[pmoriarty]

The way Shulgin tried new drugs was way safer than probably 99.9% of the people who try mystery drugs do it.

First, he knew exactly what each compound was, as he made them himself. He wasn't trying mystery drugs he was completely clueless about.

Second, he tried the smallest dose he suspected might be safe and active, based on his world-class chemical and pharmacological knowledge.

Third, he didn't (to my knowledge) mix novel compounds, but only tried pure ones.

Fourth, if he got even a hint that they might be toxic, he stopped doing them, and only if there were no hints of toxicity did he slowly, very slowly up the dosage and let his wife/friends try it to see if his experiences were unique due to maybe his own body chemistry or other factors.

This nothing like the majority of people, who often don't have the capacity, desire, patience, or knowledge to test their drugs themselves or go to the effort and expense of having someone else do it for them.

Even if the compounds are tested by, say, groups like DanceSafe at festivals, they can only tell you what in the compound they're testing matches their reference sample.. if it also contains some other novel compound that they don't have a reference sample for then they can't tell you what it is. It's a completely different situation from Shulgin, as he knew exactly what was in the compounds he made himself.

What Shulgin did was still risky... especially in the long-term.. and I personally wouldn't do it myself, just as I wouldn't climb Mt Everest, fly in a wingsuit, go extreme skiing, or risk my life/brain in a million other ways, but I'm grateful to him for doing so in the way he did and publishing the results.

Again, that's completely different from the reckless way most people do mystery drugs.

[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.

[jaminal]

what? dancesafe uses reagent-based testing. which, if used carefully, can identify many kinds of compounds with high accuracy.

it wouldn’t make any sense to compare it to an existing sample. not to mention the legality of that, depending on where the festival is happening.

if you are curious, all of their tests are available on their website

https://dancesafe.org