The Ayahuasca Hoasca Project

Okay, so this afternoon we're going to be, this section is going to be about ayahuasca and part of the session will be about this new study that the field phase, the first phase of which has just been completed that was sponsored by Botanical Dimensions which is a nonprofit foundation that I'm affiliated with in some way.

So I guess this is my opportunity to put a plug in for it. As usual I don't have enough material but I brought these. These are flyers tell you where you can find out more information. There's only a few of them but if you want to find out more about Botanical Dimensions and what it does and what it's trying to do, you can write to them at PO Box 807.

Occidental California, 95465 and you know it publishes a newsletter rather sporadically but occasionally and basically what the function of Botanical Dimensions is is to foster the investigation of ethnomedical plants, the preservation of ethnomedical plants, not only psychedelic ones but all plants that might have potential uses in medicine.

But then we are sort of biased toward the psychological. And this ayahuasca project that was just completed is something that we managed to find, you know, using Botanical Dimensions nonprofit status as a platform, we managed to actually find investors, donate, people who gave charitable donations,

who take a personal interest in seeing this work go forward. So we were able to carry off this study. We want to be able to do more of that sort of thing in the future and if so, if we're going to be able to do it, we need your support.

So anything that, you know, I mean, in doing this project, we've proven one thing, you don't need government support to do research on psychedelics. I mean, there are other venues.

If you feel that this work is important, alternative ways can be found. And actually our hope for this study is that the results will be solid enough and significant enough that they can be published in a peer reviewed journal with a fairly high profile or maybe a number of such peer reviewed papers will appear.

That's our hope. And that as a result, the medical and psychiatric community will have to sit up and take notice and at least acknowledge that there is something here worth further investigations. So that's the strategy.

We don't know what the results of the study are. We don't know what the results of the study are. We have some expectations. I don't have any results to show you yet.

Uh, just that we've only completed the field phase and now the analytical work, the biochemical work and so on, which I will describe, uh, what we are going to measure, uh, remains to be done.

Our samples of plasma and plant samples and so on are all sitting in freezers and various universities across the country. Um, but anyway, that is the thrust of the study and we want to be able to do more similar things like that.

So if you're interested, please pick one of these up. If you know of a, an angel who would like to endow us so that we can, so that our main activity becomes doing research instead of trying to find funds to do research.

Uh, we'd much appreciate that because, uh, what we want to do is research. Um, so I'll just, uh, I don't know if you can pass them around.

The other thing I wanted to mention to you in this context is that some of you may already have heard there's, there's a new initiative going on.

Uh, we just keep trying to find a way to do this kind of work and the newest thing, the newest twitch or twist on this is that

some of us have gotten together informed or we are in the process of incorporating right now, I should say, another, yet another nonprofit foundation called the Hefter Research Institute.

And those of you who have sat in on, uh, some of the talks here probably know who Arthur Hefter was.

Uh, and that probably sets you aside from, uh, 90% of the other people even who express a specific interest in psychedelics.

Arthur Hefter, of course, was the German pharmacologist and chemist who first isolated mescaline from the peyote cactus

and ascertained that it was the, that it was the active principle through self-experimentation.

Um, we chose his name because we feel that he exemplifies the, the scientific spirit in which, um, these agents and these plants should be investigated.

You know, proceeding carefully and methodically but not afraid to, you know, confirm it using, uh, the best receptor,

the best measuring instrument of all, which is your own, your own mind.

At any rate, the purpose of the Hefter Research Institute, if it ever gets going,

and as I say, it is in the process of being incorporated, is to carry out research on psychedelics.

Um, but mainstream, no shit, good FDA, DEA approved scientific research protocols, uh, on these agents.

And, uh, their therapeutic potential and their metaphysical potential.

It's, what it really is, and this is kind of the subversive part, is that it's a program to investigate the mind.

Um, the psychedelics are the molecular probes that we can utilize to increase our understanding of the mind.

And that's the, the purpose of the Hefter Research Institute, is to carry out, you know, both clinical and preclinical work.

In other words, animal studies, uh, chemical studies, structure activity investigations,

the whole gamut of work that, you know, the good work that needs, needs to be done, and should continue to be done, on these compounds.

Um, the people who are forming it are, uh, David Nichols, who is a, uh, he's the, really the original founder.

He's the, uh, professor of, uh, medicinal chemistry and pharmacology at Purdue, and probably the leading, uh, mainstream researcher on, uh, the pharmacology and chemistry of these compounds.

Rick Strassman, who many of you know, he already has FDA approval to work with DMT in humans.

He's also on the board.

Charles Grobe, who was, uh, has, uh, secured FDA approval to work with MDMA, uh, in humans,

and also was the co-investigator on this, uh, WASCA project in Brazil.

He's a psychiatrist at UC Irvine.

Uh, other members, uh, Philip Wolfson, who is a psychoanalyst, who has worked for many years with MDMA, used it successfully in therapy.

Um, Mark Geyer, who's a behavioral pharmacologist at UC San Diego.

So, the personnel are there, and myself, and I, you know, pretty much what my background is in ethno-pharmacology.

But the pert, the people are there.

What we need now is the tools and the, and the resources to be able to do it.

I only have one copy of the Hefter Research Institute prospectus.

I gave some others away.

Uh, any one of you who wants one can, can, uh, write to me, or whatever, and I'll see that you get one, if you're interested.

Um, sorry for the protracted commercial interview.

Let me see.

Anyway, this WASCA project, I guess what I'm gonna do is talk first a little bit about, go at it in a kind of a chronological way.

And, uh, talk first a little bit about how I got involved in all this.

Um, well, it goes back a long way.

I don't want to tell you my whole life story, but in a nutshell, when I was a graduate student at, uh, the University of British Columbia, I had, had a long time interest in, in these plants and these types of compounds.

So my supervisor, uh, Neil Towers called me in and asked me if I wanted to go to Peru for six months to collect plants.

He had some extra money in one of his grants.

I basically dropped what I was doing and said that my bags were packed.

So, uh, I am another graduate student, went to Peru and the, the, among other things, the problem that I chose to investigate, uh, was an investigation, a chemical and pharmacological and ethno-pharmacological investigation of ayahuasca.

And a, a, a comparison of that with a similar substance, a similar orally active, uh, tryptamine hallucinogen from Varola called, uh, Ukue, uh, which Professor Schultes had written about around 1970, around 1970.

He had first brought to the world's attention around 1970.

I'm not going to talk about the Varola work very much at all.

I'm going to concentrate on the ayahuasca work and just give you a quick recap.

But to make the story more interesting, my, one of my fundamental questions was,

these were both tryptamine-based drugs, DMT or 5-methoxy-DMT, and they were both orally active.

The thinking had been in the ethno-pharmacological literature for many years that the mechanism behind this was that the beta-carbolene alkaloids from the ayahuasca-inhibited monoamine oxidase peripherally,

and allowed the DMT, which is normally not orally active, rendered it orally active by protecting it from degradation before it could be, so it could be absorbed and enter the nervous system intact.

So, that was accepted in the, in the literature, but not really proven.

Nobody had actually done any work to show that, in fact, ayahuasca was an MAO inhibitor.

So, that seemed like a trivial question, and a kind of interesting question.

The other thing that then there, there'd been no quantitative chemical work done on it.

Or, only one previous paper, Riviere and Lindgren's paper, 1972.

And that was pretty much what was out there.

The other aspect is the varola, the orally active varola preparations were completely unstudied.

And I thought interesting from the standpoint of, here's a completely taxonomically different group.

Varola is not that related to Banisteriopsis or Socotria, but a similar chemistry and a similar postulated pharmacological mechanism.

The only difference being that in the case of the varolas, the tryptamines were the predominant alkaloid with traces or much smaller amounts of beta-carbolenes.

And, in ayahuasca, the ratio was reversed.

It was, you know, predominantly beta-carbolenes with the tryptamine admixture being the critical determinant of whether you were to get visionary activity.

So, my question became, you know, do these two work by a similar mechanism?

Is MAO inhibition also responsible for the action of the varola preparations?

And, as I say, I'm not going to go into that, but just to summarize what I found, the results were unexpected in that many of the Okuhei samples that I analyzed, I couldn't detect any beta-carbolenes in.

And, those that did, which were only about two of approximately five or seven samples I analyzed, had only traces of beta-carbolenes.

Moreover, when I screened them in the MAO assay, they were poor to midline MAO inhibitors.

And, when I extracted the tryptamines out of them, they essentially lost that MAO inhibiting activity.

So, I concluded that with the varola, the MAO inhibition didn't really or probably wouldn't explain the mechanism of action.

Of course, the other thing is they weren't always active.

There was quite a bit of chemical variation.

So, it's a chemical mishmash.

I found with ayahuasca, it was rather a more straightforward story.

The pharmacology of the Okuhei compounds really does need to be investigated somewhat further.

You know, there's a lot of work to be done.

I might also mention that my colleague, Don McCray, who traveled with me in South America,

and was the other graduate student sent, decided to do his work on the arrow poison qualities of varola,

and succeeded in extracting a fraction which was not the tryptamines, which was actually a lignan fraction

that showed a much more pronounced effect on the central nervous system of small animals,

mice I think he was using, than the tryptamine fraction.

So, for what it's worth, he concluded that the arrow poison action of the varolas was probably due to this lignan fraction.

So, you know, there's more to the psychopharmacology of varola, I think, than is explained by the tryptamines.

But as I say, with ayahuasca, the situation was somewhat more straightforward.

This, of course, is stanisteriopsis copy, which is the source of the beta-carbolines,

and it's the chief source of ayahuasca in the Amazon basin.

And, again, the chief source of the tryptamine alkaloids...

Can you stand a little bit?

Oh, sure, sorry.

...is cicotria viridis, which is shown here.

This is probably used over 80% of the basin.

One of the features of cicotria viridis, the distinguishing characteristic,

are these little spines on the other side of the leaf,

which that is kind of a signature for cicotria viridis,

although other cicotrius have those structures as well.

But these are meristematic zones, it turns out.

I was told and swallowed for many years the notion that they were dolmatia,

which is a structure that an ant or a parasite lives in, I believe.

Dr. Schultes can correct me if I'm wrong.

But there's no ant that can live in there.

They're really pretty small.

And they do, they are growing pigs.

Now, this, unfortunately, is upside down.

But this is the other major admixture plant that's used in Colombia and Ecuador.

This is Diplopterus cabarena,

formerly known as Banisteriopsis fusbiana.

And it is in the same family as Banisteriopsis,

as Jonathan Ott has already made clear to you.

But it is an alternate source of DMT in some parts of the Northwest Amazon.

Well, basically, making the ayahuasca.

This is all done in Peru.

Gee, I didn't have it two together when I took these slides.

These slides were taken by Luis Eduardo Luna.

And this is Don Emilio, one of the curanderos that he studied.

After the bark is stripped off, it's boiled in a pot together with the leaves.

And then, after a couple of boilings, the liquid is drained off and combined,

and then driven down to a smaller concentration.

Here he's, there he was singing an ikaro and blowing tobacco into the ayahuasca pot,

making an application.

And tobacco is almost always constantly used in ayahuasca ceremonies in the mestizo,

among the mestizo class in the Peruvian Amazon.

This is a pipe made from a jungle tree, tawari, which is one of the plant teachers.

And part of the technology of using ayahuasca in Peru has much to do with using ayahuasca

in conjunction with other atmosphere plants.

The shaman uses it as a technology to learn about these other plants,

and which they refer to as the plant teachers.

And, you know, they claim through this, this is how they understand what they're good for,

and how, you know, what the biodynamic applications of these things are.

That's just the pipe.

Christian elements often are prominent in the mestizo use of ayahuasca.

And usually the sessions are, are always, uh, group sessions.

They're always, it's night.

And, uh, you know, one or more ayahuascaros, or, or curing paillés,

is probably the best curing for me, is, is in charge.

And, uh, they guide the session, they dole out the material,

and, and chant, and blow tobacco smoke, and, and do their curing.

And, uh, this is a painting by Pablo Amarengo.

Many of you know the Peruvian painter that Luis Eduardo Luna has studied with.

And he, his recollection of his ayahuasca visions,

and his depiction of them in these paintings,

have really sort of opened up the world of Amazonian mythology

to the study of anthropologists, and so on.

All of these visionary paintings have symbolic elements

that have a coherent meaning,

and they all fit into the, uh, mythology of, of ayahuasca and the Amazon.

Um, but in this visionary state,

um, the ayahuasca can divine, uh,

and find the causes of illness,

and, and determine which plants to use to cure illness,

or apply other magical means to cure illness,

such as songs blowing tobacco smoke.

The phlegm is another prominent element in the Peruvian, uh, ayahuasca, uh, cosmology, mythology.

The phlegm is understood to be a magical substance produced within the chest,

within the body that the ayahuasca can summon.

It's a power substance.

He can summon it in the process of curing,

and he can use it to either cause harm or to cure,

depending on his, whether he's a lujo or not.

And again, I think that the constant smoking

has got something to do with the production of this phlegm.

In fact, I'm sure that it does.

Which is not to say that it's not real.

I mean, this is, this is a whole, uh, very interesting, uh, question about physiology.

And, and, you know, one of the things I should say,

one of the things that prompted my interest, uh, in this,

in doing this whole study in Brazil, this whole biomedical study,

even back in 1981 when we were doing this work,

I thought, you know, these people really deliberately put themselves

in a very strange place physiologically.

You know, they, they follow a most peculiar diet,

they smoke constantly, um, they take ayahuasca often,

often, often several times a week, sometimes for days in a row.

Um, they don't sleep much.

Uh, they work extremely hard.

Um, and they're as healthy as horses.

You know, and, uh, you know, mentally and physically.

And I thought, this is, this is similar to yoga in some ways.

I mean, it's, it's a, really, it's a physical, uh, uh, hardening of the body.

And, and so, you know, the question naturally arose,

is there something measurable?

What do you measure, you know?

Well, ten years later, we muddled, you know, we passed something together,

and, and we're not investigating, you know, the, what,

what, if there is a magical or, or, uh,

samadhi-type psychophysiology here, we're not to that point yet.

What we're, what we're doing with this study,

this recent study, is to try to get some data points, that's all.

Just accumulate some information.

There's no information now, so anything that you get is worthwhile.

Even if it's pretty ho-hum, which it may not be.

Um, anyway, curing in, in, uh, South America, in, in Peru,

is a big, probably the chief reason for having these sessions.

And the, the, uh, Ayahuasquera will use the phlegm and suck out the offending,

the object which causes disease, sometimes called a virote,

is conceived as a, a dart-like or a, a thorn-like thing

that's been put into the person by another, by a brujo.

And the, and the Ayahuasquera can use his phlegm and his power to take that out.

And this is, you know, this is classic shamanism.

This comes up again and again.

He'll also make passes over the person's body.

You know, using his hands or sometimes rattles made out of certain kinds of plants.

And he will use medicinal plants as well,

sometimes making poultices out of them, other times making a tea,

other times adding them to Ayahuasca and assisting that the person bring the Ayahuasca.

This is a depiction by Pablo Armarengo of some of the plant teachers.

Uh, the plant teachers tend to be tall trees, very strong trees,

with a lot of alkaloids in the bark.

There is probably, oh, there's probably a pantheon of maybe 25 or 30 or so plant teachers,

admixtures that are more or less regularly used.

And there's probably upwards of a hundred that are occasionally used.

Um, unexplored physiology.

A lot of alkaloids in this group.

Um, tryptamines and beta-carbolines are the active principles, of course, of the Ayahuasca.

So, the question was, um, there were basically two objectives with the Ayahuasca.

One was to measure the MAO activity, the MAO inhibitory activity,

of the different Ayahuasca brews.

This is, uh, number two, measure the activity of the drugs as MAO inhibitors

and determine which constituents are mainly responsible for the MAO inhibitory activity.

Is there synergistic activity?

Does the same mechanism account for the oral activity of the Varola and the Ayahuasca?

I mean, I already said we didn't cure two.

Um, the first one was to identify and quantify the active constituents

in the drug preparations and in the source plants.

Look for differences between the two, if any.

In other words, how much did the process of cooking and concentrating and all that,

did it change the chemistry from the source plants significantly?

Uh, and did the drug preparations contain physiologically active levels of alkaloids?

Knowing what we know about what kind of doses are required to really get an effect,

does the typical dose taken by a Mestizo in this context,

is it equivalent to that or are they kidding themselves or is it an overdose or what?

We have no information.

So I used different, uh, techniques to quantify, isolate and quantify the alkaloids,

among which was HPLC, high-pressure liquid chromatography,

and this just shows the Aleutian diagram.

I also used Harmol, Harmine was the main beta-carboline, followed by tetrahydroharmine,

followed by Harmeline.

Harmeline in Bansteriopsis is basically a trace constituent.

Tetrahydroharmine is much more abundant.

In Paganum, it's the main constituent, I believe, and dimethyltryptamine.

I also used a thin layer chromatography, two-dimensional thin layer chromatography,

which is very easy to do and a very good way to get a quick qualitative idea of what's in the, uh,

what's in the ayahuasca bruise.

This just shows a thin layer chromatogram of beta-carboline under UV light.

The beta-carbolines are nice and fluorescent, so when you shine a UV light on them,

um, they be, they fluoresce.

This is, uh, this is Harmine and this is Harmeline,

or, uh, yeah, I believe this is Harmeline.

And then these are the standard.

So these are different bruises.

Those are easily picked up.

Okay, I looked at a number of different samples of ayahuasca

and compared their alkaloid content, uh, from different parts of, uh, of Peru.

And, uh, this is the Harmine, tetrahydroharmine, Harmeline, and DMT.

This is the number of, uh, milligrams per gram dry weight

and the percent of the total alkaloid fraction.

And, uh, basically what I found was, if you look at the total,

total alkaloid column over here, you see that there's a great deal of variation.

The total alkaloids range from 75.6 milligrams per gram dry weight to 29.1.

You know, so some are weak, some are strong.

This really should surprise no one.

Um, some had no DMT.

This one from Terrapoto that was low on the beta-carbolines had no DMT.

So they didn't use an admixture.

They didn't use the right admixture.

Not clear.

And then the levels of DMT also varied widely.

So, I guess this is the labor in the obvious, but at least we have numbers.

The, the, uh, you know, the obvious being that the composition of these brews varies a lot

between practitioners, uh, between different ayahuascaros.

You know, and again, I mean, it's hard to say.

There's no control for, you know, how they were stored, how old they were.

But then I also had the opportunity to form, uh, a friendship with, uh, these two gentlemen,

uh, Don Goodell, Monsambite, and his friend, his, his mentor and teacher, Don Jose.

And, and I was able to collect, uh, various batches of ayahuasca from, that these ayahuasca

was made, made at different times, but all came from the same source plants and all came

from the same garden, and made by the same two people.

And some was Don Fidells and some was Don, Don Wands.

I guess his name was Don Wong.

And, uh, when I looked at it that way, it turned out that there was quite a bit of consistency

between the alkaloid profiles of different batches, made by the same people, but at different times.

Here's five different samples.

Don one, number one, and number two. Don Fidell, number one, number two, and number three.

Um, and generally, um, they, they follow along pretty closely, uh, in that, you know,

harming is the main constituent, and, you know, it's about 66% of the total alkaloids.

You know, the lowest is 53%.

Tetrahydroharming, again, hovers right around 20 to 30% of the total alkaloids.

Harming, five to six percent.

Harmeline, I mean.

And DMT, you know, 10%, 7%.

but pretty consistent across the board.

So I found for a typical 100 milliliter dose

of this ayahuasca

coming from these two practitioners,

the average alkaloid content, if you look here

on the bottom row, I found basically there was 728 milligrams

of alkaloid total in a typical 100 milliliter

dose of these ayahuascas averaged out.

And 470 milligrams

of that was harmine, 160 milligrams

was tetrahydroharmine,

41 milligrams was harmoline, and 60

milligrams was DNP. So that

kind of answers the question in

this sense. There is enough DMT to

be above threshold. The threshold of DMT

when taken

paranderally, when smoked, for example,

is around 30.

So there's plenty of DMT to be above

threshold, and there's certainly enough

of beta-carbolines to

inhibit MAO,

but probably not enough of the beta-carbolines

to be doing much on their own

in terms of psychoactivity.

Harmine is

not that active.

Even up to a gram has been

reported inactive.

Similarly, the myelamin-oxidase activity

was, this is percent of MAO

inhibition, and this is

decreasing concentrations.

So obviously, undiluted

bruise, or just

you know, cleaned up bruise,

but undiluted,

give 100% inhibition.

Unless you start diluting them

by orders of magnitude, you don't really

get a significant reduction

in activity until you've gone to

about 10 to the minus 7.

So you've diluted it to a factor

of 10 million, and even at that point

it still inhibits, you know,

close to 50% of the ophthaloids.

So, or, of the

enzyme activity.

So it is a strong

MAO inhibitor.

I also looked at DMT

and Harmine and Harmeline mixtures

of the pure compounds.

Ayahuasca analogs, if you will,

were present in either

equimolar concentration

or the same concentration

as I found in the ayahuasca.

Basically, the take-home lesson is

there was no synergistic effect.

They didn't seem to,

they were additive,

but not synchronistic.

So, the conclusion is,

acuconscriptors of ayahuasca,

the major alkaloids

detected were Harmine,

Tetrahydr, Harmine, DMT,

and Harmeline in that order.

And a typical 100 mil dose

contains about 730 milligrams

total of alkaloids,

which 65% is Harmine,

22% is Tetrahydroharmin,

8% is DMT,

and 5% is Harmeline.

And a typical dose contains

between 20 and 70 milligrams of DMT,

which is a physiologically active concentration,

and sufficient concentrations

of beta-carbolines to inhibit MAO,

but not enough to be

hallucinogenically active themselves.

And as I already said,

well, I did do,

the only thing I didn't mention here,

I mean, ayahuasca bruises were highly active

as MAO inhibitors.

This should surprise no one.

The SAR studies of the beta-carbolines,

I looked at some different beta-carboline derivatives

and found that Harmine was the most active

of the three main constituents,

so more active than Harmeline or Tetrahydroharmin,

as a monoaminoxidase inhibitor.

And again, I found no evidence of synergistic action.

Okay, so that's what I did in 71,

and that was part of my thesis work.

So now we can flash forward to 1993.

Or actually, we can flash forward to 1991.

And in 1991, I was invited to attend a conference in Sao Paulo.

Put on by an organization called the Oudave,

a Brazilian organization

that is basically a syncretic church,

an ayahuasca cult,

that in Brazil,

where ayahuasca is known either as wasca,

or the vegetal,

or sometimes just the tea,

the cha.

An interesting phenomenon has occurred,

which is there has developed the appearance

of these syncretic religious movements.

These are not who use ayahuasca ritually

in their ceremonies.

And they have a complex doctrine.

They're very moral,

and it's basically,

it's kind of like a fundamentalist Christian cult,

only without the emphasis on the Christian elements.

Their thing is about the tea,

and about the, really on the metaphysical level,

about the plant-human alliance, I think.

I mean, it's very ecologically oriented,

and it's very ethically oriented.

And, but what's interesting is that the members

are largely not mestizo.

There is a big mestizo or caboclo component,

as it's called in Brazil,

but also there are many middle-class members,

and many professionals,

including doctors, psychiatrists, scientists,

people like that.

So, this conference was hosted by a subsection of the UDV

that was assigned for medical studies,

and they hosted this conference,

the first international conference on the tea,

and they invited a number of people

to give talks at this conference,

and then they invited me because of my previous work.

So I went down, and I gave a talk.

I spent a very pleasant couple of days with them,

and I brought up this idea

of doing a biomedical study of ayahuasca,

which Eduardo Luna and I had written up in 1985

after we'd come back from Peru,

but, you know, couldn't get anyone to listen, really,

and didn't really press it.

But I brought it up to them,

and they said, well, that's great.

That's what we want to do.

So, it turns out that,

so we decided to, you know, collaborate,

and I suggested that we try to get funding

through botanical dimensions.

So I went back and wrote a proposal.

Originally, we were going to submit a grant to NIDA,

the National Institute on Drug Abuse,

try and get a government research grant to do this.

Well, the more I wrote into this proposal,

the more I worked on it, the more I realized it'll never fly.

So I thought, well, why don't we just try and find some wealthy contributors,

or semi-wealthy contributors, and get it going that way.

So we sort of used the connections we've made through botanical dimensions.

There are people who have supported and have given substantial gifts,

and so we contacted these people, and it actually was pretty easy.

They were happy to help.

And so, as a result, we were able to collect $75,000,

primarily from three main donors,

who I won't mention, but I would like to acknowledge their help.

Without them, this couldn't be done.

But I'm not going to say their names.

I'm sure lots of you know who they are.

At any rate, we were able to get this money.

Now, had we done this in the States,

and as it became clear as we were doing the study down there,

this work, the work that we were able to accomplish for $75,000,

would have taken two years,

and cost probably half a million to a million dollars.

But because we had all this cooperation from the UDV down there,

and because we were enthusiasts,

we were able to get a lot of things done for much less,

much more than I ever dared hope we would be able to do.

So, we got this money, and the field phase of this,

this took about two years.

So, two years later, it's now 1993,

and we got the money together, the financing together,

the previous fall, basically.

So, in June and July, Charlie Grobe and I,

and Jace Calloway from the University of Cupio in Finland,

Charlie Grobe is from Irvine,

Annalise Shinsinger, who's a member of the UDV,

and who acted as our translator and guide,

and has been just tremendous with everything she's done,

went down there, and we met with our Brazilian colleagues,

primarily Glaucus de Souza Brito, who's the head of the medical studies section of the UDV,

and was the medical coordinator on the Brazilian side.

So, we went down, we all traveled to Manaus.

Manaus is the largest city on the Amazon,

and it's a center of concentration of the UDV.

There's early, some of the oldest temples are there.

UDV's been around, you know, 30 years or so.

But some of the oldest temples are there.

So, we went to Manaus, there were plenty of volunteers,

people were really eager to be involved in this study.

I mean, such enthusiasm, you know.

So, we went there, and we carried out this study.

And if I had an overhead projector, I would use it, but I don't.

So, I will just summarize what the initial objectives of this study were.

First of all, we wanted to measure physiological effects,

you know, whatever we could measure.

This is a data gathering study, you know.

So, we don't know exactly what the results will be.

Any information is new information.

So, that was sort of the spirit in which we approached this.

We were interested, first of all, in long-term effects that might be measurable.

Many of these people take ayahuasca regularly on an average of once a week,

sometimes several times a week for years, most of their adult life.

They appear to suffer no ill effects.

They appear to be extremely healthy people.

Many of the older ones, you know, are now pushing 80.

And I can tell you, if I'm in that shape when I'm 80, I'll be real happy.

But, again, you know, without making judgments whether this was good or bad,

our question was, are there long-term effects?

Can you discern a biochemical marker of some sort in the people that take the stuff,

versus a similarly matched control group where people don't take it,

and otherwise a similar matched group?

So, we focused in on blood platelets as a good model in psychopharmacology,

in the psychopharmacology of depression, for example.

Blood platelets, in some ways, are considered a peripheral model of this central serotonin system.

Blood platelets have serotonin receptors on them.

Many of the same receptors are similar to those that are found in the central nervous system serotonin system.

Treatment with antidepressants, psychiatric medication will cause these platelet receptors

to up and down regulate to vary in numbers over time as you tweak them with various serotonin agents.

Platelets also have monoamine oxidase, so you can get a handle on that.

So, we decided to look at platelets because, you know,

there's some controversy as to whether it's really a true reflection of the central nervous system,

but it's a peripheral handle.

You know, and you can't really ask these people to donate their brains.

So, what we want to do, we took plasma samples from 15 subjects, volunteers,

who had all drunk ayahuasca at least 10 years,

and we had a similarly matched control group, age and sex matched.

The work was all men, initially.

Apologies to the women, but that's the next phase.

We thought, just to keep things simple, we'd hold to one sex in this initial study.

And we took platelet samples from a group of 15 matched controls,

or actually I think we ended up with 13 controls.

And Jace Calloway at the University of Tupio is going to do the platelet receptor binding and the MAO assays.

He has techniques set up to do this.

The two receptors that we want to look at, serotonin receptors, are the 5-HT2 receptors,

which we'll use cutanserin and tritiated cutanserin, radioactive 5-HT2 antagonist,

and iodine-125 labeled DOI, which is a psychotomimetic phenethylamine,

or a hallucinant, psychedelic phenethylamine.

And both of these label the 5-HT2 receptors.

So we're going to look at that to see if we can determine any modulation, basically,

in the density of the receptors, either the affinity of the receptors for different substrates,

or the overall density, the so-called B max of the receptors.

We're also going to look at the 5-HT transporter molecule, the 5-HT carrier,

which is also found on the platelets,

which can be labeled with a compound called citalopram,

or sometimes they use another one called paroxetine.

These are selective serotonin uptake blockers.

These are the receptors that are on the platelets,

and these are the ones that you would expect the ayahuasca to modulate.

I mean, these are the ones that they, in terms of what we know about its pharmacology,

that should be what it modulates.

We also measured any other acute,

the other aspect of the physiological study was acute effects.

Physiological responses, obvious ones, heart rate, blood pressure,

body temperature, pupillary diameter.

In other words, this is when we gave ayahuasca to,

we took the same group of 15 subjects.

We had them come in, in pairs or groups of three, actually, mostly,

and they all got dosed with ayahuasca.

And then, at different time points, we measured these physiological parameters

for a period of about up to 24 hours following the administration.

We also did, the other two things we did in the acute study, or will do,

is pharmacokinetics.

We drew blood samples at different times after the administration,

and put those on dry ice, spun the things down in a centrifuge,

and collected the plasma, froze those on dry ice,

and those are going to be analyzed for DMT and harming,

possibly other metabolites, but those two,

by Kim Fall at the UCLA Medical Center.

The other aspect of the acute study was a neuroendocrine challenge.

We also took aliquots of plasma samples and froze those,

and we're going to look at different hormone levels.

We're using this as a variation on the so-called tryptophan challenge test.

You can give tryptophan intravenously to challenge your serotonergic system,

while we're giving, instead of tryptophan, we're giving ayahuasca,

and we're looking for a hormonal response in hormones like prolactin, ACTH, cortisol,

and I believe we're also going to look at beta endorphins.

So that's the physiological aspect.

The psychological study was that basically two.

We used different psychological instruments, different questionnaires,

different screening scales.

One was the hallucinogen rating scale,

which Rick Strassman developed with his DMT work.

It's a questionnaire which measures personality style, traits, and brain functions,

and results in a score called the TPQ, the trigeminal personality quotient.

You have to ask a psychiatrist what that is.

But that's, you know, it's an accepted test of these sorts of things.

The CD is another test, C-I-D-I.

This is a structured psychiatric diagnostic interview linked to the ICD-10

and used by the World Health Organization.

This is an international standard for diagnosing mental conditions, mental diseases.

We used the UCLA WHO auditory memory test,

which is a test that measures memory, concentration, attention span,

and short-term memory retrieval.

And again, these were just ways to get a handle on, you know,

how are these people functioning.

The second component of this psychological study was to do open-ended psychiatric interviews,

which Charlie Crowe largely did with Annalisa's self-translating,

which was basically just, you know, interviews with each person in the study up to two hours.

And, you know, very interesting results came out of that.

I'm sorry I'm losing my voice.

Okay, so all this, the field work was done, the stuff is in the freezer,

we feel very happy about the way the field phase went, but it's all in the future.

What I'm going to show you now is just some of the, well, part of this study,

in addition to the physiological work on the human subjects,

we're also doing phytochemical analysis.

We have to analyze the brews that we used.

One research brew was prepared for this study, and they put on a special preparo for us,

as they call it, a preparo.

And that's what I'm going to show you is this preparo.

And we collected samples of the brews, samples of the plants, dried, fresh, you name it.

And that, they all will also be analyzed for alkaloid content.

This will give us a handle on, when we guesstimated the dose,

we gave the subjects two milliliters per kilogram of the ayahuasca,

to standardize the dose in terms of people's body weight.

And, but what we don't have, the missing pieces,

we don't know what that's equivalent to in alkaloids,

because we haven't done the analysis yet.

But that will be done, and that will give us an idea of dose response.

This is just a, obviously, a drawing of the ministerial offices with the flowers.

This is from the UDB's conference in 91.

The study was done at the temple in Manaus, the main temple in Manaus,

is called Nucleo Kalpari.

Kalpari is one of the varieties of ayahuasca that they use.

They recognize two varieties, Tukunica and Kalpari.

Kalpari is thought to be stronger, have more force as they conceive it.

They conceive of the combination of two plants,

as the Banasereopsis supplies the force,

and the Chacruna supplies the light.

And the Kalpari, and the light, of course, is the visionary component.

But the Kalpari has a great deal of force,

and often has a purgative effect.

Tukunica is not quite so purgative in effect,

and often more light.

I quite prefer it.

But anyway, they prepare Kalpari,

and that's largely what they have there,

and that's the type of vine that they have.

So here is, this is Glaucus, Dr. D'Souza Brito,

drinking the juice.

They just cut the ayahuasca vine,

and he's, the water is flowing out of this vine,

and they, you know, it's a bit of jungle lore

that a lot of these lianas produce water that's good to drink if you cut them,

and it's pouring out of there, and he is just swallowing it.

Good water.

Interestingly, there's a couple of morphological variants on the dentistryopsis,

which I had never encountered in Peru.

Dr. Schultes, you might be interested in this.

These, these nodes, on the Kalpari, you often find these nodes at regular intervals.

And, you know, it's even more pronounced in the older stems.

And these are maristhematic nodes,

and the tecunicod does not have this.

And, have you ever seen anything like that, Professor Schultes?

I had never seen it in Peru,

but it's, and it's not clear whether it's a varietal thing or an environment thing or not.

And that was along the whole length?

It's along the whole length, yeah, but particularly the older stems.

I mean, they're just cutting it down. This is . . .

It's really not wrong here. . . .

This is a close-up of the stem.

And, you know, you can see the pattern of the xylem and plow.

And what's interesting about this are these concentric circles.

I don't know if you can see it, but it's actually, it looks a bit like a rose.

And the rose has a lot of symbolic significance in the Udavi.

And that's what the rose, which you see depicted in the iconography, is meant to represent.

Is that true, Ganga? Am I telling crazy stories here?

The thing about the rose?

But it's this.

They told me it was this pattern in the stem that that rose motif was really about.

Yeah.

This is Maestri Florencio.

He was the head of the Nucleo Calparee and a very accomplished Maestri and a real character.

And he was very kind to us the whole time.

We had a good time with him.

This is the Secotria.

Or no, this is the Maestria.

Now, the interesting thing, unlike Peru where, you know, it's a one pot kind of deal, this is done on an industrial scale.

You know, they made a small batch for the research.

I think it was only 50 or 75 liters.

Usually they make 500 to 1,000 liters at a time.

And these purpurros go on for days.

Round the clock.

Imagine what sanders can do with them.

Right.

They throw their own or forage it all from the bottom.

They gather it, they wash it, and then they get around these logs and take clubs and they beat it.

They beat the stem to a pulp.

I don't know how they do it.

I did it for 10 minutes and I had blisters for two weeks.

Yeah, it's a problem.

They're planting it as quickly as they can.

They have plantations going.

But yes, it's getting necessary to go deeper into the jungle all the time to get the wild stuff.

And they do have plantations going.

Fortunately, it grows quickly.

So I think it's not critical.

See, when you first beat it, it's white.

And then it oxidizes very quickly to reddish brown, some kind of phenolic.

Then they add the chacruna leaves and this.

They wash the leaves first.

Now normally they do it by kind of eyeballing it.

It's by the seat of the pants.

They don't use a scale or anything like that.

Normally we insisted that they use a scale this time so we could get some data on what it took to make so many leaders and so on.

The proportions about, you mean of chacruna to about 8 to 1 by weight.

I have to look at my notes.

It was 8 or 12 to 1.

I can't remember.

Oh, sorry.

So just loading it in.

Do they strip the bark off first before they beat it?

No, they don't.

They just take the stems and they beat those stems to a pulp, to a, you know, fibers like that.

They don't strip the bark.

Which also differs sometimes from the way they do it.

Have you ever seen them use any machinery like you would think they could use one of those rollers for sugarcane, for example?

Right, a chipper, that kind of thing.

Or those, they just have those, like a ringer on a washer for sugarcane to express the juice.

Do you think that would work well for crushing them?

I don't think they would do that.

Uh-huh.

They want to do it manually.

They consider that sacrilege.

Not sacrilege, but there's a thing about it.

It's important to interact, you know.

They're all drinking at the same time.

You know, you have to drink it while you're doing this.

And especially the people that are preparing it.

And there's a whole thing about being focused on what you're doing.

I mean, in a lot of ways, when you're doing a preparo, these things go on for days.

And there's like a party atmosphere, sort of.

It's like a festival.

But the people who are actually doing it are very serious and very focused on it.

Everybody else is having a great time.

They're in, they're, you know, focused.

And they have these, you know, so they boil it.

And boil it.

And they build, you know, they do five of these big pots at a time.

They put, you know, so this is, this is a big deal.

And you can imagine, I mean, it's the Amazon in the middle of the afternoon.

It's like it's already, you know, well into the 90s.

And then you're hanging around this.

They are made out of aluminum, I think.

Maybe stainless steel, but I doubt it.

Every temple.

There are 4,000, no, there's about 7,000 members in the Udave all across Brazil.

And there are about, how many, Gunga?

And we're gonna go.

So I guess we're gonna go in here.

So we're gonna go.

We're gonna go.

So I guess we're gonna go on this one, first of all.

Nothing.

If you're gonna go, bring the people off.

You're gonna go.

I'll go.

But I've got to go in here.

We're gonna go.

You know what?

We're gonna go.

We'll go.

OK.

We're gonna go.

50 temples? 100 now? Every temple can do this on some limited scale. Is that true? Often they do collaborate. Two temples will get together and collaborate. They have to have a place to prepare it. And they also plant the plants.

They don't have a corner on the market. No, there are other groups. There's the daime, which is just about as big. And they have a completely different ritual and so on. A lot more Christian elements and so on. And they prepare it as well. They call it the daime, not the vegetal. But yeah. And there are splitter groups of both the UDV and the daime.

So is it all legal because it's under the office of the church and religion?

Basically, yes. It's legal because it's a bona fide religion. And the government has looked at this and decided that this is not a problem. And why make a problem out of it? And it isn't a problem. Quite the contrary.

Yeah. I mean, it also helps that these people have a lot of connections. I mean, they're smart, you know. Many of them are government workers. They have a lot of professionals. And they understand politics. And they, you know, they're very intelligent, I think, in the way that they go about it.

They formulated and the government formulated a commission to investigate and bring them down. After several months of investigation, they convinced a guy who couldn't understand it unless he came up with you. So he drank it and became a member and turned down the whole investigating committee.

I said they were smart.

So here they got the final batches. They're draining it through cheesecloth. It looks just like coffee latte. I mean, it's about that color, actually, except it has this iridescent chain, which, of course, ayahuasca is famous for.

As shown there, the violet cycle fluid. Disembodied eyes, right. Checking the final preparo. You see, it looks just like coffee latte. It's kind of a brownish, white brown, not very viscous liquid.

So we collected bottles of ayahuasca. We collected source plants. The whole shot pickled in alcohol and also dried as well.

Do they boil it down just once or do they do a couple of extractions?

They do a couple of extractions. They combine them. This fellow here is Jose Cabral. He's a chemist at INPUB who's also involved in the phytochemical work. He's going to be doing some analysis.

This is IMPOS, this National Institute of Amazonian Research. There were about, altogether, about 20 people are involved, at least 20 people are involved in this project.

I'm happy to say that there's a nice balance between Americans and Brazilians and people from other countries as well.

I mean, this is not the Americans coming in and doing this work and taking credit. The Brazilians are, are, you know, involved in this, just as involved, if not more so than we are.

Do you ever use the leaves of the Banisterius?

They don't, as far as I know, not for making the ayahuasca. Although Schultes has reported that they do smoke Banisteriopsis. Sometimes, certain tribes Banisteriopsis is smoked.

The whole vine or the bar? The leaves, I believe. So that was the Preparo. And then we moved into the next phase. This is the window of the temple. This is the temple. It's circular and this skylight is in the center.

Notice the Banisteriopsis flowers and the chacruna leaves in the motif and the stars. You know, very nice temple.

And this is where we did the study. This is where they hold the collective sessions most of the time. And since we couldn't arrange for any particular clinical space and didn't really need one, we just set up in here with our centrifuges and sampling equipment and did the study in the temple.

We figured that the subjects would be, you know, most at home there because that's where they were used to drinking it. So every day, on the first day we were on one subject. And then as we got into the rhythm of the thing, we ran as many as four at a time.

And they would come in, you know, they'd get instructions on what to eat. They all underwent a medical screen initially. They went to the local hospital for that. They'd come in and then they'd get wired up and, you know, to the blood pressure devices.

And we'd do a catheter, essentially a heparin lock kind of thing so we could access the blood. And then they would get the ayahuasca and stay around. And we would collect samples of plasma at different time points.

At different time points. We also collected urine. We collected accumulated urine through the end of the day. And we also collected the first urination the next day after they woke up.

They were instructed to bring that back and they did. So a lot of plasma material was collected. This was our first subject, first day. And these people were so cooperative.

I mean, you know, they were really so happy to be in this study. It was considered a great honor. And this guy, you know, after the study went on about, he felt like he was a pioneer and he felt like, you know, just really increased his status in the UDV and made it, you know, he understood that he was making history.

Because a lot of what the study, I mean, it all fits in with their mythology and their prophecies. I mean, this is stuff that their founder, Mr. Gabriel, talked about many years before that this would, you know, this kind of thing would be done.

So, you know, these people are absolutely enthusiastic about doing it. So at periodic time intervals, we, here's some of the, here's Jace Callaway, Annalise, Charlie Grove, Glaucus, the doctor from the hospital in the analysis, maybe I forget at the moment.

You were taking extractions all during your trip? Absolutely. Sure.

It didn't bother them. Huh?

That, that, that didn't affect their space that they were in, or?

They weren't even, it didn't bother them a bit.

How are you feeling now? Huh?

How are you feeling now?

They drink the tea before they, the women all take it to give birth, and they go in for an operation, they drink the tea before they do in the hospital for an operation, and they have much better effect.

Did you have any speech today? Yeah.

Yeah.

He said, he, you have to go past the blank stage.

Is that, that's it? Yeah.

Go ten minutes.

Yeah, I mean, he just said, after all this, taking all this blood and poking and prodding the guy after the session, he said, how, you know, how was that for you and the trip?

And he said, the trip was all about giving myself, giving my body substance to the experiment, which, of course, exactly what was happening.

But, you know, I mean, he, he was into it. He wanted to do it. It was this whole, you know, mystical thing about the, I don't know, the word made flesh or something.

Do you remember wired during your trip?

Uh-huh.

EKG, this is another one of the physicians.

How many subjects were in the study?

Fifteen subjects in this acute study. There was no, there were no controls in the acute study. The, the, the fifteen subjects were their own controls.

When they came in, when they reported for the study, we took blood samples at thirty minutes before they drank, and at zero time when they drank.

So those were baseline samples to give us an idea of changes in these parameters. So that was, that was how we controlled.

The long-term study had two different groups, users and non-users. A lot of blood samples. A lot of, not the best conditions to do this under.

I mean, I would have worried about exposure to blood, but I feel like probably with the UDV, there's such a decent bunch of people, I doubt that they have any venereal diseases.

This is a small part of the research team and the, and the people of the Nucleo Capri that helped make our study successful.

A really fine bunch and we're grateful to all of them. Tremendously grateful.

And our hope is that we can justify their confidence in us. Because they're convinced that this is, you know, that this is going to make a difference.

And this will be their, in some way, foot in the door as far as getting approved in the United States.

They feel that they, and they want to do this and they have to do, present this kind of data to show that it's not harmful, it's not toxic.

Before they, anyone will even listen to them about the larger religious freedom issues involved here.

So, you know, as we said, they're helping us, they're helping us do work that we've wanted to do for many years.

And, uh, we're helping them, we're all part of each other's program.

Okay, that's it. Yeah, maybe we'll, we'll hold, we'll have minimal questions so John can get on with it.

I know I've gone on for a long time.

Could you describe their ceremony of the ritual? What goes on below the glass?

Maybe Ganga would be a better person to describe that.

He's more intimately familiar with the, uh, that aspect of it since he is a, you are a member, right?

In good standing.

More or less good standing.

Maybe you should describe that.

Yeah, they wait about an hour.

During that hour, there's music.

Sometimes some announcements and logistical kind of things.

And, uh, they very carefully select the music that's going to be okay.

And they, the, the mess streets are conducted.

They're called mess streets.

And that's in sessions.

Uh, very orchestrate sessions of music according to the effects.

And after about an hour, they, they start doing the effects.

They start doing magical chance to bring on the effects and stuff, right?

And, uh, then sessions are all, they've asked about three hours after that.

Uh, usually they start at eight and finish at midnight.

And most of them at night.

Uh, although they do some at time.

And, uh, the sessions can vary a lot.

Sometimes there's a lot of talking.

Sometimes people are sharing and asking questions about personal things, their life.

Um, spiritual, psychic, anything.

Yeah.

Sometimes the mess, the mess, the mess streets, some of the counselors are giving thoughts.

Inspiring thoughts.

Sometimes there's silence.

And then it finishes in the office that came around the temple to a three-fourth and one-year.

And the set streets that finishes at night by the one-year.

How many people might be in that?

In the bigger cities up in two-hundreds and, uh, anywhere from twenty to two-hundreds.

It's pretty amazing to think about it.

Two-hundred people are sitting in this room and all together.

And you can hear a pin drop in the room.

Another aspect, I just wanted to add something to what Gunga said.

You know, a marked contrast between the way the tea is used in Brazil and the way it's

used in Peru is that in Peru it's almost always about curing.

And it's about, you know, there's a medical aspect to the thing.

And in Brazil, although individually people will tell you that it's cured them of this or

that or they think it has healing properties.

There's no formal utilization of that within the UDV.

I mean, they don't consider it a medicine.

They consider it a spiritual thing.

And in fact, they're concerned not to medicalize it.

They're afraid if they medicalize it, then they'll be faced, you know, just like if we were to try and bring it out as a drug here in the states.

The FDA, you know, would be, have all kinds of questions.

So it's not really about curing.

It's about self-discovery and about, well, Charlie says, you know, it's about, I mean, part of it is that from a psychiatrist's point of view, it makes you hyper-suggestible.

So you get people in this hyper-suggestible state and then you feed them full of all sorts of, you know, notions about the right way to behave, how to be decent to other people and this kind of thing.

So in that sense, it's much like other cults, other religions, you know.

But the ayahuasca's a vehicle for transmitting the doctrine and it's not really medical in its purpose.

It's very active, right.

They're very environmentally active and socially active.

That's right.

Yeah.

Yes, that's an important thing that should be looked at.

I don't, yes, I do.

The question was, are we going to look at the immune response?

Not this time around, but I think we will look at it differently.

No.

Well, I mean, possibly, too, on the psychological level, yes, but as a treatment for HIV, I doubt it.

Psychologically, it could be a great help.

Yeah.

Also, I think maybe it's one of its most promising applications is drug addiction and alcohol abuse.

Many of these people, when we did the open-handed psychiatric interviews, you know, I mean, there's a typical story.

It's basically, you know, many of them said that they were completely out of control and they were engaged in a variety of self-destructive behaviors.

Alcoholism, life-beating, you know, drug addiction, just out of control and psychologically dysfunctional, many of them.

And then they claim that after coming to the tea and also the context of the UNYAU and the social support that you get within that group cannot be neglected here.

It's not just the tea, but it's helped many of these people to turn their lives around and give up drugs and basically get back on track.

It's, yeah, yeah, I mean, some still do.

It's not that it's an instant cure.

It helps people to get a handle on it, you know.

It's interesting, in Peru, tobacco is a constant element of using ayahuasca.

I mean, the ayahuascaros and the people that take it smoke all the time and they smoke during the ayahuasca and it's involved ritualistically with the whole ceremony.

In the UDV, I didn't meet anyone who smoked.

It's not that there's a prohibition against it any more than there's a prohibition against drinking.

It's just that it seems that after a while when people are taking it regularly, they just don't.

They just stop, you know.

They seem to have certain perceptions about healthy behaviors and they're just kind of naturally led to, you know, a more healthy kind of lifestyle, respect for their bodies, that sort of thing.

Yes, dimethyltryptamine.

So it really sounds like the batisterioptosis is on it, but essentially...

Right.

Well, it...

The batisterioptosis?

Somewhat, somewhat.

But I don't know if you could call it visionary, you know.

I mean, I think the UDV's model that, you know, it's a balance between the force and the light is really a good model.

And the more you take it, the more you work with it, the more you understand sort of the wisdom of that perception.

You know, the chacruna, the sakotrapia supplies the light and the batisteriopsis supplies the force.

And it's to achieve a balance between us.

I asked the guy, one of the masteries, I said, why not, how come you don't put more chacruna in it?

Why don't you really amp up the chacruna so it'll be a, you know, extremely visionary brew?

And he said, well, you know, you don't want to overexpose the film, right?

Because then all you see is a white light or all you see is, you know, you completely overwhelm it, you lose, what's the word?

Resolution.

It's, you know, you want to, you know, flash out and just completely saturate or perhaps it's better to tone it down and get some texture to the thing.

I thought that was an interesting way to do it.

I'm sorry, my voice is giving out on me and I think I better let John take over at this point.