Program Notes
Guest speaker: Dennis McKenna
Today’s talk features Dennis McKenna in a June 1984 presentation of his research concerning ayahuasca. This is one of the first, if not the first, public presentation of Dennis’ early work involving this sacred medicine. For most of the last 33 years, ayahuasca has been one of the major preoccupations of his professional life, and he is considered one of the world’s leading scientific experts in this field. As Dennis says in a recent article in The Journal of Psychoactive Drugs: “In that time, I have written extensively on the botany, chemistry, and pharmacology of ayahuasca, on its potential therapeutic uses, and on the need for more, and more rigorous, scientific and clinical investigations of this remarkable plant decoction. Working with colleagues such as Dr. Grob, my good friends Jace Callaway and Dr. Luis Eduardo Luna in Finland, my mentor Dr. Neil Towers, my late and beloved brother Terence, Dr. Glaucus de Souza Brito, and others, to investigate the myriad mysteries of ayahuasca, has been as rich and rewarding an experience as any scientist could ever hope for.”
Index of Dennis McKenna Articles (from Erowid.org)
The Brotherhood of the Screaming Abyss (2012)
Dennis J. McKenna (Erowid Character Vaults)
“Ayahuasca and Human Destiny” by Dennis McKenna
Dennis McKenna on the Joe Rogan Experience
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Transcript
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Greetings from cyberdelic space.
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This is Lorenzo and I’m your host here in the psychedelic salon.
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This is Lorenzo, and I’m your host here in the Psychedelic Salon.
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And I’d like to begin first by thanking the three very wonderful fellow salonners who made donations this week to help with some of the expenses in getting these podcasts out to you.
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And I’ll be sending a personal email to each one of you as soon as I get the program notes posted for today’s podcast.
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But hey, thanks again. I really appreciate your help.
00:00:53 ►
And now for today’s talk, I’m going to return once again to the subject of ayahuasca.
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As we all know now, the brew actually consists of two main ingredients, one containing DMT and the other an MAO inhibitor so as to make the DMT orally active.
00:01:06 ►
However, what some may not know is that it’s only really in the past 30 years or so that
00:01:12 ►
we have really understood how ayahuasca worked.
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And considering the fact that this medicine has been used by humans for thousands of years
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and that science itself is now hundreds of years old, well, I think
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that it’s quite remarkable that you and I happen to be alive at a time when science
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and shamanism have come together around this sacred medicine.
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And in just a few moments, we’re going to hear from one of the key players in the scientific
00:01:41 ►
research into the activity and properties of ayahuasca.
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The researcher I’m talking about, of course, is Dennis McKenna,
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who has for many years been the less heard from, but no less important of the McKenna brothers.
00:01:56 ►
I almost just now said the infamous McKenna brothers,
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but I’ll let you read Dennis’s recent book, The Brotherhood of the Screaming Abyss,
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which is about the life and times of these two brothers. And well, you can decide then for
00:02:10 ►
yourself about the infamous part. But to me, Dennis is just, well, he’s just really a nice guy,
00:02:17 ►
you know, somebody you’d love to get to know better. Now, the talk that we’re going to hear today is one that Dennis gave way back in June of 1984.
00:02:29 ►
And Dennis tells me that this was most likely his first, or at least one of his very first, public talks
00:02:35 ►
concerning his then very recent research into the activity of ayahuasca.
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In fact, he tells me that this was most likely his thesis defense, but repackaged for a more public presentation.
00:02:49 ►
Now, I’m going to warn you ahead of time that parts of this talk are extremely technical.
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However, if you’re a layman like myself, I think you’re still going to find this quite interesting in many ways.
00:03:00 ►
For example, until now, I really never knew how many milligrams of DMT are actually contained in the average dose of ayahuasca.
00:03:09 ►
So, what we’re about to hear is essentially the first public presentation that Dennis McKenna made of his research.
00:03:17 ►
And keep in mind that back in 1984, this was really big news to the psychedelic community.
00:03:23 ►
this was really big news to the psychedelic community.
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And the only editing that I’ve done here is to remove spots where Dennis asked for the next slide to be shown.
00:03:34 ►
Obviously he was using PowerPoint or something like that.
00:03:37 ►
And even though we don’t have the slides to look at here though,
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I think that you will nonetheless find this historic talk quite interesting.
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So now let’s join Dennis McKenna on a June evening in 1984.
00:03:54 ►
Just by way of preliminary remarks, there are a couple of issues raised by this work that I find interesting and possibly will be of interest to some of the audience that
00:03:59 ►
are involved in using psychedelics in psychotherapy, so I hope that there’ll be time to touch on that tonight.
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And also a couple of questions that this raises with regard to brain chemistry
00:04:12 ►
and the possible mechanisms by which these things work.
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This is all peripheral to the work I’m going to talk about,
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which is that for the past few years, I’ve been working on the
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botany, chemistry, and ethnopharmacology, I guess you could call it, of two Amazonian
00:04:32 ►
hallucinogens. And this was sort of a comparative study between the two, although they are different
00:04:40 ►
botanically, they have similar chemistry. And so that’s what I’m going to discuss. And then
00:04:48 ►
hopefully the questions that issue from that will get into some of these other topics that I
00:04:55 ►
hope will come up. As most of you know, ayahuasca, or also called yahe in some parts of South America, is a
00:05:07 ►
hallucinogenic brew or beverage that’s made from the bark mainly of this plant in the
00:05:14 ►
Malpighiaceae, Banisteriopsis capi.
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Together with various admixture plants, the one which is most commonly used next slide please the one
00:05:25 ►
which is most commonly used in Peru is this plant here psychotria viridis which
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belongs to the coffee family in Colombia another admixture plant is commonly used
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diplo terrace cabarena which is rather closely related to Banisteriostis copy.
00:05:45 ►
Now these admixture plants are added into the ayahuasca to strengthen, prolong, and intensify the effect,
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the hallucinogenic effect of the drug.
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And the mestizo practitioners who use this drug claim that the admixture plants are necessary
00:06:01 ►
to provide the desired visionary experience.
00:06:06 ►
In manufacturing the ayahuasca, the stems of the Benisteriopsis are stripped off the vine
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and chopped up, or the bark is stripped off,
00:06:15 ►
and then this is boiled together with the leaves of the admixture plant
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for several hours over a low fire,
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and then the brew, which results after several changes of water
00:06:25 ►
plant material is removed and concentrated to a fraction of its
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original volume and then the final product which is a bitter intensely
00:06:36 ►
bitter coffee colored brew plays a very important role in mestizo ethno medicine
00:06:42 ►
in folk medicine as practiced among this group of people in
00:06:49 ►
Peru and Colombia. By interpretation of his own visions, the content of his own visions
00:06:56 ►
or his patients’ visions, the ayahuasquero, as the practitioner is called that specializes
00:07:02 ►
in the use of this drug,
00:07:08 ►
can divine the causes of illness or misfortune and decide on an appropriate remedy or intervention.
00:07:13 ►
Often the causes of illness will be attributed to supernatural origins
00:07:17 ►
and the remedies or intervention will involve
00:07:22 ►
exorcistic-type manipulations
00:07:26 ►
or other kinds of magically-based interventions.
00:07:32 ►
In other cases, however, the ayahuasquero will result to botanical medicines to treat illness.
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He and this slide just lists a few of them.
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An experienced ayahuasquero is familiar with well over 100 of these medicinal plants.
00:07:49 ►
This just shows a selection of them from the different families.
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Their common names and some of the biologically active secondary constituents,
00:08:01 ►
plant compounds that have been found in those that have been looked at.
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Actually, only a very small fraction of the commonly used admixture plants have been
00:08:13 ►
chemically examined, so this is potentially an area for pharmacologists and pharmacognosists
00:08:19 ►
to look into for sources of new pharmaceuticals.
00:08:27 ►
look into for sources of new pharmaceuticals. The ayahuasquero learns about these plants and their properties during his initiatory, his period of initiation. He learns about them by taking them
00:08:37 ►
as admixtures to ayahuasca, along with the psychotria admixture, which is a constant ingredient in ayahuasca.
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And the claim is made that by doing so, he learns about these plants and what their properties are.
00:08:53 ►
Now, whether this can be given credence or not is not clear,
00:08:58 ►
but certainly it must be said that over the years they have managed to select from their environment
00:09:05 ►
a number of plants with interesting pharmacological properties,
00:09:09 ►
both psychoactive plants and otherwise.
00:09:12 ►
Well, the other Amazon hallucinogen that I’m going to talk about
00:09:15 ►
is manufactured from certain trees belonging to the genus Varrola
00:09:20 ►
in the nutmeg family.
00:09:22 ►
And here’s one specimen that’s so utilized shown here. In most parts
00:09:30 ►
or many parts of the Amazon basin, the Varroa is made into a snuff. The Varroa tree produces
00:09:37 ►
on the inner cambial part of its bark a thick sticky red, which is shown here. And the Yanomamo Indians and related tribes
00:09:48 ►
manufacture a hallucinogenic snuff from this Varroa resin.
00:09:53 ►
The same group of Indians is also known to prepare a dart poison
00:09:57 ►
from the same species of trees that they use for the snuffs.
00:10:00 ►
And the mechanism of action of this dart poison
00:10:03 ►
has been sort of a puzzle to ethnopharmacologists.
00:10:06 ►
It’s still not resolved, but some progress has been made. Perhaps we’ll get into that later.
00:10:11 ►
This just shows a Yanomamo with his coated darts made from varroa resin. But in the region of the
00:10:19 ►
Amazon, south of the Putumayo, in the area of the Rio Ampeyacu and Rio Yaguasyacu, which
00:10:27 ►
are located between the Putumayo River and the Amazon River, which roughly parallel each
00:10:32 ►
other.
00:10:33 ►
Is that Peru or Brazil?
00:10:34 ►
In Peru, yes.
00:10:36 ►
The varrola is used in a different form than the snuff in that an orally active form of hallucinogen is made.
00:10:46 ►
And in this method, the bark, the cambial strips are stripped off of the tree
00:10:51 ►
and the resin is scraped off.
00:10:53 ►
And then the strips are soaked for a while
00:10:57 ►
and then this aqueous infusion results.
00:11:00 ►
And this is cooked down over a low fire to the consistency of a thick paste
00:11:06 ►
and then this paste is mixed with the ashes of certain other plants and rolled into little
00:11:12 ►
boluses which are or orally ingested the effect is said to be very strong and to appear very rapidly
00:11:20 ►
okay i guess so these two two Amazon hallucinogens are were the focus
00:11:27 ►
of my investigation and okay although these hallucinogens are derived from
00:11:32 ►
completely different to botanical sources their chemistry is very similar
00:11:38 ►
banisteriopsis copy the main source plant in ayahuasca contains the beta
00:11:44 ►
carboline alkaloids
00:11:45 ►
which representatives of which are shown down here the main alkaloids being
00:11:50 ►
harming harm Aline and tetra hydro harm mean while the admixture plant psychotria
00:11:55 ►
viridis or diplo terrace cab arena contains primarily tryptamines such as
00:12:01 ►
an end dimethyl tryptamine again, a selection of different psychoactive
00:12:06 ►
or biologically active triptamines are shown. An interesting feature of the pharmacology
00:12:13 ►
of dimethyltryptamine and 5-ethoxy DMT is that they’re not orally active. They have
00:12:20 ►
to be ingested parenterally, which is why the usual means of ingesting them is by smoking them,
00:12:26 ►
or in the case of the Varroa snuffs, by that route.
00:12:30 ►
So that’s the pharmacological rationale behind the activity of the Varroa snuffs.
00:12:37 ►
However, the orally active Varroa pastes and ayahuasca may work by a different mechanism.
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pastes and ayahuasca may work by a different mechanism. It turns out that the tryptamines may be orally active if they’re ingested in the presence of a monoamine oxidase inhibitor.
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This could protect the tryptamines from deamination in peripheral tissues and allow them to be
00:12:59 ►
taken up into the central nervous system in the active form. And also conveniently enough,
00:13:05 ►
it turns out that beta-carbolines
00:13:08 ►
are reversible inhibitors of monoamine oxidase,
00:13:12 ►
rather potent ones.
00:13:14 ►
They themselves are also hallucinogenic,
00:13:16 ►
but that type of activity requires doses
00:13:20 ►
that are two to three orders of magnitude greater
00:13:23 ►
than the activity at which they’re,
00:13:25 ►
the levels at which they’re effective MAO inhibitors.
00:13:28 ►
And it also is two or three orders of magnitude greater
00:13:32 ►
than the hallucinogenic threshold doses for the tryptamines.
00:13:36 ►
And in the case of ayahuasca,
00:13:40 ►
the brew contains primarily beta-carbolines
00:13:43 ►
with dimethyltryptamine from the admixture plants
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and in the case of the Varolas
00:13:47 ►
the constituents are mainly tryptamines
00:13:50 ►
either dimethyltryptamine or 5-ethoxy-DMT
00:13:53 ►
and lower levels, in some cases trace levels
00:13:58 ►
of beta-carbolines
00:14:00 ►
so one of the questions I was attempting to answer
00:14:04 ►
is does this mechanism of oral activation of the tryptamines via inhibition of monoamine oxidase make sense?
00:14:12 ►
In other words, can it be experimentally approached in the laboratory, and can we get some data that would tend to confirm or disconfirm this?
00:14:20 ►
So this just basically summarizes some of my objectives. I wanted to look at a number of different samples,
00:14:26 ►
drug samples from different parts of Peru
00:14:28 ►
prepared by different practitioners
00:14:30 ►
to find out what the variation in alkaloid content was.
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In other words, how much was there
00:14:36 ►
and what kinds of alkaloid were there.
00:14:39 ►
And secondarily, do the amounts of tryptamines or beta-carbolines
00:14:42 ►
in the drugs exceed the amounts that we know to be necessary for hallucinogenic activity?
00:14:49 ►
In other words, is a typical dose above the known thresholds?
00:14:56 ►
A third consideration was to find out if the alkaloid content of the drug samples
00:15:01 ►
was similar or how similar was it to that of their source plants.
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Obviously, in the process of preparing the drugs, they’re subjected to some rather drastic
00:15:10 ►
boiling and other extractive processes, so it’s possible that this could affect the chemistry
00:15:16 ►
of the active ingredients.
00:15:19 ►
And the fourth question was, are these drugs active as monoamine oxidase inhibitors, and
00:15:23 ►
if so, which of the constituents
00:15:25 ►
are primarily responsible for this activity? And in connection with that, I wanted to find out if,
00:15:32 ►
since these drugs are, rather than being single compounds, are rather complex mixtures of
00:15:37 ►
compounds, I wanted to see if there might be some synergistic action, at least as far as MAO
00:15:44 ►
inhibition was concerned.
00:15:45 ►
So in order to accumulate some of this analytical data on the composition of these drugs, I
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used a number of analytical techniques, including HPLC, high-pressure liquid chromatography,
00:15:56 ►
that is, gas chromatography, and thin layer, and in some cases, gas chromatography, mass spectrometry.
00:16:07 ►
This just shows a typical HPLC profile of an ayahuasca sample
00:16:12 ►
with the major four constituents and their order of elution.
00:16:17 ►
So this shows the results of an HPLC quantitation of some samples
00:16:23 ►
made by different practitioners from different
00:16:25 ►
parts of Peru. And what we find here is, not unexpectedly, there is quite a bit of variation
00:16:33 ►
in the alkaloid content, both in terms of the total alkaloids, which are shown here,
00:16:39 ►
and also in terms of the proportions of various constituents, the same four constituents were pretty much
00:16:46 ►
constantly present in all of them. That is, haramine, tetrahydroharamine, DMT, and harmaline,
00:16:53 ►
more or less in that order. What are the names of the left, by the way?
00:16:58 ►
Oh, okay. Well, these are just, the samples are named basically by the person who got them,
00:17:06 ►
These are just, the samples are named basically by the person who got them, or that they were obtained from.
00:17:11 ►
So their place of origin and the name of the ayahuasquero is how these samples were identified.
00:17:19 ►
And this shows the alkaloid contents in terms of the milligrams per gram dry weight.
00:17:22 ►
These samples were lyophilized for analysis.
00:17:27 ►
And then this just shows the percent of the total alkaloid. So as you can see, they do, both in terms of absolute alkaloid content
00:17:32 ►
and in terms of the proportions of various constituents,
00:17:35 ►
they do vary quite a bit.
00:17:37 ►
And obviously, a question is, where does this variation come from?
00:17:42 ►
Well, obviously one factor is going to be variability
00:17:45 ►
in methods of preparation.
00:17:48 ►
In other words, how much plant material is used,
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how long it’s extracted, how much admixture is added, and so on.
00:17:55 ►
And another source of variation may be the chemical differences
00:18:01 ►
between cultivars of Benisteriopsis copy.
00:18:04 ►
differences between cultivars of Benisteriopsis copy.
00:18:10 ►
The Ayahuasca girls recognize up to 10 different cultivars,
00:18:14 ►
which they give different names to and make different claims for,
00:18:17 ►
claim that they vary in their strength and their effects.
00:18:20 ►
I was able to look at some of these.
00:18:21 ►
I don’t have a slide of it, but I did find that there was quite a bit of variation in alkaloid content.
00:18:26 ►
But it wasn’t possible to, the sample wasn’t sufficient to actually correlate it to different cultivars.
00:18:32 ►
And I suspect that environmental conditions that the plants are grown under make quite a bit of variation in the strength and proportions of alkaloids.
00:18:42 ►
and proportions of alkaloids.
00:18:45 ►
Okay, so this is a similar slide,
00:18:48 ►
except that it shows the HPLC quantitation of the alkaloid content of five samples of ayahuasca
00:18:52 ►
prepared by these two gentlemen,
00:18:55 ►
and they collaborate in the preparation of their brews,
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Don Fidel and Don Juan,
00:19:01 ►
and draw their source plants basically from the same garden. So they have
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cultivars that have been established for some time of both the Banisteriopsis copy and the
00:19:12 ►
Socotria admixture. And in this case, we find that there’s remarkable little variation from
00:19:20 ►
batch to batch, both in terms of total alkaloid content and in terms of the proportions of various constituents.
00:19:28 ►
They are actually fairly close between different batches.
00:19:33 ►
And it appears that in the process of manufacturing the brew,
00:19:41 ►
given a source of genetically uniform source plants,
00:19:44 ►
these practitioners
00:19:46 ►
are able to exercise what you might call a fairly high degree of pharmaceutical quality
00:19:51 ►
control from batch to batch. And trying to relate this information to the amounts of
00:20:01 ►
active compounds that would be present in a typical dose of ayahuasca,
00:20:05 ►
we can get a ballpark idea by looking at the average of these five samples,
00:20:10 ►
which is shown down here.
00:20:12 ►
And if we say that a typical dose is 100 milliliters,
00:20:15 ►
which it’s usually close to that or perhaps slightly less,
00:20:18 ►
we can say that 100 milliliters of ayahuasca would contain around 728 milligrams of total alkaloid.
00:20:27 ►
Most of that would be haramine, 467 milligrams, 65%.
00:20:32 ►
And followed by tetrahydroharamine, followed by DMT,
00:20:37 ►
there would be about 60 milligrams of DMT and about 40 milligrams of harmaline.
00:20:42 ►
and about 40 milligrams of harmaline.
00:20:47 ►
Well, this data can be interpreted based on what we know about the required threshold doses for the activity of these compounds,
00:20:52 ►
and we can see that in the case of DMT,
00:20:58 ►
there’s about 60 milligrams in a 100-milliliter dose of this drug.
00:21:03 ►
So that’s well within the ballpark.
00:21:06 ►
I think threshold activity in a fully grown adult is around 15 milligrams,
00:21:12 ►
but optimal activity or the full spectrum of effects
00:21:16 ►
is observed around 50 to 75 milligrams.
00:21:20 ►
So this figure is well within that ballpark,
00:21:23 ►
assuming that it can somehow be orally activated.
00:21:27 ►
As far as the beta-carbolines, though, the contents of all of them are well below the amounts known to be hallucinogenic for that class of compounds.
00:21:38 ►
For instance, haramine is known to be orally inactive.
00:21:43 ►
And Sasha can correct me if I’m wrong on any of this. But it’s known to be orally.active, and Sasha can correct me if I’m wrong on any of this, but
00:21:46 ►
it’s known to be orally, there may be new work, it’s known to be orally inactive in
00:21:51 ►
doses in excess of one gram. And Harmaline exhibits threshold activity around 300 to
00:21:58 ►
400 milligrams, and the amounts of these beta-carolines found in these drugs are well below
00:22:05 ►
so a couple of orders of magnitude below those levels so from this we can infer that the activity
00:22:11 ►
of ayahuasca as a hallucinogen is probably due to the dmt and the assumption is that it may be
00:22:19 ►
orally activated by the beta carbolines There’s certainly sufficient amounts of them present to have that activity.
00:22:28 ►
I just want to say something about the admixture plant.
00:22:31 ►
Several admixture plant samples of psychotria were analyzed,
00:22:35 ►
and one sample of Diplateris cabarena was analyzed,
00:22:40 ►
and DMT was detected as the only major base in either sample.
00:22:45 ►
They basically can’t be told apart.
00:22:48 ►
One is psychotrial, one is diploterous, on the basis of their alkaloid content.
00:22:53 ►
And it was fairly substantial, between 1.5 and 2 milligrams per gram in the dry weight, in the leaves, dried leaves.
00:23:03 ►
So this is, botanically, it’s remarkable in that it’s such a clean source of DMT.
00:23:08 ►
Only traces of other compounds were detected.
00:23:12 ►
Okay, when we look at the similar quantitative data
00:23:18 ►
for some of the Varroa pastes and several samples of Yanomamo snuffs from Venezuela. These are the Varroa pastes
00:23:27 ►
with their different names, native names, and their place of origin and the person that
00:23:33 ►
manufactured it. This is the number of the voucher specimen that they came from, the
00:23:38 ►
species of the tree from which they were manufactured, and the alkaloids that were detected expressed in terms of milligrams per gram dry weight.
00:23:48 ►
And then the percent, again, of the total is shown out here.
00:23:52 ►
And this quantitation was done using gas chromatography.
00:23:57 ►
And what I found was that, unlike ayahuasca,
00:24:02 ►
there’s not only quantitative variation in the alkaloid content,
00:24:06 ►
but considerable qualitative variation as well.
00:24:09 ►
In other words, the base composition of different samples of these pastes,
00:24:14 ►
actually none is identical to any other one.
00:24:17 ►
So it appears that, and this is also true of snuffs,
00:24:21 ►
it appears that the pastes and the snuffs
00:24:24 ►
are a much more chemically
00:24:25 ►
variable drug, and this may influence their pharmacology.
00:24:30 ►
In fact, it undoubtedly does.
00:24:34 ►
Again, trying to relate this to the doses that would be required to elicit hallucinogenic
00:24:41 ►
effects, if we look at the paste and snuff samples that have the
00:24:45 ►
highest alkaloid content, some of them have extremely low alkaloid contents, others have
00:24:50 ►
substantial amounts, 18 milligrams per gram, 15 milligrams per gram, and so on.
00:24:57 ►
Well, if we try to relate that to the dose and say how much of this material, paste or snuff, would you have to ingest to exceed the threshold doses,
00:25:08 ►
it really depends on which constituent,
00:25:13 ►
DMT or 5-methoxy-DMT, is the major constituent.
00:25:17 ►
If DMT is the major constituent,
00:25:19 ►
it would require somewhere on the order of half of a gram to five grams,
00:25:28 ►
half of a gram to get threshold effects,
00:25:31 ►
five grams for the full spectrum of effects,
00:25:34 ►
which might be difficult if you’re talking about ingesting four or five grams of snuff,
00:25:39 ►
although it wouldn’t present any problem in the case of the orally active pastes.
00:25:45 ►
But if 5-methoxy-DMT is the major constituent,
00:25:48 ►
since it’s an order of magnitude more active than DMT,
00:25:52 ►
then presumably about one-tenth of that amount would be required.
00:25:56 ►
So one-tenth to one-half of a gram if 5-methoxy-DMT is the major constituent.
00:26:03 ►
And this could be readily accomplished
00:26:05 ►
even if the route of ingestion was by snuffing.
00:26:08 ►
So from this, we can infer, or we can speculate at least,
00:26:12 ►
that the most active paste and snuff samples
00:26:15 ►
are probably those that contain primarily 5-methoxy-DMT.
00:26:19 ►
And as you can see, some of them contain only 5-methoxy-DMT.
00:26:23 ►
And in other cases where both compounds are present,
00:26:27 ►
5-methoxy-DMT is usually the predominant constituent.
00:26:32 ►
Okay, this qualitative variation found in the paste and snuff sample
00:26:38 ►
seems to be a function of the source plants.
00:26:40 ►
And this slide just shows, again, not all but a selection of different source plants. And this slide just shows, again, not all but a selection of different source plants
00:26:46 ►
or related plants in the same family that were examined, that were screened for alkaloids. And
00:26:52 ►
again, some specimens have no alkaloids. Alkaloids were not detected. In other cases, they do
00:27:00 ►
have the expected tryptamines, but the distribution, both in terms of the type and where they are, is different in that sense that there was a distribution.
00:27:14 ►
Different parts of the same plant often had a different composition, and different collections of the same species often differed in their composition,
00:27:25 ►
as well, of course, as different species, which you’d expect.
00:27:29 ►
But even within a species, there appears to be a great deal of chemical variation,
00:27:34 ►
and that probably is, again, related to seasonal or environmental factors.
00:27:40 ►
Another, perhaps the most significant finding on this,
00:27:43 ►
was that most of the paste and stuff samples were examined
00:27:46 ►
contained, either did not contain beta carbolines,
00:27:50 ►
or at least they were not detected,
00:27:52 ►
or in cases where they were detected,
00:27:54 ►
they were only trace constituents.
00:27:57 ►
These two compounds, which the mass spectra has shown,
00:28:00 ►
were detected in two snuff samples,
00:28:04 ►
and all the others didn’t contain beta-carbolines
00:28:09 ►
that were detectable, at least using my methods.
00:28:12 ►
So, and the only way that these could be detected
00:28:15 ►
was by mass spectrometry,
00:28:17 ►
so, because the concentration was so low.
00:28:21 ►
So this indicates that even in the cases
00:28:23 ►
where the snuffs, where the
00:28:25 ►
pastes rather, do contain beta-carbolines, they probably are not sufficient to contribute
00:28:31 ►
significantly to its pharmacological activity. So it appears that in the case of the virola pastes,
00:28:39 ►
if they are orally active, in fact, they may be activated by some constituents other than the beta-carbolines,
00:28:45 ►
or there may be something else going on.
00:28:48 ►
Okay, so this just summarizes basically
00:28:50 ►
what was found with these two drugs,
00:28:51 ►
ayahuasca and the Varrola,
00:28:53 ►
the myristicaceous hallucinogens.
00:28:57 ►
In a case of ayahuasca,
00:28:58 ►
there was considerable quantitative variation,
00:29:01 ►
but the same constituents were consistently found
00:29:03 ►
in different batches.
00:29:06 ►
And harming was consistently the most abundant beta-carboline that was found, and harmaline
00:29:11 ►
was the least abundant, which is interesting because that’s the reverse of their hallucinogenic
00:29:17 ►
activity.
00:29:17 ►
In other words, harmaline requires the lowest dose to manifest activity as a hallucinogen,
00:29:23 ►
but it’s not found in ayahuasca in sufficient doses probably to do this.
00:29:29 ►
And the amount of DMT in most doses of ayahuasca
00:29:32 ►
did exceed the threshold dose that’s known to be required
00:29:36 ►
for hallucinogenic activity of this compound.
00:29:39 ►
Leaving aside, or perhaps should be mentioned at this time,
00:29:44 ►
is that also in the presence of beta-carbolines or other MAO inhibitors,
00:29:49 ►
significantly smaller amounts of DMT may be active
00:29:52 ►
because they may protect it from degradation
00:29:55 ►
and facilitate its reaching the site of its activity.
00:30:00 ►
In the case of the Varrola drugs,
00:30:02 ►
there was a lot of quantitative and qualitative variation as well,
00:30:08 ►
and this appeared to be a reflection of the source plants.
00:30:11 ►
The major tryptamines found in the drugs were DMT and or 5-methoxy-DMT,
00:30:19 ►
and NMT, N-methyltryptamine, was also usually present,
00:30:22 ►
but it also tended to be a trace constituent,
00:30:26 ►
except one sample had it as the main constituent.
00:30:30 ►
And the third finding is that beta-carbolines
00:30:33 ►
were not detected in most of these PACE samples,
00:30:37 ►
and in the cases where they were, they were trace constituents.
00:30:40 ►
Okay, so that sort of completed the analytical phase of this work,
00:30:44 ►
looking into the composition of these drugs
00:30:46 ►
and trying to get an idea what the alkaloid profiles looked like.
00:30:51 ►
So the next step was to investigate the activity of these drugs
00:30:55 ►
and some of their active constituents as monoamine oxidase inhibitors.
00:31:01 ►
And for this I used an in vitro assay
00:31:04 ►
using carbon-14 labeled serotonin as the substrate.
00:31:09 ►
And first I just tested several synthetic beta-carboline derivatives, or they do occur in
00:31:15 ►
nature, but they were synthetically manufactured, to get an idea of the structure activity
00:31:20 ►
relationships of these compounds in terms of their action as MAO inhibitors. And in this assay, the parameter that’s measured is the I50,
00:31:30 ►
which is the molar concentration of inhibitor that’s required
00:31:35 ►
to inhibit 50% of the enzyme activity. This is the work
00:31:40 ►
reported for my thesis, and this is for comparison work done by previous investigators. And without
00:31:48 ►
getting into the details of structure activity, I just will say that in most cases, the beta
00:31:55 ►
carbolines turned out to be very good, very potent MAO inhibitors. This is, of course,
00:32:00 ►
known from previous work. But in most cases, the I50s were on the order of 10 to the minus 6 to 10 to the minus 7 molar.
00:32:10 ►
The most active of the beta-carbolines were actually harming,
00:32:17 ►
and harmaline were very close,
00:32:18 ►
but they were an order of magnitude more active than the other ones,
00:32:23 ►
active at around 10 to the minus 8 molar in
00:32:26 ►
my assays.
00:32:28 ►
And so they are very good MAO inhibitors in vitro, and they are, of course, at least
00:32:35 ►
harming as the major constituent in ayahuasca.
00:32:38 ►
As far as the activity of mixtures of beta-carbolines. I assayed those to see if there might be
00:32:46 ►
some sort of synergistic interaction between these three main constituents found in ayahuasca
00:32:52 ►
and found that basically there wasn’t. That in other words, an ecomolar mixture of ayahuasca
00:32:59 ►
of the three main beta-carbolines had an I50 that was intermediate between the most active,
00:33:07 ►
which was harming, and the least active,
00:33:08 ►
which was tetrahydroharming.
00:33:10 ►
So there doesn’t, at least in vitro,
00:33:12 ►
appear to be synergistic activity of these compounds.
00:33:16 ►
And mixtures of beta-carbolines
00:33:18 ►
reflecting the approximate proportions and percentages
00:33:22 ►
of these constituents also showed intermediate activity,
00:33:26 ►
slightly less than the equimolar mixture.
00:33:31 ►
Okay, so as far as the activity of ayahuasca itself as an MAO inhibitor,
00:33:35 ►
this was just done by a series of log dilutions from the full-strength brew.
00:33:42 ►
And what I found was that even at dilutions of many orders of magnitude,
00:33:49 ►
these two samples, which represented the samples containing the most alkaloid,
00:33:54 ►
were rather effective as MAO inhibitors.
00:33:57 ►
Even at 10 to the minus 7th of the full strength,
00:34:00 ►
this compound shows inhibition more than 50% of the enzyme,
00:34:05 ►
and this one almost 50%, about 45% at that level.
00:34:10 ►
So it appears that in vitro, at least,
00:34:13 ►
ayahuasca is a very good, very potent inhibitor of monoamine oxidase,
00:34:19 ►
even when diluted, when greatly diluted.
00:34:23 ►
Okay, so then in order to get a comparative idea
00:34:27 ►
of the activity of various tryptamine derivatives as MAO inhibitors
00:34:31 ►
and compare them both to each other and to the beta-carbolines,
00:34:36 ►
I again did this structure activity determination using the same system
00:34:41 ►
and figuring that since the substrate for the enzyme is a tryptamine,
00:34:47 ►
that these compounds might show some degree of inhibition,
00:34:50 ►
either as competitive substrates or as inhibitors in their own right.
00:34:55 ►
And basically, again without talking about the details of the structure activity,
00:35:01 ►
basically the finding is that the tryptamines were,
00:35:04 ►
most of them did show some degree of inhibition in this system,
00:35:08 ►
but they were several orders of magnitude less active than the beta-carbolines,
00:35:13 ►
around 10 to the minus 5 or 10 to the minus 4 molar in most cases.
00:35:20 ►
Perhaps the most interesting finding is that in dimethyltryptamine,
00:35:24 ►
Perhaps the most interesting finding is that NN-dimethyltryptamine, DMT,
00:35:30 ►
was the most active as an MAO inhibitor of the beta-carbolines,
00:35:32 ►
of the tryptamines that were tested.
00:35:37 ►
In fact, its activity was comparable to tetrahydroharamine,
00:35:41 ►
which was one of the least active beta-carbolines, but still not bad.
00:35:48 ►
So perhaps this finding does bear some relation to the question of the oral activation of DMT. Okay, so having gotten some idea of the activity of various tryptamines
00:35:57 ►
as MAO inhibitors, then I went on to test various extracts and fractions from these Varrola pastes. And what was done here was that the
00:36:07 ►
paste extract was worked up for the assay and then the alkaloid
00:36:11 ►
content was quantified with HPLC and run in parallel
00:36:16 ►
with the mixture, what I call paste analogs, which
00:36:19 ►
were basically mixtures of the major tryptamines
00:36:24 ►
found in the same proportions
00:36:25 ►
and approximate concentrations as were found in the paste extracts.
00:36:32 ►
And the thinking was that if the MAO inhibition in the paste extracts was primarily due
00:36:37 ►
or solely due to the tryptamines, that they would parallel very closely the activity of the paste analogs
00:36:44 ►
in which only tryptamines
00:36:45 ►
were present.
00:36:46 ►
If other constituents were contributing to the activity, then you would expect a differing
00:36:51 ►
I50 for the paste extracts than for the analog mixtures.
00:36:56 ►
So in the case of the three pastes which had the highest alkaloid content, you can see
00:37:01 ►
that in most cases the curves parallel very closely.
00:37:06 ►
And so the I50 of the paste versus the analog of the paste did not differ greatly.
00:37:13 ►
So from this you can infer that the activity, what limited activity it has,
00:37:18 ►
is probably due to the tryptamines in it.
00:37:22 ►
This supposition is supported also by the fact that the range of the I50s
00:37:28 ►
well matches the range for individual tryptamine constituents.
00:37:33 ►
In other words, it’s not down toward the harming end of it.
00:37:37 ►
And another thing which I don’t have a slide of,
00:37:40 ►
but a couple of samples which were free of alkaloids, in one case a PACE sample
00:37:47 ►
which lacked alkaloids, and in another case a fraction of lignans from Varrola, lignans
00:37:54 ►
are another class of secondary compounds, were tested for MAO inhibition just to see
00:37:59 ►
if they might, other constituents might contribute to the activity. And basically, none was found.
00:38:05 ►
The only thing that was observed was some degree of inhibition
00:38:09 ►
only at the highest concentrations.
00:38:12 ►
So it appears that the Varroa paste are rather poor MAO inhibitors.
00:38:16 ►
And what activity they show is probably due primarily to the tryptamines.
00:38:23 ►
So it looks like, in contrast to
00:38:26 ►
ayahuasca, it may be necessary to look for some other mechanism to explain their oral activity,
00:38:33 ►
if in fact they are orally active hallucinogens. Well, one possibility is that their oral activity is not, in fact, due to the tryptamines at all.
00:38:47 ►
It might be due to some other constituents in the resin.
00:38:51 ►
One possibility is, again, these lignans.
00:38:55 ►
My colleague, Don McRae, who worked on the activity of varrola as an aeropoison,
00:39:05 ►
has isolated several biologically active lignans from the resin
00:39:09 ►
and found that they do have effects on locomotor activity
00:39:13 ►
in suppressing locomotor activity
00:39:15 ►
that are significantly greater than comparable doses of tryptamines.
00:39:20 ►
So it’s possible that this may explain its activity as an aeropoison
00:39:24 ►
and may also at least contribute to its oral activity.
00:39:30 ►
However, it’s also possible to speculate on another mechanism
00:39:35 ►
for the oral activation of the tryptamines in ferroloresin.
00:39:41 ►
So it’s possible to postulate another mechanism, and this gets to your question,
00:39:48 ►
whether DMT is a good substrate for monomamine oxidase. There have been recent experimental
00:39:56 ►
investigations of DMT metabolism in peripheral tissues. This has been done by a group in Alabama that’s been investigating the possible role of DMT
00:40:08 ►
as an endogenous, endogenously produced hallucinogens.
00:40:13 ►
And they have found that DMT is actually a rather poor substrate for MAO.
00:40:19 ►
This slide just shows some of the other pathways
00:40:23 ►
that have been characterized for DMT degradation in peripheral tissues,
00:40:28 ►
basically the rat liver homogenate,
00:40:30 ►
or in some cases the rat liver microsomal fraction.
00:40:35 ►
MAO will metabolize DMT and other tryptamines to indole acetic acid,
00:40:41 ►
and this constituent is detected in the incubation mixture,
00:40:46 ►
but it appears late in the incubation.
00:40:50 ►
And they have speculated that DMT is not directly deaminated
00:40:55 ►
to indole acetic acid by MAO,
00:40:59 ►
but rather that it is a better substrate for the hepatic monooxygenases,
00:41:06 ►
the so-called MFOs,
00:41:09 ►
the hepatic microsomal drug metabolizing enzymes,
00:41:13 ►
which metabolize it to various things.
00:41:17 ►
6-hydroxy-DMT appears to be a minor metabolite,
00:41:22 ►
and DMT-anoxide, which then by various intermediates and steps
00:41:27 ►
can eventually become, via this intermediate,
00:41:31 ►
become demethylated to form N-methyltryptamine.
00:41:35 ►
This then is readily metabolized by MAO.
00:41:39 ►
It’s metabolized about 18 times faster than DMT by MAO.
00:41:45 ►
So it’s probably that the IAA that shows up late in the incubation
00:41:51 ►
actually is a tertiary metabolite,
00:41:54 ►
and the precursor is primarily N-methyltryptamine.
00:41:58 ►
But there are other aspects of this pathway too.
00:42:02 ►
For instance, under other conditions,
00:42:04 ►
the same
00:42:05 ►
intermediate can go via this route of cyclization to form tetrahydrobeta carbolines, which that’s
00:42:13 ►
an aspect that I want to touch on later. But in other words, this is only some of the possible
00:42:21 ►
routes of transformation of this DMT, this endogenous hallucinogen.
00:42:27 ►
Well, assuming, for the sake of argument,
00:42:30 ►
that perhaps in the peripheral tissues,
00:42:33 ►
DMT is primarily inactivated or metabolized via this mechanism
00:42:39 ►
involving these microsomal MFOs,
00:42:42 ►
then it’s possible to propose a mechanism, an alternative mechanism,
00:42:48 ►
whereby it could be orally activated by other constituents in the varroa resin.
00:42:55 ►
Recent structure activity studies of MFO inhibitors have shown that compounds containing the methylene-dioxifenyl group,
00:43:06 ►
which is, for those of you who are not chemists,
00:43:09 ►
I don’t know that it would…
00:43:10 ►
But anyhow, it is a particular chemical configuration.
00:43:14 ►
It’s the same configuration, as a matter of fact,
00:43:17 ►
as found in MDMA and some of these phenethylamines.
00:43:21 ►
But it turns out that the pharmacophore,
00:43:24 ►
the required chemical configuration
00:43:26 ►
for MFO inhibitors, are compounds containing this methylene-dioxifenyl moiety. And it turns out that
00:43:34 ►
varrola resin is a particularly rich source of secondary compounds which do contain this moiety. So it’s possible that some of these constituents,
00:43:47 ►
by inhibiting this MFO-mediated pathway of degradation,
00:43:53 ►
could protect the tryptamines from peripheral degradation
00:43:56 ►
and allow them to be orally activated.
00:44:01 ►
And this alternative mechanism may underlie the oral activity of the varroa pastes.
00:44:08 ►
It may also contribute to the activity of ayahuasca.
00:44:11 ►
The action of beta-carbolines as MFO inhibitors I don’t think has been closely looked at.
00:44:19 ►
However, in the case of ayahuasca, it’s not necessary really to invoke that mechanism
00:44:24 ►
because there are sufficient beta-carbolines to effectively inhibit MAO.
00:44:29 ►
It may also be that by blocking the inhibition of MAO in the case of ayahuasca
00:44:35 ►
that there are, via feedback mechanisms, this pathway may also be affected.
00:44:43 ►
So although this last part of it is purely speculation,
00:44:47 ►
it’s not been shown that by inhibition of MFO
00:44:50 ►
that you can orally activate DMT
00:44:53 ►
or some other of these hallucinogenic tryptamines,
00:44:58 ►
it’s at least a reasonable speculation.
00:45:01 ►
And that is basically the substance of
00:45:05 ►
my findings
00:45:07 ►
that at least
00:45:10 ►
that’s what I’m going to conclude
00:45:12 ►
with tonight.
00:45:13 ►
So if anybody more questions
00:45:16 ►
or…
00:45:16 ►
Something that wasn’t clear to me from this presentation
00:45:20 ►
is the ayahuasca
00:45:21 ►
preparation.
00:45:23 ►
What happens if someone just boils the ayahuasca by itself
00:45:28 ►
and then the constituents by themselves ingest those?
00:45:32 ►
Together?
00:45:33 ►
No, separately.
00:45:35 ►
They’re always taken together.
00:45:35 ►
Nothing.
00:45:36 ►
They’re always taken together.
00:45:38 ►
Separately they’re enacted.
00:45:40 ►
Although, well, I should qualify that
00:45:43 ►
because ayahuasca is occasionally taken by itself.
00:45:46 ►
In other words, it’s occasionally manufactured only from banisteriopsis copy.
00:45:50 ►
And there may be two things going on.
00:45:52 ►
It’s possible that it’s concentrated much more or they may use more plant material
00:45:57 ►
so that in that case you do get up into these levels where the beta-carolines begin to become hallucinogenic.
00:46:06 ►
In other words, they contain more than the other.
00:46:09 ►
Or it’s possible that it’s not really a hallucinogen, but it does something.
00:46:17 ►
When it’s manufactured by itself, it does something.
00:46:21 ►
It may be a general stimulant, it may not be, the activity may not be the same.
00:46:26 ►
They don’t claim that ayahuasca is inactive by itself.
00:46:30 ►
They claim that in order to make it a hallucinogen,
00:46:33 ►
in order to make it a visionary experience,
00:46:35 ►
you have to have the admixture plan.
00:46:39 ►
That’s the thing.
00:46:40 ►
So it may have other kinds of…
00:46:41 ►
Have I checked this out? No.
00:46:44 ►
Because I haven’t…
00:46:46 ►
This is one approach,
00:46:47 ►
but I haven’t had an opportunity
00:46:49 ►
to manufacture my own ayahuasca
00:46:51 ►
in fairly careful conditions
00:46:53 ►
where I could control the amount of admixture plant
00:46:56 ►
or whether admixture plant was added or not.
00:46:59 ►
This is one direction that I think it would be good to go,
00:47:02 ►
to look at it.
00:47:03 ►
Because actually now,
00:47:04 ►
with fairly simple chemical methods,
00:47:09 ►
it’s possible for us to know more about the composition of ayahuasca
00:47:13 ►
or the drugs, the particular brews that we make,
00:47:16 ►
than the ayahuascaros ever dreamed of knowing.
00:47:19 ►
So you can actually combine the ancient shamanic approach to it
00:47:24 ►
with a little thin-layer chromatography,
00:47:26 ►
and I think you could get pretty far in altering the quality
00:47:30 ►
and the activity of your samples.
00:47:33 ►
They do claim that there are many different kinds of ayahuasca
00:47:37 ►
with many different kinds of activity,
00:47:39 ►
depending on how much of the main admixture plants
00:47:46 ►
and which other admixture plants are added into it.
00:47:49 ►
I mean, for instance, they will often add solanaceous admixture plants into these,
00:47:54 ►
detura and or brunfelsia or other things.
00:47:58 ►
There are many interesting plants that they use in conjunction with ayahuasca
00:48:02 ►
which may themselves have activity just by themselves.
00:48:08 ►
So this is another thing that needs to be looked at.
00:48:11 ►
This admixture plant technology is pretty involved and sophisticated.
00:48:16 ►
In the case of the ayahuasca, when they first looked at it,
00:48:20 ►
they found beta-carbolines.
00:48:22 ►
Well, they extracted it and initially found beta-carbolines,
00:48:26 ►
which would stick up like a sore thumb because they’d be there in much greater amounts than
00:48:32 ►
the tryptamines and would be much more easily detectable. It’s possible that you wouldn’t
00:48:36 ►
see the tryptamine if you weren’t looking for it.
00:48:38 ►
And they didn’t check then the clinical activity?
00:48:40 ►
Well, when they found beta-carbolines, they thought they knew, they thought they understood it all, because these were compounds that had been known for years. I mean, they’d
00:48:48 ►
been first isolated from, I think, Paganum harmala in the 1860s. So they looked at ayahuasca
00:48:54 ►
and they said, aha, haramine, harmaline, tetrahydroharamine, we’ve seen all these, and we know what they
00:49:00 ►
do. And so the specific, although they don’t know what they do,
00:49:05 ►
that’s a whole, they’re actually just now finding
00:49:07 ►
that they have a whole spectrum of biological activities,
00:49:11 ►
some of which is neurological and some of which
00:49:13 ►
is completely off in other areas.
00:49:17 ►
The activity of the beta-carbolines,
00:49:20 ►
the pharmacology in humans has just not been thoroughly
00:49:23 ►
looked at, actually.
00:49:25 ►
I mean, the most, the study usually cited is Naranjo’s work,
00:49:32 ►
which is, I think, most reported in the ethnopharmacologic search.
00:49:36 ►
And it was not systematic.
00:49:39 ►
Many of the trials were based on one trial and in one person so the dose is required and all this it’s
00:49:48 ►
still although since there’s been a lot of work done on this I mean I think but it’s actually a
00:49:54 ►
question you know not all the beta carbolines are hallucinogenic you know but they may have other activities or interact with other systems. Like it’s possible that by, simply by inhibiting peripheral MAO,
00:50:11 ►
if you had a brew made solely from banisteriopsis,
00:50:15 ►
it’s possible that you could affect your own amine metabolism,
00:50:19 ►
depending on other, maybe that’s a mechanism.
00:50:23 ►
In other words, maybe it affects the
00:50:26 ►
metabolism of your own DMT you know preventing the breakdown I mean I don’t really think so
00:50:32 ►
with a dietary sources is another thing yes and I didn’t yes the ayahuasca arrows are very
00:50:40 ►
insistent that you have to follow a particular diet in order to get the full benefit out of ayahuasca.
00:50:48 ►
And in its use in ethnomedicine,
00:50:52 ►
it’s different than what you might call an acute hallucinogen.
00:50:59 ►
Mushroom psilocybin is an acute hallucinogen, I would say,
00:51:03 ►
in that you take it and something happens usually.
00:51:07 ►
I mean, it’s pretty, you get off and then you come down and then it’s over.
00:51:11 ►
Ayahuasca, actually, the way they employ it
00:51:13 ►
is to take it over a period of time frequently
00:51:17 ►
while observing this diet.
00:51:19 ►
And the common observation is that the initial sessions,
00:51:24 ►
the initial trips don’t do that much.
00:51:27 ►
You don’t get off so well,
00:51:30 ►
but then as you continue to take it and continue to follow the diet,
00:51:35 ►
without increasing the dose,
00:51:37 ►
it eventually begins to become stronger and stronger as you take it.
00:51:43 ►
And also it’s claimed that these effects last over a period of time.
00:51:47 ►
In other words, a big component of the imagery has to do with dreams,
00:51:52 ►
and they’re very tuned in to alterations in dream states and this sort of thing.
00:51:58 ►
So I think ayahuasca is not…
00:52:01 ►
It really isn’t that well understood what’s going on.
00:52:04 ►
But there are a number of things,
00:52:07 ►
some of which may have long-term effects that are going on.
00:52:10 ►
I think that, well, since you brought it up,
00:52:15 ►
I think that beta-carbolines,
00:52:17 ►
this combination of beta-carbolines and tryptamines
00:52:20 ►
that we see in these two drugs,
00:52:24 ►
I think the real sort of importance of them
00:52:27 ►
is that we find the same combination in brain chemistry.
00:52:31 ►
And it’s now known that DMT is produced endogenously in normal human brain.
00:52:36 ►
It’s not known exactly what it does there.
00:52:41 ►
And it’s also known that beta-carbolines are produced in the brain and in various other
00:52:46 ►
parts of the body. And since, as shown on that next to the last slide, since beta-carbolines
00:52:53 ►
are a product of the metabolism of DMT in the periphery, there’s all sorts of opportunities
00:53:01 ►
for them to feed back on that metabolism
00:53:05 ►
because of their action as MAO inhibitors,
00:53:08 ►
because of their action as inhibitors of the uptake of neurotransmitters.
00:53:14 ►
And they are just very, very…
00:53:17 ►
This particular combination of drugs that you find,
00:53:20 ►
of alkaloids that you find in these plants
00:53:22 ►
are very close to what may be going on in brain chemistry.
00:53:25 ►
And by looking at the mechanisms by which these plants work, maybe we can get a bead
00:53:30 ►
on how mechanisms behind schizophrenia and this sort of thing.
00:53:36 ►
But I do feel that these classes, the beta carbolines and the tryptamines, are an important
00:53:42 ►
place to look because they are essentially the drugs that we have in our bodies.
00:53:47 ►
They’re the internal ones.
00:53:50 ►
And also, you’re probably aware of the connections
00:53:53 ►
that have been found recently between beta-carbolines
00:53:56 ►
and their formation in ethanol metabolism
00:53:59 ►
and this sort of thing.
00:54:02 ►
Beta-carbolines and tetrahydroisoquinolines will appear, can be detected in the urine
00:54:09 ►
a few hours after ethanol loading, and it’s thought to be a reaction between tryptamines
00:54:15 ►
and acetaldehyde, which is the metabolite of ethanol. And there have been attempts to
00:54:20 ►
link this to an etiological mechanism in alcoholism. I don’t really think
00:54:27 ►
that that’s going on, but it certainly is a possibility. It should be looked at, definitely,
00:54:32 ►
because these beta-carbolines have a wide spectrum of activities at low doses. Their
00:54:41 ►
hallucinogenic activity is perhaps the least manifest. In other words,
00:54:46 ►
they’re inhibitors of amine uptake, they’re MAO inhibitors, they’re mutagens, they’re known to
00:54:51 ►
intercalate into DNA, they’re known to be phototoxic or photoactive is a better term.
00:54:59 ►
So, who knows? It’s really wide open. Anybody have anything else they want to say?
00:55:07 ►
Thank you.
00:55:07 ►
That’s enough.
00:55:13 ►
You’re listening to The Psychedelic Salon,
00:55:16 ►
where people are changing their lives one thought at a time.
00:55:21 ►
Well, after listening with you just now to Dennis describe both how he obtained the samples
00:55:27 ►
and the wide variety of plant material used, not to mention the different parts of the jungle from which they came,
00:55:35 ►
well, it certainly explains why I’ve never had any two ayahuasca experiences that were essentially identical.
00:55:43 ►
While there have been obvious similarities between them,
00:55:46 ►
for the most part, they’ve all been quite different for me.
00:55:49 ►
And I think that you’ll probably find that’s true for a lot of people.
00:55:53 ►
Even when you’re participating in a circle with brew from the same Iowa scarrow over the years,
00:55:59 ►
there just are a lot of variables in this medicine,
00:56:02 ►
and that’s even without the admixture of other plants, as is sometimes the case.
00:56:08 ►
Now, in the program notes for this podcast, which as you know you can get to via psychedelicsalon.us,
00:56:15 ►
I’ll post links to some of Dennis’ books and papers, including a link to the abstract of the paper he was talking about in this podcast.
00:56:26 ►
the abstract of the paper he was talking about in this podcast. Also, should you have not heard it yet, I’ll post a link to the interview that Joe Rogan did with Dennis not long ago, because in my
00:56:32 ►
opinion, it’s still the best interview that Dennis has ever given. Another thing that may have some
00:56:39 ►
interest for you in the program notes is a photo that Dennis sent me to use here. It’s a picture of him and Wade
00:56:45 ►
Davis that was taken in 1981 on a river trip to the small town of Pegas on the Amazon. It’s a,
00:56:54 ►
I think, really interesting photo, at least to me, because, well, Dennis looks like a very tired
00:57:00 ►
explorer, while Wade Davis looks, well, he looks like he’s posing like a young Hollywood
00:57:05 ►
movie star. It’s an interesting picture. Now, to end today’s podcast, I want to give you a
00:57:14 ►
somewhat fuller picture of Dennis’s relationship to ayahuasca. So, I’m going to read the last few
00:57:20 ►
paragraphs of an article that he wrote and that was published just last month in the
00:57:25 ►
Journal of Psychoactive Drugs. And I want to thank Trevor S. for posting a link to this essay by
00:57:31 ►
Dennis McKenna, and it’s titled, Ayahuasca and Human Destiny. And here’s how Dennis ends.
00:57:40 ►
Within the last 30 years, ayahuasca, clever little plant intelligence that it is, has escaped from its ancestral home in the Amazon and has found haven in other parts of the world.
00:57:53 ►
With the assistance of human helpers who heard the message and heeded it, ayahuasca sent its tendrils forth to encircle the world.
00:58:06 ►
forth to encircle the world. It has found new homes and new friends in nearly every part of the world where temperatures are warm and where the ancient connections to plant spirit still
00:58:10 ►
thrive. From the islands of Hawaii to the rainforests of South Africa, from gardens in
00:58:16 ►
Florida to greenhouses in Japan. The forces of death and dominance have been outwitted.
00:58:23 ►
The forces of death and dominance have been outwitted.
00:58:25 ►
It has escaped them, outrun them.
00:58:30 ►
There is now no way that ayahuasca can ever be eliminated from the earth,
00:58:33 ►
short of toxifying the entire planet,
00:58:39 ►
which, unfortunately, the death culture is working assiduously to accomplish.
00:58:45 ►
Even if the Amazon itself is leveled for cattle pasture or burned for charcoal,
00:58:51 ►
ayahuasca, at least, will survive and will continue to engage in its dialogue with humanity.
00:58:56 ►
And, encouragingly, more and more people are listening.
00:59:01 ►
It may be too late. I have no illusions about this.
00:59:05 ►
Given that the curtain is now being run down on the drunken misadventure that we call human history, the death culture will inevitably become even more brutal and
00:59:11 ►
insane, flailing ever more violently as it sinks beneath the quicksands of time. Indeed,
00:59:17 ►
it is already happening. All you have to do is turn on the nightly news.
00:59:23 ►
Will Ayahuasca survive? I have no doubt that ayahuasca will
00:59:27 ►
survive on this planet as long as the planet remains able to sustain life. The human time
00:59:32 ►
frame is measured in years, sometimes centuries, rarely in millennia. Mere blinks when measured
00:59:39 ►
against the evolutionary time scales of planetary life, the scale on which ayahuasca wields its influence,
00:59:46 ►
it will be here long after the governments, religions, and political power structures
00:59:51 ►
that seem today so permanent and so menacing have dissolved into dust.
00:59:56 ►
It will be here long after our ephemeral species has been reduced to anomalous sediment in the fossil record.
01:00:04 ►
The real question is, will we be here long enough to hear its message,
01:00:08 ►
to integrate what it is trying to tell us,
01:00:11 ►
and to change in response before it is too late?
01:00:16 ►
Ayahuasca has the same message for us now that it has always had
01:00:20 ►
since the beginning of its symbiotic relationship with humanity.
01:00:24 ►
Are we willing to listen?
01:00:26 ►
Only time will tell.
01:00:29 ►
And for now, this is Lorenzo signing off from Cyberdelic Space.
01:00:34 ►
Be well, my friends.