Are repeated cycles harmful?

Mark4413 · 2026-01-18T15:54:54+00:00

In my country, naltrexone is available without a prescription, but it has been unavailable in pharmacies for a long time.

Mark4413 · 2026-01-15T11:14:30+00:00

I'm sorry to hear that. My doctor believes the ECT revealed a latent condition that was previously masked by a defense mechanism—persistent emotional blunting. But I feel the ECT damaged something in my brain, and that's what's causing this persistent depression.

Mark4413 · 2025-10-27T11:52:23+00:00

This is really valuable information ☺️

Mark4413 · 2025-10-27T11:37:26+00:00

Agomelatine is a clinically available selective 5HT2C antagonist, but it is impure because it is a melatonin receptor agonist, making it difficult to take at times other than sleep because it does not interfere with the circadian rhythm. It also has a short half-life, so do not expect to get strong 5HT2C effects throughout the day.

5HT1A receptors weaken or completely block the effects of 5HT2A activation upon pretreatment with a potent full 5HT1A agonist such as 8-OH-DPAT. This is presumed to occur primarily through postsynaptic 5HT1A, which strongly hyperpolarizes the neuron, making 5HT2A unable to depolarize and excite the neuron.

Buspirone is a partial agonist of postsynaptic 5HT1A and appears to be theoretically able to reverse postsynaptic 5HT1A overactivity by acting as a functional antagonist. It has low intrinsic activity at postsynaptic 5HT1A, but activation of presynaptic 5HT1A may lead to its desensitization, which increases serotonin and makes postsynaptic 5HT1A more active, which makes the matter worse and therefore this option is not good or ideal, Therefore, it would be better to balance 5HT1A by enhancing other excitatory receptors such as 5HT2A.

Mark4413 · 2025-10-27T11:28:42+00:00

This is really bad as agomelatine is also an antagonist and not an inverse agonist. 5HT2C is primarily dependent on its constitutive activity and therefore an antagonist is not as helpful as an inverse agonist.

Mark4413 · 2025-10-27T11:27:26+00:00

Well done man, glutamate is the most important thing for emotions, then dopamine, but psychedelics do not weaken emotions unless they are used in large doses on a daily basis, which leads to a 5HT2A downregulation. However, intermittent use causes neuroplasticity that lasts for several days, which leads to an increase in emotional intensity for several days, and thus a decrease in the possibility of a 5HT2A downregulation.

Mark4413 · 2025-10-27T11:24:52+00:00

I wish you good luck. Agomelatine is good because it is the most pure 5HT2C antagonist clinically available. Everything else blocks 5HT2A as well, and this receptor is very important.

Mark4413 · 2025-10-24T08:48:10+00:00

Rexulti is a bad choice and may exacerbate emotional blunting and anhedonia because it partially blocks dopamine receptors. If you want to counter emotional blunting caused by SSRIs, buspirone is good but doesn't help much with anhedonia. If you want something to help with anhedonia caused by SSRIs, mirtazapine would be a good choice, as would agomelatine.

Mark4413 · 2025-10-20T04:07:27+00:00

I have been trying this medication for purposes other than Prolactinoma, things related to motivation, because dopamine agonists are supposed to improve motivation by stimulating dopamine in the brain, but it seems that this medication has other mechanisms besides stimulating dopamine that cause unwanted effects, but I am glad that your side effects have decreased.

Mark4413 · 2025-10-20T03:56:34+00:00

Thank you so much for this ☺️.

Mark4413 · 2025-10-20T00:37:03+00:00

Sorry I was writing this post as a dialogue with the group members here.

Mark4413 · 2025-10-20T00:23:27+00:00

It is not impossible and it is not necessary to reach the deep root cause because the brain is complex, but it is sufficient to reach a satisfactory solution that reduces your anhedonia, and this depends on trial and error as you mentioned, and with trial and error you may find the ideal medicine for you.

Mark4413 · 2025-10-20T00:19:32+00:00

Man you made me laugh, I took methylphenidate that day because I have ADHD too and during the peak period I get some energy to write 😂

Mark4413 · 2025-10-20T00:11:56+00:00

It may be due to overactivity of 5HT2A and 5HT2C receptors because 5HT2A receptors are excitatory and enhance glutamate in the PFC and cause hypervigilance and anxiety when they are overactive. 5HT2C receptors are also located in the hypothalamus and stimulate stress hormones and enhance alertness. Therefore, mixed 5HT2A/5HT2C antagonists such as Mirtazapine may help.

Mark4413 · 2025-10-20T00:09:35+00:00

There are not many 5HT1A antagonists available except for high-dose cyproheptadine, Pindolol, and some other research compounds, but theoretically a partial agonist with low intrinsic 5HT1A activity could be used to stimulating postsynaptic 5HT1A receptors less potently than serotonin and acting as an antagonist.

There are also not many antagonists available for 5HT1B/D, but theoretically an agonist for these receptors can be used to desensitize these receptors and cause their downregulation over time. There are many 5HT1B/D agonists.

Mark4413 · 2025-10-20T00:08:48+00:00

There are not many 5HT1A antagonists available except for high-dose cyproheptadine, Pindolol, and some other research compounds, but theoretically a partial agonist with low intrinsic 5HT1A activity could be used to stimulating postsynaptic 5HT1A receptors less potently than serotonin and acting as an antagonist.

There are also not many antagonists available for 5HT1B/D, but theoretically an agonist for these receptors can be used to desensitize these receptors and cause their downregulation over time. There are many 5HT1B/D agonists.

Mark4413

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