[zasdffaa]

I've long wondered how Shulgin managed toxicity issues with new substances. There can be very little difference between something relatively safe and something very toxic (or even worse perhaps, cumulatively toxic) so that's very interesting - do you have a link to something Shulgin definitively wrote on this? I'd like to know more from the horse's mouth TIA

[pmoriarty]

"do you have a link to something Shulgin definitively wrote on this?"

Read the first part of PiHKAL (ie. the part that's deliberately not published on the website the parent HN post links to).

It's all there. He goes in to great detail about exactly how he did what he did and why.

[zasdffaa]

Appreciated. FYI Browsing articles this backs you up stongly, from https://erowid.org/library/books_online/pihkal/pihkal003.sht...

"EXTENSIONS AND COMMENTARY: This specific compound is probably the first sulfur-containing phenethylamine to have been evaluated as a potentially active CNS stimulant or psychedelic. It was a complete, total, absolute unknown. The first trials were made at the sub-microgram level, specifically at 0.25 micrograms, at 11:30 AM on September 3, 1975. Part of this extreme precaution was due to the uniqueness of a new heteroatom in a phenethylamine system. But part was due to the strange manic excitement that occurred at the time of the isolation and characterizing of the final product in the laboratory. Although it was certainly all placebo response, I was jumpy and unable to stay in the lab for more than a few minutes at a time. Maybe dust in the air? Maybe some skin contact with the free base? Now, I know there was nothing, but the possibility of extraordinary potency was real, and I did indeed wash everything down anyway. In fact, it took a total of 18 trials to work the experimental dosage up to as much as a single milligram. In retrospect, overly cautious. But retrospection, as they say, is cheap."

starting at 1/4 microgram (that's 250 nanograms!), took 18 steps up to a milligram. I approve. And thanks BTW.

[pmoriarty]

That's not the part I was referring to. The part I was referring to was before the entries on specific substances.

However, the entry you quote certainly does illustrate his diligence and commitment to safety. I very much doubt he would have been able to discover and sample something like 400+ psychoactive substances in probably many thousands of trials without being as careful and safety-conscious as he was.

[graderjs]

Agree. That's perhaps the biggest implicit or latent achievement of his and his wife's. Separating out the actual subject matter they worked in--which I greatly respect cuz I think there's so much potential to explore that area--you have this incredible sort of self experimentation done in a sustainable and safe Way. And I don't know that much about it but basically it seems he combines some animal assessments with reasoning based on the structure as well as trialing tiny amounts and grading it up. I haven't heard him his wife called a genius but they most certainly are, like the Curies perhaps but I suppose better at survival. And I can only hope that like the Curies their inventive era heralds a future explosion in applied technology of a similar scale but hopefully a positive valence. A Renaissance of exploration of these forms of consciousness technology.

[pmoriarty]

"I don't know that much about it but basically it seems he combines some animal assessments with reasoning based on the structure as well as trialing tiny amounts and grading it up"

Actually, he avoided animal experimentation. In PiKHAL, I believe he wrote that he hadn't experimented with animals in 20 years. His method was to first try each of the substances he discovered on himself.

[graderjs]

My friend I'm sure we probably have a different definition of animal experimentation because if you look through the write-ups from some of the chemicals there: He clearly states that he's doing rectal hyperthermia bioassays with rabbits and that he finds that you know disgusting but it's an effective way to tell if the compound is a stimulant or depressive by the respective increase or decrease in body temperature, and in the ballpark amounts in which it's effective.

To paraphrase him he says something like "inserting thermocouples into that rectums of restrained rabbits is not something that I'm much enthused about and I have a jaundiced view of."

I'll try to find that link and update it heh :)

So for your reference that's exactly what I meant by animal experimentation obviously helped him stay safe by giving him some more data on the compound before he took it himself.

edit: link: last paragraph here https://erowid.org/library/books_online/pihkal/pihkal125.sht...