034 - Psychedelic Chemistry

Program Notes

Guest speaker: Dave Nichols

Photo by Jon Hanna from the Erowid.org vault of Dr. David Nichols

Year this lecture was recorded: 2017

As the founding president of the Heffter Research Institute, a chemist who crafted some of the most important research molecules of this generation and a leader in the psychedelic community, we’re pleased to present an interview with Dr. David Nichols.

He talks about the impetus for his interest in these molecules, the potential dangers of microdosing and the feelings of a chemist whose creations escaped the laboratory and - while doing much good - also caused harm.

Microdosing with LSD and its Research Potential

Legal highs: the dark side of medicinal chemistry
http://www.nature.com/news/2011/110105/full/469007a.html

Review of psychedelics by Dr. Nichols:
http://pharmrev.aspetjournals.org/content/68/2/264

LSD Neuroscience - David E. Nichols at Psychedelic Science 2017
https://www.youtube.com/watch?v=LbUGRcuA16E

To support Lex Pelger’s Psychedelic Salon 2.0 podcasts, join the No Nonsense Club:
https://www.patreon.com/NoNonsense

Transcript

00:00:00 ►

Greetings from cyberdelic space, this is Lorenzo and I’m your host here in Psychedelic Salon

00:00:23 ►

2.0.

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And today we get to listen in on a

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conversation between Lex Pelger and Dr. David Nichols, who, as most of you likely know,

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was one of the founding members of the Hefter Research Institute and was its first president.

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Now you’re probably already familiar with the Hefter organization, and if you’ve been with us

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here in the salon for a while, you already know about much of the work of the Hefter organization.

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In fact, two of the other co-founders, Dr. Charlie Grobe and Dr. George Greer, have both

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been featured here in the salon on several occasions.

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And if I remember correctly, George Greer was a Planque Norte lecturer this year as

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well, and so you’ll be hearing from him in one of

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my Salon 1.0 podcasts later this year. Now, the Hefter Research Study that I’m most familiar with

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is the one conducted by Charlie Grobe that studied ways in which psilocybin could be used to ease the

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end-of-life issues with terminal cancer patients. And the reason that I know a lot about that

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particular study is because my wife was Dr. Groves’ research nurse on that study.

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And since 2003, the Hefter Organization has sponsored three completed Phase II studies

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at Harvard UCLA Medical Center, at Johns Hopkins University, and at New York University,

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with a total of 92 participants,

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all of whom demonstrated statistically significant improvements

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with enduring effects for months after a single psilocybin treatment session.

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And so now I’ll turn the microphone over to Lex Pelger

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to interview a man who has been involved in psychedelic research for almost 50 years now.

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Now just let that sink in for a moment. Do you know how rare it is today to find somebody who has been involved

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in this field this long? Dr. David Nichols is one of the extremely small number of scientists who

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has been able to conduct psychedelic research for such an amazingly long time,

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given the political restraints under which he’s had to work.

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So now, here’s Lex Pelger.

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I’m Lex Pelger, and this is the Psychedelic Salon 2.0.

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Today we hear from one of the great psychopharmacologists of our psychedelic movement, Dr. David Nichols.

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He has been a creative force in the synthesis of new molecules,

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and a voice of reason and caution when it comes to new issues like microdosing.

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While still a graduate student, Dr. Nichols patented the method used to make optical isomers of the hallucinogenic amphetamines.

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That’s the DOC, DOB, DOM series of compounds. Later in his career, his contributions included

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the synthesis of Escalin, LSZ, 6-APB, and 2-CI-NBOME, and other NBOME variants.

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Though this last class of compounds later caused him grief after they

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escaped a laboratory, as you’ll hear. To see some of his work, I’m including a link in the episode

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notes to his comprehensive review article on psychedelics, and it is a wonderful piece of work.

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And in further psychedelic history, Dr. Nichols was also the person to coin the term

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Dr. Nichols was also the person to coin the term Intactogen

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For dedicated Saloners

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you’ve heard him before on episode number 545

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That was a talk recorded in 1991

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at a psychedelic conference that included

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Dr. Nichols, Dr. Charlie Grobe

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a young Rick Doblin

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a very irreverent Timothy Leary

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and a prophetic Richard Jensen

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So today, after you listen to Dr. Nichols talk about drugs right now in 2017,

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go back to episode number 545 to hear what he had to say more than 25 years ago.

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Hello, everyone. This is Psychedelics Lawn 2.0.

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We are here with Dr. Dave Nichols, who many of you know about. Thanks for joining us.

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My pleasure.

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My first question was, what was it that drew you into this type of research so early in the field?

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Oh, I actually started this field in 1969 when I started my graduate studies. I just thought it would be an interesting group of compounds to study.

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graduate studies. I just thought it would be an interesting group of compounds to study.

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Was it because of what was going on in society at the time, or was it more the psychopharmacologist and you just saw fascinating substances?

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Well, I went to graduate school in 1969, and so that whole the summer love in 67 and all the

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crazy stuff in the West Coast, primarily in the 60s. None of that happened in Cincinnati.

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But a lot of my friends went away to college and would come back and visit and say,

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oh yeah, everybody’s smoking marijuana and there’s this stuff called acid that’s going around.

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So it sounded like a really interesting topic to study.

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What was it like for your school for you to go into a topic like this? Was there much pushback?

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No.

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I went to the pharmacy school at the University of Iowa.

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And actually, the guy, the fellow that I decided to do my PhD work with, Charles Barfnick,

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had actually had a student who was making potential metabolites of mescaline.

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And so it was purely academic, and nobody really cared what you did in academics.

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And at that point in time, there was really no pushback.

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So I could do what I wanted, really, for my PhD.

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So it was just a lot of fun.

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And what did you end up doing your PhD work on then?

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Primarily on inlogs of mescaline, looking at the phenethylamine compounds,

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looking at structure-activity relationships, in some ways paralleling some of the stuff that Sasha Shogun had done,

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developed an asymmetric synthesis, a way to make the optical isomers of all the

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psychotomimetics, we call them then, all the hallucinogenic or psychedelic amphetamines.

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They’re all like amphetamine. You have dextro

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and levo amphetamines. Well, you have dextro and levo psychedelic amphetamines. So I developed a

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very specific way to make each of the separate isomers. I actually got a patent on that as a

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graduate student. Oh, really? That must have been a good feather in your cap. Yeah, it was

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interesting. I was an inventor way back when. So that was kind of really cool. Yeah. And you were one of the leaders in the

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psychedelic amphetamine world, DOM, DOC and such. Yeah. I didn’t make the simple amphetamines so

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much as we looked at analogs where we changed the orientation of the side chain. We made two ring

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and three ring compounds. We tried to make compounds that were

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hybrids between LSD and mescaline. So we made some simple amphetamine analogs, but

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mostly they were attempts to construct novel molecules that would constrain them into shapes

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that might be complementary to the receptor. Did some work on mescaline, made escaline and proscaline and isoproscaline, where we

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looked at those.

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Made the first in the Aleph series, Aleph-1, 2-CT.

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And then Sasha had a friend at UCSF, Neil Castagnoli, who had a postdoc named Peyton

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Jacob. And after we made Aleph I, Sasha called and said,

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well, Neil would like to have his postdoc work on some other sulfur,

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move the sulfur around in other places in the ring,

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unless you’re going to continue to work on them.

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And I said, no, I’m only interested in that series with the sulfur in the four positions.

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So that led to the whole sulfur series, which was kind of interesting.

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You know, Sasha made 2CT2 and 2CT3,

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et cetera, et cetera, et cetera, to this 2CT infinity. Yeah, so it kind of got that started.

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And we’ll actually, you have a good review of those bromohamphetamines, and we’ll link to those

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in the episode notes afterwards. And how would you go about visualizing these new molecules, and which directions you wanted to explore out of all the possibilities?

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So a lot of organic chemists, and this was organic chemistry, is very visual.

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You have to imagine the molecule.

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And there were certain things about the molecules that we knew, like they had methoxy groups, which is a carbon attached to an oxygen attached to an aromatic ring.

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Those things can generally spin around, but we thought they probably were specific orientations

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when they bound within the receptor. So we could lock those methoxys by tethering with another

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carbon atom. We could tether them so that they would be in one orientation or in another

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orientation. So that way we could determine what were the shapes of the methoxys

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when they bound to the receptors.

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What was the shape of the side chain?

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Was it in a plane with a benzene ring?

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Or did it twist out of plane so that they were perpendicular?

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And so we did a lot of work making analogs like that.

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In the beginning, there were hypotheses by some people

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that the psychedelic amphetamines bound to the receptor in a shape that resembled LSD.

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And that was kind of widely adopted.

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And we started looking at that because there were certain reasons that it didn’t make sense.

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So we actually ended up making analogs that were very different looking than LSD but which were very active.

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And so we showed that that was not an LSD, but which were very active. And so we

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showed that that was not an apt analogy, that they didn’t bind, they bound in a completely

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different way. And when you started this work, there wasn’t as much knowledge about what the

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receptors looked like for a lot of this stuff, right? What was it like as your career went on

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and we got to know more of the receptors as well. Yeah, there wasn’t anything known about

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receptors when I started, period. They just knew there were these things called receptors that

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bound. And then the classification of the serotonin receptors, they cloned the receptors early on,

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cloned, I guess, 14 different serotonin-type receptors. There still weren’t receptor

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structures for a lot of those. That really required advances in protein

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crystallography. And those have occurred. So now we have a lot of receptor structures.

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So we actually know how a lot of these molecules bind within the protein of the receptor.

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But back then, we didn’t know. It was as if you had a lock that could take certain keys and not

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other keys. And so we’d make a molecule, and if that was a key that could take certain keys and not other keys.

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And so we’d make a molecule, and if that was a key and it would open the lock,

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then we’d say, okay, the lock must have that kind of shape inside.

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And then another molecule we’d make, and it didn’t turn the receptor on,

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so we’d say, well, that can’t be it.

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So it was kind of an indirect inferring process where,

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based on having a whole library of compounds at varying degrees of activity,

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we could say, well, the lock must be complementary to this overall shape.

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And eventually we got into molecular biology and started mutating the residues in the serotonin 2A receptor itself.

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So we had a huge library of compounds we made over the years. So if we changed one residue into another amino acid residue,

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then we’d run through all this library of compounds and see what effect that mutation had.

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So that would allow us to infer something about the three-dimensional shape of the receptor as well.

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So now, of course, this year we published the structure of LSD bound to the serotonin 2B receptor.

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And I, in 2002, had made some rigid analogs.

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Actually, one of them has become a research chemical called LSZ,

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and that compound has got the diethylamide of LSD

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is replaced with a four-membered ring with two methyls attached called an azetadide.

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And we had made, there’s three different stereoisomers of the azetadides,

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and so we had made all three and found that this one turns out to be LSZ.

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all three and found that this one turns out to be LSSZ. The SS steroid smear was the one that was most like LSD in its effects at the receptor and in rats and behavior. And so when we got the

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structure of LSD bound to the 5-HT2B receptor, the shape of LSD turned out to be superimposable

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with the prediction we’ve made using these zetadity analogs. So it’s been, everything’s kind of converged,

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so now we have a good idea of how LSD at least binds.

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But the amphetamines and mescaline analogs, we still don’t know how they bind.

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It’s still kind of an enigma.

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All those keys and you can’t see the lock.

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Yeah, that’s true.

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And with that recent binding that you did,

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you wrote something on Hefter about concerns about heart risk and microdosing.

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I was wondering if you could share more about that.

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Yeah.

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So the receptor structure that we published in Cell early this year was LSD bound to the serotonin 2B receptor.

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The actual target for psychedelics is the serotonin 2A receptor.

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So there are three classes of serotonin 2 receptors,

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the 2A, the 2B, and the 2C. Almost all the psychedelics bind to all three. The 2A and the 2C

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are more similar than the 2B, but they bind to the 2B. And so the structure we published was LSD

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bound to the 2B receptor. The 2B receptor is problematic. If a drug company develops a drug that’s an agonist at the 2B receptor,

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it will probably not be developed further.

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What happened years ago, there was a combination of drugs called phentermine

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and phenfluramine called PhenPhen that was marketed as an appetite suppressant.

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It turned out that that combination, people started having cardiac problems, cardiac valve thickening.

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And they tracked it down to the fact that fen-phen was releasing serotonin and also activating the serotonin 2B receptors.

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That’s a type of receptor that’s in connective tissue in the heart, for example.

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2B receptors are not so much in the

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brain. And then there were some drugs for Parkinson’s disease, cabergoline and pergolide,

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Permax, that were used for Parkinson’s disease. They also activated the 5-HT2B receptor. And once

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it was known that that was a target that was bad for the heart, those Parkinson’s patients who had been taking those drugs then had echocardiograms

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and a significant percentage were found to have cardiac valvulopathy.

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So activation of the serotonin 2B receptor can cause heart damage,

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and valvulopathy, if it progresses to a certain point, the only fix is a heart transplant.

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So it’s pretty severe.

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And people who take a lot of MDMA, that can also happen

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because it releases a lot of serotonin.

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So it’s not a good idea to activate that receptor.

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So when I read about this microdosing, I thought, you know,

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this doesn’t sound like a good idea to me

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because LSD activates the serotonin 2E receptor.

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Now all the other cases like FinFin and for the anti-Parkinson drugs, they were taken more or less on a daily basis.

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So, if you take, well, if you take LSD or even psilocybin, if you take it once a year or once

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a couple of times a year, it’s probably not a problem. And you know, with the microdosing of LSD, Jim Fadiman has

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suggested, you know, every three days that you take it. But then I saw somebody with a blog about

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how he does it every morning. He gets up and he does this microdose of LSD. Well, you’re activating

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that receptor. And although we think of what are called dose response curves, where the effect is

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related to the dose, so low dose has a lower effect, high dose has a higher effect. With LSD, what we found when we did the crystal

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structures, once LSD gets into the 2B receptor, there’s a piece of the receptor that folds over

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top of it and holds it in there for many hours. So even if you take, you know, say 10 micrograms,

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which would be sort of the standard microdose, it becomes sequestered in the receptor,

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and concentrated in the receptor will stay there for quite a while.

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So people who are taking it every day are probably getting chronic activation

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of that receptor, even though it’s a low dose,

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because it will accumulate because it can’t get back out of the receptor very easily.

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So I wrote that blog because I said, you know,

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you might think that people would be wise and do it maybe every three days,

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which maybe still isn’t a good idea, but people don’t behave that way.

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You know, if a little is good, a lot must be better.

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And just like this guy’s blog about how every morning I get up and I take my microdose of LSD to get me fired up for the morning,

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I thought that kind of behavior could be really dangerous.

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And ultimately, if he did that for a long period of time, he might find that he was

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developing cardiac ovulopathy, and that would be a serious problem.

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So whether or not it happens, people take small amounts or only take them occasionally,

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you know, it may not happen.

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But the issue is, if it does happen, you know, are you willing to take a risk on that just

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for the potential benefit?

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And then the other issue is LSD has this reputation of enhancing creativity when you

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take a full dose of it. But does that mean that a low dose also enhances creativity?

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I’m not sure that it does. There are pathways in the brain whereby a low dose of LSD

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can activate dopamine pathways, which are the same things that Adderall and Ritalin activate,

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or Provigil, for example.

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So those are called cyclostimulants.

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So there was also a question in my mind as to whether a microdosing LSD

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was really more effective than a standard prescription cyclostimulant like Adderall.

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No studies have been done to prove that microdosing LSD is actually better than one of these legal psychostimulants.

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So until a study is actually done to compare them head-to-head,

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I’m not sure that testimonies by people who take it and say it’s, oh, it’s wow.

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I’m not sure how reliable those are because, first of all,

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there’s a big placebo effect in psychopharmacology.

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And secondly, we don’t know if microdosing LSD is really any better

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than something like Ritalin or Modafinil or Adderall.

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And if it’s not, then you’re still having the legal risk of taking a microdose of LSD,

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which even if it’s a small dose, it’s still Schedule 1. You could still get legal trouble

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with it potentially. So I thought, you know, there’s just a lot of problems with it.

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Some of these people that are saying it’s made them more creative and really

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focused them, I don’t know whether they’ve ever taken a prescription of psychostimulant like

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Adderall or Modafinil. And if they have, then maybe what they’re saying might be true. But

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if they haven’t, it may be that those compounds would be just as effective and they would be

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legal. So that was the basis. Just a number of concerns, whether it really worked, whether it

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was a placebo effect. And there’s the legal aspect of that compared with the legal psychostimulant.

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But there’s also the more serious problem of a potential cardiotoxicity and valvulopathy,

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which in its worst form would mean you’d have to get a heart transplant.

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That’s something most people probably wouldn’t want to have to do.

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What about the heart concerns from using a psychostimulant like Adderall every day?

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So that doesn’t activate the 5-HT2B receptor. That’s a different mechanism. It causes the

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release of dopamine. You can develop tolerance to it. You can become dependent on Adderall,

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for example, amphetamines, but it wouldn’t affect the heart.

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Even the kind of the jitteriness people feel, it’s not necessarily a heart effect.

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No, no. That’s really activation of the sympathetic nervous system and

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just norepinephrine and epinephrine release. Because with your current work, you have been

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coming back to dopamine and looking at Parkinson type drugs and things like that.

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Well, when I was at Purdue, I had two parallel tracks really. I was funded by Natural Institute

00:20:01 ►

of Mental Health to develop novel types of drugs for Parkinson’s, which were dopamine D1 agonists.

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And the other panel to track was my work on psychedelics.

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We demonstrated that a dopamine D1 agonist could be just as good as any other anti-Parkinson drug,

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but we couldn’t commercialize the drugs we developed because most of them didn’t have good oral availability,

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and the drug companies wanted orally available drugs.

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There is a drug now, I understand Pfizer has a drug in clinical trials,

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which is dopamine D1 agonist.

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It is highly oral available.

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It’s a different kind of structure completely.

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But then there seemed to be a lot more interest in the psychedelic field

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than there was in what I was doing with the dopamine agonist.

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But they were both funded by, you know,

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the anti-Parkinson drug work was funded by the National Institute of Mental Health for basically the same number

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of years as my psychedelic work, which is funded by the National Institute on Drug Abuse.

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And I just want to ask two more questions before I let you go back to work. The piece you wrote

00:21:00 ►

in Nature years ago about the dark side of medicinal chemistry, I thought it was really

00:21:04 ►

impressive for your honesty about what it’s like to be someone who created these compounds to get out there and get misused.

00:21:10 ►

How has that developed for you as the gray market and the black market get bigger around these substances?

00:21:17 ►

Yeah, that was really a concern of mine. I think it turned out it was a misunderstanding.

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The people who were developing these research chemicals really didn’t understand pharmacology very well.

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And the things that we published, this fellow who was in, I think, Belgium,

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who was a former cocaine dealer or whatever that they did the interview with,

00:21:42 ►

and she asked him, you know, where do you get the ideas for these things? Well, we have a chemist, but, you know, the things that Nichols publishes are really important.

00:21:46 ►

We watch all those.

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So I thought, hmm, so people are watching what I do.

00:21:50 ►

You know, it’s like the N-Bone compounds.

00:21:52 ►

We didn’t discover those.

00:21:53 ►

They came out of Germany.

00:21:54 ►

Rolf Heim developed them in 2000 or so.

00:21:57 ►

They were about 2002, 2003, I think his thesis was.

00:22:00 ►

But we were the ones that published the first paper in English.

00:22:03 ►

His work was all in German.

00:22:05 ►

And so that’s people caught on to that there. And then we had, you know, we had MTA,

00:22:10 ►

it was a methyl thiamphetamine that looked like MDMA in rats. But the signal that the rats gave

00:22:17 ►

us was that the drug was releasing serotonin. A lot of people think MDMA, oh, it’s a serotonin

00:22:21 ►

releaser. Well, the things that make you feel euphoric if you take MDMA are not serotonin release.

00:22:26 ►

They’re dopamine and arpinephrine release.

00:22:28 ►

It’s clear serotonin release plays a part in the therapeutic action

00:22:32 ►

and probably enhances the dopaminergic effect.

00:22:35 ►

But the compound that the MTA, the methamphetamine we made,

00:22:38 ►

didn’t have any effect on dopamine at all.

00:22:40 ►

It was just pure serotonin releaser.

00:22:42 ►

And so in rats, it looked like MDMA.

00:22:44 ►

But in humans, it looked like MDMA, but in humans,

00:22:45 ►

it didn’t have the other components because MDMA is a pretty really dirty drug in terms of

00:22:49 ►

pharmacology. It does lots of things. So somebody said, oh, MTA, we can make that. It’s a really

00:22:54 ►

simple molecule. We’ll get it out there. It looks like MDMA in rats, but it’s not like MDMA in

00:22:59 ►

humans. And so what I think happened was that people took it, and it didn’t really have much of an effect,

00:23:05 ►

and so they took larger doses and larger doses.

00:23:08 ►

And that was really problematic because what we didn’t know at the time,

00:23:11 ►

which was discovered later on by another group, is that MTA was an inhibitor of monamine oxidase.

00:23:18 ►

And monamine oxidase is what breaks down the serotonin.

00:23:21 ►

So if you take this molecule and you get serotonin released from your mast cells,

00:23:24 ►

your blood’s loaded with serotonin, it builds up and builds up and builds up.

00:23:28 ►

Mono-oxidase in the liver normally would break it back down so it wouldn’t build up to dangerous

00:23:32 ►

levels. But it also inhibited the enzyme that broke it down. So what happened was people took

00:23:36 ►

multiple doses. They built up massive levels of serotonin in their blood and had serotonin

00:23:41 ►

syndrome and died. So that was really upsetting.

00:23:46 ►

And we made an analog earlier, which a couple people,

00:23:49 ►

I think not as many people had taken.

00:23:52 ►

And it was an analog of MDMA where we had extended the alpha-methyl

00:23:56 ►

in the side chain out to an alpha-ethyl.

00:23:58 ►

That also knocked down its dopaminergic effects

00:24:00 ►

and made it more of a pure serotonin norepinephrine releaser.

00:24:04 ►

And I think the same thing happened there.

00:24:06 ►

It never got popular on the black market or in the illicit market because it didn’t give

00:24:10 ►

people euphoria, which is what they were looking for.

00:24:13 ►

But I think there, again, a number of people took massive doses trying to get an effect

00:24:17 ►

like MDMA and overdosed.

00:24:20 ►

So that was really a problem.

00:24:21 ►

And the N-Bone thing was really the biggest disaster because I don’t know how many people died after taking these N-Bones

00:24:27 ►

because generally people have thought that psychedelics are not toxic.

00:24:30 ►

The LSD has never killed anybody.

00:24:32 ►

Psilocybin has never killed anybody at reasonable doses.

00:24:35 ►

And so when that came out and people started having lethality, that was really –

00:24:42 ►

and we didn’t discover them, but we thought, why are these

00:24:45 ►

compounds so active?

00:24:46 ►

Because normally, if you take something like 2C-B, if you put an N-methyl on it, make an

00:24:52 ►

N-methyl-2C-B, it loses its activity.

00:24:54 ►

And if you extend it to N-ethyl or N-propyl, it loses activity.

00:24:57 ►

But if you put a BN-benzyl on there, then you have 2,5-B-envol, and that’s a super potent

00:25:03 ►

compound.

00:25:08 ►

So we were puzzled, like, how is this possible?

00:25:14 ►

What’s happening? So what we did was make mutations in the receptor and discovered that that enbenzo was probably interacting with a particular phenylalanine residue that was in the receptor.

00:25:18 ►

So we were using it as a tool to understand the topography of the receptor, never imagining that

00:25:24 ►

it would get out on the street

00:25:25 ►

and people would start taking the stuff

00:25:27 ►

and it would be so toxic that people would die.

00:25:29 ►

So it bothers me that that happens.

00:25:34 ►

When the first article came out,

00:25:36 ►

a lot of people wrote me emails and said,

00:25:38 ►

you know, you can’t control what people do.

00:25:40 ►

People just do anything, you know.

00:25:42 ►

I mean, you’re just following science.

00:25:44 ►

And other people say, why did you publish that? Well, you know i mean you’re just following science and other people

00:25:45 ►

say why did you publish that well you know you publish your results you know it’s it’s like

00:25:50 ►

huffman and his synthetic thc can have a memetics is jwh things i mean i talked to him about that

00:25:57 ►

and he said he just never imagined he was really upset people were doing that um so you know this

00:26:03 ►

was this was really facilitated or even enabled by the internet. Before then,

00:26:08 ►

people would have to go to libraries and look up the journals and say, oh, you know, what’s

00:26:12 ►

Nicholson or what are the synthetic and abomimetics or whatever. It’s so easy now with the internet

00:26:17 ►

and online access to journals and things and social media that it’s just really allowed these

00:26:22 ►

things to proliferate. I think most of the things we’ve made that could be problematic have probably

00:26:27 ►

already been out there and tested.

00:26:29 ►

So we’re not making any new molecules.

00:26:32 ►

But it kind of upset me for a while.

00:26:37 ►

I just don’t know how to react.

00:26:40 ►

People can say, well, it’s not your fault.

00:26:43 ►

And I know that.

00:26:44 ►

And people take anything you high.

00:26:46 ►

Some people will have, you know, paint thinner and butane and so forth.

00:26:49 ►

But still, it’s you just wish they hadn’t just wish they hadn’t done it.

00:26:55 ►

But, you know, I don’t feel like there’s anything I could have done.

00:26:58 ►

Yeah, the research must continue.

00:27:01 ►

And actually, that was the last thing I wanted to ask about is, speaking of the research

00:27:07 ►

and as the founding president of Hefter, what’s the stuff coming up with Hefter that’s the most

00:27:13 ►

exciting for you? Well, Hefter, we’re a research institute and we’ve pioneered trying to discover

00:27:20 ►

the uses for these in therapy. There is a not-for-profit in Madison, Wisconsin called

00:27:25 ►

USONA, which is now doing the phase three pivotal clinical trials for psilocybin in depression.

00:27:33 ►

We have a larger study now underway for psilocybin-assisted therapy and alcoholism.

00:27:40 ►

We did the small pilot study of just, I think, 10 patients, and it looked very promising.

00:27:46 ►

So Michael Bogachews and Steve Ross at Newark University are doing a much larger study, I think 90 patients, and maybe 90 controls.

00:27:53 ►

But looking at it and treating alcoholism, we have a larger study now.

00:27:59 ►

Matt Johnson did, I think, a 12-patient study with nicotine addiction.

00:28:03 ►

People that had made four attempts to quit smoking and had failed,

00:28:06 ►

showed that 80% of them quit initially.

00:28:08 ►

And I think in long-term follow-up, 60% or 65% still were not smoking.

00:28:12 ►

So that’s pretty amazing.

00:28:13 ►

Those Chantix only gives you maybe 35% after they can quit.

00:28:18 ►

Peter Hendricks at University of Alabama has got a study underway

00:28:21 ►

to treat 40 hardcore cocaine addicts with psilocybin-assisted therapy.

00:28:27 ►

That’s about, I think, about halfway finished now.

00:28:31 ►

So that will be really interesting to see.

00:28:33 ►

We’re just starting a small study of psilocybin therapy in obsessive-compulsive disorder.

00:28:39 ►

And also we’re doing a small study in psilocybin in cluster headaches.

00:28:45 ►

And we’ve got some interest now, if we can get the funding,

00:28:49 ►

I really want to see a study of psilocybin therapy in eating disorders.

00:28:53 ►

Anorexia specifically is one of the most lethal psychiatric disorders.

00:28:57 ►

More people die of that than any other psychiatric disorder.

00:29:01 ►

And it’s very difficult to treat.

00:29:08 ►

So, and I’ve always thought, Mark Geyer,

00:29:14 ►

another board member, and Franz Wollinger, we all thought that psilocybin therapy would be a great thing for eating disorders. So I’m hoping we can get the money to do that. And we also got some

00:29:19 ►

interest in trying to see, since we’re looking at alcohol, nicotine, and cocaine, would it work in opioids?

00:29:25 ►

If we get, you know, hardcore heroin opioid addicts, could we, at least the ones that want to stop,

00:29:33 ►

could we help get them off of that addiction?

00:29:35 ►

So those are the really exciting things.

00:29:37 ►

And my biggest concern now, again, it’s all privately funded.

00:29:40 ►

So finding the funders, because a lot of the funding now is being sucked up by the

00:29:45 ►

phase three studies, because that’s going to cost $15 mi ll i o n or$ 20 million. So I’m hoping we can

00:29:53 ►

keep funding going for Hefter so we can continue to explore new avenues for these treatments. And

00:29:58 ►

if we demonstrate in pilot studies, then there may be other groups, maybe Sona and other people

00:30:02 ►

that will pick it up and say, okay, this looks like alcoholism.

00:30:05 ►

This looks really cool.

00:30:06 ►

Let’s set up a big study and start treating alcoholics.

00:30:09 ►

So I think it’s a really exciting time.

00:30:11 ►

We’ve got European people doing it now.

00:30:14 ►

You know, David Nutt and Robin Cart Harris at Imperial College are looking at treating depression.

00:30:21 ►

A lot of brain imaging stuff now.

00:30:23 ►

We’re really starting to learn how these things work in the brain.

00:30:26 ►

And I think we’re going to, the ultimate result is we’re going to find a lot more about how

00:30:29 ►

the brain works, period.

00:30:30 ►

What causes these disorders, psychiatric disorders?

00:30:33 ►

What’s happened to brain connectivity when people become addicted to various things?

00:30:37 ►

So I think it’s a really exciting time.

00:30:39 ►

And I’ve written an article saying that psychedelics as medicines represents a new paradigm for

00:30:44 ►

psychiatry.

00:30:45 ►

So I feel pretty confident that’s going to be the case and we’ll watch over the next decade what

00:30:50 ►

happens. That’s great. So if anyone out there and listeners with deep pockets or even shallow

00:30:56 ►

pockets, Hefter is a place to send your funds. So Dr. Nichols, thank you so much for your work

00:31:01 ►

and taking the time to share with us today. My pleasure. Have a good day.

00:31:12 ►

This is a non-nonsense production.

00:31:15 ►

If you like what you hear and want to help us make the Salon 2.0 bigger and better,

⚗️ alembic

Explorer

034 - Psychedelic Chemistry

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