TL;DR: I've been on around 20 different psych meds for severe depression and ADHD inattentive type. None of them ever helped and even stuff like methylphenidate at around 120mg doses never did anything at all, not even side effects. With drugs it's similar, both with opiates, stims and even ketamine, as if i was resistant. Yes, I had various combinations of meds and maxed out doses alongside therapies, same goes for drugs and the quality of the stash, or tolerance is ruled out, trust me. Even using IV doesn't do anything. So, what's wrong? Is the problem in my CYP2D6 enzyme or in my brain? I always make sure the drugs and meds i take don't inhibit each other, but well...

⚠️⚠️⚠️ Please, do NOT use these crazy combinations and enormous doses like I did! It's extremely dangerous, especially due to the immense risk of seizure! Always use harm reduction practices!!! ⚠️⚠️⚠️

Full story:

So, to start off, I've [F19] been diagnosed and treated (both medically and through psychotherapy) for severe depression since 11. When I was 11-12 I was also diagnosed with some schizoid disorder or smth but it was probably ruled out later cuz it's no longer in my medical papers. Also was several times diagnosed with ADD (ADHD - inattentive type) and suspected Asperger's.

Over the course of 8 years I've tried 20 different psych meds (for what I can count)- atypical antipsychotics (olanzapine, quetiapine), benzos (alprazolam, oxazepam, lexaurin), non-benzo anxiolytics (buspirone, hydroxyzine), antidepressants (all available SSRIs, all SNRIs, mirtazapine, trazodone, bupropion, vortioxetine), ADHD stuff (methylphenidate, tebokan) and ketamine (infusion therapy, around 10 sessions). Of course, plenty of combinations, augmentations of these meds and all sorts of dosages, even max dosages possible.

The thing is, none of the above-mentioned stuff ever worked (including therapy and yes, i had multiple therapists over the years etc) but it's ridiculous, because I don't even get side effects or anything even at max doses, and I just don't get it. I think that only quetiapine made me sleepier than usual, lexaurin when i literally took like 5x the max dose got me high and that was cool lol otheriwse nothing. Sertraline at 100mg dose just gave me severe diarrhea :D fluvoxamine made me pass out when i took it for the second time, ended up with concussion, to this day idk what happened, maybe it was some sort of serotonin syndrome. Mirtazapine works when it comes to knocking me out but only at the lowest dosages. Bupropion (max dose, too) is the only one that actually kinda did something cuz i no longer have to sleep 2x a day and I'm no longer half-asleep all the time but that's it, no other changes, not even apetite supression at all, when i take 900-1200mg (crushed) it makes me shaky and a little paranoid, occasionally a tiny bit "euphoric" and that's it. Oh and methylphenidate... Got as far as doing like 120mg and literally nothing happened AT ALL (of course, it didn't do anything even at the prescribed dosages so that's why i tried to increase the dose), not even shakiness, focus, energy, a good feeling, motivation or whatever. And what's funny is that I can still fall asleep completely fine even when i take them around lunch time.

About illicit substances, i had tramadol (up to 400mg dose, both oral and shot up), codeine (oral, ≈250mg), loperamide (I don't remember, i had like 15-20 pills idk. Oh, not to mention that i once combine all of the opiates above... Yes, I'm retarded, I could've hurt myself badly and certainly should've had seizure but I never did, even when combining 370mg tramadol with like 600-900mg bupropion which is the worst possible idea and you certainly should NEVER try it even at much lower doses!(I still don't get how i never had seizure doing these things). But guess what. Just felt a little calmer, content, peaceful but couldn't sleep at all. Also had kratom (various strains and suppliers) and i take insane doses, around 25-30mg? Only at these doses I feel smth, impossibly sleepy and unable to focus but that's pretty much it (tolerance for all the opiates including kratom is ruled out because I don't use regularly, tried them only 2-3 times over 2 months).

When it comes to stims, amphetamine just made me numb, almost dysphoric from that numbness, i could focus for so many hours nonstop, couldn't sleep, had the worst anxiety of my life, same with meth, but meth was worse, i had the worst anxiety, paranoia, panic like never before, it's undescribable. At that time when i took both (not together of course) i was on venlafaxine and was really anxious and fearful at the place I used to live, so i think that contributed to these insane comdeowns i think. Now it's cool tho, shot up meth just an hour ago and it's usually fine when it comes to comedowns but i never experience the rush, energy, euphoria or anything at all (doesn't matter if i IV it or smoke. The meth is good quality, I've got it checked, trust me), probably because less stress since I live alone and 300mg bupropion.

Weed makes me depressed ever since i smoke it until it leaves my body entirely, no matter what strain I smoke, it just makes me horribly depressed, passive, lethargic, apathic and lazy.

Ketamine is pretty interesting in that i never experienced anything CLOSE to euphoria or any sort of good feeling, no hallucinations or trips, delusions or whatever. I just go completely emotionless, sometimes i can imagine things more vividly in my brain, i get dissociated slightly but I'm fully aware of everything around me including myself (both when IV and snorted). At the highest doses everything goes grainy and it's difficult for me to see because of that, i hyperfocus sometimes, I'm clumsy and can barely walk and my speech is really slurred but that's it. After the high passes, I feel terribly numb to the point where I'm sad, lethargic, empty, apathic.

The question is, what's wrong with me? Why none of my meds don't work, why even drugs don't do much to me? Everyone gets off on the same stash I have so the drugs aren't the problem themselves. About drugs, ok, maybe the lack of response is caused by my psych meds in some way but for example ketamine shouldn't be affected by any antidepressants at all, at least that's what the doctors say. I have this theory where my CYP2D6 enzyme is either inhibited by the psych meds i took over the years or I have way too low of an amount of that enzyme (if any), but that doesn't explain drugs and meds that don't get metbaolized by CYP2D6 like ketamine.