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Ayahuasca: Healing Vine of the Soul

Ayahuasca: Healing Vine of the Soul Dennis J. McKenna, Ph.D. Heffter Research Institute www.heffter.org

Dennis J. McKenna, Ph.D. Heffter Research Institute www.heffter.org

What is Ayahuasca?

What is Ayahuasca? Image of an ayahuasca “spirit” from the NW Amazon Ayahausca is Quechua for

Image of an ayahuasca “spirit” from the NW Amazon

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 healing medicine It is also known by other names, e.g. yage, hoasca, natema, etc.

Ayahuasca has a Unique Pharmacology

Its psychoactivity depends on a synergy between two classes of active constituents:

The leaf admixtures, Psychotria or Diplopterys species, contain the potent hallucinogen, N,N-Dimethyltryptamine (DMT) DMT alone is not orally active, due to inactivation by peripheral Monoamine Oxidase (MAO) in the gut and liver DMT can be rendered orally active by co-administration with an MAO inhibitor Banisteriopsis contains harmine and other ß-carboline alkaloids, which are potent, reversible MAO inhibitors

MAO (MONOAMINE OXIDASE)

DEAMINATES (REMOVES THE AMINO GROUP) FROM TRYPTAMINES LIKE DMT OR SEROTONIN (THE NATURAL SUBSTRATE).

N CH 3 N H NH N H CH 3 N
N
CH 3
N
H
NH
N
H
CH 3
N

N,N-dimethyltryptamine (DMT)

CH 3 O

OH

C=O

CH 3

CH 3 N N,N-dimethyltryptamine (DMT) CH 3 O OH C=O CH 3 MAO (monoamine oxidase) BLOCKING

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

ß-carboline (MAOI)

MAO INHIBITORS (MAOI) LIKE THE AYAHUASCA ß- CARBOLINES BLOCK THIS REACTION.

H

Indole Acetic Acid (IAA)

QuickTime™ and a decompressor are needed to see this picture.
QuickTime™ and a decompressor are needed to see this picture.

QuickTime™ and a decompressor are needed to see this picture.

Ceremonial ayahuasca vessel from the NW Amazon
Ceremonial ayahuasca
vessel from the NW
Amazon
Left: preparation of ayahuasca by Mestizo shamans in Peruvian Amazon Below: UDV “preparo” in Manuas,
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
re needed to use this picture

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

Don Jose Coral, Curing

PERUVIAN AYAHUASQUEROS

PERUVIAN AYAHUASQUEROS

PERUVIAN AYAHUASQUEROS
PERUVIAN AYAHUASQUEROS
PERUVIAN AYAHUASQUEROS
PERUVIAN AYAHUASQUEROS

Don Fidel & Don Jose, Pucallpa

Don Emilio Andrade, Iquitos

Don Jose Coral, Smoking Mapacho

Don Jose Coral at age 99. One of the last of the “old school” of

Don Jose Coral at age 99. One of the last of the “old school” of Ayahuasqueros. Iquitos, Spring 2006

Don Jose Coral at age 99. One of the last of the “old school” of Ayahuasqueros.
Don Jose Coral at age 99. One of the last of the “old school” of Ayahuasqueros.
Don Jose Coral at age 99. One of the last of the “old school” of Ayahuasqueros.

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”)

substance (their term for the brew is “hoasca”) In 1993 at the UDV’s invitation I participated

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 35 30 25 20 15 10 5 0 1980-85 1986-1990 1991-95 1996-2000 2001-2007
45
40
35
30
25
20
15
10
5
0
1980-85
1986-1990
1991-95
1996-2000
2001-2007
# of Publications

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

Most members had histories of drug abuse, alcoholism and domestic violence before joining the UDV Initial terrifying experiences with ayahuasca helped them to change lifestyle in a more positive direction Effects of supportive context are hard to separate from effects of ayahuasca

lifestyle in a more positive direction Effects of supportive context are ha rd to separate from
lifestyle in a more positive direction Effects of supportive context are ha rd to separate from

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

Bmax (fm/mg protein)

1200

1000

1000

800

800

600

600

400

400

200

0

*

Bmax (fm/mg protein) 1200 1000 800 600 400 200 0 * Controls UDV
Bmax (fm/mg protein) 1200 1000 800 600 400 200 0 * Controls UDV
Bmax (fm/mg protein) 1200 1000 800 600 400 200 0 * Controls UDV
Bmax (fm/mg protein) 1200 1000 800 600 400 200 0 * Controls UDV
Bmax (fm/mg protein) 1200 1000 800 600 400 200 0 * Controls UDV
Bmax (fm/mg protein) 1200 1000 800 600 400 200 0 * Controls UDV
Bmax (fm/mg protein) 1200 1000 800 600 400 200 0 * Controls UDV
Bmax (fm/mg protein) 1200 1000 800 600 400 200 0 * Controls UDV
Bmax (fm/mg protein) 1200 1000 800 600 400 200 0 * Controls UDV
Bmax (fm/mg protein) 1200 1000 800 600 400 200 0 * Controls UDV
Bmax (fm/mg protein) 1200 1000 800 600 400 200 0 * Controls UDV
Bmax (fm/mg protein) 1200 1000 800 600 400 200 0 * Controls UDV

ControlsUDV

UDVControls

Kd (nM)

4

3

2

1

0

Kd (nM) 4 3 2 1 0 Controls UDV
Kd (nM) 4 3 2 1 0 Controls UDV
Kd (nM) 4 3 2 1 0 Controls UDV
Kd (nM) 4 3 2 1 0 Controls UDV
Kd (nM) 4 3 2 1 0 Controls UDV
Kd (nM) 4 3 2 1 0 Controls UDV
Kd (nM) 4 3 2 1 0 Controls UDV
Kd (nM) 4 3 2 1 0 Controls UDV
Kd (nM) 4 3 2 1 0 Controls UDV
Kd (nM) 4 3 2 1 0 Controls UDV
Kd (nM) 4 3 2 1 0 Controls UDV
Kd (nM) 4 3 2 1 0 Controls UDV

ControlsUDV

UDVControls

Deficits of brain 5HT transporters and other monoamine transporters

Have been associated with:

Alcoholism (Type II Alcoholism) Early onset alcoholism & violent/homicidal behavior Suicidal behaviors Binge eating

Alcoholism (Type II Alcoholism) Early onset alcoholism & violent/homicidal behavior Suicidal behaviors Binge eating
Alcoholism (Type II Alcoholism) Early onset alcoholism & violent/homicidal behavior Suicidal behaviors Binge eating
Alcoholism (Type II Alcoholism) Early onset alcoholism & violent/homicidal behavior Suicidal behaviors 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

BEHAVIORAL CHANGES IN LONG-

TERM MEMBERS OF THE UDV WITH

LONG-TERM ELEVATION IN THE

DENSITIES OF SEROTONIN

TRANSPORTERS SUGGESTS A POSSIBLE NEUROCHEMICAL MECHANISM FOR THE BEHAVIORAL CHANGES.

Pablo Amaringo: The Plant Teachers
Pablo Amaringo: The Plant Teachers