Program Notes
Guest speaker: Paul Daley
Today’s podcast features the 2013 Palenque Norte Lecture by Dr. Paul Daley in which he talks about Sasha Shulgin, his life and his work. Paul is one of the key people who has stepped in to consolidate and continue the experimental research begun by Dr. Shulgin. In addition to telling about Sasha’s chemical research, Dr. Daley also talks about some of the reasons Sasha has given for why he does what he does. And we also hear about some of the ongoing research taking place in Sasha’s laboratory, including research into a possible remedy for cluster headaches.
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Transcript
00:00:00 ►
Greetings from Cyberdelic Space.
00:00:19 ►
This is Lorenzo, and I’m your host here in the Psychedelic Salon.
00:00:23 ►
And I’m going to be your host here for the next year, now that we have successfully completed our fun drive.
00:00:30 ►
Over 200 of our fellow salonners have chipped in to ensure another year of podcasts from here in the salon.
00:00:37 ►
And to them, we all owe a great big thank you.
00:00:41 ►
And I’ll have more to say about the fun drive after we first listen to today’s talk, which is one that I think you’re going to get a lot out of.
00:00:49 ►
What I’m about to play for you is a talk that Paul Daly gave at the 2013 Palenque Norte lectures.
00:00:56 ►
Paul, as you will hear, is the person who is completing some of Sascha Shulgin’s research and who has been one of the key individuals responsible for preserving the enormous intellectual legacy of Dr. Shulgin’s research and who has been one of the key individuals responsible for preserving the
00:01:05 ►
enormous intellectual legacy of Dr. Shulgin, who, in my opinion, is the greatest research chemist
00:01:11 ►
to have lived during my own lifetime. And I’ll be back after Paul’s talk to say a little bit more
00:01:16 ►
about Sasha as well. And I’m sure that you’re going to learn some things about our dear Sasha
00:01:21 ►
that you didn’t know before. Also, I hope that you pay attention to the trajectory of Paul’s involvement with Dr.
00:01:28 ►
Shulgin and see if possibly there may be ways for you to insert yourself into the world
00:01:34 ►
of psychedelic research as well.
00:01:36 ►
So now let’s join Pez as he introduces Dr. Daly.
00:01:40 ►
All right.
00:01:41 ►
I’m very excited to introduce our next speaker.
00:01:43 ►
We have Dr. Paul Daly here with us.
00:01:46 ►
And Paul is the lead research chemist at the Alexander Shulgin Research Institute,
00:01:51 ►
otherwise known as the Shulgin Farm.
00:01:54 ►
So he’s going to give us a quick update, 90 minutes,
00:01:58 ►
on all the happenings that are going on there.
00:02:01 ►
90 minutes is not quick by anybody’s standards.
00:02:06 ►
Well, thank you for being here with us, Paul.
00:02:09 ►
Thank you.
00:02:10 ►
So the talk that I’m going to try to string together here
00:02:16 ►
is about my friend Sasha Shulgin.
00:02:20 ►
Now, I met Sasha.
00:02:21 ►
He’s the wild-looking guy on the far left there.
00:02:26 ►
I met him about 36 years ago at a meeting.
00:02:30 ►
I was a freshly-mitted graduate student in entomology at UC Berkeley.
00:02:36 ►
And I showed up down there, you know, freshly thinking that,
00:02:42 ►
oh, I was going to put all my psychedelic interests aside and focus on being an environmental scientist and get down into hard agriculture, agricultural research.
00:02:54 ►
And then I ran into a copy of the Berkeley Bar with an ad that was announcing the second international conference on hallucinogenic mushrooms.
00:03:04 ►
was announcing the second international conference on hallucinogenic mushrooms.
00:03:12 ►
And I looked at the ad and I thought, well, I’m supposed to be a button-down young scientist here. I can’t go traipsing off to Washington State to go talk about hallucinogenic mushrooms,
00:03:18 ►
much as I love the things.
00:03:21 ►
And so I thought, well, I can’t do that.
00:03:23 ►
And then a couple of weeks went by
00:03:25 ►
and the bar published the same ad again
00:03:28 ►
and I said I looked at the speakers
00:03:30 ►
well it’s going to be Albert Hoffman
00:03:32 ►
Richard Evans Schultes
00:03:34 ►
Gordon Wasson
00:03:36 ►
and you know people whose work I’d read
00:03:38 ►
for probably the previous 10 years
00:03:40 ►
and it all of a sudden occurred to me
00:03:43 ►
well there’s no way I can’t be at that meeting
00:03:45 ►
and i was kind of shocked to even think that there were such things as meetings that where
00:03:49 ►
people talked about psychedelic drugs openly so i i bought myself a ticket hustled myself up there
00:03:57 ►
and at the first social i got my uh obligatory glass of cheap red wine and a couple pieces of cheese
00:04:05 ►
and walked up to the first three people in the hall there.
00:04:09 ►
And one guy with kind of a funny long beard and a receding hairline
00:04:13 ►
and a guy with a big shock of white hair and a big toothy grin on his face
00:04:17 ►
and another kind of more conservative looking guy.
00:04:20 ►
And so I introduced myself.
00:04:21 ►
Well, the funny guy with the long beard was Andrew Weil.
00:04:45 ►
I just read his The Natural Mind, and it had totally registered with me that probably all animals, humans not the least of which, have like an innate drive to alter our consciousnesses and to look at the world in different ways based on substances that we take.
00:04:51 ►
And I loved the book, and it was a real pleasure to meet him,
00:04:54 ►
and we chatted for a minute, and I turned to this next gentleman,
00:04:57 ►
and he said, well, you know, why are you here?
00:05:00 ►
And, well, you know, it turns out that about five years earlier,
00:05:10 ►
I had, as a young toxicology student, I found an older project studying sheep poisonings by phalaris grass in northern California.
00:05:13 ►
Kind of no one was working on it anymore,
00:05:15 ►
but I had this understanding that dimethyltryptamine
00:05:22 ►
and other hallucinogenic compounds in these grasses
00:05:24 ►
might have been causing poisonings in these range animals.
00:05:28 ►
And so I said, well, I had been working on this,
00:05:30 ►
and this, of course, was Sasha.
00:05:33 ►
His immediate reaction was, oh, well, then maybe you can answer this.
00:05:38 ►
I’ve come to realize in the ensuing years
00:05:40 ►
that this is a typical reaction of Sasha
00:05:43 ►
to just about any new person that he had never met. And so we chatted very animatedly for 15 or 20 minutes, and I turned
00:05:52 ►
to the third gentleman, and he said, well, you’re interested in analytical chemistry.
00:05:58 ►
You’d probably enjoy visiting my laboratory. I’m the chief of the Drug Enforcement Administration Analytical Laboratory in San Francisco.
00:06:08 ►
Of course, I didn’t know that this was Bob Sager, who had already forged a long-term friendship with Sasha
00:06:15 ►
and was really kind of at the verge of being on the outs with the DEA
00:06:20 ►
because he actually didn’t think that a lot of what the DEA was starting to do was useful.
00:06:27 ►
And I didn’t run into Bob for another 25 years, but
00:06:31 ►
when I met him at a Fourth of July party at the Shulgin’s place,
00:06:36 ►
I said, well, you probably don’t remember me, but I certainly remember meeting you
00:06:39 ►
because as soon as you announced who you were and where you worked, I think my face turned white
00:06:43 ►
and my pants turned brown.
00:06:47 ►
And I also had the thought that either I’ve really arrived or I’m in trouble now.
00:06:52 ►
So in any event, Sasha invited me out to the farm.
00:06:57 ►
He found out that I was a student at Cal.
00:07:00 ►
He had been an undergraduate and graduate student at Berkeley.
00:07:04 ►
And so there was sort of an instant alumni bond.
00:07:08 ►
And so I visited the Shulgin Farm for the first time in late 1977,
00:07:16 ►
and Sasha was alone at that point.
00:07:19 ►
He had not met his wife, Ann, who he married in 1981,
00:07:24 ►
and so he walked me out to the lab and showed me boxes of compounds that he had made.
00:07:30 ►
I had had a little exposure to his work.
00:07:33 ►
There was a seminal paper in 1969,
00:07:36 ►
Structure-Activity Relationships of the One-Ring Psychotomimetics.
00:07:42 ►
I had read this paper when I was doing that work on phalaris grass. It was way over my
00:07:48 ►
head, but I could tell that there was really something serious that was happening in that
00:07:52 ►
discussion. So in any event, Sasha and I got to know each other a little bit at that point,
00:07:59 ►
and then I went off still with the idea in mind that the incipient drug war was an insurmountable barrier
00:08:09 ►
to a young scientist interested in psychedelics in entering a field where you could seriously do work in that area.
00:08:16 ►
So I kind of sidestepped my way into continuing to work in agricultural research,
00:08:23 ►
studying photosynthesis, crop protection,
00:08:27 ►
pesticides in the environment.
00:08:29 ►
Ended up doing a lot of basic work in vegetation responses to elevated carbon dioxide, kind
00:08:36 ►
of sidestepped into environmental chemistry, and 30 years went away in a real hurry.
00:08:42 ►
But then towards the latter 1990s, early 2000s, I realized that there was
00:08:48 ►
kind of a gap in my passion for work. And I called up Sasha and started chatting again. And
00:08:58 ►
over the next few years between repairing his computers and just kind of hanging out and watching how he interacted with his many visitors and you know learning a
00:09:11 ►
little bit more about the the details of what he’d been working on for 50 years
00:09:15 ►
in that funky little lab we developed kind of a working relationship and I
00:09:20 ►
actually started working with him in 2007 Sasha married my wife and I actually started working with him in 2007.
00:09:31 ►
Sasha married my wife and I at the farm on 7-7-0-7.
00:09:37 ►
And in the midst of a really great dance party that was happening outside,
00:09:41 ►
I walked in on a conversation that his wife was having with a close friend.
00:09:48 ►
And they’d been approached by a benefactor who was offering to mount a search for a chemist who could help work with Sasha and kind of pick up some of his effort,
00:09:54 ►
because he’d lost his eyesight to macular degeneration and really couldn’t continue
00:09:59 ►
working in the lab. And so my immediate response was, now wait wait a minute let me get this straight
00:10:05 ►
you’re looking for a chemist to work with Sasha and work on psychedelics here
00:10:11 ►
that would be me and so to kind of make a long story short I cut back my other
00:10:20 ►
my day job to 50% and about three months later started working half-time at the farm.
00:10:27 ►
So where I found things, Sasha had a very checkered career.
00:10:35 ►
And here I’m going to kind of fill in a little bit about who Sasha is, what he did.
00:10:43 ►
who Sasha is, what he did.
00:10:46 ►
The last two talks that were presented tonight focused on a substance that a lot of people know now, MDMA.
00:10:54 ►
Sasha was credited, for better or worse,
00:10:57 ►
not for inventing MDMA,
00:10:59 ►
although by the time that he kind of rediscovered it,
00:11:13 ►
Although by the time that he kind of rediscovered it, he was the first to synthesize many, many compounds that are powerful psychedelics.
00:11:24 ►
He was presented with information from students, really, that, oh, there’s this new substance that’s kind of out there.
00:11:27 ►
This maybe was around 1972, 73 or so.
00:11:30 ►
Even the Drug Enforcement Administration was unaware of it.
00:11:33 ►
There had been a couple of reports of a new substance,
00:11:37 ►
a substituted methylene dioxide amphetamine,
00:11:40 ►
but there was very little known about it and certainly nothing known about its psychological effects. So in 1978,
00:11:46 ►
Sasha published the first really outline of what MDMA was and how it differed from
00:11:55 ►
other psychedelic drugs and its effects and how it might in fact be a useful tool in psychotherapy.
00:12:03 ►
in fact, be a useful tool in psychotherapy.
00:12:05 ►
So that was 1978.
00:12:06 ►
Let’s go way back.
00:12:10 ►
To give a sketch of Sasha and who he was,
00:12:12 ►
he was born in 1925.
00:12:17 ►
He was the only child of a father who was a Russian immigrant.
00:12:18 ►
He escaped the Bolshevik Revolution
00:12:22 ►
by escaping through Siberia and Alaska,
00:12:23 ►
coming down into California.
00:12:27 ►
Sasha’s mom was a teacher from,
00:12:34 ►
I forget, is it Illinois or Indiana? Anyway, one of the two. They met in Berkeley, and Sasha was the product of that union in 1925. He was their only child, and they doted on him and he was a really a prodigy kid
00:12:45 ►
in kind of
00:12:47 ►
going through the papers in the household
00:12:50 ►
I’ve come to
00:12:52 ►
appreciate how much of a prodigy he was
00:12:53 ►
I think he taught himself how to type by the time
00:12:55 ►
he was five. To give you an idea
00:12:58 ►
Sasha
00:13:00 ►
finished the little bit of high school
00:13:03 ►
that he seemed to need
00:13:05 ►
and enrolled at Harvard University at age of 15.
00:13:11 ►
Now, he hung out at Harvard for about a year and a half,
00:13:14 ►
never really liking it all that much because he didn’t fit in.
00:13:17 ►
And I can only imagine.
00:13:18 ►
I mean, Harvard seems to be the host of people like anyone from Timothy Leary to George Bush and mostly people who are fairly wealthy
00:13:26 ►
and maybe are
00:13:27 ►
legacies from past
00:13:29 ►
generations but
00:13:31 ►
a smart ass extremely
00:13:33 ►
bright kid interested
00:13:36 ►
in sciences probably not
00:13:38 ►
a real good match for Harvard
00:13:39 ►
so at age approximately 16
00:13:42 ►
and a half Sasha enlisted in the
00:13:44 ►
Navy and spent the next couple of years,
00:13:47 ►
this would be in the sort of middle years of World War II,
00:13:50 ►
on a submarine destroyer in the North Atlantic,
00:13:55 ►
varying between abject fear and total boredom,
00:13:59 ►
hunting German submarines.
00:14:01 ►
He had one book with him,
00:14:04 ►
Castle’s Organic Chemistry, which he memorized. And coming
00:14:09 ►
back from the war, he decided to go back to Berkeley, which was sort of home ground for him,
00:14:15 ►
and enrolled in an organic chemistry class. This is kind of one of the few stories that comes
00:14:21 ►
through about his college experience. You know, got started, they went through their first midterm,
00:14:29 ►
and the prof of the class stopped him in the halls
00:14:32 ►
one day and said, Shulgin, come here.
00:14:37 ►
You know, you don’t really have to take any of
00:14:40 ►
the other exams in the class if you don’t want. And he said,
00:14:44 ►
well, why would that be?
00:14:46 ►
He said, well, the first midterm scores are in.
00:14:49 ►
The class average was 40%.
00:14:52 ►
And you got 100%.
00:14:55 ►
So if you want to take the test, that’s fine.
00:14:59 ►
But, you know, just come to the classes.
00:15:01 ►
You’ll probably learn a little bit that you don’t know already.
00:15:04 ►
Anyway, to make a long story short, Sasha was a brilliant chemist.
00:15:06 ►
He excelled throughout, finished an organic chemistry undergraduate program,
00:15:12 ►
then went on to become a kind of new program, biochemist, as a Ph.D. student at Berkeley.
00:15:19 ►
Finished that in 1955.
00:15:22 ►
Knocked around, started some clinical laboratories.
00:15:26 ►
The clinical lab business was really sort of just getting started at that point. So, you know, basic measurements for
00:15:30 ►
medical use, you know, blood testing, urine testing, that kind of thing was just getting
00:15:36 ►
off the ground. So he started a couple of successful laboratories in Berkeley,
00:15:40 ►
was a research director at BioRad, which is still a going concern,
00:15:45 ►
making materials for biotechnology.
00:15:48 ►
By the late 50s, started work at Dow Chemical
00:15:52 ►
in their pesticide division in Benicia, California.
00:15:56 ►
All this is really close to his stomping grounds in the East Bay.
00:16:01 ►
At Dow, he identified a waste product from one process that he had a pretty, you know,
00:16:11 ►
he had a good intuition that it might be a good starting material, a precursor for pesticide
00:16:19 ►
that also might be biodegradable, might be broken down quickly in the environment.
00:16:24 ►
And both of those things turned out to be true.
00:16:26 ►
So he basically helped Dow make their first biodegradable insecticide,
00:16:30 ►
a carbamate called Zectran, made them a pile of money.
00:16:35 ►
This would have been like late 1959, 1960.
00:16:39 ►
Right around that same time, Sasha had his first experience with a compound called
00:16:42 ►
3, 4, 5-trimethoxyphenethylamine,
00:16:46 ►
also known as mescaline. He was very impressed with mescaline. A lot of the effects that
00:16:55 ►
people now know to be sort of classic psychedelic effects, total transformation of your appreciation of color, texture,
00:17:06 ►
fundamental transformation of your experience of the outside world and your sense of yourself.
00:17:15 ►
All of these things were very powerfully delivered to him, and he’s many times made the remark,
00:17:22 ►
I had a quarter of a teaspoon of a white crystalline solid
00:17:25 ►
that I took into my body
00:17:27 ►
and I had this experience.
00:17:30 ►
This profound experience
00:17:32 ►
was not in that
00:17:34 ►
white crystalline solid.
00:17:36 ►
It was in me.
00:17:37 ►
The solid just allowed me
00:17:39 ►
to experience what was already there.
00:17:43 ►
And what Rick
00:17:44 ►
and Alicia talked about earlier
00:17:46 ►
is really kind of the same thing. Maybe a little different flavor
00:17:49 ►
but really very similar kind of recognition
00:17:52 ►
that these materials are
00:17:55 ►
catalytic. They let us experience
00:17:58 ►
things that are maybe hidden but are
00:18:01 ►
within us. Well anyway, so at that point in time
00:18:04 ►
there was no but are within us. Well, anyway, so at that point in time,
00:18:09 ►
there was no stigma about psychedelic drugs.
00:18:10 ►
There was no drug scene.
00:18:16 ►
In fact, the sort of prevailing thought in the chemistry community was that psychedelic drugs might, in fact, be useful materials
00:18:23 ►
to help us understand mental illness.
00:18:24 ►
might in fact be useful materials to help us understand metal illness.
00:18:31 ►
I’ve found a chemistry and engineering news in Sasha’s files with a lot of white-coated guys standing around going,
00:18:33 ►
can chemistry help us understand metal illness?
00:18:37 ►
So this was very much on the mind of science at that time.
00:18:42 ►
And yet Dow Chemical was really, after the first couple of years,
00:18:46 ►
once Sasha produced Zectran,
00:18:48 ►
they said, whatever you’d like to work on
00:18:51 ►
is fine with us.
00:18:52 ►
You’ve got a lab, you’ve got a small staff,
00:18:54 ►
go for it and we’ll see what comes.
00:18:58 ►
So in the next couple of years,
00:19:00 ►
this would have been again,
00:19:01 ►
59, 60, 61,
00:19:04 ►
he started to explore substances that were related to mescaline
00:19:09 ►
but were derived from natural products,
00:19:13 ►
particularly substances, essential oils, basically,
00:19:17 ►
things that could be isolated from natural products like nutmeg oil,
00:19:21 ►
mace, and those kinds of spices, you know, the candy shop. So MMDA, a number of other
00:19:32 ►
variants came out of that work. But Dow eventually sort of surveyed this and said, well, you know,
00:19:41 ►
when we really look at it, we’re not a pharmaceutical company.
00:19:46 ►
We’re interested in pesticides and kind of bulk chemicals, so this is really not our bag.
00:19:54 ►
And so they parted amicably, and by that time, Sasha, I think, had kind of seen the writing on the wall,
00:20:00 ►
and he had built a small lab at his family farm in Lafayette, California.
00:20:07 ►
So he started working there and to make a long story short, in the next roughly 50 years
00:20:16 ►
he produced a couple of hundred compounds that we know as interesting and useful psychedelics.
00:20:24 ►
we know as interesting and useful psychedelics.
00:20:28 ►
It started out with variants of mescaline,
00:20:33 ►
one of the first semi-synthetic derivatives of mescaline.
00:20:38 ►
And I’m not blessed with a blackboard where I can start drawing what Sasha lovingly called dirty pictures
00:20:41 ►
to kind of lead the discussion in that direction.
00:20:46 ►
But mescaline has a six-sided ring.
00:20:50 ►
It has three methoxy groups.
00:20:52 ►
That’s like three oxygens with methyl groups hanging off.
00:20:56 ►
And then there’s a two-carbon side chain that ends in an amino group.
00:21:01 ►
So that’s the classical phenylethylamine structure. The first
00:21:07 ►
semi-synthetic compound that was sort of based on that framework was a compound that became known
00:21:13 ►
as TMA, trimethoxyamphetamine. So the only variation was that on the side chain, instead
00:21:20 ►
of being two carbons, there were now three carbons. There was an alpha-methyl group.
00:21:24 ►
Here’s a question.
00:21:22 ►
Instead of being two carbons, there were now three carbons.
00:21:24 ►
There was an alpha-methyl group.
00:21:24 ►
Here’s a question.
00:21:31 ►
Tell you what, anyone who’s really interested in dirty pictures,
00:21:33 ►
come and talk to me afterwards and I’ll draw you a bunch.
00:21:34 ►
Great.
00:21:38 ►
In any event, TMA was not one of Sasha’s compounds.
00:21:41 ►
It was synthesized for the first time in 1947. It was discovered to be psychoactive in 1949.
00:21:46 ►
Sasha made some, tried it.
00:21:48 ►
This was much later.
00:21:50 ►
Found that it is much more potent, about twice as potent as mescaline.
00:21:55 ►
Mescaline is an interesting compound.
00:21:57 ►
Classic, wonderful, psychedelic, but not very potent.
00:22:01 ►
It takes about 350 milligrams to maybe 500 milligrams to create a full psychedelic
00:22:07 ►
experience. TMA was roughly twice as potent, so maybe somewhere in the 150 milligram range.
00:22:16 ►
Sasha says, well, it was nice, but it was not friendly. So there was the first indication that
00:22:23 ►
these things not only differed in potency, but maybe differed in character.
00:22:28 ►
Now, when I was a young guy in the late 60s, there was very little information about any psychedelic at all.
00:22:38 ►
We knew of LSD, mescaline, and psilocybin, but the dogma at that time was that they were all, they basically
00:22:45 ►
created the same effect, they differed only in potency and duration. Well, Sasha already by that
00:22:52 ►
time had pretty well put to rest that there’s a wide variety of not only potency, but also
00:22:59 ►
character. So anyway, I’ll kind of get back to that so in his earliest efforts Sasha looked at the
00:23:06 ►
structure of mescaline and TMA and said
00:23:08 ►
okay well there’s
00:23:10 ►
a 3-4-5
00:23:12 ►
arrangement there are at least 6 other
00:23:14 ►
arrangements of those methoxy
00:23:16 ►
groups around the ring of
00:23:18 ►
TMA mescaline
00:23:20 ►
what happens if we make all those other variants
00:23:22 ►
this is the classic business of a
00:23:24 ►
medicinal chemist you find a molecule that has an action that you’re interested in, whether it’s,
00:23:29 ►
you know, an ergot alkaloid or salicylic acid that gave us aspirin or an opiate like morphine.
00:23:38 ►
You start with the basic structure and you start making systematic modifications of it
00:23:42 ►
and then figure out, well, did those modifications make a stronger drug, a weaker drug?
00:23:49 ►
Did they change the character of it?
00:23:51 ►
Did they change the pharmacological activity in some fundamental way, creating some new activity that wasn’t expected?
00:23:58 ►
So this is the nature of the business of medicinal chemistry. So Sasha started with these trimethoxyamphetamines,
00:24:05 ►
and one of the kind of neat discoveries was TMA2,
00:24:10 ►
which is 2,4,5-trimethoxyamphetamine.
00:24:14 ►
Pretty rare compound.
00:24:16 ►
Not very many people have had it.
00:24:18 ►
But it was, again, maybe as much as 10 times more potent
00:24:23 ►
than the 3,4,5- 5 trimethoxyamphetamine.
00:24:26 ►
And it had more of the sort of buoyant, lovely character of mescaline.
00:24:33 ►
Kind of the interesting thing.
00:24:35 ►
Any of you are aware of Sasha’s books, T-Cal, P-Cal?
00:24:40 ►
Okay, there are a couple of people.
00:24:44 ►
In P-Cal, which is an acronym, it’s phenethylamines I have known and loved,
00:24:50 ►
Sasha has ranges of dosage for a lot of these materials.
00:24:56 ►
And for TMA2 in particular, the dosage range is 12 to 24 milligrams.
00:25:02 ►
So since by the time that he made that compound, which would again
00:25:07 ►
have been, you know, mid-60s, the experience that Albert Hoffman had in the discovery of LSD was
00:25:13 ►
already well known. And to just summarize it for those who might not know, Hoffman had been working
00:25:19 ►
for, you know, maybe a decade, 15 years, maybe a little longer, with ergot alkaloids
00:25:25 ►
and knew that they were very powerful pharmacologically active compounds.
00:25:29 ►
A lot of them have very specific action that is not psychoactivity at all.
00:25:38 ►
In fact, one of his first discoveries was a rational synthesis for a material called Ergonovine. Ergonovine has
00:25:47 ►
probably saved the lives of maybe 100 million women, maybe more, since he first figured out
00:25:53 ►
how to synthesize it rationally. It has a very specific action on the uterus.
00:25:59 ►
When given to a woman who’s hemorrhaging following childbirth, it causes a rapid, strong, and sustained contraction of the uterus that’s so strong,
00:26:10 ►
it’s like pressing on an open wound.
00:26:13 ►
It’s enough that the action of the ergonovian will stop hemorrhage.
00:26:16 ►
So in the thousands of years before that discovery was systematized,
00:26:24 ►
when women died in childbirth, largely it was because of hemorrhage
00:26:28 ►
following the actual delivery. So Hoffman
00:26:32 ►
worked out a method where he could turn any ergot alkaloid
00:26:36 ►
of which there are many, into a basic material and then
00:26:40 ►
add on groups to that. And so he would start
00:26:44 ►
from something like ergometrine or ergotamine,
00:26:49 ►
render it down to lysergic acid,
00:26:51 ►
and then he could synthesize whatever he needed from that.
00:26:55 ►
So it was in that process that he was looking for stimulants
00:26:58 ►
of the circulatory system.
00:27:02 ►
He first synthesized lsd in 1938 was tested not found to have the
00:27:08 ►
circulatory stimulant stimulant effect that he was looking for it was shelved so a few years later he
00:27:14 ►
had this premonition that you know it really needed to be looked at again made some had a
00:27:20 ►
strange experience one afternoon not a full lSD experience, but he felt strange.
00:27:27 ►
Came back a week later and took the smallest amount that could be possibly thought to have any effect at all,
00:27:36 ►
a quarter of a milligram, and of course had a full-blown LSD experience.
00:27:42 ►
So that was already well known.
00:27:44 ►
That was 1943.
00:27:46 ►
Sasha didn’t start any of this work until the early 1960s.
00:27:49 ►
So his strategy for discovering new drug activity
00:27:53 ►
was to start with very, very tiny doses,
00:27:55 ►
maybe on the order of 10 to 25 micrograms,
00:27:58 ►
and then slowly work up to doses where you could start to feel some effect,
00:28:03 ►
always looking for untoward somatic
00:28:07 ►
effects, you know, changes in, you know, bad effects on blood pressure or pulse rate or,
00:28:12 ►
you know, other sort of medical effects.
00:28:16 ►
And so with TMA2, he had already been well into that process and was at the point where he wanted to start a 12 milligram experience
00:28:25 ►
took that dose after an hour nothing was happening so he had had prepared another 12 milligram dose
00:28:33 ►
decided okay well i’ll just take that and about 10 minutes later started to feel the effects of
00:28:40 ►
the first dose so he ended up discovering that he was going to have a very interesting afternoon.
00:28:46 ►
And so that strategy for discovering activity was already kind of well established.
00:28:54 ►
So Sasha went on to discover quite a number of modifications of the TMA series, taking away an oxygen here, putting in a sulfur there.
00:29:06 ►
And that process went on for basically about three decades.
00:29:12 ►
He would work on compounds pretty much in solitude, test them himself.
00:29:18 ►
When he met Ann, his wife, and they got married in 1981,
00:29:24 ►
they partnered in this process.
00:29:27 ►
So he would try substances, try to establish an activity level.
00:29:32 ►
If he found the effects to be desirable, he would share them with his wife.
00:29:37 ►
If they concurred that, oh, okay, this is good, there are not any bad side effects,
00:29:44 ►
they had what they called the group, which was maybe about a dozen, 15 close friends,
00:29:49 ►
mostly middle-aged, serious people, you know, doctors, lawyers, psychiatrists,
00:29:54 ►
and they would have Sunday experiences.
00:29:56 ►
And so they would bring out, you know, whatever the latest was,
00:29:59 ►
try to establish dosage ranges and kind of forge ahead.
00:30:09 ►
dosage ranges and kind of forge ahead. So it was with that background that Sasha was given MDMA as kind of a leading substance that was out there in the environment but really unreported. And so
00:30:18 ►
he discovered the right dosage level and found that it was not a psychedelic,
00:30:26 ►
but had another type of activity, which we now refer to as an antactogen or empathogen.
00:30:33 ►
There was a question in the back.
00:30:36 ►
Great question.
00:30:36 ►
So the question is, what was he attempting to achieve?
00:30:41 ►
The mescaline experience was kind of the lead.
00:30:44 ►
the mescaline experience was kind of the lead.
00:30:50 ►
So he sensed that there was something important here.
00:30:55 ►
And I think the motivation was kind of pure exploration.
00:31:01 ►
You know, why do you want to climb Everest or another mountain? To see what the experience is like to be there.
00:31:04 ►
and other mountains, to see what the experience is like to be there.
00:31:15 ►
And since very early on, he discovered that there were not just simple differences in potency and duration, but there were very profound differences in the character, the qualitative experience that these substances produced.
00:31:24 ►
the character, the qualitative experience that these substances produced. So he became both a fan and a proponent of honest, serious exploration of these substances for their own value.
00:31:39 ►
What can we learn from exploring?
00:31:42 ►
So I don’t know if that answers or not.
00:31:48 ►
Absolutely.
00:31:49 ►
So the question is, you know,
00:31:51 ►
was there a thought of there being therapeutic benefit?
00:31:54 ►
Absolutely.
00:31:56 ►
Sasha was very closely allied
00:32:01 ►
and associated with psychologists and psychiatrists,
00:32:04 ►
and they had many deep discussions about how these things could be used
00:32:08 ►
to open people, to facilitate internal exploration.
00:32:14 ►
I mean, there are many, many drugs that have been produced by Big Pharma
00:32:19 ►
with the foundation, actually, that Sasha produced. His work started in really the dawn of neurochemistry.
00:32:31 ►
Before the mid-1950s, it was really thought that mental illness,
00:32:39 ►
psychosomatic disease, psychological difficulties were strictly based on bad upbringing.
00:32:49 ►
Maybe you were taken off the mother’s breast too early.
00:32:52 ►
Maybe your toilet training was bad.
00:32:54 ►
But there was really no foundation for an appreciation that neurochemistry could be a foundation for mental or psychological difficulties or illness.
00:33:09 ►
And so it was kind of a shock that serotonin, for instance,
00:33:14 ►
was found to not be only a substance in the bloodstream.
00:33:18 ►
It has the name serotonin because it’s serological, has to do with blood.
00:33:24 ►
It was first found in red blood cells.
00:33:26 ►
When it was first found in the brain, it was a total shock.
00:33:30 ►
Now we realize that serotonin, as a fundamental neurotransmitter,
00:33:36 ►
is at the root of many of our most basic drives,
00:33:42 ►
appetite, wakefulness and sleep, sexuality. So the recognition that
00:33:49 ►
psychedelic drugs were structurally related to things like serotonin, dopamine, epinephrine,
00:33:55 ►
really kind of emerged very closely allied to discoveries of the first psychedelic drugs starting with LSD, which of
00:34:06 ►
course has structural relation both to serotonin and to dopamine. So Sasha’s work was fundamental
00:34:15 ►
medicinal chemistry, but it was targeted at trying to understand what the relationship between chemical structure and psychological effect were.
00:34:27 ►
And this is really well in advance of any appreciation of serotonin receptors or the
00:34:34 ►
whole concept of drug receptors or neurotransmitter receptors.
00:34:39 ►
So much of Sasha’s work actually sort of burgeoned into what we now know as neuropharmacology.
00:34:46 ►
So his legacy is broad.
00:34:51 ►
So at any event, to make a long story short,
00:34:57 ►
Sasha and his wife had a lot of presentations at meetings like this,
00:35:03 ►
and they tend to speak much more briefly than I
00:35:06 ►
just have and try to open things to questions. And maybe I’ll just kind of give a little sketch
00:35:12 ►
of where we are right now at the farm. As I said, I started working there in 2007.
00:35:20 ►
First few months were pretty much exclusively in the laboratory,
00:35:27 ►
kind of bringing things to a more sound housekeeping status
00:35:31 ►
to where we could actually start doing some chemistry again.
00:35:34 ►
Sasha, as I mentioned before, lost his eyesight,
00:35:38 ►
and with elderly folks, housekeeping kind of goes as eyesight goes.
00:35:42 ►
So I got to the point where we could start doing some chemistry,
00:35:46 ►
but then by late 2007,
00:35:50 ►
Sasha asked me if I’d be willing to work on a writing project
00:35:54 ►
that he’d had kind of in the works for a while,
00:35:58 ►
but they were a little bit stalled on.
00:36:00 ►
So to make a long story short again,
00:36:03 ►
after three years we published another major book,
00:36:08 ►
The Shulgin Index, Psychedelic Phenethylamines and Related Compounds.
00:36:12 ►
This is more of a reference work, so it’s kind of aimed at scientists,
00:36:16 ►
sort of a one-stop review of probably about 50 years’ worth of research into psychedelic phenethylamines,
00:36:25 ►
psychedelic amphetamines, and some more recent compounds.
00:36:30 ►
It’s designed a little bit as a hybrid between the Merck Index,
00:36:35 ►
for those who are familiar with that, which is a general reference for organic chemists,
00:36:51 ►
and the kind of review style that you’d find in the annual review of physiology or plant physiology.
00:37:02 ►
So once we wrapped that up, about 815 pages worth and lots of tables and cross-references. We went back to work in the lab,
00:37:06 ►
and we started to kind of identify tracks of work
00:37:10 ►
that looked like they could have some legs
00:37:12 ►
and not get us in too deep a trouble with the Drug Enforcement Agency.
00:37:18 ►
So Sasha had a DEA license for quite a number of years
00:37:21 ►
and actually was given awards from the DEA in their early years,
00:37:26 ►
helping them both identify substances that they didn’t have the ability to unequivocally identify,
00:37:36 ►
suggesting analytical methods. But as their agency evolved and their politics evolved,
00:37:47 ►
they began to look at his sort of more open-ended, open science,
00:37:54 ►
open communication strategy a little bit askance.
00:37:58 ►
And so they kind of came down on him pretty hard in 1993,
00:38:03 ►
a couple of years after the publication of PCOL,
00:38:06 ►
particularly since they had busted a lot of labs where they found PCOL on the shelf.
00:38:12 ►
So sort of an indicator that his influence was not necessarily purely academic.
00:38:33 ►
They harassed him a bit and fined him $24,000 for inadequate administrative controls over drug samples that he had received for analysis. And in the dust-up from that whole experience, he voluntarily relinquished his Schedule I license.
00:38:43 ►
voluntarily relinquished his Schedule I license.
00:38:50 ►
So since that time, he kind of delved back into natural products chemistry, which kept him away from any controlled substances,
00:38:54 ►
and I’ve kind of continued some of that.
00:38:56 ►
So I’ve picked up a little bit of his tryptamine research,
00:39:02 ►
which would be new chemistry, looking at new compounds.
00:39:07 ►
Also started to do some natural products chemistry.
00:39:10 ►
I have a colleague in Texas who’s working on conservation of peyote.
00:39:18 ►
Peyote is an interesting Schedule I plant.
00:39:22 ►
It’s the, along with cannabis, the only schedule one plant.
00:39:26 ►
But at the same time, it’s received state sanction and federal sanction for use in
00:39:33 ►
for religious purposes by the Native American church. And that’s withstood both stood both litigation in court
00:39:45 ►
and also legislation.
00:39:48 ►
So the Native American folks
00:39:49 ►
can consume that plant,
00:39:52 ►
but unfortunately, they’ve
00:39:54 ►
really consumed
00:39:56 ►
a bit too much.
00:39:57 ►
And it’s now an
00:39:59 ►
endangered plant, and
00:40:01 ►
although it’s
00:40:04 ►
still desired, and it’s the principal medicine of the Native
00:40:08 ►
American church, there is a very real possibility that continued harvesting may in fact wipe it out.
00:40:16 ►
So my colleague Martin Terry and I are working on kind of different aspects of how to conserve
00:40:22 ►
this going into the future. He’s been working on basic population ecology of the plant in the field, looking at how harvesting
00:40:28 ►
practices affect the reproduction and survival of older plants, and I’ve been
00:40:35 ►
helping him work on the chemistry of mescaline in both seedling plants and in
00:40:43 ►
regrowth to kind of establish a foundation that will let us look forward to a time
00:40:50 ►
when production by cultivation may be legally possible.
00:40:55 ►
It’s not legally sanctioned today,
00:40:58 ►
and it’s actually not even desired by the older folks in the Native American church. It’s a matter of faith on their part that the concept is that God put it here for us.
00:41:12 ►
When we need it, it will be there.
00:41:14 ►
So the older folks really don’t have any particular desire to see any controlled cultivation take place,
00:41:24 ►
but the younger folks are open to that.
00:41:27 ►
So I kind of kid people and say,
00:41:29 ►
well, you know, as soon as we get to the state
00:41:31 ►
where we can legally start to discuss peyote agronomy,
00:41:35 ►
we’ll have to start thinking about greenhouses
00:41:37 ►
on top of all those Indian casinos.
00:41:39 ►
They’ve got all the security, they’ve got the real estate,
00:41:42 ►
now all we have to do is have a planting situation that can sustain the production.
00:41:48 ►
So that’s one project. We’ve also
00:41:51 ►
had a long-term interest in lysergemide chemistry. Just in the last
00:41:56 ►
year we’ve started to work with a group of patients that
00:42:00 ►
suffer from cluster headache. For those of you who have not heard of it,
00:42:04 ►
cluster headache is probably one of the more intractable,
00:42:09 ►
troublesome neurological disorders.
00:42:12 ►
It’s pretty rare, much more rare than migraine,
00:42:17 ►
and much more debilitating.
00:42:20 ►
They’re called clusters because they occur in windows of time during the year
00:42:24 ►
that can last many weeks to months
00:42:27 ►
and during those cluster windows
00:42:31 ►
you can have anywhere from 3 to 18 of these attacks a day
00:42:35 ►
and they’re described as the most excruciating pain that humans endure
00:42:41 ►
they’re sometimes called suicide headaches
00:42:44 ►
because people that experience
00:42:45 ►
these things, and it’s about a five or six to one ratio of men to women that have these things,
00:42:52 ►
they are so severe, so prolonged, and so incapacitating that people are willing to
00:43:01 ►
just end their lives because they can’t deal with it. So kind of fortuitously in the late 1990s, there was a cluster headache sufferer in Scotland who
00:43:10 ►
had a dose of, well, now it’s kind of lost in time, either psilocybin or LSD, right around the
00:43:15 ►
time that his cluster period would have started, and no cluster. The whole cluster cycle did not occur. So he wondered, well, what happened? Why didn’t
00:43:30 ►
this happen? One of the kind of strange aspects of cluster headaches is that for many, many people,
00:43:36 ►
they’re quite predictable. They’ll be like, oh, two weeks after the summer solstice, my cluster will start. And that predictability is kind of a hallmark of this disorder.
00:43:49 ►
So that patient zero experimented a bit, found that, oh, in fact,
00:43:54 ►
the psychedelic seemed to have this blocking action.
00:43:58 ►
And so by the middle 2000s, this word got out in the cluster headache community and people
00:44:06 ►
were starting to experiment a patient advocacy organization called cluster
00:44:10 ►
busters formed and they approached some researchers at Harvard who in 2010 did
00:44:21 ►
an experiment with a related drug or a drug related to LSD, kind of on a dare almost from Harvard.
00:44:30 ►
So one psychiatrist was working at Harvard, another German colleague from Hanover,
00:44:36 ►
approached the staff at McLean Hospital at Harvard,
00:44:42 ►
and they said, well, we want to do this LSD study with cluster headache because we think it could be a little breakthrough drug to
00:44:47 ►
be a very unusual preventative
00:44:51 ►
for this awful condition.
00:44:55 ►
They had a meeting with one of these oak
00:44:59 ►
paneled conference rooms with a big table and lots of
00:45:03 ►
very cushy chairs.
00:45:08 ►
So they said, okay, we want to do this LSD study.
00:45:13 ►
And one of the older executives leans forward and says,
00:45:19 ►
you know, we had Leary here.
00:45:24 ►
So to make a long story short,
00:45:26 ►
they were so skittish about the possibility of any of these lsd research being done at harvard that they they they pleaded is there is there nothing else that’s
00:45:31 ►
even structurally related that might have any possibility of of working or can you eliminate
00:45:37 ►
that so that we can we can go to our uh institutional review board and say well you know we we’ve we’ve
00:45:43 ►
tried everything else that’s
00:45:45 ►
structurally related, and this is our only alternative is to go back to LSD.
00:45:50 ►
So one of the two psychiatrists proposing the study knew of a drug called Tuberomol-LSD,
00:45:57 ►
or BOL-148, an old drug. It had been first synthesized by Albert Hoffman and Company,
00:46:02 ►
patented in 1950,
00:46:09 ►
experimented with a little bit as a possible migraine drug, didn’t pan out.
00:46:12 ►
He said, well, we know of this drug.
00:46:17 ►
It has some pharmacological similarities to LSD,
00:46:19 ►
but it doesn’t produce a psychedelic effect.
00:46:22 ►
Even at doses 1,000 times higher than LSD, no psychedelic effect.
00:46:28 ►
So they tried this on a very small group of cluster headache patients in Germany,
00:46:34 ►
and in fact it worked as well, maybe even better, than either LSD or psilocybin.
00:46:48 ►
So unfortunately, the patient population that they’re trying to address with this is just large enough that the the fda cannot sweep this into the orphan drug act which allows drugs that might help patients suffering from an illness who number
00:46:57 ►
200 000 and below in the united states underphan Drug Act, substances can be, the clinical testing
00:47:08 ►
can be lessened to a very dramatic degree, so drugs can be mobilized into clinical experimentation
00:47:14 ►
more rapidly. There are probably on the order of 300,000 to 350,000 cluster headache patients,
00:47:21 ►
so unfortunately they blew that qualifier, and the whole project kind of
00:47:27 ►
stalled. So the Cluster Busters organization who initially brought that product or project to
00:47:35 ►
Harvard approached us, and we’re now working on basically synthesis methods to discover
00:47:41 ►
alternative methods for manufacturing that drug.
00:47:50 ►
And there have been a very few patients that have had some of that substance, and the prognosis looks very good. The kinds of results that we’ve heard back are that, you know, my
00:47:58 ►
husband was able to sleep through the night in his own bed for the first time in years,
00:48:02 ►
and that kind of thing. So it’s very hopeful. We don’t know
00:48:05 ►
exactly how it’s going to go, but we’re continuing to try to use our chemistry expertise and kind of
00:48:11 ►
the history of what Sasha did and the kind of unique environment of the farm to push research
00:48:18 ►
forward. So he was a tremendously prolific scientist for on the order of 50 years.
00:48:27 ►
There may be on the order of 150 to 200 psychedelics that he produced that are kind of known.
00:48:34 ►
There are a number of other compounds that were not psychedelics but may have other potential benefit.
00:48:42 ►
Some have actually been patented and tested for use in treatment
00:48:46 ►
of what we now would call Alzheimer’s disease.
00:48:49 ►
So there’s a lot of work to kind of bring his legacy forward,
00:48:54 ►
and that’s kind of what’s falling to me.
00:48:56 ►
So we’re trying to kind of organize our forces to digitize his work,
00:49:04 ►
create an archive that’s accessible to other researchers,
00:49:07 ►
and keep a little bit of chemistry going out in the lab.
00:49:11 ►
So that’s kind of my basic presentation.
00:49:16 ►
I’d love to answer any questions that you might have.
00:49:20 ►
So go to it.
00:49:24 ►
Okay, the question is, was Sasha’s first experience with synthetic or organic mescaline?
00:49:30 ►
Now, first off, if organic mescaline, mescaline that’s isolated from natural sources,
00:49:37 ►
often has other things present.
00:49:39 ►
If you really did a good job and isolated mescaline from an organic source
00:49:45 ►
and there was nothing else present but mescaline itself,
00:49:50 ►
and you compared that with synthetic mescaline,
00:49:52 ►
there theoretically should be no difference except the isotopic composition.
00:49:56 ►
So that said, you can get a nearly crystalline product from peyote or from trichocerous or a number of other mescaline
00:50:07 ►
containing plants, and it could be very qualitatively different than pure mescaline.
00:50:13 ►
So can’t answer that question. At the time, it probably was synthetic, but I’m not sure 100%.
00:50:20 ►
Actually, Sasha didn’t. If you’re familiar with his second book, Tikal, there are some
00:50:28 ►
little hints in there that some of the methods actually were not things that Sasha did. I
00:50:33 ►
only kind of figured this out after working in his lab a bit. There are some particular
00:50:37 ►
techniques, particularly purification methods, that Sasha never did. So some of that work was done in other labs and probably principally by
00:50:46 ►
Dave Nichols. David was an early acolyte student of Sasha’s, but he really focused on
00:50:57 ►
lysergemides almost exclusively. Well, I can’t say that. He did a tremendous amount of lysergemides
00:51:04 ►
and really advanced our understanding of structure-activity relationships with those compounds,
00:51:09 ►
but that was not a principal interest of Sasha’s.
00:51:13 ►
Sasha worked primarily with phenethylamines and the more simple tryptamines
00:51:17 ►
and made quite a bit of progress with those.
00:51:21 ►
There’s something over here?
00:51:23 ►
Yes.
00:51:24 ►
Oh, no. Oh, no. no, no, there are always more.
00:51:30 ►
In fact, I’ve got a colleague in Liverpool who’s kind of hooked in with the sort of early
00:51:39 ►
warning system that the EU has in place to analyze new substances
00:51:47 ►
that come out in kind of the gray drug market.
00:51:51 ►
In the past couple of years in particular,
00:51:53 ►
there have been a lot of cathinone derivatives.
00:51:58 ►
So in the States, there’s been a little bit of interest
00:52:02 ►
in what have been called bath salts compounds.
00:52:06 ►
So there were three that were scheduled just this last summer, well, pardon me, summer a year ago.
00:52:16 ►
Methadrone, which is 4-methylmethcathinone, a substance called methalone,
00:52:22 ►
which is actually one of Sasha’s compounds, that would be the beta-keto analog of MDMA,
00:52:29 ►
and another substance called methylene-dioxypyrovaluron, MDPV.
00:52:35 ►
Okay, so those three were scheduled, but my colleague in Liverpool informs me
00:52:42 ►
that there have been, in just 2012,
00:52:49 ►
85 new cathinone derivatives that have shown up in the European marketplace.
00:52:54 ►
A number of them never before reported in the literature anywhere. A number of them kind of gleaned from earlier pharmaceutical patent applications and reports
00:53:05 ►
but never really extensively experimented with in humans
00:53:09 ►
but in terms of
00:53:12 ►
even those core structures there are even
00:53:14 ►
substances that Sasha made which he never actually worked up in terms of
00:53:18 ►
personal exposure so it’s still
00:53:21 ►
kind of a wide open field
00:53:23 ►
and the way things have kind of developed historically
00:53:27 ►
from, say, the late 1950s through maybe the mid-1980s,
00:53:35 ►
the only way to demonstrate that any of those substances had activity
00:53:40 ►
was to have humans test them.
00:53:44 ►
There were no useful animal models at that time.
00:53:48 ►
The whole concept of a receptor-binding assay
00:53:52 ►
or a neurotransmitter reuptake assay hadn’t emerged yet.
00:53:59 ►
Those kinds of technologies really are sort of spin-offs
00:54:02 ►
from the Human Genome Project
00:54:04 ►
because we now know how to clone genes we can clone genes that produce the
00:54:09 ►
proteins that are in fact receptors and so we now have a wide variety of you
00:54:14 ►
know kind of you know in the test tube kinds of tools that didn’t exist before
00:54:17 ►
the mid 1980s so the way the whole scientific literature developed there
00:54:24 ►
there was maybe maybe 20 years worth of structure-activity relationships
00:54:28 ►
that was backed by human reports of activity.
00:54:33 ►
And then after the mid-’80s, these new techniques became available,
00:54:38 ►
but also journals became very skittish about reporting human exposures.
00:54:44 ►
So the two kind of combined, and so now we’ve got maybe
00:54:47 ►
25 years worth of very detailed molecular data about
00:54:52 ►
how these things interact with receptors, but
00:54:55 ►
almost no new human exposure data.
00:55:00 ►
So it’s kind of a funny dichotomy, you know, historically.
00:55:03 ►
Yes?
00:55:06 ►
Thank you.
00:55:10 ►
So we’ve already discussed the tryptamines and the phenylethylamines.
00:55:13 ►
And you mentioned cathinones,
00:55:17 ►
although I’m not sure if they’d be considered classical psychedelics.
00:55:20 ►
That’s a good point. The associatives, the ketamine, methoxetamine family, again debatably psychedelic
00:55:27 ►
in that strict sense. Are there any other major groups?
00:55:35 ►
Well,
00:55:35 ►
these base structures that you mentioned, the phenethylamines
00:55:40 ►
and the tryptamines seem to crop up in a lot of other areas. So for instance
00:55:44 ►
something like ibogaine has a tryptamine core.
00:55:50 ►
There’s an endol structure embedded in ibogaine.
00:55:54 ►
In terms of new substances, like with entirely different structures,
00:56:00 ►
they keep cropping up, but this is not an area that’s really been able to develop
00:56:08 ►
because there’s been such a social rejection of them
00:56:13 ►
as being valuable substance to investigate.
00:56:16 ►
Just in the last couple of years
00:56:18 ►
there have been some new derivatives
00:56:21 ►
of both phenethylamines and tryptamines, the end bone derivatives,
00:56:28 ►
where an extra ring is added out at the end of the side chain.
00:56:33 ►
Those actually have been quite a surprise.
00:56:38 ►
In the earlier development of all of these substances, substitutions out on the side chain end,
00:56:48 ►
like off the amine end of phenethylamines,
00:56:51 ►
all but exclusively destroyed activity
00:56:54 ►
or created some other kind of activity.
00:56:59 ►
But with these new substances that really were only discovered
00:57:02 ►
in the last three or four years,
00:57:04 ►
where an extra ring
00:57:05 ►
is added out there they are now known to be slightly more specific serotonin 2a receptor
00:57:15 ►
agonist so they’re more a little bit more like lsd in their effect although they’re they’re
00:57:20 ►
there there are some interesting kind of toxicological aspects of these that have yet to be investigated thoroughly.
00:57:31 ►
The N-BOMES, you’ll hear reference to 2,5-I, 2,5-C, 2,5-B, N-BOMES.
00:57:40 ►
These are N-methoxybenzyl derivatives of what would be 2CB, 2CI, 2CC.
00:57:48 ►
These substances are where, say, 2CB is active maybe in the 12 to 40 milligram range.
00:57:57 ►
The N-bone derivative is probably active at under a milligram. And there is a suggestion out there
00:58:06 ►
from just sort of anecdotal reports
00:58:07 ►
that taking larger doses
00:58:11 ►
could be very problematic.
00:58:13 ►
And there are so few reports
00:58:16 ►
that we can’t even, I think, really say
00:58:17 ►
what the nature of toxicological problems might be.
00:58:22 ►
So we just really need to
00:58:25 ►
emphasize caution
00:58:26 ►
in testing any of those substances.
00:58:30 ►
Okay. Thank you.
00:58:31 ►
So you mentioned
00:58:33 ►
toxicological problems with
00:58:35 ►
larger doses. Is there any
00:58:37 ►
indication that at the active doses
00:58:39 ►
they might be toxic?
00:58:43 ►
I appreciate you can’t know at this stage
00:58:45 ►
that’s an excellent question
00:58:46 ►
actually I was asked this a little earlier
00:58:49 ►
with respect to
00:58:51 ►
are there long term negative effects
00:58:53 ►
of psychedelics
00:58:54 ►
there was just a paper
00:58:57 ►
published within the last
00:58:59 ►
10 days in the public
00:59:01 ►
library of science plus one
00:59:03 ►
by two researchers who did quite a large horizontal study.
00:59:10 ►
I think they looked at over 130,000 individuals
00:59:14 ►
to assess the kind of background accessing and need for mental health services.
00:59:23 ►
accessing and need for mental health services.
00:59:29 ►
And of those 135,000, they identified around 30,000, I believe,
00:59:33 ►
is the number who had some experience with psychedelics.
00:59:39 ►
And the abstract take-home message was that there was no evidence that long-term exposure to psychedelic drugs had any effect on increased need for mental health services,
00:59:49 ►
and there, in fact, may have been a sort of statistically significant indication that there might have been benefit,
00:59:59 ►
like less need for mental health intervention with psychedelics exposure.
01:00:06 ►
That said, it’s possible for people to have a hard time
01:00:11 ►
if they take substances that they don’t know
01:00:13 ►
or in circumstances where they’re not comfortable
01:00:18 ►
or feel like they don’t have, it’s not a supportive environment,
01:00:23 ►
or they may not know the dosage.
01:00:27 ►
And this goes back a long way into the sort of modern era of experimentation with psychedelic drugs.
01:00:37 ►
We need to know set and setting.
01:00:40 ►
In other words, what’s your expectation of what the experience is going to be like?
01:00:45 ►
What’s your environment in which you’re going to experiment with the substance?
01:00:51 ►
And I would go one step further.
01:00:52 ►
There’s unfortunately been a tremendous lack of real solid understanding of what a substance is and how much you’re taking.
01:01:04 ►
of what a substance is and how much you’re taking.
01:01:07 ►
And those things, unfortunately, are kind of untoward byproducts of the drug war.
01:01:14 ►
As long as everything is underground,
01:01:18 ►
no one really knows what and how much you’re taking.
01:01:21 ►
And this is a very unfortunate consequence.
01:01:26 ►
Yes?
01:01:29 ►
I’ve not
01:01:30 ►
personally.
01:01:32 ►
My first, actually,
01:01:33 ►
getting back to this question of
01:01:35 ►
known substances at known dosages.
01:01:38 ►
Back in the early
01:01:39 ►
1970s when I was doing
01:01:41 ►
work on range grass toxicity
01:01:43 ►
by tryptamines I had my first it was
01:01:47 ►
the first ability to take pure dimethyltryptamine at a known dosage and it was it was really kind
01:01:57 ►
of a turning point in my relationship with the the whole business of exploring psychedelics. I had had street acid and other substances before that
01:02:07 ►
but it’s
01:02:11 ►
a completely different thing to know exactly what’s going on or at least
01:02:16 ►
what’s going in. What’s going on may be another question.
01:02:21 ►
Yes, another question.
01:02:23 ►
Yes, hi.
01:02:29 ►
So we haven’t touched on it, but if it’s too personal, we could not.
01:02:33 ►
But how is Sasha doing health-wise?
01:02:33 ►
Okay.
01:02:38 ►
Well, it’s kind of a difficult thing to answer.
01:02:48 ►
For any of you in the audience who have seen Sasha speak in the past, he was the most captivating personality.
01:03:00 ►
You know, extremely loquacious, verbal, funny, you know, broad interests, you know, a musician, you know, interested in politics.
01:03:12 ►
So starting in 2009, health effects started to rear their heads. He had a need for a heart valve replacement, and we were warned that in the elderly, heart valve replacements
01:03:20 ►
often predispose a patient to cognitive decline. So that happened, and then
01:03:26 ►
within a year, Sasha developed sort of a secondary cardiovascular collapse in one of his legs.
01:03:37 ►
So this showed up as wounds that would not heal, and basically the circulation in that leg was so bad that there was a threat that he might
01:03:47 ►
might have to have it amputated. Finally some physicians kind of within the circle closed in
01:03:54 ►
and very aggressively treated him and they were able to avoid amputation but during that treatment
01:04:01 ►
he was on a trip across the Bay Bridge to have a doctor’s appointment and suffered a minor stroke.
01:04:07 ►
So the stroke, unfortunately, affected his speech centers.
01:04:11 ►
And so today, we would say that Sasha is stable.
01:04:17 ►
He is experiencing dementia.
01:04:19 ►
So his short-term memory processing, processing current events into working memory, is severely impacted.
01:04:30 ►
He is ambulatory, so he’s able to walk, but he basically requires 24-hour care.
01:04:39 ►
Whenever I’m out at the farm and I’m working in the lab. Sasha comes out and spends time with me in the lab.
01:04:46 ►
And I do everything that I possibly can to keep him engaged,
01:04:51 ►
whether it’s yakking at him about left-wing politics
01:04:53 ►
or putting on Grateful Dead or playing classical music.
01:04:58 ►
I try to keep him as engaged as I’m able.
01:05:01 ►
And he still cracks a lot of really corny jokes and they all seem to
01:05:06 ►
be pretty relevant to what’s going on conversationally so he’s he’s impaired
01:05:12 ►
but he’s still with us so I hope that answers any other questions well thank
01:05:23 ►
you for having me I really appreciate being able to speak with you.
01:05:29 ►
Thank you, Paul.
01:05:30 ►
You’re listening to The Psychedelic Salon,
01:05:33 ►
where people are changing their lives one thought at a time.
01:05:37 ►
Before I go on, I first want to emphasize a fact that Paul just touched on,
01:05:42 ►
and that is, not only are there an ever-increasing number of
01:05:46 ►
new psychoactive substances hitting the street, and not only does one have to be extremely careful
01:05:52 ►
about the source and purity of these compounds, but you should also pay very close attention to
01:05:57 ►
the fact that these new substances are also becoming considerably more powerful, which
01:06:02 ►
means that smaller doses are the new standard.
01:06:06 ►
And while I may sound like a broken record,
01:06:08 ►
the best advice you’ll ever hear in these podcasts is that before,
01:06:12 ►
long before you ever consider testing one of these substances yourself,
01:06:17 ►
you owe it to yourself, your family, and your friends
01:06:20 ►
to get all of the latest information about the substance from Arrowid.
01:06:24 ►
That’s E-R-O-W-I-D dot org. Arrowid dot org.
01:06:29 ►
And without any exceptions, it is the best and most reliable source of information
01:06:34 ►
about these substances that you’re going to be able to find.
01:06:37 ►
Now, to add a brief footnote to what we just heard Paul say about Sasha’s current physical condition,
01:06:44 ►
well, a couple of days ago I was talking with Jean Stolaroff,
01:06:47 ►
who, I should add, is one of the last surviving members of the study group
01:06:51 ►
that the Shulgens worked with in their study of the compounds listed in PCOL and T-COL.
01:06:57 ►
And Jean told me that in recent conversation,
01:07:00 ►
Ann Shulgen told her that a couple of times each week,
01:07:03 ►
they help Sasha get to a nearby coffee shop
01:07:05 ►
where he sits and tells jokes with a few of his friends.
01:07:09 ►
Apparently his sense of humor remains completely intact
01:07:12 ►
and for those of us who know Sasha, we generally rate his sense of humor as, well, maybe his most enduring trait.
01:07:19 ►
For my own favorite story about Sasha, well, you’ve already heard it if you’ve either watched the video
01:07:24 ►
or heard my podcast titled Confessions of an Ecstasy Advocate.
01:07:29 ►
Anne and Sasha Shogun, in my mind, are two very remarkable people.
01:07:34 ►
And our world has been greatly enhanced by the work that they and a few of their closest friends have done.
01:07:40 ►
And a huge thank you also goes out to Paul Daly.
01:07:43 ►
Without his dedication and selfless work,
01:07:46 ►
well, maybe some of Sasha’s work would have been lost.
01:07:48 ►
So thank you so much, Paul, for everything you’re doing.
01:07:52 ►
And speaking of thank yous,
01:07:54 ►
I want to extend my sincere thanks
01:07:56 ►
to the 212 or so fellow Saloners
01:07:58 ►
who rose to the occasion and made donations
01:08:01 ►
that collectively will ensure that these podcasts
01:08:04 ►
continue through the end of February 2015.
01:08:08 ►
And most likely well beyond that.
01:08:11 ►
But for now, I don’t have to do any more thinking about how long I’m going to keep podcasting from here in the salon.
01:08:17 ►
We’re here for another year at least, for sure.
01:08:21 ►
Now, it’s going to take me most of April to send personal emails to each of our donors, but don’t give up on me.
01:08:27 ►
I’ll be doing a few each day, but I don’t want to just send out a group message.
01:08:33 ►
Well, particularly since I have to confirm with each of you how you want your name to appear on our sponsor’s webpage.
01:08:40 ►
Also, for our salonners who contributed $45 or more, I’ll be confirming the address to which I’ll be sending your USB thumb drive.
01:08:48 ►
And on that drive will be the first 400 podcasts from the salon.
01:08:53 ►
And since this is $3.94, I guess, I better get busy and get the next six podcasts out as soon as I can.
01:09:00 ►
Also, those drives will have about 100 of my favorite Terrence McKenna soundbites.
01:09:04 ►
And it looks like all of that’s going to just about fill a 16 gigabyte LumDrive.
01:09:10 ►
And I’ll do my best to get it out shortly after my 400th podcast,
01:09:14 ►
which means that you should expect your drives sometime in June.
01:09:17 ►
Maybe before, if I don’t get too lazy when spring fever hits.
01:09:22 ►
So for now, this is Lorenzo, signing off from cyberdelic space.
01:09:26 ►
Be well my friends.