Ayahuasca: Healing Vine of the Soul

Dennis J. McKenna, Ph.D.

Heffter Research Institute
www.heffter.org
 What is Ayahuasca?
#Ayahausca is Quechua for “vine of the souls”
#It is a hallucinogenic beverage that forms an
important component of Amazonian
shamanism and ethnomedicine
#It is the legal “sacrament” for at least three
syncretic religions in Brasil
#It has a reputation (deserved or not) as a
Image of an healing medicine
ayahuasca “spirit”
from the NW #It is also known by other names, e.g. yage,
Amazon
hoasca, natema, etc.
 Ayahuasca has a Unique Pharmacology
#Its psychoactivity depends on a synergy between two
classes of active constituents:
z The leaf admixtures, Psychotria or Diplopterys species,
contain the potent hallucinogen, N,N-Dimethyltryptamine
(DMT)
z DMT alone is not orally active, due to inactivation by
peripheral Monoamine Oxidase (MAO) in the gut and
liver
z DMT can be rendered orally active by co-administration
with an MAO inhibitor
z Banisteriopsis contains harmine and other ß-carboline
alkaloids, which are potent, reversible MAO inhibitors
 CH3 MAO (MONOAMINE OXIDASE)
N DEAMINATES (REMOVES THE
CH3 AMINO GROUP) FROM TRYPTAMINES LIKE
DMT OR SEROTONIN (THE NATURAL
N SUBSTRATE).
H

N,N-dimethyltryptamine (DMT)

MAO (monoamine oxidase)

BLOCKING THE DEGRADATION

OF DMT IN THE LIVER AND GUT
ENABLES IT TO CROSS THE
BLOOD/BRAIN BARRIER IN AN
INTACT FORM
OH

NH C=O
CH3O N
H CH3
N
H
ß-carboline (MAOI)
Indole Acetic Acid (IAA)
MAO INHIBITORS (MAOI)
LIKE THE AYAHUASCA ß-
CARBOLINES BLOCK THIS
REACTION.
 QuickTime™ and a
decompressor
are needed to see this picture.
 Left: preparation of ayahuasca by
Mestizo shamans in Peruvian
Amazon
Below: UDV “preparo” in Manuas,
Brasil. The brew is prepared on an
industrial scale, and it is not
uncommon for several hundred
parishioners to consume it in group
ceremonies

QuickTime™ and a
Photo CD Decompressor
are needed to use this picture

Ceremonial ayahuasca
vessel from the NW
Amazon
In the preparo, the quality is
assessed, by both appearance and
bioassay
 The visionary states
induced by ayahuasca
resemble dreams or other
psychedelic states like
those induced by
psilocybin mushrooms.
For the ayahuasquero,
they are a window into a
supernatural realm of
myth and symbol, magic
and witchcraft.

The ayahuasca state is the

dimension in which
ayahuasqueros can do
their healing, or the
brujos do their harm.

“SYNAESTHESIA” BY PABLO AMARINGO, PERUVIAN PAINTER &

AYAHUASQUERO
 PERUVIAN AYAHUASQUEROS

Don Jose Coral, Curing

Don Emilio Andrade,
Don Fidel & Don Jose, Iquitos
Pucallpa

Don Jose Coral, Smoking

Mapacho
Don Jose Coral at age 99. One of
the last of the “old school” of
Ayahuasqueros.
Iquitos, Spring 2006
 The UDV/Hoasca Study
The UDV is a Brasilian
religious group that uses
ayahuasca as a sacramental
substance (their term for the
brew is “hoasca”)

In 1993 at the UDV’s invitation I participated in a biomedical study of

long-term hoasca drinkers that came to be known as the Hoasca Study

It was a truly international collaboration of scientists, including

physicians, pharmacologists, chemists, and psychiatrists from the US,
Brasil, and Finland
Hoasca Study Results
The results of the Hoasca Study have been published in over 8 peer-
reviewed publications. The study sparked a revival of
research interest in ayahuasca.
Growth in Peer-Reviewed
Publications on Ayahuasca
45
40
# of Publications

35
30
25
20
15
10
5
0
1980-85 1986-1990 1991-95 1996-2000 2001-2007
 Key findings from the Hoasca
study
# No evidence of acute toxicity
# No evidence of neurological, cognitive, or personality dysfunctions
in long-term users
# Strong evidence of positive behavioral changes
z Most members had histories of drug abuse, alcoholism and domestic
violence before joining the UDV
z Initial terrifying experiences with ayahuasca helped them to change
lifestyle in a more positive direction
z Effects of supportive context are hard to separate from effects of
ayahuasca
 Upregulaton of Serotonin Transporters
An unexpected finding was that long-term users had significantly elevated densities
(Bmax) of serotonin transporters in platelets compared to matched controls

Receptor affinity (Kd) was not significantly different between groups

J. C. Callaway, M. M. Airaksinen, Dennis J. McKenna, Glacus S. Brito, & Charles S. Grob (1994) Platelet serotonin
uptake sites increased in drinkers of ayahuasca. Psychopharmacology 116: 385-387

1200 4
Bmax (fm/mg protein)

*
1000 3 Controls
Controls Kd (nM) UDV
800
UDV
600 2
400 1
200
0 0
 Deficits of brain 5HT transporters and other monoamine
transporters
Have been associated with:
z Alcoholism (Type II Alcoholism)
z Early onset alcoholism & violent/homicidal behavior
z Suicidal behaviors
z Binge eating

Mantere T, Tupala E, et al. Serotonin transporter distribution and density

in the cerebral cortex of alcoholic and nonalcoholic comparison subjects:
a whole-hemisphere autoradiography study. Am J Psychiatry. 2002
Apr;159(4):599-606.

Hallikainen T, Saito T, Lachman HM, et al. Association between low

activity serotonin transporter promoter genotype and early onset
alcoholism with habitual impulsive violent behavior. Mol Psychiatry. 1999
Jul;4(4):385-8.
 Unanswered questions:
THE CORRELATION OF POSITIVE
Could long-term use of ayahuasca actually reverse
BEHAVIORAL CHANGES IN LONG-
these transporter deficits?
TERM MEMBERS OF THE UDV WITH
LONG-TERM
Could it thereforeELEVATION IN THE
be used in the treatment of
alcoholism andOF
DENSITIES other behavioral dysfunctions
SEROTONIN
associated with reduced
TRANSPORTERS SUGGESTS A transporter expression?
POSSIBLE NEUROCHEMICAL
MECHANISM FOR THE BEHAVIORAL
CHANGES.
Pablo Amaringo: The Plant Teachers