Functional Connectivity Issues and the Role of 5-HT2A Receptors in Low Serotonin Levels:
When serotonin (5-HT) levels are low, the brain often compensates by upregulating 5-HT2A receptors, meaning there are more receptors available or that they become more sensitive to serotonin. This upregulation results in an increased sensitivity to any available serotonin, leading to an exaggerated response even though the overall serotonin levels are reduced.
Impact on Functional Connectivity:

1. Low Serotonin Levels: Reduced serotonin availability prompts the brain to upregulate 5-HT2A receptors. This compensatory mechanism ensures that the limited serotonin can have a more pronounced effect by increasing receptor sensitivity or number.
2. Receptor Upregulation: Upregulation means there are more 5-HT2A receptors or that the existing receptors are more efficient at binding serotonin. This heightened sensitivity can disrupt normal neurotransmission and brain network interactions.
3. Functional Connectivity Issues: The increased sensitivity and number of 5-HT2A receptors can cause abnormal brain network interactions, leading to functional connectivity issues. These disruptions can affect mood, cognition, and perception, contributing to neuropsychiatric conditions like anxiety, depression, and perceptual disorders such as Visual Snow Syndrome (VSS) and Hallucinogen Persisting Perception Disorder (HPPD).

In summary, low serotonin levels lead to the upregulation of 5-HT2A receptors, resulting in increased receptor sensitivity. This heightened sensitivity can cause functional connectivity issues in the brain, affecting various cognitive and perceptual functions.
low serotonin levels and upregulated 5-HT2A receptors can contribute to a lack of inhibitory response in the brain. Benzodiazepines (benzos) can counteract this issue by enhancing GABAergic (gamma-aminobutyric acid) functioning, which promotes inhibitory signaling in the brain. Here’s how this interplay works:

Impact on GABAergic Functioning:

1. Low Serotonin and 5-HT2A Upregulation:
   • Low Serotonin Levels: When serotonin levels are low, it can disrupt the balance of excitatory and inhibitory neurotransmission in the brain.
   • Upregulation of 5-HT2A Receptors: Increased sensitivity and number of 5-HT2A receptors can lead to enhanced excitatory neurotransmission, contributing to a hyperexcitable state in the brain.
2. GABAergic Functioning:
   • GABA as an Inhibitory Neurotransmitter: GABA is the primary inhibitory neurotransmitter in the brain, responsible for reducing neuronal excitability and promoting relaxation and calmness.
   • Impact of 5-HT2A Receptor Activity on GABA: Enhanced activity of upregulated 5-HT2A receptors can interfere with GABAergic signaling. This can happen because 5-HT2A receptor activation generally promotes excitatory neurotransmission, which can counteract the inhibitory effects of GABA.

Role of Benzodiazepines:

• Mechanism of Benzodiazepines: Benzodiazepines enhance the effect of GABA by binding to GABA_A receptors and increasing the frequency of chloride channel opening. This hyperpolarizes the neuron, making it less likely to fire and promoting an overall inhibitory effect.
• Counteracting Hyperexcitability: By enhancing GABAergic inhibition, benzodiazepines can counteract the hyperexcitability caused by upregulated 5-HT2A receptors. This helps restore the balance between excitatory and inhibitory neurotransmission in the brain.

Low serotonin levels lead to upregulation and increased sensitivity of 5-HT2A receptors, resulting in enhanced excitatory neurotransmission. This can negatively impact GABAergic functioning by reducing the overall inhibitory tone in the brain, contributing to a hyperexcitable state. Benzodiazepines counteract this by enhancing GABAergic inhibition, promoting neuronal hyperpolarization, and restoring the balance between excitation and inhibition.
Taking an SSRI (Selective Serotonin Reuptake Inhibitor) to counterbalance low serotonin levels can sometimes make things worse initially due to several factors:

1. Initial Increase in Serotonin:
   • Mechanism of SSRIs: SSRIs work by blocking the reuptake of serotonin into the presynaptic neuron, increasing its availability in the synaptic cleft and enhancing serotonergic transmission.
   • Initial Effects: The sudden increase in serotonin levels can initially overstimulate serotonin receptors, including 5-HT2A receptors, which might already be upregulated and sensitive.
2. Overstimulation of 5-HT2A Receptors:
   • Enhanced Excitatory Activity: The upregulated and sensitive 5-HT2A receptors can become overstimulated by the increased serotonin, potentially exacerbating excitatory neurotransmission and leading to increased anxiety, agitation, or other side effects.
   • Adaptation Period: The brain needs time to adjust to the increased serotonin levels. During this adaptation period, the overstimulation of 5-HT2A receptors might cause temporary worsening of symptoms.
3. Impact on GABAergic Function:
   • Disruption of Inhibitory Balance: The initial increase in excitatory activity due to 5-HT2A receptor overstimulation can further disrupt the balance between excitatory and inhibitory neurotransmission, potentially reducing the efficacy of GABAergic inhibition.
   • Potential for Increased Anxiety: This disruption can lead to symptoms such as increased anxiety, restlessness, or insomnia, especially in the early stages of SSRI treatment.
4. Time for Therapeutic Effects:
   • Delayed Onset of Benefits: The therapeutic benefits of SSRIs often take several weeks to manifest as the brain gradually adjusts to the new serotonin levels and receptor sensitivities normalize.
   • Side Effects Management: During the initial period, side effects may be more prominent, and it is crucial to work closely with a healthcare provider to manage these effects and adjust the dosage as needed.

When starting SSRI treatment to counterbalance low serotonin levels, the initial increase in serotonin can overstimulate upregulated and sensitive 5-HT2A receptors, potentially worsening symptoms temporarily. This overstimulation can disrupt the balance between excitatory and inhibitory neurotransmission, impacting GABAergic function and possibly leading to increased anxiety or other side effects. The brain needs time to adjust, and the therapeutic benefits of SSRIs typically take several weeks to become evident. Close monitoring and support from a healthcare provider can help manage these initial side effects.
SSRIs primarily work by blocking the reuptake of serotonin, thereby increasing its availability in the synaptic cleft. They do not directly increase the production of serotonin but rather enhance the efficacy of existing serotonin. Here’s a detailed explanation of how SSRIs affect serotonin levels and why discontinuation can lead to worsening symptoms:

SSRIs and Serotonin Levels:

1. Mechanism of SSRIs:
   • Reuptake Inhibition: SSRIs block the serotonin transporter (SERT), which is responsible for the reuptake of serotonin from the synaptic cleft back into the presynaptic neuron.
   • Increased Availability: By inhibiting reuptake, SSRIs increase the concentration of serotonin in the synaptic cleft, allowing for prolonged activation of serotonin receptors.
2. Indirect Effects:
   • No Direct Production Increase: SSRIs do not directly increase the synthesis of serotonin. They rely on the body’s existing serotonin stores to maintain increased levels in the synaptic cleft.
   • Receptor Modulation: Over time, the increased availability of serotonin can lead to changes in receptor sensitivity and density, such as the downregulation of 5-HT2A receptors.

Discontinuation of SSRIs:

1. Reduction in Synaptic Serotonin:
   • Resumption of Reuptake: When SSRIs are discontinued, the reuptake of serotonin resumes, leading to a reduction in the concentration of serotonin in the synaptic cleft.
   • Decreased Activation: The sudden decrease in synaptic serotonin can lead to reduced activation of serotonin receptors, which can cause a return or worsening of symptoms.
2. Withdrawal Symptoms:
   • Receptor Sensitivity: During SSRI treatment, the brain may adapt by altering receptor sensitivity and density. Discontinuation can disrupt this balance, leading to withdrawal symptoms such as anxiety, depression, irritability, and flu-like symptoms.
   • Neurochemical Imbalance: The abrupt change in serotonin levels can cause a temporary neurochemical imbalance, exacerbating symptoms until the brain readjusts.

While SSRIs increase the availability of serotonin in the synaptic cleft by inhibiting reuptake, they do not directly address the underlying issue of serotonin production. Discontinuing SSRIs can lead to a reduction in synaptic serotonin, potentially causing withdrawal symptoms and a worsening of underlying conditions due to receptor and neurochemical imbalances. This is why it is crucial to taper off SSRIs gradually under medical supervision to allow the brain time to readjust to the changes in serotonin levels. Functional connectivity refers to the statistical association between the activities of different brain regions, often observed through imaging techniques like fMRI. It doesn't necessarily imply a loss of neurons. Instead, it reflects how different brain areas work together or communicate with each other, which can be influenced by factors like neuronal activity, neurotransmitter levels, and network, Functional connectivity itself doesn't directly imply a loss of specific types of neurons, such as serotoninergic (related to serotonin) or GABAergic (related to GABA, an inhibitory neurotransmitter) neurons. It's more about how these neurons or neural networks are functioning and communicating with each other
how to increase serotonin naturally
Vitamin D 1000-2000IU daily with vitamin K2-MK4 Activate folate B9 The active form of vitamin B9 is a type of folate known as 5-methyltetrahydrofolate (5-MTHF) not folic acid (best taking in conjunction with vitamin B6 (make sure B6 isn't in the 100MG and more in the lower figure of 25MG to avoid toxicity)and B12 make sure those are active forms as well Plenty of rich Tryptophan foods Lactobacillus Plantarum 299V ( https://pubmed.ncbi.nlm.nih.gov/30388595/ )
that's the best information I have for naturally increasing serotonin levels

Inflammation and Serotonin

• Inflammation: Brain inflammation releases pro-inflammatory cytokines, which can alter neurotransmitter systems, including serotonin.
• Serotonin Imbalance: Inflammation often increases the activity of the serotonin transporter (SERT), leading to faster reuptake of serotonin. This reduces serotonin availability in the synaptic cleft, affecting overall serotonin signaling.

Serotonin Receptors

• 5-HT1A Receptors: These receptors generally inhibit neuronal firing and promote inhibitory signaling. Reduced serotonin levels due to fast reuptake can lead to less activation of 5-HT1A receptors, impairing inhibitory control.
• 5-HT2A Receptors: These receptors are involved in excitatory signaling and play a role in visual processing. Low serotonin levels can lead to increased sensitivity or upregulation of 5-HT2A receptors, contributing to neuronal hyperexcitability.

Functional Connectivity

• Functional Connectivity: Refers to the coordinated activity and communication between different brain regions. Inflammation and altered serotonin signaling can disrupt functional connectivity, leading to impaired cognitive and perceptual processes, including visual disturbances.

Glutamate and GABA

• Glutamate: The main excitatory neurotransmitter in the brain. Inflammation can increase glutamate levels, leading to excitotoxicity and further contributing to hyperexcitability and functional connectivity disruptions.
• GABA (Gamma-Aminobutyric Acid): The main inhibitory neurotransmitter. Reduced serotonin levels can impair GABAergic inhibition, exacerbating neuronal hyperexcitability and functional connectivity issues.

NKCC1 and KCC2

• NKCC1 (Sodium-Potassium-Chloride Cotransporter 1): Inflammation can affect the function of NKCC1, which is involved in maintaining chloride ion homeostasis in neurons. Dysregulation of NKCC1 can lead to altered neuronal excitability.
• KCC2 (Potassium-Chloride Cotransporter 2): KCC2 helps extrude chloride ions from neurons, contributing to inhibitory signaling. Reduced serotonin levels can impair KCC2 function, leading to reduced inhibitory signaling and increased neuronal excitability.

KCNQ2/3 Channels

• KCNQ2/3 Channels: These potassium channels are crucial for maintaining neuronal excitability and preventing hyperexcitability. Inflammation and reduced serotonin levels can decrease the activity of KCNQ2/3 channels, further contributing to neuronal hyperexcitability and related visual disturbances.

SSRIs and SERT

• SSRIs: Selective serotonin reuptake inhibitors block the serotonin transporter (SERT), slowing down serotonin reuptake and increasing serotonin levels in the synaptic cleft. This enhances serotonin signaling and helps restore the balance between excitation and inhibition.
• Non-SSRI Conditions: Without SSRIs, fast reuptake of serotonin due to increased SERT activity can persist, reducing serotonin availability and impairing receptor activation, leading to hyperexcitability and visual disturbances.

Palinopsia and Inhibition

• Palinopsia: A visual disturbance where images persist or recur after the original stimulus is gone. This can result from neuronal hyperexcitability and impaired resetting of visual pathways.
• Inhibition: Adequate serotonin levels are needed for proper inhibitory signaling through 5-HT1A receptors. Fast reuptake reduces serotonin availability, weakening inhibition and contributing to hyperexcitability.

Summary of Interactions

• Inflammation increases SERT activity, leading to fast reuptake and reduced serotonin levels.
• Reduced serotonin affects both 5-HT1A and 5-HT2A receptors: less activation of inhibitory 5-HT1A receptors and potential upregulation of excitatory 5-HT2A receptors.
• Disrupted Functional Connectivity: Inflammation and altered serotonin signaling can impair functional connectivity, affecting cognitive and perceptual processes.
• Glutamate and GABA Imbalance: Increased glutamate and decreased GABA due to reduced serotonin contribute to hyperexcitability and disrupted functional connectivity.
• NKCC1 and KCC2: Inflammation and serotonin imbalance can dysregulate NKCC1 and impair KCC2 function, leading to increased neuronal excitability.
• KCNQ2/3 Channels: Inflammation and reduced serotonin levels can decrease KCNQ2/3 channel activity, further contributing to hyperexcitability.
• SSRIs block SERT, slow down reuptake, increase serotonin levels, and help restore balance between excitatory and inhibitory signaling.
• Hyperexcitability and impaired inhibition due to low serotonin can lead to visual disturbances like palinopsia.

No, SSRIs do not create extra serotonin. They only prevent the reuptake of the serotonin already present in the brain, thereby increasing its availability in the synaptic cleft. To increase serotonin levels naturally, one would need to adopt strategies that promote serotonin synthesis or release.

Ways to Naturally Increase Serotonin

1. Diet: Eating foods rich in tryptophan (a precursor to serotonin) like turkey, eggs, cheese, nuts, and seeds can help boost serotonin production.
2. Exercise: Regular physical activity, especially aerobic exercise, can increase serotonin levels.
3. Sunlight Exposure: Exposure to natural sunlight can help increase serotonin levels.
4. Healthy Lifestyle: Maintaining a healthy lifestyle with proper sleep, stress management, and social connections can also support serotonin production.
5. Supplements: In some cases, supplements like tryptophan, 5-HTP (5-hydroxytryptophan), or certain vitamins and minerals (e.g., vitamin B6, magnesium) can help support serotonin synthesis.
6. Probiotic 299V: specifically the Lactobacillus plantarum 299v strain, has been linked to serotonin production in the gut, which can have significant implications for mental and emotional well-being. Here's a summary focusing on this aspect:

Probiotic 299V, containing Lactobacillus plantarum 299v, plays a role in serotonin production within the gut. Serotonin is a neurotransmitter that affects mood, behavior, and overall mental health. The gut-brain axis, a bidirectional communication network between the gut and the brain, is influenced by the gut microbiota.
In summary, SSRIs increase the availability of existing serotonin by preventing its reuptake, but they do not create additional serotonin. Increasing serotonin levels naturally involves strategies that promote its production and release.

DPH 1000 mgs/Olanzapine 5 mgs/Mirtazapine 7.5 mgs/GABA 3000 mgs/Fluoxetine 260 mgs/Promethazine 125 mgs/Dextromethorphan 200 mgs/Pseudoephedrine 120 mgs/THC/Phenylephrine 30 mgs/Caffeine ≈450 mgs/Nicotine
I have just dosed all of these together at around
Diphenhydramine 1000 mgs Olanzapine 5 mgs Mirtazapine 7.5 mgs GABA 3000 mgs Fluoxetine 260 mgs Promethazine 125 mgs Dextromethorphan 200 mgs Pseudoephedrine 120 mgs THC Phenylephrine 30 mgs Caffeine ≈450 mgs Nicotine
Not sure what'll happen i have bought a vape but my thc cart is on it's last leg the past few times I've tripped dph at night i always get paranoid because we got real spiders and snakes here there's too many scary folk tales about my houses area for me to be on the front porch smoking a cigarette even with a great dane guard dog outside dph be making everything way too scary so i rest my case I thought about not trying to trip so hard tonight and maybe give most the drugs a break for at least 18 hours because in a few hours (like 13 hours more) I'm adopting a kitten and i love cats I can't fucking wait but also couldn't wait to do these drugs either i just hope I'll be able to speak english by the time the people with the cat get here not sure how the antipsychotic effects of mirtazapine and olanzapine are going to work qith the psychotic Nature of the dph or how fluoxetine is going to mix with it all yeah 260 mgs of fluoxetine (aka prozac) is a lot of prozac but idk i once had a bunch of prozac that they kept prescribing me literally every time i overdosed the hospital people say “well we shouldn't just let you walk outta here without something that's working towards a solution” so it's always prozac or zoloft but what i was saying was that i had ≈200 prozac 20 mgs each i didn't know if it'd kill me but at that time i didn't care (still don't obviously) i was outta drugs and was in withdrawal coming off heroin gabapentin & meth i took all the prozac that i had prozac is an SSRI (selective serotonin reuptake inhibitor) so now that i understand the drug a little better and have mixed prozac with a bunch of different things i feel like i have good reason to believe that prozac is like a lot of other drugs that you can't even feel a buzz off of alone even at super high mgs if you mix even only a medium dose it seems to do a lot more when my brain actually gets any serotonin which only happens when I'm high (a bit dramatic i know) but it could just be placebo I don't know I'm a drug addict not a biochemist last night also freaked me out pretty bad on my 2250mgs dph trip so maybe i threw in the 3000mgs of gaba because I'm being a pussy and getting that scared night after night has started to take a toll on me i threw in phenylephrine I'm surprised that of all of the drugs for me to have little experience with it's odd that i never did much dosing with phenylephrine usually when i did it was because it was in a cough syrup that was the only thing on the shelf because y'all other dextromethorphan enthusiasts keep buying all the delsym leaving me with guanfacine phenylephrine alcohol acetaminophen and dextromethorphan mixes that taste like shit i probably won't be learning much about phenylephrine on this trip because I'm coming up on so many things right now that i won't be able to distinguish on what drug is doing what really hoping that the spiders will chill out a little idk outta all the weirdness Of eiriel the thing that I'm stuck on most is what the fuck did i do to these multidimensional dph spiders if anyone has figured out how to befriend the spiders of eiriel let me know because those motherfuckers hate my guts the dph snakes shadow people and the hatman have all been pretty peaceful to me always besides this one shadow person that i kept hallucinating while on a meth bender but as far as dph goes the only non diplomatic and unwelcoming creatures are the spiders as far as my experience goes there's a good chance of serotonin syndrome with this dose i understand if you care about your health at all tho then just don't do dph (my kidneys have been failing since i was 19 even with all the other drugs dph is 100% responsible for 90+% of that) and especially don't mix ssris like olanzapine (aka zyprexa) and fluoxetine not sure how I've avoided seratonin syndrome and death after all of these crazy years but I've heard about people that got seratonin syndrome off way less than my dose my pupils was still dilated from yesterdays 2250mg dph trip when i took this dose not sure if I've fucked up my brain or not and not sure how temporary or permanent this mydriasis is i mean i know that i have some brain damage from all of the drugs and injuries that have become so common in my life the trip hasn't really started yet it's been about 30minutes tho so no surprise I don't know which drug did this but for some reason i think it was the phenylephrine but I'm tasting metal flavored saliva from something even tho I'm still an addict tho reddit has restored a bit of hope for humanity yeah it's demolished some hope too even tho reddit has it's own problems when it comes to the users of reddit compared to the toxicity and hate of literally every other social media on reddit i feel like especially on dph people will take time outta their days just to be there for a person that they'd never spoken to before it's not like people are coming to dph for likes and the free almost like a volunteer just writing the same stuff over and over again to try and make sure if anyone on this subreddit needs someone to talk to or the people that don't understand dph and post's to give them the much needed advice you'd think that some of these redditors on here are getting paaaaid to write helpful things i still don't think that I'll be getting sober for dph anytime soon especially not with whats been going on in my life

Hi,
I have marked most important parts as how long I use each meds in what dose, info of me, my questions, supplements used, nootropics thinking of, new meds for panic disorder treatment, plan to quit benzos, advice about Memantine. If you want, there is whole story and treatment:) Thx I have a lifetime nonmedicated ADHD + OCD (will finally have atomoexin in july after like 8 docs) but mainly severe panic disorder since 12/23 caused by badly burning out and not stopping work + too much stress from all sides, mostly family and workspace/company. It started close to xmas and wanted to finish year and worked until my body completely disabled to it to me but right after it came xmas, which is not my fav time of year ending in keeping me in attacks 24/7. Btw Im 29yo man, 193cm, 90kg, sporting, financial advisor solo businessman, living alone, used to be really busy all the time and I want to be healthy and free! Lesson learned, did major changes in life, know I have limits and can say NO to people.
I am currently getting off xanax and on SSRI, starting my new recovery plan below as previous didnt help enough and asking if you know anything that could help me get my full life back sooner I work as I can/want, mostly 2-6 h/day and only from home, going to multiple types of therapy, investing insane money to get recovered and looking for every possible way. I am open for any tip or advice on nootropic, peptide, maybe even SARMs that could help me get over this. New meds are imo most I can use, wanna get rid of addictive stuff and SSRI, ideally only buspiron + non addictive anxiety meds, or SNRI/Bupropion instead of Citalopram. . Even if you dont have time or dont want to read all previous treatment and new plan and have idea what could help me, write it please. But I have to be careful with anything interacts with SSRI as I will be also on buspar, I have a safe med for serotonin syndrome if needed.. Also if you see gaps or risks in my meds plan, some ideas, useful info or better ways, I will be glad to know it:)
I use/tried almost every useful supplement wo AD interaction including adaptogens, herbs, expensive vitamins, mushrooms, gotu kola, NAC, tyrosine, inositol and just anything that could be useful + basics use all year. Also have Alpha GPC which made my adhd brain supercomputer before I got beaten but now doesnt work. Tried before noopept and a lot of racetams, idra21 and some more but with no effect and modafinil before with effect, but mostly anxiety, too much concentrating on one thing and severe insomnia.
I am already pretty sure about Agmatine, Sulbutiamine instead of Benfotiamine (any difference?), not sure of Bromantane on ssri (?), 9-me is no go guess, maybe NALT (?), Theacrine as Im tired from SSRI all the time and too much coffee makes me axnious, maybe Vinpocetine or Uridine triacetate? centrophenoxine? dihexa?
My treatment from december to now:
I had no idea wth is this, told my psychologist what is happening to me and asking many times if its serious and casually replied that is probably from stress. So I treated it as burnout by resting, then removing original causes and triggers, removing problems from my mind and life, reducing stress to minimum, even leaving my pretty good paid job after 9 yers. But nothing helped besides benzos which made me not feel attacks so much and when I went off after 6 weeks, symptoms came back the same day.
I always said no to ADs but this time I didnt see any other option besides staying on benzos for a long time so I got SSRI citalopram 20, later 30mg now 6 weeks, first weeks were hell of anxiety and tiredness, last 2 weeks they help but effect is enough to keep me attack free only at home, outside flat still almost instant PA + side effects are still bad.
Same with benzos now again for 6 weeks afte break from previous cycle, mostly xanax 1,5-2mg a day, when Im home with no problems I can stay on 0,5mg with no WD. But want to quit asap, Im standing on the edge of little discomfort or living hell WDs. Also it makes me dumb, careless and not caring, but dont have cravings or abuse them, until now there was no other medication in my country :/ Also I already had GABA WDs pretty bad from alcohol many times and from phenibut in february by mistake (3 weeks of 2-3x a week before I had benzos). I would rather skip this opportunity to be on boat walking simulator with scary shadowy guy in my bedroom.
Next week I will make a big changes:
Will to add Buspar in small doses to SSRI, probably 30mg citalopram + 2x7,5mg buspar for long term and propranolol instead benzos before I leave flat for panic attacks - I have mostly physical symptoms and over these months my brain has learned to go panic mode when I go around people or noise but im not scared, wanting to hide or anxious, want to go out. Hope this will allow me to relearn the BIOS of my brain and body they wont start panicking as it has learned over months of nonstop attack (january until end of april, just moving on scale 1-10 but never off). Propranolon as beta-blocker should not allow my body to go panic defense mode and mental anxiety I can handle now. My mind is still quite ok, not much depressed or in bad mood, last days even thinking a bit sharper and can handle it but body/brain program are stuck. Hope this will allow me over time to get off SSRI to just Buspar + non addictive anxiety aid as needed or at least switch to SNRI or Wellbutrin as im energetic person but with this SSRI im meeeeeeeh all the time.
As propranolon arrives I will cut benzos to lowest dosage where I wont feel WD, probably 0,5mg/day and switch to Clonazepam (have benzos and can ask doc anytime), keep this dose for 2-3 weeks, taper to 0,35mg, wait and this until i go down around 0,2mg/day. Maybe slower if it will be painful or risk worse WDs when i cut them off.
For quitting benzos I have clonidine (WD reduce, camling, ADHD), pregabalin (GABA substance replacement, anti seizure but addictive), baclofen (GABA substance replacement, anti seizure also addictive)), Etifoxine (nonbenzo anxiolytics, I guess mostly PAWS) and Topiramate (seizure and migraine prevention, WD reduce) and Hydroxyzine (sleepy antihistamine nonaddictive) to get off them asap with no risk seizure and suffering for weeks in terrible WDs. I wont use all the aids together but as needed for current symptoms and not get hooked on none of them as only atarax is safe in long term.
Also finally will get ADHD meds atomoxetin, but as I have no energy, even adhd is not so present and clonidine also helps for adhd. And I have found one super special med you will be interested about- Memantine, do you have experiences about this so called miracle drug? It make you feel softly with unlimited brain power, also it shall lower tolerances to almost all substances and by 30-60% over 7-14 days and then make WDs easier + also helps ADHD. But have no idea when to use it in my plan, I got 2 packs and its cheap so can buy more but dont want to mess with getting off bzs and learning to manage going out. Same question with atomoxetin - when to start? its not stimulant so it should not affect attacks nor benzo WD but idk.
Just in case there would be too much serotonin I will have Cyproheptadine for SS. It should not happen from SSRI+Buspiron but some nootropic or WD med can cause it.
I will still go for checks to doc and psychiatrist but the medical procedures in my country got stuck in time in year when producers of SSRI/benzos gave some gifts for doctors or politics. So they just give you this combo announcing you it will work (didnt) and you wont get addicted in 3 months of xan (would). Mainly propranolon is not approved med for anxiety/panic in my county, only bzds and buspirone, but after trying several ADs on you :/
Thank you so much for any knowledge you share with me!

Hi,
I have marked most imporant parts as how long I use each meds in what dose, info of me, my questions, supplements used, nootropics thinking of, new meds for panic disorder treatment, plan to quit benzos, asking about Memantine. If you want, here is whole story and treatment:) Thx I have a lifetime nonmedicated ADHD + OCD (will finally have atomoexin in july after like 8 docs) but mainly severe panic disorder since 12/23 caused by badly burning out and not stopping work + too much stress from all sides, mostly family and workspace/company. It started close to xmas and wanted to finish year and worked until my body completely disabled to it to me but right after it came xmas, which is not my fav time of year ending in keeping me in attacks 24/7. Btw Im 29yo man, 193cm, 90kg, sporting, financial advisor solo businessman, living alone, used to be really busy all the time, multiple addictions behind me mostly because depression (alcohol),pain (kratom) and stimulants bcs its so addictive with adhd :D But I dont abuse anything since 02/23 when I barely survived WD from forced CT a lot of alcohol every day and I want to be healthy and drugs free!
I am currently getting off xanax and on SSRI, starting my new recovery plan below as previous didnt help enough and asking if you know anything that could help me get my full life back sooner I work as I can/want, mostly 2-6 h/day and only from home, going to multiple types of therapy, investing insane money to get recovered and looking for every possible way. I am open for any tip or suggestion on nootropic, peptide, maybe even SARMs that could help me get over this. Even if you dont have time or dont want to read all previous treatment and new plan and have idea what could help me, write it please. But I have to be careful with anything interacts with SSRI as I will be also on buspar, I have a safe med for serotonin syndrome if needed.. Also if you see gaps or risks in my meds plan, some ideas, useful info or better ways, I will be glad to know it:) Mostly about Memantine - when to use, in which part of protocol it will be most beneficial or what to expect.
I use/tried almost every useful supplement including adaptogens, herbs, expensive vitamins, mushrooms, gotu kola, NAC, tyrosine, inositol and just anything that could be useful + basics use all year. Also have Alpha GPC which made my adhd brain supercomputer before I got beaten but now doesnt work. Tried before noopept and a lot of racetams, idra21 and some more but with no effect and modafinil before with effect, but mostly anxiety, too much concentrating on one thing and severe insomnia.
I am already pretty sure about Agmatine, Sulbutiamine instead of Benfotiamine (any difference?), not sure of Bromantane on ssri (?), 9-me is no go, maybe NALT (?), Theacrine as Im tired from SSRI all the time and too much coffee makes me axnious, maybe Vinpocetine or Uridine triacetate? centrophenoxine? dihexa?
My treatment from december to now:
I had no idea wth is this, told my psychologist what is happening to me and asking many times if its serious and casually replied that is probably from stress. So I treated it as burnout by resting, then removing original causes and triggers, removing problems from my mind and life, reducing stress to minimum, even leaving my pretty good paid job after 9 yers. But nothing helped besides benzos which made me not feel attacks so much and when I went off after 6 weeks, symptoms came back the same day.
I always said no to ADs but this time I didnt see any other option so I got SSRI citalopram 20, later 30mg now 6 weeks, first weeks were hell of anxiety and tiredness, last 2 weeks they help but effect is enough to keep me attack free only at home, outside flat still almost instant PA + side effects are still bad.
Same with benzos now again for 6 weeks afte break from previous cycle, mostly xanax 1,5-2mg a day, when Im home with no problems I can stay on 0,5mg with no WD. But want to quit asap, Im standing on the edge of little discomfort or living hell WDs. Also it makes me dumb, careless and not caring, but dont have cravings or abuse them, until now there was no other medication in my country :/ Also I already had GABA WDs pretty bad from alcohol many times and from phenibut in february by mistake (3 weeks of 2-3x a week before I had benzos). I would rather skip this opportunity to be on boat walking simulator with scary shadowy guy in my bedroom.
Next week I will make a big changes:
Will to add Buspar in small doses to SSRI, probably 30mg citalopram + 2x7,5mg buspar for long term and propranolol over benzos before I leave flat for panic attacks - I have mostly physical symptoms and over these months my brain has learned to go panic mode when I go around people or noise but im not scared, wanting to hide or anxious, want to go out. Hope this will allow me to relearn the BIOS of my brain and body they wont start panicking as it has learned over months of nonstop attack (january until end of april, just moving on scale 1-10 but never off). Propranolon as beta-blocker should not allow my body to go panic defense mode and mental anxiety I can handle now. My mind is still quite ok, not much depressed or in bad mood, last days even thinking a bit sharper and can handle it but body/brain program are stuck. Hope this will allow me over time to get off SSRI to just Buspar + non addictive anxiety aid as needed or at least switch to SNRI or Wellbutrin as im energetic person but with this SSRI im meeeeeeeh all the time.
As propranolon arrives I will cut benzos to lowest dosage where I wont feel WD, probably 0,5mg/day and switch to Clonazepam (have benzos and can ask doc anytime), keep this dose for 2-3 weeks, taper to 0,35mg, wait and this until i go down around 0,2mg/day. Maybe slower if it will be painful or risk worse WDs when i cut them off.
For quitting benzos I have clonidine (WD reduce, camling, ADHD), pregabalin (GABA substance replacement, anti seizure but addictive), baclofen (GABA substance replacement, anti seizure also addictive)), Etifoxine (nonbenzo anxiolytics, I guess mostly PAWS) and Topiramate (seizure and migraine prevention, WD reduce) and Hydroxyzine (sleepy antihistamine nonaddictive) to get off them asap with no risk seizure and suffering for weeks in terrible WDs. I wont use all the aids together but as needed for current symptoms and not get hooked on none of them as only atarax is safe.
Also finally will get ADHD meds atomoxetin, but as I have no energy, even adhd is not so present and clonidine also helps for adhd. And I have found one super special med you will be interested about- Memantine (bgpharm), do you have experiences about this so called miracle drug? It make you feel softly with unlimited brain power, also it shall lower tolerances to almost all substances and by 30-60% over 7-14 days and then make WDs easier + also helps ADHD. But have no idea when to use it in my plan, I got 2 packs and its cheap so can buy more but dont want to mess with getting off bzs and learning to manage going out. Same question with atomoxetin - when to start? its not stimulant so it should not affect attacks nor benzo WD but idk.
Just in case there would be too much serotonin I will have Cyproheptadine for SS. It should not happen from SSRI+Buspiron but some nootropic or WD med can cause it. And just remembered I shall take some ephedrine/yohimbine if my BP or HB goes too slow from propranolon/clonidine... :/
I will still go for checks to doc and psychiatrist but the medical procedures in my country got stuck in time in year when producers of SSRI/benzos gave some gifts for doctors or politics. So they just give you this combo announcing you it will work (didnt) and you wont get addicted in 3 months of xan (would). Also propranolon is not approved med for anxiety in my county, only bzds and buspirone, but after trying several ADs on you :/
Thank you so much for any knowledge you share with me!

Hi,
I have marked most imporant parts as how long I use each meds in what dose, info of me, my questions, supplements used, nootropics thinking of, new meds for panic disorder treatment, plan to quit benzos, advice about Memantine. If you want, there is whole story and treatment:) Thx I have a lifetime nonmedicated ADHD + OCD (will finally have atomoexin in july after like 8 docs) but mainly severe panic disorder since 12/23 caused by badly burning out and not stopping work + too much stress from all sides, mostly family and workspace/company. It started close to xmas and wanted to finish year and worked until my body completely disabled to it to me but right after it came xmas, which is not my fav time of year ending in keeping me in attacks 24/7. Btw Im 29yo man, 193cm, 90kg, sporting, financial advisor self employed, living alone, used to be really busy all the time, multiple addictions behind me mostly because depression (alcohol),pain (kratom) and stimulants bcs its so addictive with adhd :D But I dont abuse anything since 02/23 when I barely survived WD from forced CT a lot of alcohol every day and I want to be healthy and drugs free!
I am currently getting off xanax and on SSRI, starting my new recovery plan below as previous didnt help enough and asking if you know anything that could help me get my full life back sooner I work as I can/want, mostly 2-6 h/day and only from home, going to multiple types of therapy, investing insane money to get recovered and looking for every possible way. I am open for any tip or advice on nootropic, peptide, maybe even SARMs that could help me get over this. Even if you dont have time or dont want to read all previous treatment and new plan and have idea what could help me, write it please. But I have to be careful with anything interacts with SSRI as I will be also on buspar, I have a safe med for serotonin syndrome if needed.. Also if you see gaps or risks in my meds plan, some ideas, useful info or better ways, I will be glad to know it:) Mostly about Memantine - when to use, in which part of protocol it will be most beneficial or what to expect.
I use/tried almost every useful supplement including adaptogens, herbs, expensive vitamins, mushrooms, gotu kola, NAC, tyrosine, inositol and just anything that could be useful + basics use all year. Also have Alpha GPC which made my adhd brain supercomputer before I got beaten but now doesnt work. Tried before noopept and a lot of racetams, idra21 and some more but with no effect and modafinil before with effect, but mostly anxiety, too much concentrating on one thing and severe insomnia.
I am already pretty sure about Agmatine, Sulbutiamine instead of Benfotiamine (any difference?), not sure of Bromantane on ssri (?), 9-me is no go, maybe NALT (?), Theacrine as Im tired from SSRI all the time and too much coffee makes me axnious, maybe Vinpocetine or Uridine triacetate? centrophenoxine? dihexa?
My treatment from december to now:
I had no idea wth is this, told my psychologist what is happening to me and asking many times if its serious and casually replied that is probably from stress. So I treated it as burnout by resting, then removing original causes and triggers, removing problems from my mind and life, reducing stress to minimum, even leaving my pretty good paid job after 9 yers. But nothing helped besides benzos which made me not feel attacks so much and when I went off after 6 weeks, symptoms came back the same day.
I always said no to ADs but this time I didnt see any other option so I got SSRI citalopram 20, later 30mg now 6 weeks, first weeks were hell of anxiety and tiredness, last 2 weeks they help but effect is enough to keep me attack free only at home, outside flat still almost instant PA + side effects are still bad.
Same with benzos now again for 6 weeks afte break from previous cycle, mostly xanax 1,5-2mg a day, when Im home with no problems I can stay on 0,5mg with no WD. But want to quit asap, Im standing on the edge of little discomfort or living hell WDs. Also it makes me dumb, careless and not caring, but dont have cravings or abuse them, until now there was no other medication in my country :/ Also I already had GABA WDs pretty bad from alcohol many times and from phenibut in february by mistake (3 weeks of 2-3x a week before I had benzos). I would rather skip this opportunity to be on boat walking simulator with scary shadowy guy in my bedroom.
Next week I will make a big changes:
Will to add Buspar in small doses to SSRI, probably 30mg citalopram + 2x7,5mg buspar for long term and propranolol over benzos before I leave flat for panic attacks - I have mostly physical symptoms and over these months my brain has learned to go panic mode when I go around people or noise but im not scared, wanting to hide or anxious, want to go out. Hope this will allow me to relearn the BIOS of my brain and body they wont start panicking as it has learned over months of nonstop attack (january until end of april, just moving on scale 1-10 but never off). Propranolon as beta-blocker should not allow my body to go panic defense mode and mental anxiety I can handle now. My mind is still quite ok, not much depressed or in bad mood, last days even thinking a bit sharper and can handle it but body/brain program are stuck. Hope this will allow me over time to get off SSRI to just Buspar + non addictive anxiety aid as needed or at least switch to SNRI or Wellbutrin as im energetic person but with this SSRI im meeeeeeeh all the time.
As propranolon arrives I will cut benzos to lowest dosage where I wont feel WD, probably 0,5mg/day and switch to Clonazepam (have benzos and can ask doc anytime), keep this dose for 2-3 weeks, taper to 0,35mg, wait and this until i go down around 0,2mg/day. Maybe slower if it will be painful or risk worse WDs when i cut them off.
For quitting benzos I have clonidine (WD reduce, camling, ADHD), pregabalin (GABA substance replacement, anti seizure but addictive), baclofen (GABA substance replacement, anti seizure also addictive)), Etifoxine (nonbenzo anxiolytics, I guess mostly PAWS) and Topiramate (seizure and migraine prevention, WD reduce) and Hydroxyzine (sleepy antihistamine nonaddictive) to get off them asap with no risk seizure and suffering for weeks in terrible WDs. I wont use all the aids together but as needed for current symptoms and not get hooked on none of them as only atarax is safe.
Also finally will get ADHD meds atomoxetin, but as I have no energy, even adhd is not so present and clonidine also helps for adhd. And I have found one super special med you will be interested about- Memantine (bgpharm), do you have experiences about this so called miracle drug? It make you feel softly with unlimited brain power, also it shall lower tolerances to almost all substances and by 30-60% over 7-14 days and then make WDs easier + also helps ADHD. But have no idea when to use it in my plan, I got 2 packs and its cheap so can buy more but dont want to mess with getting off bzs and learning to manage going out. Same question with atomoxetin - when to start? its not stimulant so it should not affect attacks nor benzo WD but idk.
Just in case there would be too much serotonin I will have Cyproheptadine for SS. It should not happen from SSRI+Buspiron but some nootropic or WD med can cause it. And just remembered I shall take some ephedrine/yohimbine if my BP or HB goes too slow from propranolon/clonidine... :/
I will still go for checks to doc and psychiatrist but the medical procedures in my country got stuck in time in year when producers of SSRI/benzos gave some gifts for doctors or politics. So they just give you this combo announcing you it will work (didnt) and you wont get addicted in 3 months of xan (would). Also propranolon is not approved med for anxiety in my county, only bzds and buspirone, but after trying several ADs on you :/
Thank you so much for any knowledge you share with me!

Hi,
I have marked most imporant parts as how long I use each meds in what dose, info of me, my questions, supplements used, nootropics thinking of, new meds for panic disorder treatment, plan to quit benzos, advice about Memantine. If you want, there is whole story and treatment:) Thx I have a lifetime nonmedicated ADHD + OCD (will finally have atomoexin in july after like 8 docs) but mainly severe panic disorder since 12/23 caused by badly burning out and not stopping work + too much stress from all sides, mostly family and workspace/company. It started close to xmas and wanted to finish year and worked until my body completely disabled to it to me but right after it came xmas, which is not my fav time of year ending in keeping me in attacks 24/7. Btw Im 29yo man, 193cm, 90kg, sporting, financial advisor self employed, living alone, used to be really busy all the time, multiple addictions behind me mostly because depression (alcohol),pain (kratom) and stimulants bcs its so addictive with adhd :D But I dont abuse anything since 02/23 when I barely survived WD from forced CT a lot of alcohol every day and I want to be healthy and drugs free!
I am currently getting off xanax and on SSRI, starting my new recovery plan below as previous didnt help enough and asking if you know anything that could help me get my full life back sooner I work as I can/want, mostly 2-6 h/day and only from home, going to multiple types of therapy, investing insane money to get recovered and looking for every possible way. I am open for any tip or advice on nootropic, peptide, maybe even SARMs that could help me get over this. Even if you dont have time or dont want to read all previous treatment and new plan and have idea what could help me, write it please. But I have to be careful with anything interacts with SSRI as I will be also on buspar, I have a safe med for serotonin syndrome if needed.. Also if you see gaps or risks in my meds plan, some ideas, useful info or better ways, I will be glad to know it:) Mostly about Memantine - when to use, in which part of protocol it will be most beneficial or what to expect.
I use/tried almost every useful supplement including adaptogens, herbs, expensive vitamins, mushrooms, gotu kola, NAC, tyrosine, inositol and just anything that could be useful + basics use all year. Also have Alpha GPC which made my adhd brain supercomputer before I got beaten but now doesnt work. Tried before noopept and a lot of racetams, idra21 and some more but with no effect and modafinil before with effect, but mostly anxiety, too much concentrating on one thing and severe insomnia.
I am already pretty sure about Agmatine, Sulbutiamine instead of Benfotiamine (any difference?), not sure of Bromantane on ssri (?), 9-me is no go, maybe NALT (?), Theacrine as Im tired from SSRI all the time and too much coffee makes me axnious, maybe Vinpocetine or Uridine triacetate? centrophenoxine? dihexa?
My treatment from december to now:
I had no idea wth is this, told my psychologist what is happening to me and asking many times if its serious and casually replied that is probably from stress. So I treated it as burnout by resting, then removing original causes and triggers, removing problems from my mind and life, reducing stress to minimum, even leaving my pretty good paid job after 9 yers. But nothing helped besides benzos which made me not feel attacks so much and when I went off after 6 weeks, symptoms came back the same day.
I always said no to ADs but this time I didnt see any other option so I got SSRI citalopram 20, later 30mg now 6 weeks, first weeks were hell of anxiety and tiredness, last 2 weeks they help but effect is enough to keep me attack free only at home, outside flat still almost instant PA + side effects are still bad.
Same with benzos now again for 6 weeks afte break from previous cycle, mostly xanax 1,5-2mg a day, when Im home with no problems I can stay on 0,5mg with no WD. But want to quit asap, Im standing on the edge of little discomfort or living hell WDs. Also it makes me dumb, careless and not caring, but dont have cravings or abuse them, until now there was no other medication in my country :/ Also I already had GABA WDs pretty bad from alcohol many times and from phenibut in february by mistake (3 weeks of 2-3x a week before I had benzos). I would rather skip this opportunity to be on boat walking simulator with scary shadowy guy in my bedroom.
Next week I will make a big changes:
Will to add Buspar in small doses to SSRI, probably 30mg citalopram + 2x7,5mg buspar for long term and propranolol over benzos before I leave flat for panic attacks - I have mostly physical symptoms and over these months my brain has learned to go panic mode when I go around people or noise but im not scared, wanting to hide or anxious, want to go out. Hope this will allow me to relearn the BIOS of my brain and body they wont start panicking as it has learned over months of nonstop attack (january until end of april, just moving on scale 1-10 but never off). Propranolon as beta-blocker should not allow my body to go panic defense mode and mental anxiety I can handle now. My mind is still quite ok, not much depressed or in bad mood, last days even thinking a bit sharper and can handle it but body/brain program are stuck. Hope this will allow me over time to get off SSRI to just Buspar + non addictive anxiety aid as needed or at least switch to SNRI or Wellbutrin as im energetic person but with this SSRI im meeeeeeeh all the time.
As propranolon arrives I will cut benzos to lowest dosage where I wont feel WD, probably 0,5mg/day and switch to Clonazepam (have benzos and can ask doc anytime), keep this dose for 2-3 weeks, taper to 0,35mg, wait and this until i go down around 0,2mg/day. Maybe slower if it will be painful or risk worse WDs when i cut them off.
For quitting benzos I have clonidine (WD reduce, camling, ADHD), pregabalin (GABA substance replacement, anti seizure but addictive), baclofen (GABA substance replacement, anti seizure also addictive)), Etifoxine (nonbenzo anxiolytics, I guess mostly PAWS) and Topiramate (seizure and migraine prevention, WD reduce) and Hydroxyzine (sleepy antihistamine nonaddictive) to get off them asap with no risk seizure and suffering for weeks in terrible WDs. I wont use all the aids together but as needed for current symptoms and not get hooked on none of them as only atarax is safe.
Also finally will get ADHD meds atomoxetin, but as I have no energy, even adhd is not so present and clonidine also helps for adhd. And I have found one super special med you will be interested about- Memantine (bgpharm), do you have experiences about this so called miracle drug? It make you feel softly with unlimited brain power, also it shall lower tolerances to almost all substances and by 30-60% over 7-14 days and then make WDs easier + also helps ADHD. But have no idea when to use it in my plan, I got 2 packs and its cheap so can buy more but dont want to mess with getting off bzs and learning to manage going out. Same question with atomoxetin - when to start? its not stimulant so it should not affect attacks nor benzo WD but idk.
Just in case there would be too much serotonin I will have Cyproheptadine for SS. It should not happen from SSRI+Buspiron but some nootropic or WD med can cause it. And just remembered I shall take some ephedrine/yohimbine if my BP or HB goes too slow from propranolon/clonidine... :/
I will still go for checks to doc and psychiatrist but the medical procedures in my country got stuck in time in year when producers of SSRI/benzos gave some gifts for doctors or politics. So they just give you this combo announcing you it will work (didnt) and you wont get addicted in 3 months of xan (would). Also propranolon is not approved med for anxiety in my county, only bzds and buspirone, but after trying several ADs on you :/
Thank you so much for any knowledge you share with me!

Ban me if you want but this is my story and I want my voice to be heard before I die. I realize ultimately all is my fault but there are third parties involved in my ultimate demise.
I got floxed. Lost sleep.
Biggest mistake was finding the floxies subreddit.
I post my symptoms tehre, This touchfuzzy guy jumps in suggesting antidepressants.
I go to the doc, they put me on antidepressants, namely mirtazapine, over time my symptoms start getting worse.
I post about the worsenings and tinnitus, this bastard says mirtazapine isnt ototoxic, it is all fluoroquinolones etc.
I have chatted with him privately and since he is a nurse practicioner aka a drug dealer, he tells me it is all fluoroquinolones etc. never had me suspect mirtazapine.
Been to many doctors too, only for them to give me more antipsychotics, never took them since i was deteriorating all the time, I was getting wrose and worse and never was suspecting antipsychotics.
Until I found survivingantidepressants.org
Turns out all antipsychotics damage mitochondria, cause tinnitus, insomnia, neuropathy and alike. This paper also sasys so among many others :https://pubmed.ncbi.nlm.nih.gov/18626887/
Many people are there suffering from the same symptoms we do minus tendon rupture. Soudns similar?
I texted their head mod drhungrytheshiteatinggrinface about it the ego on him so so large he never responded back on it.
Why, WHY would you suggest antipsychotics to people wo got FQ damage.
not only touchfuzzy does it but drhungry has a billion posts defendint them in the name of science.
I got banned when I laashed against these mods, and I went creazy. They were right in banning me in hindsight but get this.
I dont sleep anymore I deceloped full blown HPPD/VSS I have terrible akathisia and want to kill myself24/7 terrible headaches terrible tinnitus and hyperacusis.
Just like FQs downregulate gaba receptors, antidepressants downregulate serotonin, dopamine, noradrelaine etc.
I know I will have to kill myself due to enourmous amount of pain I am in but I want to fight against this injustice in my remaining days.
Here's a repost of what I posted over at VSS subreddit. It goes into detail of what these mods do and the extend o the damage I am suffering from due to these mods. and me being stupid and gullible enough to trust them. and the doctors. you can stop reading here.....
But saying stuff like "oh you are a grown up man you should have made your own decisions, you decided to take these pills" and pushing the ENTIRE BLAME on me, sounds like nobody wants to take responsibility for their misguided advice.
I'll try to cut it short. But don't know how.
I got floxed and lost sleep. That was the only issue. While doing research I found out the floxies subreddit. Wish I hadn't.
There is a "nurse practicioner" mod there of psychiatry (drug dealer lol), suggested antidepressants. Ok, fair advice. Went to the doctors, told about my situation, was laughed at, and I was put on mirtazapine.
Over time, I started developing weird symptoms, was suspecting mirtazapine as well, but whenever I posted there of my suspicions, this mod in particular said, mirtazapine is harmless, it isnt ototoxic etc etc. I still have the screens of the private chats I had with him, and he even suggested that I updose.
Later on it got so bad, I was dizzy all the time, was seeing green, was having nightmares, couldn't sleep etc. Then found out survivingantidepressants.org. My symptoms aligned with the ones posted tehre for mirtazapine adverse reactions. I also developed visual snow syndrome on it.
Now, been to many doctors, only to be gaslit and put on many many more meds. Never took them of course..
When I raised my voice on that subforum, And I went crazy doing that I get that, I got banned. This was partially my fault.
This subreddit fully realizes messing with serotonin is bad. Floxies subforum however, STILL recommends floxed people mirtazapine and other stuff and say, these antidepressants are harmless.
Hairy camel posted his chat with a doctor, analysing his qEEG. the doctor specifically says, he is prone to floxing since ssris hurt him and explains the reason why. Meaning antidepressans should be avoided if you got floxed, is my take on the 45 min conversation he had with him. The doctor mentions SSRIs may alter the mitochondrial function, which the fluoroquinolones also do. LOL...
The problem is, the conceit these mods have is unprecedented and they still indirectly suggest mirtazapine ad other meds for fq insomnia, because one of them has a masters on chemistry and the other is a nurse practicioner of psychiatry, and he reads a few papers and thinks he can fix all problems. None of them have any masters on mitochondrial damage, antibiotic toxicity etc. but fine.
You would think at least they'd say things might go worng with antidepressants since you got floxed etc. but no. They still think fq insomnia is the same as normal insomnia and "scientifically" suggest antidepressants.
this nurse practicioner in question is so full of conceit, he claims he fixed his tinnitus and visual snow by taking ketamine. and wants to open a tinnitus clinic since he healed himself by taking ketamine. wow man such a genious, there are hundreds of millions of people living with tinnitus and lots of tinnitus support forums, but this guy, he is gonna open a tinnitus clinic and will cure people with ketamine, he is the only one who figured this stuff out... Before ketamine however, he said he treated his tinnitus with naltrexone because he read the paper on it by dr. de ridder. then said it didn't work lol. Also in his recovery story, he posted he used TONS of supplements, then when someone asked him if anyone healed without any supplements, he said yes I healed without any supplements.
This mod in question, thinks all the other ones on facebook floxies group are mental, toxic hypochondriacs and whatever he says fly. As expected by someone who studies psychiatry.
And we know some of us developed VSS after covid vax. Just because two floxies did not have any reactions to this vax, it was decided vaccines were safe and the further discussion was closed on that topic by another mod.
Pretty sure floxies subreddit will hurt many others in the future by their advice. Surely I won't be the only one.
Yes, it is my fault fofr ever looking up why I couldn't sleep and ending up on the floxies subreddit. Learn from my mistakes and never ever trust random "nurse practicioners of psychology" online. Trust your gut. Now on top of insomnia, I have VSS, I have tinnitus, hyperacusis, TTTS, headaches...
Do your own research. never trust medical professionals. And if you decide to pur your trust in one, such as in my case, I should have gone to a toxicology expert (even then they wouldnt have any idea on fq toxicity or ssri toxicty imo) though nobody will suggest you that. They are in it for the money and you are just a statistic to them.

Naturally, it’s nearly impossible to play with 5ht2a, for someone who got VSS from SSRI, weed, lsd. But if you have high norepinephrine and dopamine, then you will have symptoms of hyperarousal, addiction to a few things (shopping, researching, etc). High norepinephrine will cause heart palpitations, dysfunctional breathing, tremors. Playing with 5ht2a isn’t going to do anything, it’ll make matters worse.
Break down the catecholamines (dopamine, norepinephrine) in amygdala, hippocampus, pre-frontal cortex. Hydroxyb12 helps, niacinamide helps, b2, b6, b9 help, Abstaining from caffeine, nicotine, chocolate, green tea, carbs helps. Adding gaba alternatives such as lavender oil capsules, gotu kola to the mix calms overall circuitry.
Grab it from all corners, trauma, hyper-arousal, heavy breathing, stress, calming brain circuitry. That’s my thought. I’ve recovered about 50% without any meds in 15 weeks. But the remaining 50% still feels like hell. I still feel like wanting to end it, I’m trying to hold myself together.
5ht2a manipulation also brings on suicidal feelings, I know I feel this feeling less and less, but I also know it’s not me, it’s my excessive stress feeling that’s making me feel this way. It’s not possible that someone improves by 50% and still feels this way. Fuck these brain chemicals!

A lot of gratitude to everyone for the support I received during this time with this crazy thing called VSS.
The sooner I accept that VSS is FND. The better my chances of “possible recovery” with EMDR therapy in conjunction with some supplements for stress reduction If not, I’ve said my goodbyes to friends and family and am absolutely prepared to follow through with medical assistance in dying. The symptoms and the trauma are equally burdensome.
In my personal opinion, MAID should be available in every country. It gives people the chance to talk openly about their feelings, and proceed with dignity.
I wanted to thank everyone, including the ones who called my knowledge junk. Honestly it’s fine, if I knew everything I’d be healed by now.
The best knowledge I can impart is how to DIY lamotrigine.

• P5P or Gotu Kola (glutamate to gaba converter in temporal lobe)
• Niacinamide (dopamine, norepinephrine stress deleter in amygdala, HPA axis manager, helps to stop fighting with symptoms - works great for ptsd and anxiety)
• Hydroxy B12 (COMT enhancer, naturally lowers dopamine, norepinephrine hyperactivity in pre-frontal cortex - hypervigilance and focus deleter, helps you get close to acceptance and not feel traumatized, brings calm)

Take lots of antioxidants, great for anxiety and oxidative stress.
Don’t waste your time with serotonin. Don’t play with 5ht2a, can make anyone suicidal for no reason and used vss. And has no connection to VSS.
The initial worsening from SSRI is because of its side effects, that activate amygdala even more. I still don’t recommend SSRI to anyone. Don’t trust a drug that can make you worse before it gets better, is the motto.
Other than that if you know you have trauma, definitely attend trauma therapy.
I couldn’t find an appropriate flair for this post. I just picked one.
I bid my goodbyes with my parting words, knowing that what I have is FND. I don’t know what you have.
My tinnitus goes down when I get up and walk, when I lay down it goes up, when I put maskers on, pins and needles come on. It can only and only mean one thing, my brain is in a state of trauma. It’s giving me these symptoms in response to trauma. The more I suppress one symptom, it produces another symptom. Everyday is different, symptom wise, can only mean it’s an FND for me.
SSRI’s are glutamate + gaba agonists. Sometimes the glutamate kicks off a state of trauma, brings subjective akathisia or past trauma to the surface. VSS comes on as a mode of protection.
Antibiotics are gaba-antagonists. Do the same thing as above.
The above activates the amygdala and goes into trauma and fear mode activating a loop with the frontal cortex, releases enormous amounts of dopamine and norepinephrine in response and creates a maladaptive brain cycle.
The amygdala connects to several cortexes, visual, perceptual, motor, vestibular, auditory. The symptoms are an overflow of this mechanism to keep you safe, because the brain recognizes you’re traumatized. Neurological PTSD.
For anyone who experiences natural remissions during another illness, and then it comes back once you’ve recovered. Know that because your brain has another source of pain to keep you safe, it turns off VSS for that duration.
If you know your trauma resolve it: - PTSD - drug induced akathisia - underlying illness
Listen to EMDR audios on YouTube daily. Do parasympathetic breathing exercises. Focus on breath, slow down your thoughts.
If you don’t know your trauma, then do vision therapy. It helps overcome the “fear” of symptoms, eventually symptoms reduce. NORT is expensive. YouTube vision therapy videos are free.
There are people who recovered by mediation and running.
Meditation - Relax and Calm Running - Conquer fear
Increasing CBF in the brain is good for ptsd.
Lots of gratitude to everyone. It’s not a fun ride with PTSD. 🙏✌️

I am recovering from SSRI withdrawal (have been off for years) and have nervous exhaustion. Pretty severe anxiety has been helped tremendously by Bacopa Monnieri (Nootropics Depot Bacognize).
After a while I have noticed that I have gained some tolerance to it and was looking for something else that helps anxiety. I think that Bacopa helps due to its serotonergic effects because anything serotonergic seems to help me out. However, most anxiolytic herbs seem to work more on the GABA system, which helps me some but not nearly the way serotonergics help.
I have tried:
Ashwagandha (which didn’t really help all that much)
California Poppy (not much effect)
Passionflower (helps with sleep but not much for anxiety)
Theanine (caused headaches)
Rhodiola (too stimulating, causes anxiety)
Lavender (not much effect)
Among other things (including non herbal supplements)
What are the options out there for serotonergic herbs? It would be nice to have something that could be taken for several months at a time.
Thanks for the help in advance!

Understanding the mechanisms behind benzodiazepine withdrawal

Other resources may offer insights into the processes occurring in your brain. You might encounter advice encouraging you to embrace symptoms as signs of healing or come across imaginative analogies. However, this guide takes a different approach. It provides an evidence-based, scientifically grounded explanation of what is probably occurring in your brain. It's important to note that neuroscience is still developing, and much remains unknown. Nevertheless, these insights serve as valuable pieces of the puzzle, helping us to approach our situation with thoughtfulness and understanding.
GABA and glutamate, often considered primary neurotransmitters in the brain, are just two among many. Let's liken them to wind and water. Both have multiple receptor targets that serve various functions. In this discussion, we'll view glutamate as excitatory. When stimulating signals are present, you feel alert, focused, upbeat, and energetic. However, insufficient stimulation or excess can lead to brain fog, depression, and even pain.
GABA primarily targets inhibitory receptors, affecting mood, sensory, and motor functions in both the brain and spinal cord. Benzodiazepines induce inhibition, easing anxiety, reducing pain and muscle spasm, and inducing sleep. They can also treat seizures, which are excitatory events. However, imbalance without sufficient glutamate can lead to depression, brain fog, and excessive sedation.
Glutamate acts as the counterbalance to GABA. While GABA induces relaxation and relieves anxiety, it can also result in lethargy and fatigue. Glutamate, on the other hand, stimulates the brain, energizing you, enhancing focus, improving mood, and promoting a positive outlook.
Balance is key; the brain seeks equilibrium. When on benzodiazepines, the brain compensates by sending an opposing signal to counter excessive inhibition. Scientists have observed that the issue lies not in the binding of GABA receptors but in the number of receptor types bound. Natural GABA agonists bind to fewer receptor types, while benzodiazepines bind to more, leading to excessive relaxation.
The problem often stems from glutamate receptor hypersensitivity, where normal levels of glutamate produce exaggerated signals, causing imbalance when not under the influence of benzodiazepines. This hypersensitivity can be long-lasting and is likely responsible for prolonged symptoms.
Tolerance, tolerance withdrawal, interdose withdrawal, and paradoxical reactions are all manifestations of compensation or over-compensation, often accompanied by glutamate receptor hypersensitivity. Imagine it as a balancing act—the brain strives for equilibrium. Intolerance, signals match, resulting in minimal effects. Tolerance withdrawal involves minimal benzodiazepine effects and withdrawal between doses, possibly signaling an imbalance with periodic over-compensation. Paradoxical reactions occur when the brain over-expresses glutamate receptors, leading to excitation instead of inhibition, likely due to excessive glutamate sensitivity.
Once excitatory signals dominate the nervous system (such as when removing the benzodiazepine), the brain interprets this as a threat. The brain increases the expression of serotonin receptors during a threat. This will allow additional glutamate to go to the amygdala to “teach” you to avoid the threat. It has been scientifically demonstrated that states such as anxiety, depression, PTSD, and OCD all share a state of increased serotonin receptor expression. The amygdala is the fear and alarm center and is designed to teach you to avoid threats. In this case, it is faulty, as there is no threat.
Serotonin is not the “happy” neurotransmitter. Excess signaling, as stated above, wreaks havoc on the brain. Studies are underway, but it is possible that people with a history of trauma or the above mental health conditions may have a more difficult time with benzodiazepine withdrawal.
When serotonin signaling is high, dopamine is suppressed. Dopamine is thought to control the reward center - it keeps you going back to tasty food or having sex, and it is also involved in memory, movement, motivation, mood, and attention. You can see how lowered dopamine might lead to depression, lack of motivation, and cognitive issues. More than that, dopamine is likely anti-inflammatory for both the brain and the body. The reduction in dopamine can lead to wide-spread inflammation. This has been seen in chronic fatigue syndrome and fibromyalgia and is under study.
Norepinephrine is made from dopamine, so while this neurotransmitter is reduced, the receptors upregulate making you hypersensitive to every excitatory adrenaline signal.Acetylcholine, an excitatory neurotransmitter associated with depression and anxiety in excess, is increased because the brain needs more dopamine and acetylcholine can induce its production. Histamine often goes hand-in-hand with acetylcholine and is known to cause wakefulness. In excess, it can cause anxiety in the brain. In the body it’s well known to cause gastrointestinal issues and allergic reactions.
You can start to observe the imbalance present. While GABA levels may be adequate, there's an excess of glutamate. Serotonin signaling is heightened, contributing to fear despite sufficient GABA, due to glutamate overload in the amygdala. Decreased dopamine levels from elevated serotonin result in depressed memory, mood, and attention. Increased sensitivity of adrenaline receptors stems from reduced norepinephrine levels caused by low dopamine. Acetylcholine rises in an attempt to boost dopamine, leading to heightened excitatory signals. It's akin to an orchestra where each instrument and section must harmonize—neither too loud nor too soft, all playing in synchrony. Should one section be too loud, too soft, or out of rhythm, the music ceases to flow harmoniously.
It is important to note here that the medical literature has shown that GABA receptors bounce back very quickly, within weeks. They have to because this is what protects you from seizures. There is a very small proportion of patients that do end up with chronic seizures, but this is extremely rare.
The problem is that glutamate receptors must reverse their hypersensitivity reaction. There is no known way to induce this so we have to support the brain until it adapts. This means optimizing GABA and controlling glutamate. No, natural GABAergic compounds such as chamomile tea or other herbs (other than benzodiazepines) will not inhibit your healing. Your GABA receptors are intact and ready to work for you. You already make one of the most powerful GABA-ergic compounds available, allopreganolone, in your brain, everyday. In fact, depressed levels of allopregnanolone may play a role in withdrawal as well, and is associated with chronic stress.
Interestingly, glutamate should not necessarily be reduced. In fact, the brain does this on its own to protect you from the hypersensitive receptors. This causes brain fog and cognitive dysfunction. So we need glutamate, just not too much or too little (as usual, balance).
It’s important to note - we are not “growing back” receptors. This is not how it works. Receptors are up and down regulated millions of times a day. It’s about the brain trying to achieve balance amidst this chaos. The less chaos, the better the chance of rebuilding. Think of repairing a roof in a hurricane versus a gentle rain.
“Why do I get waves with supplements?”
If a supplement causes a nice reduction in neural excitation but then you stop it, of course you will feel worse. If you find a good one, you always need consistent dosing daily. You will always need to taper off. Your nervous system probably cannot handle the normal ups and downs of any supplement. That doesn’t mean it’s bad - it might be really good - your brain just needs more consistency.
So what can we do to use this information to facilitate healing through non-medical approaches, supplements, and helper drugs in crisis?
This is a subject for a different document called helper meds. It is essential because what is the point of learning the information if there is no way to use it to heal?
A preview: by mitigating the stress response, we can decrease serotonin receptor upregulation, resulting in the brain reducing its threat response to the amygdala. Medications that temporarily lower serotonin signaling, such as cyproheptadine and mirtazapine, can disrupt the cycle of hyperresponsiveness in the amygdala. Lowering norepinephrine with medications like clonidine and gabapentinoids can reduce the heightened signal from excess receptor expression, alleviating both pain and anxiety. Similarly, decreasing acetylcholine and histamine levels with medications like hydroxyzine and cyproheptadine can lessen excitation, depression, and anxiety. Boosting GABA reduces neural excitation, while reducing glutamate achieves the same effect.
Think of it this way: there's a storm brewing in your brain. We need to calm the rain and wind, shield the damaged areas with a protective covering, and catch the dripping water in a bucket. Multiple interventions are necessary to reach a point where we can repair the roof torn off by the storm.
Other resources have delved into brain regions and their functions. All the neurotransmitters mentioned are essential for proper functioning of these regions. Imbalanced signaling can lead to dysfunction. For instance, an excess or deficiency of signaling can induce fear, aggression, or emotional numbness in the amygdala. Understanding the functions of brain regions can provide insight into your emotional experiences, considering the interplay of neurotransmitters and their effects.
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None of your symptoms are welcome or normal, but there’s still no need to panic. They are all evidence of brain malfunction, but they do tend to fade, so there is comfort in that. That said, we need to recognize when and how much we need to help ourselves.
Rather than reinventing the wheel, I will link to websites friendly, simple and inviting to the average person. These are written by true experts in the field and will give you the best information as you need it.
Amygdala:
“It is part of the limbic system and plays a key role in processing emotions and emotional reactions.”
https://www.simplypsychology.org/amygdala.html
Hippocampus:
“It plays a vital role in forming and retrieving memories, spatial navigation, and emotional responses. Damage to the hippocampus can lead to memory impairments and difficulty forming new memories, highlighting its importance in learning and cognition.”
https://www.simplypsychology.org/hippocampus.html
Hypothalamus
“It controls autonomic functions such as hunger, thirst, body temperature, and sexual activity. To do this, the hypothalamus integrates information from different brain parts and responds to various stimuli such as light, odor, and stress.”
https://www.simplypsychology.org/anatomy-of-the-brain.html
Frontal Lobe
“The frontal lobe’s main functions are typically associated with ‘higher’ cognitive functions, including decision-making, problem-solving, thought, and attention.”
https://www.simplypsychology.org/frontal-lobe.html
Occipital lobe
“The occipital lobes play a crucial role in tasks such as object recognition, color perception, depth perception, and motion detection.”
https://www.simplypsychology.org/occipital-lobe.html
Temporal Lobe
“The temporal lobe plays a key role in processing auditory information, memory formation, language comprehension, and some aspects of emotion and speech production. It houses structures like the hippocampus, crucial for long-term memory, and the primary auditory cortex, essential for interpreting sounds.”
https://www.simplypsychology.org/temporal-lobe.html
Vestibular branch of the cranial nerve system
“The vestibular branch collects information regarding the inner ear and head orientation and balance. The cochlear branch is concerned with sound and hearing signals from the ear, detecting vibrations from a sound’s volume and pitch. This information is sensory to the special somatic sensory modality.”
https://www.simplypsychology.org/12-cranial-nerves.html
Major brain dysfunction - kindling and akathisia
There have been entire articles written on these subjects. Kindling occurs when there is repeated neural excitation. It is not caused by updosing and reinstatement. Kindling means that every new event that causes excitation is more likely to cause withdrawal. We want to avoid this with a slow taper.
Akathisia is thought to be caused by faulty dopamine firing. It occurs with benzodiazepine, SSRI and antipsychotic withdrawal. It is likely also influenced by serotonin, since this causes depressed dopamine signaling. There are many medications that have been successfully used including beta blockers. It is beyond the scope of this discussion, but when I find a good, succinct link, I will provide one.
What’s missing?
A lot is still missing. Sex hormones, insulin, cortisol, inflammation, neurosteroids (our natural GABA chemical in the brain), and past trauma are all factors that we haven’t even discussed (coming soon). I imagine that isn’t even all, but I’ll be updating per requests and as I think of things.

It took only 5 days taking GABA with b6 for my twitches to almost dissapear and my one sided leg stiffness to go away too. I recommend this supplement to everyone whose muscle twitching started after interaction with SSRI medicine.

THIS IS UPDATE 1
( For First post, comments, and the healing program i use see here :
RECOVERY by unmethylating DNA with Natural Products
https://www.reddit.com/PSSD/comments/1boh8vz/recovery\_by\_unmethylating\_dna\_with\_natural/ )
Hi Guys so here are some updates and answer many questions of yours:
SYMPTOMS I HAD :
Genital Numbness (!) like not feeling my genitals anymore
Anorgasmia
Severe erectile dysfonction like my organ was dead (never had this even in depression)
No more libido neither interest or repulse or fear by the other gender
Dick changed of size, Sperm was like caoutchouc, odors different, sweating odors
Of body also different
Extreme Fatigue
Restless Sleep
Emotionnal blunting (feeling only negative emotions)
Severe blunting affect ( not being able to go outside in town feeling always not at ease)
feeling "disconnected" from everyone
not wanting to contact anyone i knew before (friends, associations, or groups)
(like shuting down the celllular)
gradually feeling unable to go to the supermarket and being able to cook for me
contast Fight or flight state
(see continuing list at the end of mail it is impresive the harm done)
Music was a noise to me no more satisfaction hearing anytime (even ones I liked
Before !!! Was a question of life or death for me as I am musician since I am 8 !!!
in april 2023 i took 2 drops of CBG and i instantly felt something got in my forehead
(i was told on forum it could heal my PSSD....)
Had then constant PAIN in feet !!! Always when walking !!!
As soon as i took the GABA pills ( 4 x 500mg)... i felt something in my brain like pressure
and the most horrible thing was that my penis Shrinked ! i also couldnt feel any
of my belly and was unable to push my nerves to make me Poo. I lost sensations
of my anus like numbed too ! my bowel movement was stopped.
(since then i must regulary take something called transipeg to make me go
to the toilets otherwise i am fully constipated ).
SYMPTOMS LEFT
IN ONLY 4 MONTH I GOT RID OFF MANY OF VERY ALL DISTURBING SYMPTOMS
I also want to mention I had Bladder pain and sort of prostate pain
( i perforées radiographie echography and urine test all normal !!)
AFTER 1 WEEK OF VITAMIN C no more pain !!! Just gone !!!
SLEEP IMPROVED AFTER 4 OR 5 DAYS OF VITAMIN C ! (Really amazing)
ALL OTHER SYMPTOMS Healed , still those 2 remaining :
1) STILL A BIT GENITAL NUMBNESS TO A LARGER LESS DEGREE
2) LIBIDO WEAK (I don’t want relationships, as I was a porn addict and want to
Stop this addiction I don’t know where I am on this, also I lost confidence in
myself and prefer to wait being 100% recovered to go with someone)
Now I sleep normally (no more restless sleep), can drive again, extreme fatigue is gone
I don’t have lots of energy the whole day but I see it is increasing every day !
I FOUND THAT MY MOTIVATION TO OLD HOBBIES CAME BACK SLOWLY
MUSIC IS NOT A DISTURBING NOISE ANYMORE !! I CAN FEEL DOPAMINE much more !! (Vitamin C again…)
I can play again Video Games I like them again (it was same as music !!)
I had to stop garlic due to hemorrhoid crisis , ( I don’t know if it plays a role but I will
take 1 glove in morning again soon , and will let you know about any improvements )
I just began again Garlic this morning it makes a difference
I am still struggling with breathing I notice my breath is almost at stop every time !!
Oxygen is required for unmethylating DNA …
Masturbation is normal, I have orgasm and sperm is normal
I allow myself one ejaculation every two month. (tested few days ago now will perform a 2 month no ejaculating..)
I also had days when my constant pain was removed by having sort of tingling in my nerves
It is hard to describe but it looked like it happened when everything improved
ESSENTIAL OILS I USE : and WHAT FOR
LAVENDER (true or Fine) : I put directly on skin when numbness comes it calm the pain associated.
SCOTS PINE : I open the essential oil and directly smell it, it is for oxygen rising in blood
LEMON : One or two drops on biscuit in the morning. This helps with sugar kept low while
Digesting (this is a Diabete people technique btw…)
WHAT I WILL ADD TO HEALING PROGRAM SOON :
Fasting
Exercising again :
Swimming pool Running
And PRAYING GOD
As this PSSD puts us in a very lonely condition in every part of life,
Praying was a great help ( and sometimes my only help, despite family
Members - that was not always very supportive…-)
Respecting your own religion or beliefs I urge you to pray and connect yourself
To higher Being that loves everyone.Of course no obligations, but i was helped
Tremendously…
ALSO I NEED SOME VOLONTEERS HERE !!!
I tested it on me, and all I gave you is fully harmless.
If at least 10 people could try the advises on FIRST POST (see beginning of
This post for link)
And then report here what it had done for you (and what you tried)
THAT IS ALL I ASK FROM YOU PLEASE COME BACK AND SHARE
ANY EXPERIMENTS YOU TRIED , THIS COMMUNITY NEEDS YOU
AND YOUR TESTIMONY , AS MINE CAN HEAL MANY I AM SURE !
SO HERE ARE LINKS AND STUDIES :
Here is a BIG LIST of all studies I collected since months … the first links are the « latest » ones
Meaning the newer ones I found… I assume the time it will take
To you to read but some are really worth reading !
https://www.sciencedirect.com/science/article/pii/S1053811919308316
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2430669/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471069/
https://personalizedprescribing.com/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10290282/
https://www.amboss.com/us/knowledge/basics-of-human-genetics
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9840351/
https://www.sciencedirect.com/science/article/pii/S2213231723001544
https://www.researchgate.net/publication/293045292_The_Epigenetic_Role_of_Vitamin_C_in_Health_and_Disease
https://www.sciencedirect.com/science/article/abs/pii/S0306453023002615
https://bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-018-1850-4
https://www.sciencedirect.com/science/article/abs/pii/S1773035X15301581
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10017928/
https://www.reddit.com/PSSD/comments/zgytb2/dna_test/
https://www.reddit.com/PSSD/comments/t2g385/post_drug_theory_epigenome/
https://www.reddit.com/PSSD/comments/x88yie/how_to_get_fda_recognition_with_dna_sequencing/
https://www.reddit.com/PSSDreality/comments/vysreb/pssd_is_genetic_and_probably_determinable_before/
https://www.reddit.com/PSSD/comments/45qy0q/looking_for_a_cure_are_why_focusing_on_the_right/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3092901/
https://www.frontiersin.org/articles/10.3389/fgene.2019.00079/full
https://www.sciencedirect.com/science/article/pii/S216183132200552X
https://www.biorxiv.org/content/10.1101/2021.09.15.460473v1.full
https://onlinelibrary.wiley.com/doi/abs/10.1111/jnc.15015
https://www.degruyter.com/document/doi/10.1515/med-2023-0688/html
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037192/
https://www.semanticscholar.org/papeReprogramming-the-Epigenome-With-Vitamin-C-Chong-Ahearn/02d0b1fda52d9d26d0c79fdceb28a13280387131
https://www.whatisepigenetics.com/vitamins-a-and-c-could-erase-epigenetic-marks-on-dna/
https://ods.od.nih.gov/factsheets/VitaminC-HealthProfessional/
https://pubmed.ncbi.nlm.nih.gov/19501473/
https://selfdecode.com/app/gene/slc6a4/
https://www.mdpi.com/2076-3921/12/2/231
https://m.youtube.com/watch?v=ICXltEUJ41U&list=PL4C2B927EC9AE13C7&pp=iAQB8AUB
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6083487/
https://london-andrology.co.uk/news/stem-cell-treatment-for-erectile-dysfunction/
https://london-andrology.co.uk/services/sexual-health/
https://en.m.wikipedia.org/wiki/TET_enzymes
https://www.researchgate.net/publication/367149838_Vitamin_C_boosts_DNA_demethylation_in_TET2_germline_mutation_carriers
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC53061/
https://classic.clinicaltrials.gov/ct2/show/NCT01926132
https://mentalhealthdaily.com/2015/03/21/undermethylation-vs-overmethylation-causes-symptoms-treatments/
https://askdrgil.com/colossal-mistake-everyone-taking-folic-acid/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6004927/
https://www.reddit.com/hangovereffect/comments/asbbw5/resveratrol_seems_the_real_deal_atleast_fo
https://ruor.uottawa.ca/handle/10393/28437
https://content.iospress.com/articles/brain-plasticity/bpl150022
https://pubmed.ncbi.nlm.nih.gov/23432968/
https://royalsocietypublishing.org/doi/full/10.1098/rstb.2011.0361
http://ortolang107.inist.fcatalog/these_277_bio_boulet_divnote?locale=en
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3547474/
https://www.sciencedirect.com/science/article/pii/S0163725821000747
http://www.dr-bob.org/babble/20101203/msgs/973053.html
https://www.mdpi.com/2076-3425/11/12/1602
https://www.madintheuk.com/2023/03/understanding-neurobiology-post-ssri-sexual-dysfunction/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1566169/
https://ambio.life/
https://www.researchgate.net/publication/346061089_Structure_dynamics_and_lipid_interactions_of_serotonin_receptors_excitements_and_challenges
https://www.researchgate.net/figure/A-schematic-representation-depicting-the-topological-features-and-amino-acid-sequence-of_fig5_346061089
https://www.researchgate.net/figure/Classification-and-molecular-architecture-of-human-serotonin-5-HT-receptors-a-Chemical_fig1_346061089
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3318857/
https://raypeatforum.com/community/threads/ssri-induced-serotonin-transporter-degradation-now-reversible.44954/
https://www.frontiersin.org/articles/10.3389/fcell.2021.667815/full
https://thebiogrid.org/138001/publication/role-of-c-cbl-carboxyl-terminus-in-serotonin-5-ht2a-receptor-recycling-and-resensitization.html
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5609825/
https://www.imb.de/research/niehrs/research
https://onlinelibrary.wiley.com/doi/full/10.1111/bcpt.13713
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3405674/
https://typeset.io/questions/can-you-rebuild-serotonin-receptors-15yoa6bm
https://pubs.acs.org/doi/10.1021/acschemneuro.6b00343
https://pubmed.ncbi.nlm.nih.gov/17310063/
https://pubmed.ncbi.nlm.nih.gov/22942288/
https://triggered.clockss.org/ServeContent?url=http://molinterv.aspetjournals.org%2Fcontent%2F4%2F2%2F109.full
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370302/
https://www.molcells.org/journal/view.html?uid=3628&vmd=Full
https://link.springer.com/article/10.1007/s12975-022-01007-6
https://pubmed.ncbi.nlm.nih.gov/25560757/
https://www.sciencedirect.com/science/article/pii/S0163725821000097
https://www.sciencedirect.com/science/article/pii/S0163725821000097#bb2615
https://www.sciencedirect.com/science/article/pii/S2211124720307506
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3405675/
https://www.pnas.org/doi/10.1073/pnas.1608679113
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246826/
https://www.researchgate.net/figure/Retinol-and-ascorbate-enhance-DNA-demethylation-5hmC-production-and-pluripotent-stem_fig3_308995345
https://pubmed.ncbi.nlm.nih.gov/27729528/
https://www.researchgate.net/publication/308995345_Retinol_and_ascorbate_drive_erasure_of_epigenetic_memory_and_enhance_reprogramming_to_naive_pluripotency_by_complementary_mechanisms?_tp=eyJjb250ZXh0Ijp7ImZpcnN0UGFnZSI6Il9kaXJlY3QiLCJwYWdlIjoiX2RpcmVjdCJ9fQ
https://pubmed.ncbi.nlm.nih.gov/28721271/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3262611/
Other Studies links:
https://www.researchgate.net/post/Gepirone_ER_how_long_does_a_pharmaceutical_development_process_take_after_entering_the_NDA_new_drug_application_stage
https://genesight.com/white-papers/get-to-know-a-gene-slc6a4/
https://atlasgeneticsoncology.org/gene/49951/slc6a4-(solute-carrier-family-6-member-4))
https://www.pssdforum.org/viewtopic.php?p=27345&hilit=ibogaine#p27345
https://genomind.com/patients/slc6a4-your-immediate-response-to-stress-what-you-should-know/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037192/
https://rxisk.org/forum/epigenetics/
https://www.mdpi.com/1422-0067/21/3/826
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8616462/
https://www.sciencedirect.com/science/article/pii/S2589004223003553
https://www.pnas.org/doi/10.1073/pnas.1002130107
https://pubmed.ncbi.nlm.nih.gov/31572171/
https://www.nature.com/articles/s41598-020-57506-9
https://www.jbc.org/article/S0021-9258(22)00477-X/fulltext00477-X/fulltext)
https://pubmed.ncbi.nlm.nih.gov/29334761/
https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/dna-demethylation
https://atm.amegroups.org/article/view/26175/html
https://epigeneticsandchromatin.biomedcentral.com/articles/10.1186/s13072-023-00514-6
https://stemcellsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/stem.493
https://www.intechopen.com/chapters/64868
https://www.frontiersin.org/articles/10.3389/fcell.2019.00128/full
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9231292/
https://pubmed.ncbi.nlm.nih.gov/16567755/
https://www.cancer.gov/research/key-initiatives/ras/news-events/dialogue-blog/2020/yun-cantley-vitamin-c
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129186/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9694147/
Links to Studies :
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4898786/
https://www.nih.gov/news-events/nih-research-matters/serotonin-transporter-structure-revealed
http://structbio.pitt.edu/index.php/12-faculty/50-jonathan-coleman
https://www.colemanlab.structbio.pitt.edu/
https://www.nature.com/articles/s41586-019-1135-1
https://www.ucsf.edu/news/2023/05/425246/psychedelic-inspires-new-treatments-addiction-and-depression
https://www.jbc.org/article/S0021-9258(20)50094-X/fulltext50094-X/fulltext)
https://www.erowid.org/columns/teafaerie/2014/12/18/hard-reset/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10588653/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9375667/
https://reviews.webmd.com/vitamins-supplements/ingredientreview-440-iboga
https://hightimes.com/health/people-microdosing-iboga-you-need-know/
https://ibogainecancun.mx/microdosing-ibogaine/
https://www.ibogaworld.com/the-essential-guide-to-microdosing-ibogaine/
https://www.cairn.info/revue-psychotropes-2017-3-page-125.htm
https://www.nature.com/articles/s41591-023-02705-w
https://www.reddit.com/anhedonia/comments/q0j33amino_acid_protocol_for_depression_anxiety_and/
https://www.nutrixeal.f34-acides-amines
https://www.sunday.fthreonine/
https://www.sunday.fdl-phenylalanine-gelules-500-mg-coffret.html?klar_source=google&klar_cpid=18267341225&gad_source=1&gclid=CjwKCAiA75itBhA6EiwAkho9ezB_nhAc6oBnsKLfop22j5zo0Oo8A7oQtZyIvcXRU7W-1Ex4UfOyvRoCCQsQAvD_BwE
https://m.youtube.com/watch?time_continue=82&v=bx_NNe6xMkk&embeds_referring_euri=https%3A%2F%2Fpssdlab.wordpress.com%2F&source_ve_path=MTM5MTE3LDI4NjY2&feature=emb_logo
https://www.researchgate.net/publication/10628825_The_effect_of_natural_clinoptilolite_on_the_serotonergic_receptors_in_the_brain_of_mice_with_mammary_carcinoma
https://m.youtube.com/watch?v=tfDt8q5AC6k&pp=ygUMcHNzZCBoZWFsaW5n
https://beondibogaine.com/
https://www.apeacockconsulting.com/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC446220/
https://psychscenehub.com/video/psychopharmacology-of-selective-serotonin-re-uptake-inhibitors-ssris-mechanism-of-action/
https://m.youtube.com/watch?v=bXFbDFPoiXE
https://en.m.wikipedia.org/wiki/Selective_serotonin_reuptake_inhibitor
https://fr.m.wikipedia.org/wiki/R%C3%A9cepteur_s%C3%A9rotoninergique
https://www.scripps.edu/newsandviews/e_20030929/print-parsons.html
https://www.researchgate.net/post/Gepirone_ER_how_long_does_a_pharmaceutical_development_process_take_after_entering_the_NDA_new_drug_application_stage
Links to Various Studies :
https://www.columbiapsychiatry.org/news/blocking-5-ht2c-receptors-reduce-side-effects-and-potentiate-efficacy-ssri-antidepressants
https://www.emerald-neuro-recover.com/blog/neurorecover-new-and-effective-therapy-for-damaged-brains/
https://texasintegrative.com/health-treatments/nad-amino-acid/
https://www.psychrecoveryandrehab.com/bio/
https://www.anazaohealth.com/mental-clarity-and-acuity
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9036060/
https://www.science.org/doi/10.1126/sciadv.adi4862
https://www.nature.com/articles/s41467-023-43514-6
https://www.medicalnewstoday.com/articles/alzheimers-vitamin-b-supplementation-could-slow-aging-of-neurons
https://www.orlandomedicalnews.com/article/1090/amino-acid-therapy-for-addiction
https://agelessrx.com/should-you-boost-nad-directly-or-use-precursors-nmn-n
https://www.science.org/doi/10.1126/sciadv.abb9766
https://www.nmn.com/news/latest-findings-nmn-reverses-cognitive-impairment-from-exposure-to-common-environmental-pollutant
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9474872/
https://www.mdpi.com/2076-3921/9/5/425
https://www.rvd-psychologue.com/
https://podbay.fm/p/medical-error-interviews-podcast/e/1580721600
https://newliferecovery.us/infusion-therapy-for-addiction/
https://kffhealthnews.org/news/addiction-clinics-expensive-unproven-infusion-treatments-desperate-patients/
https://www.nmn.com/precursors/nmn-vs-nr
https://m.youtube.com/watch?v=rof_30zq3Jg
https://nadresearch.org/dr-she-describes-his-research-into-testing-and-supplementing-intracellular-nad-levels/
https://pubmed.ncbi.nlm.nih.gov/7904781/
https://www.jinfiniti.com/
https://www.jinfiniti.com/the-role-and-benefits-of-nad-supplements-in-cellular-health/
https://www.jinfiniti.com/andrew-huberman-is-wrong-about-nad-nmn-nr-longevity/
https://jbiomedsci.biomedcentral.com/articles/10.1186/s12929-016-0267-y
https://www.vitalplus.com/produit/acides-amines-complexe/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787556/
https://m.youtube.com/watch?v=Ieoi68-TBus
https://www.astuces-aide-informatique.info/1075/debloquer-video-youtube
https://www.nad.com/news/nad-iv-drip-therapy
https://nadresearch.org/brnad-reduces-cravings/
https://renuebyscience.com/product/pure-nad-nasal-spray-10-grams-pure-nicotinamide-adenine-dinucleotide-nad-new/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6751327/
https://www.reddit.com/NicotinamideRiboside/comments/osuqwt/nad_1000mg_iv_for_4_to_6_days_monthly/
https://www.reddit.com/useAlivebyscience/
https://m.yelp.com/biz/emerald-neuro-recover-carmel-2
https://www.reddit.com/NicotinamideRiboside/comments/v4nvlp/comment/ibecf29/
https://portlandpress.com/biochemsoctrans/article/47/3/861/219656/How-to-rescue-misfolded-SERT-DAT-and-NET-targeting
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033614/
https://ibogaineguidelines.com/clinical-guidelines/antidepressants/
https://www.thorne.com/take-5-daily/article/why-its-important-to-methylate-while-taking-nicotinamide-riboside
https://www.reddit.com/anhedonia/comments/funege/anhedonia_cured/
https://www.reddit.com/PSSD/comments/162ecrd/does_ivig_cure_pssd_for_good/
https://www.reddit.com/NicotinamideRiboside/comments/uo7kuv/worst_pain_ive_been_in_during_nad/
https://hormonereplacementtherapyla.com/post-ssri-sexual-dysfunction-treatment-all-you-need-to-know-about/
https://www.pssdforum.org/viewtopic.php?t=4481
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061256/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6411846/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6082376/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9190277/
https://chacruna.net/ibogaine-heal-repair-protect-brain/
https://www.reddit.com/PSSD/comments/18m4qlq/is_this_all_about_inflammation/
https://www.reddit.com/PSSD/comments/16fac2c/my_neurologists_take_on_the_pathology_of_my_pssd/
https://www.reddit.com/PSSD/comments/esxrt6/ibogaine_mexico/
https://m.facebook.com/search_results/?q=Dylan+Vincent&locale=fr_FR
https://www.google.com/search?q=stem%20cells%20therapy%20mexico&ie=utf-8&oe=utf-8&client=firefox-b-m
https://www.swissmountainclinic.com/therapies/hyperbaric-oxidation-therapy
https://www.reddit.com/PSSD/comments/160vkqk/why_ayahuasca_could_help_pssd_neurocovid/
https://www.reddit.com/PSSD/comments/10uueux/my_swiss_clinic_treatment_plan/
https://clearskyibogaine.com/medications-that-compete-with-ibogaine/
https://chwbonline.com/medical-services/nad-iv-therapy/
https://sites.google.com/view/amino-acid-infusion-therapy/home
Cheers and hold on Guys !

My journey with perimenopause and sudden perimenopause anxiety.
April 7th 2024 update
Seeing more improvement overall in anxiety, definitely went through some more extreme ups and downs in between though, my hormones must still be fluctuating a lot and I think my estrogen has gone through several drops because my hot flashes have gotten worse in stages. My whole face turns red during a hot flash now and feels like sunburn. My anxiety is improving even as my physical symptoms fluctuate. I think it's easier to realize now that something physical is happening so my mind doesn't worry about what's happening it understands what's happening. My moods have become less fearful and more angry. Sex has lost all appeal, which is weird I used to be very sexual and now it just sounds gross and exhausting. I don't even want men to talk to me, they just want to take so much and I'm running on empty I need all my self care to go towards me.
Still taking my Nortrel 5/35 birth control, multi vitamin, probiotic, vitamin C, salmon oil, cod liver oil, D3, calcium and magnesium glycinate supplements. Have added taking a pinch of salt in the morning, mid day and before bed for electrolytes. Am eating more frequently as I've discovered my hot flashes are worse between meals especially if I go to long without eating. Have increased my carb intake and sugar intake and that's helping me feel a lot less weak confused achy and anxious. Or maybe it's the salt that's helping 🤔
Also tried yoga but a very easy simple yoga that is more stretching and gentle rest called restorative yoga. The peace of the nature sounds music, the happy ladies, the colorful studio, I almost fell asleep while in a comfortable pose. I'll definitely keep doing it for flexibility, mental peace and a sense of community ❤️
Hung a hammock and bamboo wind chimes in the yard so now I have a peaceful spot to sit 🥰
Because massage has been so beneficial for everything I am also going to try acupuncture, my appointment is towards the middle of the month. I'll report back on how that goes.
I got a light therapy box. Unsure if that helps but I'm using it every morning while I eat breakfast.
I'm trying to give myself things to look forward to to give me hope and keep me going, have plans to go see a comedian perform and going to a concert once I've saved up for tickets.
Tried the over the counter estrogen cream with my continuous birth control and they do NOT play well together. I'm not sure if they were canceling each other out or just giving me the wrong amount of hormones but my fluctuates felt worse so I stopped the cream.
I definitely feel like Nortrel makes the waves of hormonal ups and downs less extreme but doesn't eliminate them or reduce them as much as I'd like. I feel like it eliminates the good ups I used to have when I was ovulating and estrogen was high but doesn't eliminate the lows whenever my estrogen drops, sort of hard to explain but it's like I feel less awful because I feel less good, my body has gotten used to consistent mid level suck, no more crushing lows but no more wonderful highs. I feel like I used to feel on my menstrual cycle all the time, emotional and physically icky, I think I need more estrogen and real estrogen not birth control estrogen that holds you at the luteal phase, I want to still experience the follicular phase where estrogen is high and I feel good. I'm hoping to get a Dr to prescribe me the Dotti estrogen patch and Nora-BE Norethindrone progestin only birth control pill because it's the only kind of progesterone I've been able to tolerate. My primary care Dr is referring me to a gynecologist who will hopefully be willing to try that, my primary is amazing but due to my age, 37, she is uncomfortable going outside the general medical guidelines and prescribing me HRT she is only comfortable prescribing birth control. Hope this gives y'all some hope, I definitely feel more hopeful, the fact that things are fluctuating and changing gives me the hope that they can continue to change and change for the better. Just being able to read everyone else's experiences and see I'm not alone helps so much 💖☺️
March 2nd 2024 update
Have seen a lot of improvement since my last post! Anxiety is lower, feeling about 80% normal, hot flashes are almost gone and night sweats have stopped completely!! 😃🥰
Still taking my Nortrel 5/35 birth control, salmon oil, cod liver oil, D3, calcium and magnesium glycinate supplements.
Changes I made around the time of my last update that I think deserve the credit for my improvement:
My new Life Extension multivitamin.
Making sure to take my probiotics every single day instead of just randomly when I remembered. I was inspired because I read probiotics can help with anxiety.
Started increasing my vitamin C because I used to take a LOT of vitamin C to help with allergies and also had lowest anxiety those years of my life but didn't make the connection it might have been the vitamin C helping until I recently read vitamin C lowers cortisol so went back to taking large amounts of vitamin C and the same brand I was taking years ago. I take 1,000mg when I wake up, a 1,000mg 5 hours later, 1,000mg 5 hours after that and 1,000mg right before bed.
Have been using Life-Flo estriol and estradiol cream every morning as soon as I wake up.
I'm not sure which of those things are helping or if they are all helping but because I finally feel alive I won't be stopping any of them to see which ones are helpful. Right when I started trying those things I tried cutting my birth control pill in half and had the worst day of my life so as much as I'd like to stop birth control and switch to just the cream and supplements I can't do that yet 😣
Getting a massage with lavender oil once a week is still extremely helpful in releasing tension from my body which reduces my mental anxiety 💜
I've also been standing up for myself more with people, finding things to look forward to in the future, doing anything that makes me feel safe and happy, I got an extremely short haircut for me because I love how it looks and how easy is to style even though I knew it would make others unhappy because I wouldn't look how they wanted me to look, we don't owe anyone sacrificing our comfort for their comfort if someone in your life doesn't support you being happy and healthy they don't deserve to be in your life. As someone who has put everyone else's needs before their own this is hard to learn but worth it ☺️💕
Best wishes to you all, there is hope, perimenopause and anxiety are a rough healing process and transformation but it gets better, you WILL GET BETTER!! ❤️☺️
February 17th 2024 update
PS: I only posted my first update on Facebook so if I post this somewhere else sorry if that's confusing, I included my first update below ☺️❤️
I tried Nortrel 1/35 birth control because I've had the most relief from Nortrel 5/35, the increase in progestin progesterone made my anxiety worse and brought back my hot flashes. In my mind that and all the other birth control types and usp real progesterone cream I've tried confirm that at least currently my issue is being to low in estrogen and anything that raises my progesterone level makes the estrogen deficiency symptoms worse because I'm further off balancing the ratio of progesterone to already low estrogen. Oh and the other brands of birth control I've used sound lower in progesterone because of the dose but the types of progesterone are stronger so as far as my research has lead me in the USA at least Nortrel is the lowest dose progestin progesterone birth control because the Northrindone is the weakest progestin progesterone 🙂
In my opinion my remaining options to try and combat this anxiety are:
Number #1 trying to stick Nortrel 5/35 out longer than 3 months, I've been on it 3 different times and then got off to try different BC pills, I've heard some people feel even more relief at 6 months so I could try to stick it out 6 months.
Number #2 trying Nortrel 5/35 plus the addition of an over the counter usp estrogen estriol or estriol and estradiol cream. Estro-life brand usp estriol cream or Life-flo estriol and estradiol cream. I've read conflicting things about wether they'd work while on a birth control pill or if the birth control pill cancels them out.
Number #3 trying a .35mg Norethindrone progestin progesterone only birth control because that's the same progestin in Nortrel but less and that would be a good way to lower my progesterone and eliminate the artificial estrogen in the birth control pills sort of weaning myself to less birth control. I could also ad estrogen by using one of the above mentioned estrogen creams.
Number #4 try to convince my Dr to prescribe me real prescription estrogen pills that I can take with a .35mg Norethindrone only birth control.
Number #5 if none of these gives me additional relief or if they do but it's still not enough relief trying the 5mg Paxil my Dr prescribed. I've read Paxil and other SSRIS actually RAISE estrogen levels in the men and women that take them. My hope is just raising my estrogen levels will help and I can avoid the Paxil completely. If I try the Paxil I've read being on birth control or HRT actually makes it more effective so I might try it in addition to one of those 🤔
I'll probably try these options in the order listed above since I listed them in the order of easiest to hardest for me and because I'm already on Nortrel 5/35 so I should stick out trying it a little longer before trying the other options 🙂
Also since my first update I have tried lemon balm, passion flower and chamomile supplements and the only one that worked for my anxiety was chamomile but it actually works pretty well! 😃 I take it in the morning when my anxiety is at it's worst, Vitacost brand 900mg capsules. Chamomile tea has worked for me too in the evening before bed.
I have also switched brands of multivitamin to Life Extension Plant Based multivitamin. I like that it's cheaper lol 😂 than my previous multi, I'm poor 😆 and that the B vitamin levels are lower than my prior multivitamin because I've tested unsafely high in B levels before. I also like that the Folate they used is a more absorbable type, some people are genetically unable to absorb certain types of folate but everyone can absorb this type, also like the high levels of zinc and selenium and now that I'm not bleeding the fact that it doesn't contain iron ☺️❤️ If you're still menstruating you might need an additional iron supplement. Oh and the fact that it doesn't contain copper, LOTS of multivitamins contain copper and that makes my anxiety WAY worse!!
Hope my trial and error helps save someone else trying so many things or leads them in the direction of what works for them. Wishing you health and happiness and peace on this journey we will make it through stronger and happier 🙏❤️☺️
January 20th 2024 update:
Warning loong post lol. Hope but also trigger warning 🙏❤️⚠️ depression and anxiety.
Because other women have given me the hope to try and survive this stage, this transformation , even though I feel like I am walking through quicksand, piloting my body like a ghost, I know I have made tiny bits of progress every day and that my mind has already blocked out some of the worst stages so I feel I should document to the best of my recollection what I can remember of the waves of upes and downs before I forget. Try and give others hope and to myself when I forget I've made any progress.
I started out in 2023 a bit before my 37th birthday thinking I was dying. Had EVERY test possible, blood, hormone, vitamin, genetic, head MRI, chest x-rays, EKGs, thyroid, diabetic, iron, upper endoscopy, ultrasound, h-pilori, STD, tick born illness, and others I can't think of off the top of my head. Wracked up a wild amount of medical bills because I was experiencing, chest pain, shortness of breath, anxiety, panic attacks, numb hands and sometimes feet, face numbness, tingling, depression, left rib pain, matching back/spine pain, tingling brain, dizziness, vertigo, nausea, digestive issues, eye floaters, thinning vaginal lips, drenching night sweats, hot flashes that felt like panic attacks, bad dreams, paranoia, missed menstrual cycles, painful menstrual cycles, heavy long menstrual cycles, clots, ovarian pain, cramps, brain fog, forgetting simple words and having to point at things, and maybe more symptoms I'm forgetting.
It's been about 8 months since I was hit like a train with the worst of it. Looking back I think perimenopause may have started 3-4 years ago around 2020 with a slight drop in sex drive, thinning vaginal lips, morning diarrhea and eye floaters.
2021 sex drive dropped a little more, menstrual cycles got shorter, went from a consistent medium flow 7 days to a heavy 4.
2022 I don't remember any huge changes.
2023 was of course when I got hit with the worst of it and realized I was in perimenopause.
Now in January 2024 I have added worse depression and extreme loss of libido but brain fog has improved, sleep has improved, dreams aren't as bad, paranoia and digestive issues are mostly gone.
Things I've tried within the last 8 months.
Things that have helped a little:
For Sleep;
Goli Dreamy Sleep gummies, one before bed, only 2 or 3 nights a week as it seems to loose effectiveness if taken to often.
Traditional Medicine Nighty Night Original tea with passion flower a cup anywhere from an hour to 30 minutes before bed.
Watching ASMR videos on YouTube especially nature ones or soothing anxiety cutting or plucking, lots of types to many to mention.
For overall wellbeing;
Magnesium glycinate 100mg in the morning and 100mg at night for anxiety reduction.
Nortrel continuous birth control norethindrone-eth estradiol 0.5-35 MG-MCG TABS skipping placebo pills as prescribed by my Dr for both regulating hormonal fluctuates and endometriosis. Helps with mental health and physically painful menstrual cycles. My vaginal pain and anxiety were the worst a day or two before my menstrual cycles and the first few days of my cycle. I've been on it twice, made the mistake of stopping to try other formulas of birth control to see if they'd help more. From my experience Nortrel takes about 21 days to start seeing any relief and then I see more relief at 2 months, then feel a little worse, then feel a little better at 3 months. Then I unfortunately tried other ones that set back my progress.
Vitamin C 1,000mg when I wake up, 500mg mid day, 500mg in the evening and 1,000mg before bed. Helps with anxiety.
Vitamin D3, 2,000mg with lunch, 2,000mg with dinner. Might be helping with depression I can't tell, probably to soon to tell. Might make me a bit anxious. Going to give it more time to decide.
Was taking iron for awhile when my cycles were heavy to combat anemia.
Garden of Life women's multi vitamin only half a serving, one tablet because it's higher in B vitamins than I like, I've tested unsafely high in B vitamins before so I'm cautious.
A probiotic, True Grace women's probiotic.
1,000mg of salmon oil and 1,000mg of cod liver oil, helps with joint pain for sure and is supposed to help with anxiety and depression but I'm unsure if it's helping with that.
Sage capsules help stop the frequency and severity of night sweats, 570mg two hours before bed. Also sleeping with socks on works 9 out of 10 times for me.
CalmAid silexan lavender capsules, I might try these again, they were helping a little bit before I tried birth control, stopped them because I read conflicting things about them interfering with birth control.
Buspirone 2.5mg will stop anxiety and panic for me in 38 minutes BUT it saves the emotions for later and that leads to a big horrible emotional moment 😔 Sometimes I take one to get me through the day but they also make me extremely drowsy.
Bach rescue remedy tablets but weirdly only the flavor elderflower orange helps my anxiety, and only if it's not to bad.
Self care, sitting in the sun, walks in nature, salt baths, reading books, good smelling things like essential oils, anything that brings you peace 🌞💚
Getting a deep tissue massage, I get 3-5 days without a panic attack!
Talk therapy was helpful for the couple months I could afford it.
THC deltas 9 and 8, vaped and gummies, mildy helpful and calming depending on brand and form either indica or sativa. Everyone is different worth trying in my opinion. At least didn't make things worse. Gummies were the most helpful, start slow, cut a gummy in half. Seriously go to a local smoke shop or store if it's legal in your state and the workers will show you so much kindness and knowledge 💕🙏
Gaining weight! We store so many things our bodies need to carry us through these stressful times in our fat reserves and I only weighed 109 pounds. I'm up to 123 and would like to get back up to the 145 it was when I felt healthiest.
Eating more protein.
Cutting out as much stress and toxic people as you can out of your life. I had a lot of traumatic life events happening in a short period of time and I think they could have thrown me in to perimenopause or overwhelmed my body and soul and made things worse. I don't care how selfish or irresponsible it seems cut loose anything you can before it breaks you, I think I should have switched jobs before I started getting panic attacks and I would have prevented them from starting. Also unsure if it's a factor but I had 3 courses of antibiotics in very short period of time and think that wore my immune system down, if I could go back in time I'd only take the 2 most important courses of antibiotics.
St. John's Wort, I tried this yearssss ago in my early 20s and forgot about it, it was the most helpful with my anxiety of anything I've ever tried. I stopped using it because it made me have my menstrual cycle for a month and a half straight. I can't try it now because I'm on birth control and it says it interacts with it but I wish I'd remembered it before trying birth control because I'd try St. John's Wort first, now that my menstrual cycles are short and light or skipped maybe long bleed wouldn't be a problem.
Things that didn't work or only sort of worked for me;
CBD, 15-30mg capsules. No effect.
Weed smoked, caused anxiety.
Kava Kava tea Yogi brand Stress Relief formula, caused anxiety similar to smoking weed.
Apri birth control I didn't sleep for 9 days and felt wired but also felt no anxiety, it was weird and awful I wish I could have stayed on it for less anxiety but I needed to sleep 😕
Amethyst birth control, my anxiety was through the roof and I was nonstop heavy bleeding, only tried it for 5 days couldn't take the anxiety.
Natural usp bioidentical progesterone cream, DEPRESSION.
Not sure if I should include it because it wasn't recently that I tried it but in early 2020 I tried Yaz and had horrible anxiety and depression and diarrhea. I think it was to high in progestin progesterone for me.
B vitamins can increase my anxiety and my vitamin tests came back to high in them which can cause numbness and tingling so I have to use in moderation.
Ashwagandha, one brand didn't do anything at all and the other one gave me TERRIFYING trippy nightmares.
Lion's main mushroom cause the worst panic attack and brain tingling and I threw up a bunch.
Cutting out gluten caffeine and sugar for 4 months did nothing.
Lexapro 5mg for 5 days made me want to k*ll myself and I had horrible digestive issues.
GABA, didn't notice any changes.
Vitex made me worse emotionally, I think it increases progesterone and I ether have to much or to much in relation to low estrogen so more just unbalances me more.
Things I'd like to try;
Maybe Paxil, my Dr prescribed 5mg to help with anxiety and hot flashes. I'm just afraid to try it after my experience with Lexapro.
Chamomile capsules, I've heard they help with digestion and anxiety.
Hops capsules, I've heard they help with aches and pains and are calming.
Mother wort, supposedly soothing and comforting of emotions.
Passion Flower, supposed to help with anxiety and sleep.
Lemon balm, helpful for anxiety.
Consuming more water and electrolytes, I probably don't get enough of either.
Light therapy SAD lamp. I live in a cold dark climate and I think I probably don't get enough sunlight.
Acupuncture, I've heard good things.
5-htp, supposed to be a natural SSRI but also has withdrawals and side effects like one so I'm cautious about trying it. Have heard it can only be used for a short time and then needs to be gradually reduced.
NAC, my friend has had good luck with this. A bit unsure if it would interact with my birth control and hate to risk loosing any tiny amount of progress I've made.
DHEA, I don't remember why this was supposed to help lol, just that I have a bottle I've never tried. Same thing with DIM.
Boron, supposed to be the building block for hormones, not sure if I can take it while on birth control.
Natural estrogen cream or patches, real HRT. Hard to get because of my age, 37, my insurance and Drs don't think it's a first line in perimenopause but I can probably get it once I'm older or in menopause. To be fair I've read in perimenopause when hormones are fluctuating birth control is actually more effective than HRT. And the Combi Patch HRT is the same hormones as the Nortrel birth control I'm on just a different dosage so not all HRT is natural or different from birth control.
Joining a ladies group or religion or coven, really some type of community, I don't think I have a social support system.
None of this constitutes medical advice, we are all so different I just want to give others and myself hope when it seems hopeless. I know I've heard from many women in my life that once they were through the ups and downs of perimenopause actual menopause brought so much peace 🕊️✌️💖
I'll try to post updates if I'm not to overwhelmed, if I try anything else or see any improvement or worsening. I really wish I knew how long perimenopause would last, what stage I'm in, how many years or months I have left. My Mom thinks she reached full menopause in her mid 40s if she remembers correctly, maybe 45/46. She doesn't think her symptoms were as extreme as mine but maybe time heals and mercifully allows us to forget because as a child I remember some really emotional times she had that scared me. Unsure if it's a factor but I've never had kids she's had 2, my menstrual cycles start at 11 hers started at 15 or 16.
Wishing you all peace, health and happiness 🙏❤️😊

Has anyone else experienced taking the Gaba supplement and then feeling brain fog the next day?
Im not sure if it is interacting with SSRI or ADHD meds I take. ANd wondering if it could.

Hello, Has anyone ever asked the neurologist why the twitches get stronger after movement? Because "we are weak" isn't an explanation, is it, because there are a lot of sportsmen in the group, too? Do ALS patients also have this process of becoming stronger for movement? I always see on video that they twitch in a state of rest as much as I don't twitch in a half marathon (if I could run that much it would be a good example...yeah😅). The other thing that concerns me (obviously a strong concern) is what signs do those who experience clinical weakness (e.g. the foot falls off) notice before it? Everywhere, it is wrongly stated that ALS begins with clinical weakness. But this is not true, because it is not true that without some "process" you cannot do something overnight. Unfortunately, I have a serious concern, I will be 4 months old now, I always test myself, but the calves do not rest, they are constantly moving 24/7. My right foot sometimes feels "strange" in shoes, as if the shoes are looser. But this is not always the case, and it does not exist without shoes. Sometimes my right leg tingles, but sometimes the left too. (I have a l4/l5 disc problem, sometimes my lower back hurts). My legs and hands are equally strong, and now I exercise every day (treadmill walking, short running, weight lifting, squatting). In the last 4 months, I feel that my strength has not changed. I've been taking the SSRI for two weeks, but I don't feel any change in my symptoms. I have just started taking Gaba and Potassium, I am receiving b12 by injection, the 2nd dose next week.

Hello,
I came across this study (https://www.sciencedirect.com/science/article/abs/pii/S1569904822000040) last night as I was doing some research into the hormonal effect of apnea training. As I looked further into the adrenal and sex steroids discussed, I got a few ideas hypothetically playing roles in the mental aspects of this sport.
Perhaps best to disclose here that albeit I’m a master's level graduate in the field of science relevant to this, I’m no doctor or physiologist. However, I’m relatively confident in my ability to interpret this kind of data and in recognizing where I’m drawing my own conclusions and where I’m actually making a synthesis from the data given. Not that I’d be free of any blindspots, personal bias and what not (I mean I do like jumping into conclusions lol).
Yet, when it comes to freediving and apnea training I just got into this two weeks ago. My best dry static was 4:42 after my third CO2 table training. Haven’t retested since but I’m rather confident that I could now push past that 5 min mark as I have trained both dry static (CO2 tables) or dynamic apnea (in a pool) at least every other day since getting sucked into this. I’m considering switching from the CO2 tables into O2 tables soon. While I do know that these are not perhaps too favoured anymore for training, I’ve been partly doing the CO2 tables “recreationally”, as I’m very much infatuated by the mental (side) effects them have on me. :)
So let's first look at the results of the paper.
“Results
Corticosterone, progesterone, cortisol, 17−OH-progesterone, dehydroepiandrosterone (DHEA) and androstenedione showed a significant continuous increase with a maximum at 0.5 h after apnea, followed by a decrease back to or below baseline at 4 h after apnea. Testosterone, estradiol, cortisone and dihydrotestosterone showed a decrease 4 h after apnea. Dehydroepiandrosteronesulfate, luteinizing hormone (LH) and follicle stimulating hormone (FSH) showed no significant changes.”
All in all the breath holding or hypercapnia, perhaps unsurprisingly so, yields changes in most of the circulating hormone levels assessed. Nevertheless, I found these hormonal changes interesting and compelling in explaining some of the experiences reported in the discussions around apnea training and free diving in general, and additionally things I’ve experienced myself. Namely, the two main effects I'm talking about here being the sense of increased “peace” and the importance of “not pushing it” too much (at least not all the time) when training for the breath holds and dives.
First looking at the anecdotally experienced sense of peace or serenity or something. I found it interesting that at least two of these hormones actually had some interactions going on with GABA circuitry.
GABA
Short introduction to GABA from wikipedia: “γ-Aminobutyric acid (gamma-aminobutyric acid), or GABA, is the chief inhibitory neurotransmitter in the developmentally mature mammalian central nervous system. Its principal role is reducing neuronal excitability throughout the nervous system.” Now, got to keep in mind not to draw too far fetching and set in stone conclusions from these coarse generalisations as the neurotransmitters and their effects are very convoluted and the nuances are largely ill understood, not to mention the individual differences and the brain area specific effects (and not only brain but the whole body!).
However, what piqued my interest in this regard was progesterone and dehydroepiandrosterone. Short excerpts from wiki:

• Progesterone: Through its neurosteroid active metabolites such as 5α-dihydroprogesterone and allopregnanolone, acts indirectly as a positive allosteric modulator of the GABAA receptor.
• Dehydroepiandrosterone: has been found to directly act on several neurotransmitter receptors, including acting as a positive allosteric modulator of the NMDA receptor, as a negative allosteric modulator of the GABAA receptor, and as an agonist of the σ1 receptor.

While these effects are indeed quite the opposite, it would appear that these hormones would actually directly or indirectly have an effect for the GABAergic signalling. Moreso, as these receptors (GABA) are known for their relatively rapid desensitisation and/or down and up regulation depending on the stimulus received.
Furthermore, Dehydroepiandrosterone has been previously reported alleviating depressive-like behaviour via GABA-ergic modulation of the mesolimbic system (in rats!). The same study states: “In humans, DHEA has antidepressive effects; however, the mechanism is unknown.” (https://pubmed.ncbi.nlm.nih.gov/18496525/). Perhaps referring to this study: “ Higher serum DHEA concentrations before and after SSRI treatment are associated with remission of major depression” (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5336487/), which asserts: “Preclinical studies suggest that DHEA(S) has antidepressant/neuroprotective properties, and exogenously administered DHEA has shown antidepressant efficacy in humans. Nonetheless, the role of endogenous DHEA(S) levels in major depressive disorder (MDD) and antidepressant outcomes remains unclear.”.
On the other hand, a metabolite of progesterone; allopregnanolone has been reported yielding rapid potentiation of the inhibitory neurotransmission mediated through the GABAARs (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821816/).
Additionally, NMDA receptor modulation is yet another interesting avenue as recent studies shedding light to some compounds affecting these receptors (i.e., ketamine) being reported yielding rapid and lasting improvements for patients suffering from depression.
Won’t go any deeper into this GABA stuff here. To me these seem explanatory in the perceived increases in the peace of mind and sense of well being (which for me following apnea training have been indeed quite “dramatic”!).
Corticosteroids
Moving forward, an intriguing aspect to consider is the gradual approach to extending breath-holding durations rather than persistently pushing one’s limits. The article from Frontiers in Cellular Neuroscience Interactions between noradrenaline and corticosteroids in the brain: from electrical activity to cognitive performance (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3321636/) elucidates the significant role of corticosterone and noradrenaline in memory, particularly in relation to emotional memories and long-term memory (LTM). These hormones are shown to regulate synaptic transmission and memory performance, both individually and synergistically.
Corticosterone, in concert with noradrenaline, can rapidly but also persistently regulate neuronal function, affecting memory processes. The timing of corticosterone relative to stress exposure is critical, as it can either enhance or disrupt the encoding and consolidation of fear memories. The article highlights that corticosteroid hormones, through their respective receptors, mediate the memory-enhancing effects of stress and emotion.
Moreover, the interaction between corticosteroids and noradrenaline at the cellular level suggests that these hormones can modulate memory formation in a time-dependent manner. Rapid non-genomic actions of corticosteroids, coinciding with the effects of noradrenaline, can facilitate synaptic transmission and potentiation in limbic cells shortly after stress. However, slow genomic actions of corticosteroids may attenuate the effects of noradrenaline, influencing memory consolidation and retrieval.
To me the most important take-away from the paper is this: “Subjects receiving both reboxetine and hydrocortisone showed reduced amygdala activity to happy faces but enhanced activity to fearful facial expressions. This suggests that noradrenaline in interaction with cortisol gives rise to a negative bias of emotional functions.” (it should perhaps be noted here that reboxetine is an noradrenaline reuptake inhibitor, therefore increasing the noradrenaline in the synaptic cleft) What’s notable here is as stated by the first paper discussed, circulating cortisol levels are elevated in response to the apnea training, while noradrenaline perhaps not (this wasn’t studied in the paper however). Therefore, this might suggest a rather direct vector for affecting the apnea training largely dependent on the reprogramming of one's psychological responses.
I imagine this information could be useful when considering the psychological aspects of apnea training. It supports the notion that excessive training within the discomfort zone can lead to counterproductive outcomes. Understanding the nuanced effects of stress hormones on memory and behaviour could inform more effective apnea training strategies, emphasising the importance of balanced training intensity and the potential benefits of stress management techniques.
On a tangent I’d like to add that I find it interesting how some of these hormones induced by hypercapnia are also reported interacting with sigma-1 alpha receptors. This is intriguing as it’s been suggested that sigma-1 alpha receptor activation may alleviate hypoxia-induced cellular stress and increase survival in a HIF-1-independent manner. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5021697/)
Would be intrigued in hearing your take on this. While I do understand that not everybody is nor should be interested in the mechanistic aspect of these things, personally I find that this way of understanding might well clarify the approaches (or at least the reasons), yet at best yield some novel insight into the practice or atleast help prune some counterproductive practices from the training.
This is actually a self promo ;) https://soundcloud.com/vn820hbn20nb
Cheers!

This is an article from my website. To view all references visit here: https://pas-secondlife.com/2024/03/18/restoring-the-reward-system/
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An epigenetic basis for PSSD:

It seems trivial to most people that medications, including over the counter medications, can cause unwanted side effects in some people. It’s also taken for granted that to remediate any unintended side effects, all that’s needed is to simply discontinue to perpetrating medication. But what if the side effects don’t resolve themselves. What if instead they continue for years or even indefinitely. This is situation not as readily acknowledged by the average person, or even within the medical community, and yet it’s the reality for a great many people treated with certain medications including SSRIs. For most people this class of antidepressants are well tolerated and effective, however a minority of patients suffer a spectrum of lasting changes to their health and mental wellbeing. Whilst there’s some degree of individual variation, the most typical symptoms are a complete loss of sexual interest and a general state of anhedonia. Perhaps just as troubling as the symptoms themselves is that apparent inability by doctors to explain why these side effects can persist long after the drug has fully metabolised out of the body. It’s only been in recent years with the advent of epigenetics that a plausible explanation has presented itself.
Epigenetics is the field of genetics that explains how gene expression can be altered without changing the underlying genetic code directly. Epigenetic mechanisms can essentially switch genes on and off in a lasting manner, and thereby influence an organism’s traits and behaviour. Two twins sharing the same genes can experience vastly different health outcomes based on their exposure to epigenetic agents. SSRIs are one such type of agent, that are now understood to have lasting impacts on gene expression, which might elucidate the lasting nature of PSSD. In this post I’ll delve into a crucial piece of evidence for SSRI induced epigenetic changes and do my best to convey the science in a way that’s accessible to the layman. The evidence presented in this post reveals specifically how SSRI’s can negatively impact sexual behaviour long after discontinuation.
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Key points summary:

• Epigenetics is the study of how gene expression can be altered without changing the underlying genetic code. Changes to epigenetics can have a lasting impact, changing an organism’s traits or behaviour.
• SSRIs exert their therapeutic (and adverse) effects primarily through the 5-HT1A serotonin receptor. This is the most abundant type of serotonin receptor and has the most significant impact on serotonin effects on cognition, mood, and libido.
• The 5-HT1A receptor can be subdivided into two categories: autoreceptor and heteroreceptor.
• The Autoreceptor exerts a self-limiting effect on serotonin transmission, whilst the heteroreceptor influences cortical activity.
• When SSRIs are used chronically, they causes the autoreceptor to desensitise, which in turn allows for greater serotonin transmission to interneurons.
• Interneuron 5-HT1A binding is linked to increased cognition and libido and is believed to be the therapeutic mechanism of Buspirone, by boosting cortical activity.
• The beneficial of SSRIs appear to be undermined by ultimately causing the same desensitisation of the 5-HT1A receptor on interneurons, thereby increasing serotonin transmission to pyramidal neurons.
• Serotonin binding to pyramidal neurons suppresses an important kinase involved in attention, memory and mood called CaMKII.
• When CaMKII is inhibited, there is a significant reduction in memory formation through the process of ‘Long Term Potentiation’.
• CaMKII regulates glutamate transmission and therefor is also implicated in the reward experience of stimulants, as well as reproductive behaviours and social interaction.
• CaMKII neurons are particularly relevant in explaining the hypersexualising effects of stimulants such as amphetamine.
• Fluoxetine has been found to exert epigenetic changes to CaMKII, particularly within the Nucleus Accumbens, which is the main reward centre of the brain.
• SSRIs make the gene less available and would therefor theoretically dampen the reward system. The researchers who identified this epigenetic modification found this change paradoxical, as it contradicts the expected effect of an antidepressant.
• CaMKII notoriously possesses a ‘molecular memory’, as changes to its activation can have lasting effects.
• The effect of Fluoxetine on CaMKII is contrasted against Lithium or Tianeptine, both of which enhance CaMKII activation, and through this possess antidepressant effects.
• A course of Lithium can allow for enhanced CaMKII activity even 28 days after the end of treatment.
• Furthermore, Lithium enhances gene expression within the Nucleus Accumbens through the opposite epigenetic mechanisms of Fluoxetine.

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5-HT1A: How SSRIs Work

Serotonin is a neurotransmitter that’s widely distributed throughout the brain, but its specific effect on different structures will depend on which type of serotonin receptor it binds to. The most pertinent type of receptor in explaining the therapeutic effects of SSRIs is the 5-HT1A receptor. Despite this type of receptor being the target of perhaps the majority of psychiatric medications, its behaviour is still somewhat mysterious and occasionally paradoxical. I’ve written fairly extensively about 5-HT1A in another article, so for a thorough explanation and all references, read here. Whilst this article heavily implicates 5-HT1A, I’ll only give an executive summary for the sake of being concise.
The serotonin system originates in centre of the brain in the region called Raphe Nuclei, which projects widely into the corticolimbic system to regulate emotions and cognition. The receptor can be subdivided into type subtypes: the heteroreceptor and the autoreceptor. The difference between these two subtypes results in vastly different regional effects in response to serotonin binding. The autoreceptor is present on the serotonin neurons within the Raphe Nuclei, and the release of serotonin from these neurons exerts a self-limiting effect. Serotonin binds to these autoreceptors to inhibit the further release of serotonin in negative feedback loop. This is because serotonin has an inhibitory hyperpolarising effect on neurons, reducing their firing rate.
5-HT1A heteroreceptors are present on two sets of neurons projecting out from the Raphe Nuclei. The prefrontal cortical neurons, as well as the interneurons which feed into them. The prefrontal pyramidal neurons are excitatory and release excitatory neurotransmitters such as dopamine and glutamate. Alternatively, the interneurons that feed into those pyramidal neurons are inhibitory, and release GABA. As serotonin binding to the 5-HT1A receptor on either of these subtypes results in a reduction in firing rate, we can observe opposing behavioural effects depending on which set of neurons is targeted. Selectively binding to the interneurons reduces their firing rate and prevents them from inhibiting the pyramidal neurons and resulting in elevated dopamine transmission in the prefrontal cortex. This is why medications that more selectively bind to the interneuron heteroreceptors such as Buspirone can improve cognition in certain circumstances. Furthermore, dopamine transmission is needed more generally to mediate feelings of reward, including sexual reward, which is why heighten libido is a reported side effect of these medications.
The purported goal of SSRI’s is to elevate the presence of serotonin within the Raphe Nuclei by blocking the action of the serotonin transporter. Initially this results in the autoreceptor negative feedback mechanism mentioned previously - however after chronic application these receptors become desensitised and no longer have an inhibitory effect. This in theory allows for more serotonin to reach the heteroreceptor sites and exert beneficial effects on mood and cognition.
More recent evidence has revealed that in practice, the effects of SSRI treatment is more complex, and ultimately the heteroreceptor will in turn undergo desensitisation. This can manifest in negative symptoms regarding cognition, and more notably, libido. However, this can be corrected with the application of targeted 5-HT1A antagonists such as Pindolol, binding to the autoreceptor sites, and thereby redressing the imbalance between hetero- and auto-receptor activation. The use of Pindolol in this way has even been found to be effective in restoring lost libido consequent to SSRI treatment.
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5-HT1A and CaMKII

Whilst 5-HT1A receptors are G-protein coupled receptors and subsequently undergo desensitisation or sensitisation in response to stimuli, there is another perhaps more lasting way by which SSRIs impact 5-HT1A. Serotonin results in reduced neuronal activity when applied directly to the prefrontal cortex, by binding to the 5-HT1A receptor on pyramidal neurons (it’s important to note the distinction here between heteroreceptors on interneurons and pyramidal neurons, as serotonin binding to interneurons boosts cortical activity). 5-HT1A binding suppresses glutamate activity in the prefrontal cortex by reducing the activity of a protein called CaMKII. This kinase is activated by Calcium and is essential for a variety of synaptic processes including memory, cognition, and reward. CaMKII is particularly crucial in the prefrontal cortex pyramidal neurons, and when suppressed by serotonin, result in decreases AMPA currents. [1] Mice that lack 5-HT1A on excitatory pyramidal neurons are found to experience heightened anxiety and stress, due to an increase in CaMKII activity. [2] Conversely, mice that lack CaMKII are shown to have decreased attention, memory, and cognition – as predicted by lower cortical activity. [3][4]
Given that CaMKII is associated with glutamate, it’s perhaps unsurprising that its tightly interconnected to the reward systems of the brain. The Nucleus Accumbens is considered the primary reward centre of the brain and is the target of many addictive drugs like cocaine. The elevation in glutamate in response to administering addictive drugs is a consequence of elevated CaMKII within the Nucleus Accumbens. [5] In fact, CaMKII neurons have even been implicated in explaining the excessive hypersexuality caused by these stimulants. [6]
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How do SSRI’s impact CaMKII?

CaMKII has long been of interest in neuroscience as it possesses an interesting property of ‘self-perpetuation’. This means that once activated by Calcium, it can translocate to NDMA receptor sites and remain there long after the original source of Calcium has been lost. This is sometimes referred to as ‘molecular memory’. [7] This lasting complex formed by NDMA receptors and activated CaMKII is believed to underly the process of memory formation called ‘Long Term Potentiation’. [8] Therefore any medication that could influence CaMKII might have some lasting impact. One medication known to influence CaMKII is the SSRI fluoxetine. In fact, Fluoxetine has been found to repress CaMKII expression in the Nucleus Accumbens through epigenetic modification. Chronic Fluoxetine reduces the H3 acetylation of the CaMKII promoter which prevents the binding of FosB. The researchers who identified this repression of CaMKII considered this finding ‘paradoxical’, as such a change would dampen the reward system. Crucially the researchers found the same changes in H3 acetylation at the CaMKII promoter in postmortems of depressed patients taking antidepressants at time of death. [9] The authors of the study were ultimately unable to explain why an antidepressant would induce epigenetic changes otherwise linked to depression but hypothesise that it might be a compensating for the increase synaptic plasticity. In fact, Histone Deacetylase Inhibitors (HDACis) are known to have an antidepressant effect when administered directly into the Nucleus Accumbens, by enhancing gene expression – an effect opposite to that of Fluoxetine on the CaMKII promotor in the Nucleus Accumbens. [10]
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What are the effects of impaired CaMKII, and how can it be restored?

Given that FosB is reward sensitising, the inability for FosB to bind to the promotor of CaMKII in the Nucleus Accumbens would in theory hamper the reward system. We can contrast the effect of Fluoxetine on CaMKII with other substances known to enhance FosB. Tianeptine is an atypical older antidepressant, that has been mostly abandoned as it was found to potentially cause liver damage, although this has been disputed. Unlike Fluoxetine, Tianeptine can enhance glutamate expression through CaMKII activation. This exerts an antidepressant effect, preventing neuronal loss and dendritic atrophy. [11]
Given that CaMKII is intimately interconnected to processes involving neuroplasticity and growth, its unsurprising that Lithium also interacts with CaMKII through PI3K. Lithium boosts long term potentiation through elevated CaMKII. Even after Lithium was ceased, CaMKII remained elevated for another 28 days. [12] Lithium is even able to attenuate brain injury by restoring activated CaMKII, through PI3K and calcium mobilisation. [13] The effect of Lithium is further contrasted against Fluoxetine via opposing epigenetic effects. Whilst Fluoxetine induced repressive epigenetic changes to the H3 histone, Lithium enhances H3 histone acetylation in the Nucleus Accumbens. [14] Given the evidence for CaMKII possessing self-persistence through autophosphorylation, it is not unreasonable to expect that a course of Lithium may have lasting effects. [15]

In addition to prescription medication, I have tried or researched a few promising remedies. What are your experiences with any of the following treatments: Infrared light therapy for pain Pulsated electromagnetic therapy (the bemer may) for fatigue GABA and l-theanine combo for sleep Essential oil self massage for pain, fatigue and anxiety (lavender, rosemary, mints) Meditation for sleep, pain Yoga - Yin, Kundalini for overall improvement
Very curious about our willingness to actively seek out and attempt non western-medically prescribed treatments. I've had excellent results from some of these. I want to start infrared light treatment. I've only used a bemer mat a couple of times, just wondering if anyone else does. What other treatments have helped you?
I don't condemn the use of pharmaceuticals at all but I recognize them as sources of relief but not healing and sometimes you suffer such bad side effects. I only take pain killer, muscle relaxer as needed and I won't touch any ssri or related medication. But like I said, I've had great results in my healing. My fibro is episodic and mild comparatively to others. 5 years ago though, I thought I was dying.