1. University of Debrecen
The Therapeutic Potentials of Ayahuasca and Its Psychoactive Components
2016
Ede Frecska
University of Debrecen
Hungary

2. Offering
In memoriam of the wise people of Pre-Columbian America of whom we know painstakingly little

3. New World crops 3/5 of total food
Grains: amaranth, corn, maygrass, sunflower, wild rice Fruits: avocado, blueberries, cranberries, papaya, passionfruit, pepper, pineapple, pumpkin, tomato Legumes: common bean, lima bean, peanut Meat: llama, turkey Nuts: black walnut, cashew, hickory, pecan Roots and Tubers: manioc, potato, sweet potato Other: chocolate, rubber, maple syrup, tobacco, vanilla, and ayahuasca

4. Altmetric score 38: in the top 5% of all research outputs

5. Ayahuasca components: teacher plants
Harmine (RIMA) + DMT
ayahuasca
Psychotria viridis
yajé
Banisteriopsis caapi
Diplopterys cabrerana

6. A question taken from Jesuits
How do you know what you know
about hallucinogens, psychedelics, whatever you call them?

7. Sign of knowledge? - psychedelics (mind manifesting)
- hallucinogens (producing hallucinations)
- illusogens (producing illusions)
- entheogens (generating the divine within)
- mysticomimetics (mimicking the mystical state)
- oneirogens (generating dreams)
- phanerothymics (making feelings visible)
- phantasticants (eliciting fantasy)
- psychodysleptics (distorting or disrupting the mind)
- psychotomimetics (mimicking psychosis)
- psychotogens (generating psychosis)
- psychotoxins (toxic to the mind)
- schizotoxins (a toxin causing schizophrenia)
- deliriants (causing delirium)
after Strassman, R

8. Psychosis vs. Psychedelic effect proper
Lack of reality control
Involuntary
Comes with defragmentation
Brain imaging studies reveal disorganization
Inability to navigate
In case of experience and right set and setting:
Distinction of “here” and “there”
A condition actively searched for
No defragmentation
Brain imaging studies reveal a different pattern of organization
The experienced user is a “codancer” with the drug (Benny Shanon, 2002)

10. Indigenous groups that used or still use Banisteriopsis caapi
Achual [Jívaro]
Aguaruna [Jívaro]
Amahuaca [Pano]
Anguteros [Tucano]
Awisiri [Auishiri]
Banivas [Arawak]
Barasana [Tucano]
Bares [Arawak]
Campa [Arawak]
Canelos [Quichua]
Carijonas [Caribe]
Cashinahua [Pano]
Cayápa [Chibcha]
Chamicura [Arawak]
Chasutinos [Munichi]
Chayavita [Kahuapana]
Chebero [Kahuapana]
Chocó [Choco]
Colorados [Chibcha]
Conibo [Pano]
Coreguaje [Tukano]
Cubeo [Tukano]
Culina [Arawak]
Desana [Tukano]
Emberá [Chocó]
Eseejja [Takana]
Guahibo [Arawak]
Guanano [Tukano]
Hianakota [Caribe]
Huambiza [Jívaro]
Huaoranis [Sabela]
Huitoto [Uitoto]
Iquito [Záparo]
Ingano [Quechua]
Isconahua [Pano]
Kabuvari [Arawak]
Kamsá [Kamsá]
Kandoshi [Murato]
Kofán [Kofán]
Lama [Quechua]
Macuna [Tukano]
Maihuna [Tukano]
Maku [Maku]
Mandavaka [Arawak]
Marinahua [Pano]
Matsigenka [Arawak]
Mayoruna [Arawak]
Mazán [Yagua]
Menimehe [Tucano]
Noanamá [Chocó]
Omagua [Tupi]
Panobo [Pano]
Piapoko [Arawak]
Pioché [Tukano]
Piro [Arawak]
Puinabe [Makú]
Quijos [Quechua]
Remos [Pano]
Secoya [Tucano]
Sharanahua [Pano]
Shipibo [Pano]
Siona [Tucano]
Taiwano [Tucano]
Tamas [Tucano]
Tarianas [Caribe]
Tatuyo [Tucano]
Tikuna [Tucuna]
Yagua [Yagua]
Zaparo [Záparo]
from Luna, LE

11. Shuars (Jívaro headhunters)
Rafael Karsten
( )
Shuars (Jívaro headhunters)

12. Irving Goldman
( )
Cubeos

13. Initiation of Macuna boys
Richard Evans Schultes
( )
Initiation of Macuna boys

14. Gerardo Reichel-Dolmatoff
Barasanas
Gerardo Reichel-Dolmatoff
( )

15. Shipibos
Luis Eduardo Luna

16. Vernacular names of Banisteriopsis caapi preparations
Ayahuasca (Quechua)
Biaxii (Kamsá)
Caapi, capi, cabi, Caji, Gahpi, Kahi (Tupi)
Caapi pinima, Caapi colorida (Macu)
Cadána, Cadána píra (Tukano del Vaupés)
Caupurí (União do Vegetal)
Cofa, Oofa (Kofán)
Dapa (Noanamá, tierras bajas del Pacífico)
Hananeroca (Matsigenka)
?ko, (Siona)
Iyona (Záparo)
Jagubi (Alto Santo, CEFLURIS, Barquinha)
Jauma (grupos Guaraní del Amazonas medio)
Kamárampi (Matsigenka)
Mihi, mii (Aucas, Ecuador)
Nape, nepe, nep (Chocó, Cayapas, Colorados)
Natema, natem (Shuar)
Natja (Piro)
Njaxe (Coto)
Nishi (Shipibo)
Nixi pae (Cashinahua)
Oni xuma (Amawaca)
Pindé, pildé (Colorados, Cayapas, Emberá)
Purga, Purga huasca (Amazonía peruana)
Ramanujú (Yagua)
Raminó (Katukina)
Santo Daime (Alto Santo, CEFLURIS, Barquinha)
Shuri, rambi, undi (Pano del río Purús)
Timbó branco (Río Tapajos)
Totsha (Piro del Bajo Urubamba)
Trabajo (Meztizos)
Tucondi (Marinahuas)
Uipa (Guahibo)
Uní (Conibo)
Vegetal (União do Vegetal)
Yajé, yagé (Tupi)
from Luna, LE

17. A master of nonlocality

18. Don Emilio Andrade Gómez and Don José Coral, mestizo vegetalistas of Cocama

19. Why indigenous groups of the Upper Amazon take ayahuasca?
One type of use is associated with great collective ceremonies of a magic-religious nature, such as initiation rites for youths, healing rituals, funeral ceremonies, etc. in which manioc beer and other plants such as coca, or tobacco are also consumed. These ceremonies include dances, the interplay of light and shadows, and so on.
A second type of use is associated with more intimate ceremonies in which ayahuasca is usually taken in the dark only by a shaman or a few other people, with the purpose of healing, divination, and for contacting the spiritual world.
from Luna, LE

20. Why Westerners take ayahuasca?
Self knowledge
To find new direction or meaning in life
New perspectives on relationships
A step in their spiritual path/growth
Healing
Forgiveness
Belonging-bonding with others
Communion with the natural world
Desire to change, to be a better person
Finding creativity or inspiration
Curiosity
Because their partner takes it
Not for contacting the spiritual world

21. Psychological effects of ayahuasca
Anxiety with ego-dissolution (gringo effect)
Oceanic boundlessness (narcissistic effect)
Visions (often with mithological content)
Feeling of a wise presence (e.g., a moral teacher)
Cathartic emotions (awe, gratitude, feeling of bliss, being loved, redemption, humbleness)
Insights
life review with lie review
inpact of own deeds on others (bad words are falling back!)
about own motivations and/or social relationships
the ironic or flip side of life situations
what is beyond the mundane
what is under the rug
Cognitive reframing

22. Drug use vs. Psychedelic use proper
Drops out of Life
Tools of escapism:
If it is a “downer”, it helps forgetting and keeps one in the comfort zone
If it is an “upper”, it gives one artificial pleasure
Confronts with Life
In proper set and setting:
Works against denial
Helps to improve insight
Reveals hidden problematic issues
Kicks one out of the comfort zone
“Cleanses the doors of perception” (Aldous Huxley, 1953) e X i s t n Z

23. Possible changes after ayahuasca-assisted treatment of addictions
Participant
Structured Setting
Acute Biological Effects
Direct effect on serotonin receptors
Secondary effects (e.g. on glutamate)
Acute Psychological Effects
Impulse control
Self-reflection, insight
Mystical experience
Acute Sociological effects
Empathy
Tolerant behavior
Social cohesion
Persisting Effects
Neuroplastic changes
Decreased anxiety
Improved mood
Changes in values
Changes in personality
Final Change Mechanisms
Decreased craving
Enhanced self-efficacy
Increased motivation
Reduced Substance Use
After Bogenschutz MP, 2012

24. Why is ayahuasca called as medicine by indigenous groups?

25. Stephen Szára used it first for human research in 1955
An endohallucinogen
Credit to Alex Grey
Dimethyltryptamine (DMT): endohallucinogen acting at the 5-HT1A/5-HT2A+mGlu2 and sigma-1 receptor
Stephen Szára used it first for human research in 1955

26. #1 piece of the mosaic: INMT
The enzyme indolealkylamine-N-methyl transferase (INMT) catalyzes the synthesis of DMT from tryptamine 1
1: Barker, SA et al 1981.

27. #2 piece of the mosaic: lungs
Lungs are the largest reservoir of INMT in human and animal body 1
The INMT gene is fully expressed and INMT is conti-nuously present in high amount during the life span 2 – indicating some sort of “readiness”
An endogenous dialyzable inhibitor keeps it shut off 2,3
1: Thompson, MA et al : Lin, RL et al : Marzullo, G et al 1977.

28. #3 piece of the mosaic: plasma MAO
DMT is not substrate of the plasma monoamine oxidase (MAO) 1 – indicating some sort of “sparing”
1. McEwen, CM & Sober, AJ 1967.

29. #4 piece of the mosaic: active transports
DMT enters the brain in a facilitated manner passing through three barriers with the help of active transport mechanisms 1,2 – indicating some sort of “urgency”
After its uptake, DMT is concentrated and stored in synaptic vesicles up to 1 week 3 – indicating “frugality”
1: Takahashi, T et al : Cozzi, NV et al : Vitale, AA et al 2011.

30. #5 piece of the mosaic: sigma-1 receptor
The sigma-1 receptor (sigmaR-1) is an intracellular chaperone located between the mitochondria and endoplasmic reticulum as part of a safety mechanism against oxidative stress 1
DMT is one of the few endogenous ligands of sigmaR – indicating a vital, physiological role
1: Hayashi, T & Su, TP : Fontanilla, D et al 2009.

31. Characteristics of the DMT effect
strange noise, pulsating bright light, bodily vibrations, paralysis, feeling of presence
sudden transition (through membrane or tunnel), experiencing lucidity, feeling super- reality, entities (reptiles frequently) appear, who operate, communicate, teach (the latter in case of surrender)
review of past events with moral charge
dual presence (being „here” and „over there” at the same time)
Phenomenological similarities with near death experiences (NDEs) and alien abductions
after Strassman, R

32. The last minute scenario
Steps of the final effort to save the queen (the brain) under the ultimate threat of checking out (clinical death):
In response to the first signs of agony the lungs synthetize a huge amount of DMT within seconds
The synthetized DMT is getting dumped into the arterial side of the circulation
Plasma MAO leaves the released DMT intact
While the heart is kicking the lasts, the brain has no time to waste: she uses her three active transport mechanisms for DMT uptake
The concentrated DMT mitigates the effect of hypoxia and prevents apoptotic death of the brain cells

33. What about the first minute scenario?
A similar protective mechanism might come useful in the perinatal period, especially during delivery. Passing through the birth canal represents high risk of hypoxic brain damage to the newborn:
At this developmental stage placenta can be the source of DMT. Indeed, it shows high expression of the INMT gene 1
INMT is an agent of the “child protective services” 2
SigmaR-1 helps neuroplastic recovery of hypoxic damages 3,4
Lung INMT activity is the highest during the first 2 weeks 5
1: Thompson, MA et al : Nuno-Ayala, M et al 2012.
3: Griesmaier, E et al : Yang, ZJ et al : Lin, RL et al 1974.

34. SigmaR-1 dependent effect of NN-DMT treatment on the survival of human
iPSC*-derived cortical neurons and dendritic cells in hypoxic environment
*induced pluripotent stem cell

35. NN-DMT and 5-MeO-DMT alters the cytokine profile of LPS-activated DCs
ELISA
n=4
NN-DMT/5-MeO-DMT:
1h pre-treatment,
100 µM cc.
Szabo and Frecska et al. (2014) PLoS ONE 9:e

36. NN-DMT and 5-MeO-DMT alters the cytokine profile of polyI:C-activated DCs
ELISA
n=4
NN-DMT/5-MeO-DMT:
1h pre-treatment,
100 µM cc.
Szabo and Frecska et al. (2014) PLoS ONE 9:e

37. The role of sigmaR-1 is essential (but not absolute) in the mediation of anti-inflammatory effects.
ELISA
n=3
Szabo and Frecska et al. (2014) PLoS ONE 9:e

38. Conclusion: a paradigm-shift?
The psychedelic effects of DMT represent an island with a huge amusement park on it.
The physiological (somatedelic ) effects of DMT is a continent to be discovered.

39. Investigare necesse est!