What causes someone to be completely resistant to the effects of psychedelics?

[CHAO_CHAO]

I have a friend (literally SWIM) who is completely almost completely unaffected by psychedelic drugs, primarily the 5ht2a based ones, LSD, psilocybin and DMT. Even in massive doses and when taken in various cocktails, he reports minimal effects for such high doses of multiple drugs. No visuals, at best a strong body trip.

I am a seasoned psychonaut and can boast a formidable constitution when it comes to taking these kinds of drugs, and I don't see how anyone can see anything BUT visuals when mixing 500ug of LSD with 5 grams of shrooms or a strong dose of MDMA, or all three, which I have personally seen him do and he doesn't seem to be significantly effected.

What could possibly be going on with him neurologically that could cause such wonderful drugs not to work? I even turned him on to DMT, and at doses that would be a strong breakthrough for me he reports intense body loads, sound distortion, and some disassociation but no real psychedelic experience.

He has been trying different cocktails in greater amounts in an attempt to reach the kind of experience I have been preaching to him for years (I have known him since he was a little kid) and has even started experimenting with ketamine, which also has little effect on him.

Now, I know he is not bullshitting me, I have seen him drop 4000ug of LSD and not really seem effected. I have not personally witnessed every attempt but I have seen him do some extraordinary amounts of psychedelics.

The closest he has come to being able to actually use the Shulgin rating scale is when mixing LSD (6 hits 350ug a hit), Ketamine, and MDMA at a festival (a small local burn actually), dosing it all at once and blissing out on the music and fire dancers was the closest he has come, the way he described it to me, to what I would classify as a truly psychedelic experience. He even had some mild visuals

Now I can take LSD and Molly and smoke DMT and mega dose in combinations and still hold my composure for the most part, but I am definitely altered beyond anything that can be described in words and it pains me that such a dear friend is incapable of having said experience.

I am dying to know what could cause this, if it has been reported in other users (I've never heard of anything this severe), if it is known and is a thing exactly what is going on here?

I mean, on a neurological level.

Please let me know if any of you have heard of something like this and/or have an explanation.

Thanks,

 

[serotonin2A]

It is possible that your friend has a gene mutation or polymorphism. 5-HT2A receptor polymorphisms exist, and it is possible that one of the polymorphisms could alter the response to serotonergic hallucinogens. Alterations of a variety of other genes could also potentially modify the response to psychedelics.

It is actually possible to pay to have the entire human genome sequenced. The price to do the analysis is continually decreasing, meaning that over the next few years it may be cost effective to look for a genetic explanation.

Alternatively, certain psychiatric medications can dampen the response to psychedelics. My answer above is based on the assumption that he doesn't take any medication to treat depression, schizophrenia, or bipolar disorder.

 

[Ligaturd]

Yeah. Anti-psychotics are my first thought. They are used to abort trips for this reason.

 

[εὔνοια]

Benzodiazepines like diazepam can cause an extremely diminished response to the effects of psychedelic (serotinergic) drugs. They are really commonly prescribed. Barring that, the only other thing I can think of is a mutation in specific serotonin receptors, which would be really rare, but not impossible.