HT2A receptor antagonist and has the capacity to inhibit serotonin-enhanced ADP-induced platelet aggregation[2].

[1]5-HT2 receptor antagonists and migraine therapy - PubMed

If aswagandha made epigenetic changes they do not recover suddenly over time.

 

[InChristAlone]

Ashwaganda is a dangerous herb. It is a cholinesterase inhibitor causing high acetylcholine. Excessive acetylcholine overstimulates the nervous system particularly the parasympathetic which can lead to depression and low blood sugar. The cholinergic syndrome in learned helplessness. Cyproheptadine is an anticholinergic so it should be helping to turn things on again, the antagonism of dopamine could be having paradoxical effects increasing the ratio of acetylcholine to dopamine and contributing to cholinesterase inhibitor sensitivity. Have you ever tested cholinesterase? Those with a genetic variant for low cholinesterase enzymes can have paradoxical effects from anticholinergic drugs.

This site has more info: Anne Wright - Cholinesterase Inhibitors

 

[PeskyPeater]

It is highly interesting to see how that 5ht2 antagonist is going to work for this, I hope it will have good effects, but I find a single substance approach somewhat meager though.

Seems to me the neurosteroids are responsible for lot's of expressions of genes and systems in the CNS and brain that affect pleasure and interact with the GABA system and σ1 sigma system. GABA-A has recently been indicated to be involved with the synergy between the 5ht1 and σ1 system on dopamine.

And I know that dopamine has been indicated responsible for the pleasure part of the brain, but more recent finding suggest GABA to play a more important role. Involvement of GABAA receptors in 5-HT1A and σ1 receptor synergism on prefrontal dopaminergic transmission under circulating neurosteroid deficiency - PubMed

So I would concentrate on improving the neurosteroids, with PEA for example and Androsterone together with DHEA. Psychomotor and rewarding properties of the neurosteroids dehydroepiandrosterone sulphate and androsterone: effects on monoamine and steroid metabolism - PubMed

Palmitoylethanolamide stimulation induces allopregnanolone synthesis in C6 Cells and primary astrocytes: involvement of peroxisome-proliferator activated receptor-α - PubMed

Abstract​

Palmitoylethanolamide (PEA) regulates many pathophysiological processes in the central nervous system, including pain perception, convulsions and neurotoxicity, and increasing evidence points to its neuroprotective action. In the present study, we report that PEA, acting as a ligand of peroxisome-proliferator activated receptor (PPAR)-α, might regulate neurosteroidogenesis in astrocytes, which, similar to other glial cells and neurones, have the enzymatic machinery for neurosteroid de novo synthesis. Accordingly, we used the C6 glioma cell line and primary murine astrocytes. In the mitochondrial fraction from cells stimulated with PEA, we demonstrated an increase in steroidogenic acute regulatory protein (StAR) and cytochrome P450 enzyme (P450scc) expression, both comprising proteins considered to be involved in crucial steps of neurosteroid formation. ...

 

[TMCMac]

It is highly interesting to see how that 5ht2 antagonist is going to work for this, I hope it will have good effects, but I find a single substance approach somewhat meager though.

Seems to me the neurosteroids are responsible for lot's of expressions of genes and systems in the CNS and brain that affect pleasure and interact with the GABA system and σ1 sigma system. GABA-A has recently been indicated to be involved with the synergy between the 5ht1 and σ1 system on dopamine.

And I know that dopamine has been indicated responsible for the pleasure part of the brain, but more recent finding suggest GABA to play a more important role. Involvement of GABAA receptors in 5-HT1A and σ1 receptor synergism on prefrontal dopaminergic transmission under circulating neurosteroid deficiency - PubMed

So I would concentrate on improving the neurosteroids, with PEA for example and Androsterone together with DHEA. Psychomotor and rewarding properties of the neurosteroids dehydroepiandrosterone sulphate and androsterone: effects on monoamine and steroid metabolism - PubMed

What dosage of pea, androsterone, and dhea would work?

 

[PeskyPeater]

What dosage of pea, androsterone, and dhea would work?

I would carefully read the label of PEA and the thread by Haidut about Andro and DHEA

 

[miquelangeles]

@Lokzo have you tried the EGb 761 ginkgo biloba extract? It binds to 5-HT2A. Several studies showing that it decreases anxiety and aggression by reducing 5-HT activity. It often used to counteract the loss of libido caused by antidepressants. Tanakan brand comes in a liquid version as well that you can dilute in water, I like it better than the tablets.

 

[JamesGatz]

Does anyone have Cypro's OLDER brother because theres some peeps on this forum that NEED it

 

[Lokzo]

It is highly interesting to see how that 5ht2 antagonist is going to work for this, I hope it will have good effects, but I find a single substance approach somewhat meager though.

Seems to me the neurosteroids are responsible for lot's of expressions of genes and systems in the CNS and brain that affect pleasure and interact with the GABA system and σ1 sigma system. GABA-A has recently been indicated to be involved with the synergy between the 5ht1 and σ1 system on dopamine.

And I know that dopamine has been indicated responsible for the pleasure part of the brain, but more recent finding suggest GABA to play a more important role. Involvement of GABAA receptors in 5-HT1A and σ1 receptor synergism on prefrontal dopaminergic transmission under circulating neurosteroid deficiency - PubMed

So I would concentrate on improving the neurosteroids, with PEA for example and Androsterone together with DHEA. Psychomotor and rewarding properties of the neurosteroids dehydroepiandrosterone sulphate and androsterone: effects on monoamine and steroid metabolism - PubMed

I may trial DHEA and Andro when I am back in Australia.

 

[Lokzo]

@Lokzo have you tried the EGb 761 ginkgo biloba extract? It binds to 5-HT2A. Several studies showing that it decreases anxiety and aggression by reducing 5-HT activity. It often used to counteract the loss of libido caused by antidepressants. Tanakan brand comes in a liquid version as well that you can dilute in water, I like it better than the tablets.

I did try it, but I felt more "Tense" and "Uptight" on it, kind of like it was ramping up norepinephrine and blocking GABA, which I could feel the anti-social effects.

 

[Lokzo]

Does anyone have Cypro's OLDER brother because theres some peeps on this forum that NEED it

If it isn't the Great James Gatz... You consistently make me day a little brighter whenever I read your posts and comments. Thank you for staying authentically low serotonin.

 

[Basonh]

@

If it isn't the Great James Gatz... You consistently make me day a little brighter whenever I read your posts and comments. Thank you for staying authentically low serotonin.

As many of you would know by now... I am the guy who gets a SPECTACULAR rebound effect from Cyproheptadine.

This is what happens:

Now, what I need help with is developing THEORIES, as to WHY CYPRO WORKS.

But it doesn't work when we dose it acutely.

In fact, a single dose of cyproheptadine (<1mg), will cause the following effects:
-Horrible libido.
-Fatigue.
-Ravenous appetite.
-Incredible digestion.
-Numbing of all my emotions.
-Zero Anxiety
-Amazing sleep.


BUT...... It's the REBOUND of cypro.... That CURES me of PSSD.

DAY 4 and 5 AFTER using 1mg of cypro, there's this incredible SNAPBACK effect....

Orgasm returns, no more blunted libido, everything amazing.


But WHY....

What is happening 4 days after Cypro?

I need help understanding how to replicate these effects.

So I will be testing the 5-HT2A Antagonism theory by using Pizotifen.

Has anyone had any experience with this drug?

Any updates? Regarding pizotifen experimentation

 

[Lokzo]

@


Any updates? Regarding pizotifen experimentation

I am waiting til I return to Australia to try it. Currently travelling europe, in Copenhagen now.

 

[Lokzo]

Guys, I dosed 500mcg 1 hour ago. I will monitor symptoms and report back. Hoping it can offer me what Cyproheptadine does for the Anhedonia/PSSD.

 

[golder]

Guys, I dosed 500mcg 1 hour ago. I will monitor symptoms and report back. Hoping it can offer me what Cyproheptadine does for the Anhedonia/PSSD.

Watching this space!

 

[Lokzo]

Update:

It took 5 hours post dosage to feel the sedation.
I felt groggy, miserable, anti social, numbed, just disgusting… similar traits to cypro. Robotic.
I’ve woken up feeling groggy, sleepy and almost stoned. Yucky feeling. Last night I was deliberately eating more carbs due to such a flat mood… didn’t help. Let’s see how the next 24 hours goes.

 

[Lokzo]

Today has been an ABSOLUTE NIGHTMARE....
I will update you all when I write a log of my experience on pizotifen. I literally feel like my IQ is 40 points lower than normal today.

 

[Lokzo]

I’ve recorded a voice message (log) of my experience with Pizotifen

I attribute majority of my negative effects due to the anti-muscarinic and anti-cholinergic properties.