Well, it took me 10 years to figure it out but eventually I healed my brain from both chronic serotonin toxicity/sensitivity and GABAergic kindling.
It all started with certain bad life decisions culminating in 2012 with MAOI (moclobemide) use, which I eventually tried to withdraw from, the withdrawal was so bad I desperately added some tryptophan to try to ease it. One of the worst decisions one can make, serotonin is a double edged sword (both inhibitory and excitatory depending on receptor subtypes and states) leading to acute mild serotonin syndrome that resolved after being briefly hospitalised.
However residual damage and symptoms persisted for many years such as mental pain, agitation, anxiety, depression, and bipolar-like symptoms. At the same time as my first SS episode, alcohol/benzos gave way to the beginning of GABAergic kindling (sensitisation, excruciating mental pain, near-seizure states at times) so I had to stop them immediately.
Things that initially helped the worst stages included Seroquel (quetiapine - strongest anti-serotonin antipsychotic but also anti-dopaminergic), cyproheptadine (strong in a bind, but amnesic side effects). Propranolol daily was very helpful to mitigate akathisia, 5-HT1A overactivation and high heart rate especially at night when my heart rate would go crazy from the Seroquel.
Things that set me back by making serotonin symptoms worse for months after trying included Lithium and Lamictal (lamotrigine). Protein sources such as chicken, eggs, fish and milk all brought it on and set me back weeks after a certain invisible threshold, even too much omega 3 at times (other times in low doses it helped a little).
Kindling developed further over time, I'd try alcohol again after periods of abstinence without symptoms but every time that threshold would be lower before withdrawal, no matter how long I left it, until 1 drink precipitated almost immediate withdrawal, so eventually had to give up alcohol completely in 2015, even herbs in food, certain vinegars such as balsamic/cider and de-alcoholised wine that have minute amounts of GHB, GABAergic supplements/herbs and even a stabilisation neurofeedback protocol all precipitated excruciating withdrawal leading to extreme dietary restrictions. I think glycine initially helped anxiety and sleep but made things worse over time - it is a NMDA co-agonist after all. I couldn't take magnesium either (mild GABA-A agonist).
With such a restricted diet I got protein calorie malnutrition, and various consequences such as slow or incomplete healing (e.g. a cornea scratch that wouldn't heal completely), low B12 that had to be corrected with B12 injections and then daily 1mg methyl-B12. Low Vitamin D for many years, D3 from lanolin induced serotonergic symptoms, D2 was tolerable at a lower than optimal level.
I was on Seroquel for a decade until my psychiatrist suggested ketamine for treatment resistant depression in 2024. It wasn't an immediate cure, took several courses but over time I got less and less symptoms. Ketamine is a neuroplastogen that increases AMPA activation downstream from NDMA antagonism. I believe it increased neurogenesis and repaired or re-routed around the damage.
Ketamine promotes rapid and sustained antidepressant effects by increasing adult hippocampal neurogenesis, specifically by fostering the growth and activity of immature neurons. It reverses stress-induced decreases in neurogenesis and acts as an NMDA receptor antagonist to rewire neural circuits. Studies indicate both R- and S-ketamine have pro-neurogenic and anti-inflammatory properties, with effects linked to increased neuronal differentiation.
Over time I introduced more and more protein, backing off whenever I got symptoms. I will say going from vegetarian to a meat eater was incredible. Beef especially has been very healing to my body.
I also started CBD and medical cannabis in 2023 which I believe also played a role in GABAergic kindling desensitisation, but I also believe ketamine played a major role there too.
Tianeptine was also super helpful as needed and remains in my arsenal for social anxiety/depression, even after briefly becoming dependent on it.
Tried many things over the years to try and get off the high dose Seroquel including cold turkey, cariprazine, lurasidone, pimavanserin, but nothing helped. Interestingly, tapering slowly never worked and always went back up. Until Mirtazapine. One of the better older antidepressants, no sexual side effects. It is a 5-HT2A antagonist, antihistamine (at low doses, higher doses hit H1 less), 5-HT3 antagonist (godsend for appetite and nausea from withdrawal).
I was able to reduce Quetiapine from 600mg-300mg-0mg in just a couple of weeks by substituting with the mirtazapine. Adding nicotine also helped. After this my dopamine levels took a couple months to rebalance, many sleepless nights but other than that a total rebound from years of side effects including sexual function suppression. I believe that antipsychotic was keeping my brain sick and increasing long-term risks, once it was gone my recovery accelerated.
Now I could tolerate mildly serotonergic substances again such as Vyvanse/dexamphetamine for my ADHD, and added Intuniv (guanfacine) which helped balance it, along with improving executive function, memory, and even anxiety.
Went on Memantine for a while, was helpful but felt rather dulling so I limited it to short low-dose cycles when needed.
I have been trying scores of supplements. My favourites so far for brain health are Magnesium L-threonate, NAC Ethyl Ester, NMN, and Omega 3.
Unfortunately Lions Mane was a total flop, just increased rumination to an unbearable level.
NSI-189 recently has been a much better alternative and has continued the healing.
Recently started bromantane that I seem to tolerate even better than Dex for ADHD.
I can also tolerate L-theanine, chamomile, taurine, ashwagandha, hops, lavender, magnesium, <0.5% alcohol drinks, none of which were ok before.
I am living proof that brain damage of these types can be healed with neuroplasticity modulation.
One of my best recent decisions for brain and body health has been taking up weight lifting for 4 months so far under the guidance of a personal trainer, protein intake skyrocketing from whey, chicken, beef, fish, eggs, up to 200g/day sometimes along with creatine, etc. From thin/skinny fat I've gone to slim-muscular - 51% muscle mass, 8.9% body fat.
There are potential alternatives to ketamine, most notably ACD-856: "a novel, selective PAM for TrkA, TrkB, and TrkC receptors. It enhances the effect of neurotrophins like BDNF (brain-derived neurotrophic factor) and NGF (nerve growth factor), which are crucial for neuron survival and memory function." I've tried for a short time so far so no verdict yet, but it feels beneficial.
There's also TAK-653 (osavampator) which is on my list: "an investigational, potent, and selective AMPA receptor positive allosteric modulator (AMPAR-PAM) being developed by Takeda Pharmaceuticals for treating major depressive disorder (MDD) and treatment-resistant depression (TRD). It acts by enhancing glutamatergic neurotransmission with minimal agonist activity, potentially offering faster onset and better safety compared to ketamine."
I also recently started BPC-157, which does have brain health as well as body healing and workout recovery effects. I don't inject it, have been using a nano sublingual formulation. Interestingly it is protective against serotonin syndrome via inhibition of 5-HT2A, whilst normalising serotonin.
If anyone has questions I'm happy to help from my experience. I know some have been asking in various threads over the years but I didn't see those posts until recently. Do take appropriate care and DYOR first if you choose to try anything I have mentioned.
Edited by healthack, Today, 05:24 AM.
