Comment by mtlmtlmtlmtl | Hacker News Reader

Comment by mtlmtlmtlmtl | Hacker News Reader

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This isn't completely true. Tolerance to psychedelics is a thing, and can often ve extremely long lasting. I have a friend that when given heroic doses of 2C-B(50mg or more, orally), hardly experienced more than threshold level effects. This was 2C-B tested and confirmed to have 95% purity, and it affected me exactly as expected. He was not on any drugs except hash, which is typically synergistic.

In his case, according to him he yad used 2C-B very heavily many years previously, and it seems he developed an extremely high level of tolerance which remained unchanged for many years of non-use.

In the cases discussed in the thread, it's possible that something similar was happening. Indeed, many antidepressants also alter serotonin receptor expression over time, and it's plausible that in some people, these effects could linger for a long time.

I agree in that case, long-term SSRI and psychedelic use complicates things. But in general, I would not say the literature points to tolerance being long lasting. Tolerance is built up quickly, and then quickly lost. There have been many (reproduced) studies on the effects of psychedelics and tolerance build up, and they show it doesn't last for more than a few weeks (psilocybin / LSD).

I'd be interested to see those studies. I think there could be a couple different types of tolerance, one of which only occurs with rather heavy use. It's something I've seen reported anecdotally from a number of people who've used psychedelics very heavily. It might not show up in human studies because of ethical concerns. There could be some interesting pharmacological differences too, where this only occurs with specific drugs. The psychedelics are quite varied in terms of pharmacodynamics beyond just the 5-HT-2 receptor subfamily.

Here's the OG tolerance study done on psilocybin and LSD: https://link.springer.com/article/10.1007/BF00407974

We need more studies on the long term effects of heavy psilocybin use. We know how chronic use of alcohol and cannabis affect people fairly well at this point. We also know a lot about regular psilocybin use, but not a whole lot about what happens to people if they take it for 20 years.

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