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SSRI long term Dysphoria/Anhedonia ?

Kurko's Photo Kurko 29 Jul 2016

 

Good evening,

I'm posting here because I'm totally desperate and your help could be really useful for me. In advance I am sorry for my English because I'm French. So here is my problem:

 

Naturally very anxious since I was child, I started smoking cigarette and weed 2 years ago. The high and the well-being was amazing and it makes me want to treat my psychological problems. So I consulted a psychiatrist a few days later who prescribed Paxil. 3 month after taking it I felt no difference and I decided to stop it.

During the SSRI discontinuation I feel like the high of Weed and Cigarette began to decline. And the more days pass it becomes more worse : No Euphoria.

 

I began to realize that I was being Anhedonic: No Sex Drive, No pleasure (go outside, watch tv.....), Nada.

I also have very low motivation, brain fog (low creativity/immagination) , obsessive negative thoughts,Anxiety, no excitement but desperation and frustration.

Physical symptoms : clammy hands, trembling muscles, pressure around the head and a completely stiff neck.

 

I tried many supplements and drugs but the well-being or euphoria' effect is completely blocked. Here the list. Nothing works: 

 

-Alcohol: Only if I drink more than 10 glass I begin to feel a slight decrease in anxiety. But no mental or physical well-being.

-Weed: No euphoria, no relaxation, nothing appart be weirder and anxious. Pressure around the head and cognition worse.
-Cigarette : I dont take more pleasure in smoking. I stopped
-Additional Food/Supplement: tyrosine, 5-htp, Vitamine B/D/C, Fish Oil,Ginseng, St. John's Wort, Bacopa,Theanine,Gotu Kola, Shisandra, Ginko,Passiflore,Rhodiola and Phenibut (I tested a year ago and it made me feel great) but now I do not even feel anything also in high-dose (2g),

-Coke: No euphoria, heart beating faster, high anxiety and a worse pression around the head and cognitive abilities worst
-Ritalin: Liltle  more confident but that apart, nothing .Heart which beats faster and worse cognition.
-LSD: I tried microdosing I felt nothing. A higher dose I was just more anxious and always this impression of head pressure and have the impression of being weird. But when I closed my eyes I had some hallucinations.
-SSRI/SNRI: Paxil, effexor, celexa, fluoxetine, effexor made me into a worse state. A true zombie.
-Low dose Antipsychotic: Solian Abilify and felt no effects.
-Benzo: Feel  like a vegetable, no desire, only the desire to sleep and do nothing.

-Nootropic: Piracetam, Aniracetam,Noopept, Choline, Alpha GPC

 

I started CBT therapy and exercise every day but I do not feel positive impact. I feel that there is something that blocks positive feeling and I think this is definitely come from the SSRI Discontinuation.

 

Next try : CBD Oil, High dose INOSITOL, Low dose Lamictal, Low dose Ketamine, NSI 189.

 

Some suggestion please?

I Will keep you update  ;)

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PeaceAndProsperity's Photo PeaceAndProsperity 29 Jul 2016

Try BCAA amino acids with tyrosine to reduce serotonin and increase dopamine. Seems to slightly help me (I take BCAA complex before bed for better sleep quality).

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Kurko's Photo Kurko 29 Jul 2016

Thanks my friend i will add this to my next try

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jaiho's Photo jaiho 29 Jul 2016

Had the exact same symptoms as you after using SSRIs alone, and tried everything to get a feeling of euphoria back.

All drugs stopped working, and i was using LSD/ Shrooms to get some kind of feeling, these were the only drugs to break through it somewhat, but nothing like before.

 

Funnily enough, it took an SSRI + TCA to do it. SSRIs alone are OK for a certain type of depression/anxiety, but to really punch through the dysphoria & disassociation it took an augmented approach.

 

Zoloft + Nortriptyline did it for me.

 

After going on this combination, weed, alcohol, music, everything came back. can feel euphoria again.

 

And this is after trying all the hard hitting meds like MAOIs, SNRIs, all the SSRIs, NSi-189 etc.

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Kurko's Photo Kurko 29 Jul 2016

Oh my friend glad to see you on this post because i saw your username in a lot of topic about anhedonia.

Do you get also the head pressure with very little energy and brain fog (before you found this combo)?

 

I tried LSD at low dose (20ug and 100ug) but my head pressure became worse... Like all the euphoria is blocked and anxiety become worse.No hallucination even at 100ug.

Did you try low dose lamictal? Because i read it can recover from SSRI discontinuation.

 

 

Nortriptyline is not available on my country, have you tried an other TCA? And what about sex drive?

 

Thanks a lot for your help 

 

Had the exact same symptoms as you after using SSRIs alone, and tried everything to get a feeling of euphoria back.

All drugs stopped working, and i was using LSD/ Shrooms to get some kind of feeling, these were the only drugs to break through it somewhat, but nothing like before.

 

Funnily enough, it took an SSRI + TCA to do it. SSRIs alone are OK for a certain type of depression/anxiety, but to really punch through the dysphoria & disassociation it took an augmented approach.

 

Zoloft + Nortriptyline did it for me.

 

After going on this combination, weed, alcohol, music, everything came back. can feel euphoria again.

 

And this is after trying all the hard hitting meds like MAOIs, SNRIs, all the SSRIs, NSi-189 etc.

 

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jaiho's Photo jaiho 29 Jul 2016

Yep. Grey foggy head feeling, with IBS, extreme fatigue.

I think SSRIs are actually useful but only with 5ht2c blocked & an NRI. 

You can buy Nortriptyline online at Geoff pharmacy, or use desipramine.

The other option is using an SNRI like Cymbalta, and adding an anti psychotic like Geodon. The point here being, ensuring 5ht2c is potently blocked, NRI & SRI.

 

But for least side effects, Zoloft + Nortriptyline is the way to go. It doesn't have sexual side effects due to the NRI & 5ht2c properties.

 

NSI-189 used to work for me but i still couldn't feel euphoria. I dont think its a strong enough AD for Anhedonia.

 

 

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Galaxyshock's Photo Galaxyshock 30 Jul 2016

Do you get pleasure effect from opiates?

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Kurko's Photo Kurko 30 Jul 2016

I never tried opiates. Why not some Kratom or Tramadol?

 

Do you get pleasure effect from opiates?

 

 

Nortriptyline and desipramine are not available in my country. And i dont know if i can buy it on online pharma without prescription.

I have a prescription for Cymbalta but i dont want to take it sole. Can a combo Cymbalta+Mirtazapine be helpful?

Really I am very afraid to come back on SNRI/SSRI.

I think SSRIs are actually useful but only with 5ht2c blocked & an NRI. 

You can buy Nortriptyline online at Geoff pharmacy, or use desipramine.

The other option is using an SNRI like Cymbalta, and adding an anti psychotic like Geodon. The point here being, ensuring 5ht2c is potently blocked, NRI & SRI.

 

But for least side effects, Zoloft + Nortriptyline is the way to go. It doesn't have sexual side effects due to the NRI & 5ht2c properties.

 

NSI-189 used to work for me but i still couldn't feel euphoria. I dont think its a strong enough AD for Anhedonia.

 

 

 

Thank you guys

---

 

I received my CBD Oil yesterday. I took two capsules but I did not feel anything. I will try to increase the dosage.

 

Next test: Inositol

Edited by Kurko, 30 July 2016 - 12:17 PM.
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jaiho's Photo jaiho 30 Jul 2016

Yes, Cymbalta + Mirtazapine is similar to Effexor + Mirtazapine, which is called California Rocket fuel, for depression.

I prefer Cymbalta since it binds stronger to NE compared to Effexor at lower dosages. For Effexor to bind strong to NE it requires high doses, and not to mention Effexor has a very unpleasant withdrawal (due to its short half life)

 

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Kurko's Photo Kurko 30 Jul 2016

I wil try the Mirtazapine only and if I do not see any improvements i will add the Cymbalta.

Yes, Cymbalta + Mirtazapine is similar to Effexor + Mirtazapine, which is called California Rocket fuel, for depression.

I prefer Cymbalta since it binds stronger to NE compared to Effexor at lower dosages. For Effexor to bind strong to NE it requires high doses, and not to mention Effexor has a very unpleasant withdrawal (due to its short half life)

 

Thanks.

Keep you update

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thedevinroy's Photo thedevinroy 31 Jul 2016

Are you currently taking anything? I know for me, cat's claw prevents a lot of adrenaline from forming into the next day, for instance. I wouldn't call it anhedonia, but it is similar in that I am not easily excited or anxious. Not really my cup of tea...

Striatal dopamine levels are a really sensitive thing. A lot of people don't realize just how sensitive dopamine metabolites can kill their striatum. Some meth addicts literally never fully recover this part of the brain. Interestingly, delusions are associated with increased dopamine activity in this part of the brain, so there is an overkill possibility.

http://www.ncbi.nlm....ubmed/19204262/

I suspect this is why delusional patients are treated with clozapine like drugs.

So what you need to do is looks at ways of increasing striatum activity without tipping the scale into the schizophrenia zone. Dopamine is usually the neurotransmitter of focus in the striatum, but interestingly GABA also has an effect of note. Rather than going for the benzodiazepines, which don't typically affect GABA-B, a whole rise in GABA levels in that section of the brain should be associated with a balanced cognition when combined with equivalent rises in dopamine levels.

Basically what I'm saying is that your anxiety is from too little inhibition (think GABA but also serotonin and canabanoids) and your anhedonia is from too little pleasure (think dopamine). You want a balance, which is why weed was so nice for you...

For a line of drug combo's that would work, I think your should look at treating your symptoms in a totally removed point of view and consider that BP2 is a real possibility. Valproic acid is a learning enhancer that also treats BP2 by lowering your clock speed just to the point where you can listen more clearly. Being that it is for BP, it will help smooth out any potential ups and more importantly, your downs, too.

I'm not done yet.

Exercise needs to be moderate to intense 3 to 5 days a week - and extremely consistent for the first 20 minutes. You want to completely remove glycogen at least once a week, meaning a hike or bike ride lasting 45 to 2 hours. No week can be an exception - this initiates a fasting process that continues to reset your insulin tolerance (among other things that fasting can do for you). Insulin is required for cognition, so that's why.

Your liver hates it when you smoke. Be nice to it. I'm not just talking about increasing water intake and reducing sugars. That helps for sure, but I'm more talking about increasing omega 3's from fish oil and phospholipids which is used extensively by your liver as well as considering an occasional milk thistle extract. High dose fish oil can reverse some damage associate with methamphetamine abuse, so it may help with your striatum activity, too.

Lastly, you need to boost your dopamine levels as gradually and as naturally as possible. I'm talking GDNF, myelinogenesis, angiogenesis, phospholipid synthesis, and other fun stuff but only when you are positive enough for neuroplasticity. Until then, dopamine from moderately high sources is fine, so long as you are getting enough sleep (with some extra magnesium or NMDA antagonism), GABA, exercise, cofactor support (either niacin or folate, depending on your methylation status ATM), and antioxidant support. An example of a stack for a 2x a day with anxiety would be Hops, Caffeine, Maca, Citicoline, Niacin, and Fish Oil. The sleep cocktail could be either Valerian and Cat's Claw or Magnesium and Lemon Balm.

Please remember that adaptogens that you cannot feel can be increased 3x or more. I keep saying it because it's true. The doses they give you on the bottle for any herbal supplement may only work for people with lower body weight or metabolisms or are just sensitive to their effects. This is based on a minimum dose that appears safe, and therefore is not actually a dose that tends to develop side effects in normal people, even something as benign as farting more frequently. You don't claim to be normal, so I say go for it. If 1000mg of high strength Ashwagandha or Maca or Gotu Kola gives you the desired effect, you wouldn't know until you tried to defy the manufacturer of the bottle, and it could totally be worth it...

EDIT: You ever try Selank? https://www.nootropi...-from-research/
Edited by devinthayer, 31 July 2016 - 04:44 AM.
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ThreeKings12341's Photo ThreeKings12341 31 Jul 2016

Yes, Cymbalta + Mirtazapine is similar to Effexor + Mirtazapine, which is called California Rocket fuel, for depression.
I prefer Cymbalta since it binds stronger to NE compared to Effexor at lower dosages. For Effexor to bind strong to NE it requires high doses, and not to mention Effexor has a very unpleasant withdrawal (due to its short half life)


Hey there .. Have u been emotional numbed also? Or just anedhonia?
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thedevinroy's Photo thedevinroy 31 Jul 2016

http://link.springer...0702-006-0562-y

Galantamine was able to reverse the effects of dopamine loss in the striatum from kynurenic acid by increasing alpha7 nicotinic receptor activity. Although alpha7 nicotinic receptors are not necessarily anxiogenic in all cases, Galantamine often is due to it's AChE inhibition. In which case, nefiracetam is sometimes used as the alternative.


Sent from my iPhone using Tapatalk
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Kurko's Photo Kurko 31 Jul 2016

Oh thanks for a reply like this.

Not now, no treatment, only these supplements:

-Vitamin B12/Folic Acid 

-Vitamin D3

-Fish Oil

 
Infact what I feel is purely anhedonia, apathy associated with anxiety and cognitive disorders. These anxiety and cognitive disorders I had them before starting Paxil but not anhedonia and apathy.
Before taking the antidepressant, cannabis gave me some cognitive power with well being. It improve my speech and my episodic memory.
But since the discontinuation of antidepressant weed make me anxious without any positive effect. Other drugs too.
 
But since i stopped the SSRI I feel that the molecule is still present in my brain and it partially inhibits the production of Dopamine. Or perhaps I damaged my serotoninergic system. That is why nothing works for me or make me worse off. Even sports does not help me feel better.
The electrical stimuli that give you joy and excitement disappeared.
Even sleep is disrupted. In the morning I wake up with a heavy head and super dry eyes.
 
The doctors here say I am a moderate depression but the problem is that I do not feel sad. I have a kind of apathy with emotions blocked ... l  will not go out, I do not want to talk with friends. The only thing I want is to resolve my dramatic situation.
 But I do not despair and continue to try things.
 
 
 
The problem is that the Galantamine can not be prescribed in my country because it is used only for Alzheimer's disease.
I will add Selank to my list.  
 
Thanks a lot

 

Are you currently taking anything? I know for me, cat's claw prevents a lot of adrenaline from forming into the next day, for instance. I wouldn't call it anhedonia, but it is similar in that I am not easily excited or anxious. Not really my cup of tea...

Striatal dopamine levels are a really sensitive thing. A lot of people don't realize just how sensitive dopamine metabolites can kill their striatum. Some meth addicts literally never fully recover this part of the brain. Interestingly, delusions are associated with increased dopamine activity in this part of the brain, so there is an overkill possibility.

http://www.ncbi.nlm....ubmed/19204262/

I suspect this is why delusional patients are treated with clozapine like drugs.

So what you need to do is looks at ways of increasing striatum activity without tipping the scale into the schizophrenia zone. Dopamine is usually the neurotransmitter of focus in the striatum, but interestingly GABA also has an effect of note. Rather than going for the benzodiazepines, which don't typically affect GABA-B, a whole rise in GABA levels in that section of the brain should be associated with a balanced cognition when combined with equivalent rises in dopamine levels.

Basically what I'm saying is that your anxiety is from too little inhibition (think GABA but also serotonin and canabanoids) and your anhedonia is from too little pleasure (think dopamine). You want a balance, which is why weed was so nice for you...

For a line of drug combo's that would work, I think your should look at treating your symptoms in a totally removed point of view and consider that BP2 is a real possibility. Valproic acid is a learning enhancer that also treats BP2 by lowering your clock speed just to the point where you can listen more clearly. Being that it is for BP, it will help smooth out any potential ups and more importantly, your downs, too.

I'm not done yet.

Exercise needs to be moderate to intense 3 to 5 days a week .High dose fish oil can reverse some damage associate with methamphetamine abuse, so it may help with your striatum activity, too.

Lastly, you need to boost your dopamine levels as gradually and as naturally as possible. I'm talking GDNF, myelinogenesis, angiogenesis, phospholipid synthesis, and other fun stuff but only when you are positive enough for neuroplasticity. Until then, dopamine from moderately high sources is fine, so long as you are getting enough sleep (with some extra magnesium or NMDA antagonism), GABA, exercise, cofactor support (either niacin or folate, depending on your methylation status ATM), and antioxidant support. An example of a stack for a 2x a day with anxiety would be Hops, Caffeine, Maca, Citicoline, Niacin, and Fish Oil. The sleep cocktail could be either Valerian and Cat's Claw or Magnesium and Lemon Balm.

Please remember that adaptogens that you cannot feel can be increased 3x or more. 

EDIT: You ever try Selank? https://www.nootropi...-from-research/

 


Edited by Kurko, 31 July 2016 - 10:29 PM.
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Kurko's Photo Kurko 31 Jul 2016

Update:

 

I tried today CBD again : 4 capsule 50mg (16% CBD).

After I went outside, and told me in my head "remains positive, stay positive" because i always have negative rumination. After 30/40 minutes I noticed that I had an anxiety and social anxiety more manageable. Anhedonia/Apathy still there. The feeling of pressure around the head disappeared. but the effect did not last long.Placebo? I dont think .. I feel unstable :/.

 

Even being less anxious I always have the feeling of having no stimulation.

When I'm with friends I often feel I have nothing to say, and when they talk to me the only thing I want is to stop talking, because I have trouble finding the right words to answer. That may be because I lack empathy, or my creativity and imagination no longer exist.

 

Really I feel lost because I am young and I want to enjoy some things. But I will continue the fight.
Next step : Inositol. 
 
Thank you guys 

Edited by Kurko, 31 July 2016 - 11:05 PM.
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thedevinroy's Photo thedevinroy 31 Jul 2016

I do not think it is serotonin related directly. I think your serotonin system is inherently bad, but the dopamine system got burnt out and needs some repair. This is not uncommon in bipolar patients, and the way doctors help them recover is by giving them GABAergics or Serotonergics. The latter I would tend to wonder can make damage from dopamine metabolism more severe as well as encouraging nerve growth adjustments from psychedelics leading to reduced frontal lobe function. GABAergics on the other hand only make things worse with alcohol and better with everything else. Burnouts can also be caused by stress and doctors often put patients on a small dose of a benzo to help the patients calm down and naturally recharge.

Citicoline is not only a building block of nerve repair but also increases Striatal dopamine levels over the course of several days, possibly via increased tyrosine hydroxylase activity. Effective human equivalent dose seems to be between 150mg and 1.5g per day for 7 days. See effect on neurotransmitters section:

http://the-medical-d...e_article_2.htm

Does decrease serotonin, so Bacopa or 5-HTP at night would help to balance that out. Meditation is another technique that increases serotonin production.
Edited by devinthayer, 31 July 2016 - 11:15 PM.
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ThreeKings12341's Photo ThreeKings12341 01 Aug 2016

I feel just like you kurko..! Lets say not feel.. Rather i have wuite the same sate like u ..

Have u tried NAC? It helped me to overcome anedhonia for 2 months.. Now gone and i am motivated 2 do skmething about my emotional numbness or flat affect u call it..

Do u feel like me also that u dont feel emotions?
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Kurko's Photo Kurko 01 Aug 2016

I already asked myself about bipolar disorder. But my symptoms do not match.

 

I think this is much more my dopamine system that is affected (creativity, bein well, pleasure, sex drive....). Although sometimes dopamine and serotonin are connected, since some serotonin antagonist allow dopamine release. 
 
I tried 5-htp but my symptoms became worse, my hands get sweaty and I feel more disconnected. Bacopa zero effect :/

I do not think it is serotonin related directly. I think your serotonin system is inherently bad, but the dopamine system got burnt out and needs some repair. This is not uncommon in bipolar patients, and the way doctors help them recover is by giving them GABAergics or Serotonergics. The latter I would tend to wonder can make damage from dopamine metabolism more severe as well as encouraging nerve growth adjustments from psychedelics leading to reduced frontal lobe function. GABAergics on the other hand only make things worse with alcohol and better with everything else. Burnouts can also be caused by stress and doctors often put patients on a small dose of a benzo to help the patients calm down and naturally recharge.

Citicoline is not only a building block of nerve repair but also increases Striatal dopamine levels over the course of several days, possibly via increased tyrosine hydroxylase activity. Effective human equivalent dose seems to be between 150mg and 1.5g per day for 7 days. See effect on neurotransmitters section:

http://the-medical-d...e_article_2.htm

Does decrease serotonin, so Bacopa or 5-HTP at night would help to balance that out. Meditation is another technique that increases serotonin production.

 

 

You're in the same state because of the discontinuation of antidepressant?

Yes exact, i feel my emotions are blunted . . I can't cry , I feel I live like a robot.

I read NAC could help with neurotoxicity thats can be great. After the effect wear off,, how you felt?

 

I feel just like you kurko..! Lets say not feel.. Rather i have wuite the same sate like u ..

Have u tried NAC? It helped me to overcome anedhonia for 2 months.. Now gone and i am motivated 2 do skmething about my emotional numbness or flat affect u call it..

Do u feel like me also that u dont feel emotions?

 

 

I am french, sorry for my english guys I hope you understand me :-).

 

Keep you update

 

 


Edited by Kurko, 01 August 2016 - 08:52 PM.
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Ricah's Photo Ricah 02 Aug 2016

If SSRI made things worse, I recommend you to try upregulate 5-HT1, 5-HT2 receptors and serotonin transporter, as they downregulate with SSRI use and if you agonise these receptors (naturally via serotonin), the dopamine and oxytocin will be released. You can do it by few supplements, st. john's wort (but be careful using it in summer, due to photosensitising effect), inositol, rhodiola rosea (5-ht1), ginkgo biloba (5-ht1), lotus seeds, clonazepam (receptors and transporter, but it's benzo so it's not best idea), berberine&evodiamine (transporter), bacopa monnieri (transporter, but also tryptophan hydroxylase, but can't remember which one, so maybe it's not best idea).

 

I tried st. john's wort 1,8g for 20 days (history similar to you, SSRI made things worse, symptomps are anhedonia, apathy, lack of libido etc.) and effects were pretty good for that amount of time. Now I'm waiting to autumn to back again on this (but higher dose).

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ThreeKings12341's Photo ThreeKings12341 02 Aug 2016

Well i dont know if it comes from antidepressiva because now im 24 and i have this since the age of 16.... I cried a. Lot when i was 16. and then shut myself and smoked weed.. So maybe weed or ebv or crying closed me down emotionally...

Nac does only work now and then but i think it changed a bit my way of thinking .. Positiv!

But it doesnt work that well like it did on the begining...


But 5htp makes things worse - the skin picking on my fingers get even worse...Ssri dont help me. The one now i dont see a change at all.

I stopped smoking which gave me dopamin boost.. Nac helped me which gave me euphoria and motivation and loss of anhedonia ..
And the day of a hangover of drinking i feel released ..but i dont drink since 6 months and dont smoke anything .. And i feel flat the whole time .. No emotions...


Would love to know what i can try .. :-/ and what combination...
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Kurko's Photo Kurko 02 Aug 2016

I tried st. john's wort and Panax ginseng. I know SJW upregulate cortical 5-HT2A and I just tried 900 mg / day for 2 weeks...no improvement. it is safe to take higher dose?

+ Add to this a 5HT2C antagonist, will result in a much greater release of dopamine ,can be a good idea no?

 

If SSRI made things worse, I recommend you to try upregulate 5-HT1, 5-HT2 receptors and serotonin transporter, as they downregulate with SSRI use and if you agonise these receptors (naturally via serotonin), the dopamine and oxytocin will be released. You can do it by few supplements, st. john's wort (but be careful using it in summer, due to photosensitising effect), inositol, rhodiola rosea (5-ht1), ginkgo biloba (5-ht1), lotus seeds, clonazepam (receptors and transporter, but it's benzo so it's not best idea), berberine&evodiamine (transporter), bacopa monnieri (transporter, but also tryptophan hydroxylase, but can't remember which one, so maybe it's not best idea).

 

I tried st. john's wort 1,8g for 20 days (history similar to you, SSRI made things worse, symptomps are anhedonia, apathy, lack of libido etc.) and effects were pretty good for that amount of time. Now I'm waiting to autumn to back again on this (but higher dose).

 

 

Thank you for your contribution I read that the NAC could optimize the functioning of neurotransmitters. Interesting :

"It is believed to modulating NMDA glutamate receptors or by increasing glutathione. N-Acetyl-Cysteine increases the concentration of glutamate which restores the plasticity of synapses."

 

 

I think like me, the weed has worsened my condition. Especially because of the panic attacks and hallucinations.
I think the best solution was to try a dopaminergic antidepressant before starting the weed and SSRIs.
But I think this is not the time for regrets.  You tried St. John's wort ? 
 

Well i dont know if it comes from antidepressiva because now im 24 and i have this since the age of 16.... I cried a. Lot when i was 16. and then shut myself and smoked weed.. So maybe weed or ebv or crying closed me down emotionally...

Nac does only work now and then but i think it changed a bit my way of thinking .. Positiv!

But it doesnt work that well like it did on the begining...


But 5htp makes things worse - the skin picking on my fingers get even worse...Ssri dont help me. The one now i dont see a change at all.

I stopped smoking which gave me dopamin boost.. Nac helped me which gave me euphoria and motivation and loss of anhedonia ..
And the day of a hangover of drinking i feel released ..but i dont drink since 6 months and dont smoke anything .. And i feel flat the whole time .. No emotions...


Would love to know what i can try .. :-/ and what combination...

 

 

Keep you update


Edited by Kurko, 02 August 2016 - 10:32 PM.
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thedevinroy's Photo thedevinroy 02 Aug 2016

I got a supplement called Zembrin (a patented Kana extract) to help me focus. It's a PDE4 inhibitor, which has some science in enhancing cognition. I took it several times at different times in the day to confirm its effects were not just me. Sure enough, each time I took it, an hour later I needed a sleep (not just a nap). I thought maybe the increased cAMP raised my AChE levels, so I took my Huperzine and Ashwagandha a little early - barely moved the needle of sleepiness. I took a nap, and It barely made a dent.

Turns out, it is also an SSRI. After learning that, I thought... Why don't I see if it helps me sleep? Took one at 9:30 last night and here was my sleep cycle report:

c6c897e478f2a4f15ce281054a305b46.png

Never have I had that perfect of a rhythm. The closest was this one, a few nights back:

bed8c4913a6fa602c3a64ac69adc65cc.png

The most obvious difference is the time I woke up. Before my alarm, I was already thinking about the next day. I hear people are able to do that, but I've never experienced such wakefulness and alertness that early - not since a child waiting for the alarm to ring so he can go play. This one was more like extreme motivation to pay bills... Which is rare for me... I usually can't even think about being an adult until I'm practically in trouble.

Once is a fluke. Twice is a coincidence. Three times is a pattern. I'll keep you posted if I notice continual effects after removing some supplements from potential synergy vicinity. Removed my late afternoon multimineral, fish oil, and Maca to see if the effects still remain - since those I also added yesterday. Tomorrow, I'll remove late night Hops, magnesium bicarbonate water, garlic, and policosinol. If the effects remain, we'll have a victor.
Edited by devinthayer, 02 August 2016 - 11:20 PM.
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thedevinroy's Photo thedevinroy 03 Aug 2016

Follow up on Zembrin. The perfect sleep was a myth. I'm super groggy this morning, and I woke up in the middle of the night with a brilliant uncommunicative thought about systems thinking and realized that the the thought wasn't so brilliant - I just had to pee and my body was using excitement to get me up. I wonder what caused such perfect rhythm yesterday night and extreme motivation yesterday morning? I'm thinking it was probably the multiminerals I took pretty late... Should try that again.

Anyhow, here is the sleep report:

f27b43d04cd99948f771068f9126e467.png

I still think Zembrin is a fine serotonergic, at least for someone else. I don't typically respond well to serotonergics, so don't take my experience as a gold standard for expected side effects. The fact that it always makes me tired is an indicator of a melatonin-like effect. The relaxation lasts into the next day. I'll take it for a week and see if things change like they often do overtime on antidepressants.
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PeaceAndProsperity's Photo PeaceAndProsperity 03 Aug 2016

I still think Zembrin is a fine serotonergic, at least for someone else. I don't typically respond well to serotonergics, so don't take my experience as a gold standard for expected side effects. The fact that it always makes me tired is an indicator of a melatonin-like effect. 

It doesn't have to. Serotonin can cause CNS fatigue independent of melatonin. Even 10mg or 20mg of melatonin does not produce anything close to the fatigue that serotonings do in myself. It's definitely not melatonin.

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thedevinroy's Photo thedevinroy 03 Aug 2016

I still think Zembrin is a fine serotonergic, at least for someone else. I don't typically respond well to serotonergics, so don't take my experience as a gold standard for expected side effects. The fact that it always makes me tired is an indicator of a melatonin-like effect.

It doesn't have to. Serotonin can cause CNS fatigue independent of melatonin. Even 10mg or 20mg of melatonin does not produce anything close to the fatigue that serotonings do in myself. It's definitely not melatonin.

Yeah I used the word melatonin-like since it's a bit clearer of an effect than serotonin for me. Thanks for the clarity.
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Kurko's Photo Kurko 03 Aug 2016

These are good things to know. What are your impressions about your mood level on Zembrin? because I read that it is a very good anti-depressant.
the subtle effect you had the third time Perhaps you have developed a tolerance no?
 

I got a supplement called Zembrin (a patented Kana extract) to help me focus. It's a PDE4 inhibitor, which has some science in enhancing cognition. I took it several times at different times in the day to confirm its effects were not just me. Sure enough, each time I took it, an hour later I needed a sleep (not just a nap). I thought maybe the increased cAMP raised my AChE levels, so I took my Huperzine and Ashwagandha a little early - barely moved the needle of sleepiness. I took a nap, and It barely made a dent.

Turns out, it is also an SSRI. After learning that, I thought... Why don't I see if it helps me sleep? Took one at 9:30 last night and here was my sleep cycle report:

 

Tomorrow I get my pack inositol. I'll keep you informed 

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thedevinroy's Photo thedevinroy 04 Aug 2016

 

These are good things to know. What are your impressions about your mood level on Zembrin? because I read that it is a very good anti-depressant.
the subtle effect you had the third time Perhaps you have developed a tolerance no?
 

I got a supplement called Zembrin (a patented Kana extract) to help me focus. It's a PDE4 inhibitor, which has some science in enhancing cognition. I took it several times at different times in the day to confirm its effects were not just me. Sure enough, each time I took it, an hour later I needed a sleep (not just a nap). I thought maybe the increased cAMP raised my AChE levels, so I took my Huperzine and Ashwagandha a little early - barely moved the needle of sleepiness. I took a nap, and It barely made a dent.

Turns out, it is also an SSRI. After learning that, I thought... Why don't I see if it helps me sleep? Took one at 9:30 last night and here was my sleep cycle report:

 

Tomorrow I get my pack inositol. I'll keep you informed 

 

 

Every single time the effects have been signicantly noticeable.  It's easily a 24hr drug, even longer.  It was so intense the second day in a row that I decided... I'm only going to take half a pill tonight.  I had to fight through the "CNS fatigue" as RatherBeUnknown calls it... but I don't know if I could call it fatigue.  It feels more like an ease to relax, let things slide if they don't matter, even a confidence in my decision to shift focus... all the while with a grogginess - a physical resistance to move.  It's so easy to laugh and joke about it, though.

 

So yeah, we'll see where a half a pill takes me.

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Ricah's Photo Ricah 04 Aug 2016

I tried st. john's wort and Panax ginseng. I know SJW upregulate cortical 5-HT2A and I just tried 900 mg / day for 2 weeks...no improvement. it is safe to take higher dose?

+ Add to this a 5HT2C antagonist, will result in a much greater release of dopamine ,can be a good idea no?

Make sure about that st. john's wort is an extract (not bulk plant, tea or smth like this) or some tincture with ethanol (sorry if i mistranslated tincture, hope you understand what i'm saying), otherwise it doesn't have any effect on CNS. Also, there're extract's standarized to hyperycin's or hyperforin's and it does matter. As i read in some article's and research, only hyperycin has the ability to upregulate receptors, hyperforin is responsible for blocking neurotransmitter's transporters etc.

Also, like in the case of using SSRI's, you have to give some time for receptors to upregulate (SSRI often needs 6 weeks or more), so 2 weeks isn't so much. And last, but not least, 900 mg is not high dose, as i said. This dose is usually used in research (but I seen even 1,8 g), but all the research was for antidepressant effect (no specified symptoms or smth), so we can't really tell where starts the proper dose for these purposes.

 

And about safety. Like i just said, I read research where used 1,8 g but nothing higher. In conclusion, it is well tolerated antidepressant, more than many any other known antidepressants and is stronger than placebo. But there comes case reports (I know it says nothing, but at least you don't have to worry that you're the first). To make matters worse, most of the them comes from people, that lost "magic" (they call it that way) due to abusing MDMA (some serotonergic, they believe it downregulate these receptors) so they're not so useful. Most of them used 6g of this substance and felt good, the effects were also nice (heard few times about cured anhedonia, so it is promising). But there were rare cases when it caused blurred vision or caused something bad with eyes, but it was temporarily and disappeared after some time by itself.

But keep remember, that st. john's wort is photosensitizing, so maybe here's the problem. Maybe if you will keep in mind, that you should avoid Sun (like i said, i'm waiting to autumn where there won't be so much Sun), then maybe there won't be problems with that either. And you also have to keep in mind, that it interacts with many other drugs (due to cyp450 mostly), so you have to be careful here too. I'm thinking about 4g in the next time, but I'm doing this on my own risk.

 

Yeah, 5-HT2c antagonists are pretty good idea, they should enhance the effect. But there're some problems with them, they're weak, expensive or unavailable. You have agomelatine, which is weak antagonist and is really expensive. Nortryptyline or amitryptyline, but they have many other mechanisms of action (H1 antagonism, NET&SERT inhibition, muscarinic receptors etc., but also 5-HT2a antagonism which is not beneficial in our case, also nortryptyline is a metabolite of amitryptyline). Many other drugs are inverse agonist rather than antagonists (for example mirtazapine) and it makes difference here. Tramadol which is narcotics. Fluoxetine, but it is stronger SERT inhibitor and also upregulates these receptors taken for long time.

Also heard about few natural antagonists - kudzu, rikkunshinto and amentoflavone (about third one i'm not sure, couldn't find any research about this).

 

 

I think the best solution was to try a dopaminergic antidepressant before starting the weed and SSRIs.
But I think this is not the time for regrets.  You tried St. John's wort ? 

Yeah, it was, I agree. But I bet that PhD is responsible for this (in my case too) and his lack of knowledge.

Yeah, tried 1,8 g for 20 days standarized extract to 0,1-0,3% hypercin's. Effects? Could'nt call it a motivation, but after few years of sitting on my ass i started to run (because i wanted it!). Also hearing music was much better (again, couldn't call it pleasure, but listening music wasn't so boring and mechanical). Felt some feeling (some kind of sadness after seing strirring movie) for first time after few years (it wasn't strong, but it was a feeling). And had great improvement in erection and libido. Tried almost every antidepressant but who would think, that antidepressant considered as a weak, can make such a difference?

But I must also add this. I still have fucked up serotonergic system (I bet that SERT are downregulated due to SSRI use, also 5-HT1a autoreceptors are downregulated (downregulated -> harder to agonise -> harder to block release of serotonin)) and effect's disappeared after 2-3 months. Running also rises serotonin levels and I bet I should avoid this (but have some fat to burn after mirtazapine use), so the problem is not solved yet.

Hope I helped.

 

 

 

 


Edited by Ricah, 04 August 2016 - 08:38 AM.
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thedevinroy's Photo thedevinroy 04 Aug 2016

That's a long and well thought out post by Ricah.

Regarding the effects of Zembrin. It was winding gown in my system last night when I noticed I was laughing more and feeling more connected to the characters on TV. After taking the half pill of Zembrin, I was silly like you are when you're a kid that's too laugh happy to go to bed. Maybe you can start alternating days at 1/2 a pill every other afternoon, then a 1/2 every afternoon, then alternating a whole pill and 1/2 pill, and then one full half pill per afternoon. This will help you avoid building too much in your system too quickly.

Here is my sleep cycle:

d9aa4a9785ab2c4075a49a53b94cd6f1.png

Not as good as it was lately, but I'm not as groggy. Grogginess is one of those things that often either goes away or becomes more bearable over time on antidepressants. A few people like myself will experience long term grogginess and not develop tolerance to the side effects. Mind you, I also did not take the Hops, magnesium bicarbonate water, garlic, or policosinol last night. Only the magnesium bicarbonate water is really all that sedating for me, maybe policosinol a tad.

I think I'll be taking them tomorrow night. Also, today, I'm back on the fish oil and multimineral. I don't think anything has nearly the affect on relaxation as the Zembrin had so far, and therefore, will not affect its effect.
Edited by devinthayer, 04 August 2016 - 11:19 AM.
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ThreeKings12341's Photo ThreeKings12341 04 Aug 2016

Kurko

Nope havent tried st johns wort.. Wel i hae but not really longn and thats years ago..

U think that'd help?
What can u imagine i could try else which could work. U think the nmda route or the dopamin route???

At rhe moment (i started today because my doc says so ) venlafaxin
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