Renaissance of Psychedelics:A New Medical ParadigmSources:1) How to Change Your Mind:…Science of Psychedelics, by Michael Pollan

2) Coffee w. David E. Nichols, PhD…semi-retired @ UNC Eshelman School of Pharmacy

David C. Sokal, MD

OLLI: Frontiers of Medicine // Science Book Club Sokal, 2019

Overview

Informal poll

1) Renaissance

2) Natural History

3) History – Promise n Crackup

4) What’s a Trip Like?

5) Neuroscience

6) Trip Treatment // Awe

Your thoughts / stories?Sokal, 2019

Poll: in this class…

… what percentage would you guess tried LSD or magic mushrooms in the 1960’s through the 1980’s?

• 10% or less

• 10 to 20%

• 20 to 40%

• Over 40%

… how many of you have tried LSD or magic mushrooms?

2006 – The Renaissance Begins: 3 Events # 1

• 100th Birthday celebration for Albert Hoffman, Swiss chemist who discovered LSD – and he attended! He lived to be 102.

• 3 day symposium at Basel Conference Center; 200 journalists and over 1,000 practitioners / researchers

The Renaissance … 2006 – #2

• Supreme Court Decision –approving use of ayahusca or Hoasca – a Brazilian herbal psychedelic – for religious ceremonies by UDV,* a small religious sect

• Unanimous decision with John Roberts presiding, based on Religious Freedom Restoration Act of 1993, allowing Native Americans to use peyote

* UDV = União do Vegetal, and their website is here

The Renaissance … 2006 – 3rd Event

• Publication by Griffiths @ Hopkins: “Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance.”

• Positive commentaries:• Herbert Kleber, former Drug War /

Bush: “major therapeutic possibilities… NIH support”

• Charles “Bob” Schuster, NIDA under two Republican Presidents: “…landmark paper… might prove useful in treating addiction”

• Harriet de Wit, Univ Chicago: “…time has come…”

Natural History / Early Human Use

Paul Stamets – mycologist• Psicolcybin Mushrooms of the World

• Various Ted Talks

Interesting speculative theories • Did psychedelic experiences

contribute to formation of religions?

• Evolution of plants: did human consumption select for psychedelic strains?

• Did psychedelics effect evolution of human consciousness / language?

Historic Human Use, e.g. by the Mayans

Latin America & Spanish / Catholic Colonization

• Mayan mushroom sacrament –bread & wine paled in comparison

• Catholic priests condemned: “work of the Devil,” and forcibly suppressed its use, and destroyed sculptures

• Seeking the Magic Mushroom(Life Mag., June 10, 1957)

History – Promise n Crackup

Promise:

• Albert Hofmann 1943 @Sandoz

• Research efforts 1950’s – 1960’s

• Clinical breakthroughs

Crackup

• Ken Kesey & the Merry Pranksters

• Timothy Leary – “Turn on, tune in & drop out”

History – Albert Hofmann

• 1943: Hofmann, @Sandoz Pharma, took the first LSD trip.

• Appears to be a very safe and very interesting drug, but what’s it good for?

• 1949 – 1966: Sandoz crowd-sourced research on LSD, supplying researchers in Europe & North America

The Promise: 1950’s & early 1960’s – 1

• What’s it good for?

• “… a window into biochemistry of mental illness…” i.e. what it’s like to be psychotic

• Some alcoholics quit after having the DT’s (delirium tremens) – could LSD mimic that?

• “the power of the experience itself… therapeutic benefit?”

• Led to successful trials of LSD for alcoholism & then other disorders

• “… a window into biochemistry of mental illness…” i.e. what it’s like to be psychotic

• What does that mean?

• Could mental illness really be due to chemical imbalances?

=> Led to research on biochemistry of brain & eventually to new drugs, the SSRI’s – antidepressants like Prozac

The Promise: 1950’s & early 1960’s – 2

• Forgotten history of psychedelic research

• Stephen Ross: “I felt like an archaeologist… in early 50’s, psychedelics had been used to treat… addiction, depression, obsessive compulsive disorder, autism and end-of-life anxiety”

• “American Psychiatric Association had whole meetings centered around LSD, this new wonder drug.” …over a thousand clinical papers … 40,000 study participants

• Bill Wilson, founder of Alcoholics Anonymous, tried to introduce LSD into AA in the 1950’s.

• “Bill W” credited his sobriety to a mystical experience he had in 1934, when given a psychedelic agent at Towns Hospital, Manhattan.

• AA’s second step, to trust in a “power greater than ourselves,” began with a psychedelic experience.

History – Crackup

• 1960 – Leary started at Harvard, after psilocybin in Mexico

• His slogan, “Turn on, tune in, drop out,” helped ignite a panic about psychedelics

• Ken Kesey & the Merry Pranksters –CIA paid volunteer Kesey $75 to take his first dose as part of “MK Ultra.”

• April 1966 – Sandoz stopped providing LSD to researchers

• May, 1966 – Leary testified before a Senate committee

• October, 1966 – FDA halts research

Writers Describing Trips: Michael Pollan

“…my LSD epiphany about the supreme importance of love, following a series of encounters with my wife and son in which I was overwhelmed with gratitude for their existence… the nakedness of the emotions …made them embarrassing to write about… what I had felt and experienced … had the power of a revealed truth.” ineffable: unable to describe in words

Writers Describing Trips: Aldous Huxley

• Huxley – Doors of Perception (page 35):

“This is how one ought to see, how things really are. …

Just looking, just being the divine Not-self of flower, of book, of chair, of flannel.

I longed to be left alone with Eternity in a flower…”

Georgia O’Keefe

Scientist Describing Trips: Griffiths

Roland Griffiths, 2015 Ted Talk on psilocybin with Q’airres designed to measure naturally occurring mystical experiences, most people report:• A sense of unity – all people & things

connected• A sense of sacredness, joy, love• An experience of ultimate realityIt was among the most meaningful experiences of their livesLong term f’up – one year:• Family members / colleagues: positive

changes persistedSokal, 2019

Neuroscience

Default Node Network (DMN)

• Coordinates other parts of the brain, central hub for connections

• Seat of ego / self-consciousness / reflection / rumination

Psychedelics suppress the DMN, and allow / promote? more connectivity

=> feelings: “Not-self” / ego dissolution / unity

Source: Nichols, DE, et al. Psychedelics as Medicines: An Emerging New Paradigm; Clin Pharm & Therapeut, 2017.

Neuroscience – LSD

David Nichols’ 2017 lecture, “LSD Gives up a Secret”

• LSD versus other psychedelics• Extremely potent, i.e. tiny doses• Long duration of action• Oral and iv dosage both take

about a half hour before felt

• Due to lock and key characteristics of LSD molecule and brain cell serotonin receptors

Trip TreatmentSafety Issues*

Avoid bad trips:

• Two guides, pleasant environment, music, eyeshades

• The setting and a person’s expectations influence the trip

Physiologic dangers, e.g. high blood pressure – negligible

Not addictive – rodents n psilocybin vs rodents n opioids

*Comfortable environment and two guides; picture from “Human Hallucinogen Research: Guidelines for Safety,” Griffiths et al, J Psychopharm, 2008.

Trip Treatment(from Griffiths Ted Talk 2015)

Terminally ill cancer patients with depression / anxiety Hopkins & NYU studies (2016)

Smokers

Long-term meditators

Clinically significant improvement in depressed mood. Griffiths, 2015

Trip Treatment

Smokers

• 80% abstinent at 6 month f’up

• Most treatments only 15-30% abstinent at 6 months

Smokers. Griffiths, 2015

Trip Treatment

Long-term meditators (healthy)

• Meditation – learning about your own consciousness

• Psilocybin – a crash course in consciousness

• Beneficial effects reported

In most people – ill or healthy –mystical experiences with positive changes in mood, attitudes and behavior

Two veterans who had had severe PTSD, after taking ayahusca, still from movie trailer, From Shock to Awe.

Trip Treatment

Future directions

• Depression

• Addictive behaviors, e.g. opioids

• Anorexia nervosa

• Post traumatic stress disorder• Movie about veterans – “From

Shock to Awe” trailer

Trip Treatment

FDA status of treatments with psychedelics• August, 2017: FDA Grants “Breakthrough

Therapy” designation for MDMA for PTSD

• October, 2018: FDA Grants “Breakthrough Therapy” designation for psilocybin for treatment-resistant depression

• Right to Try law• If you have PTSD, or treatment-

resistant depression, or a terminal diagnosis, ask your doctor about MDMA or psilocybin, respectively

Breakthrough Therapy designation is … designed to expedite the development and review of drugs … [when] preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy…

Awe: Mechanism of Psychedelic Effects?Hendricks, 2018

• Psychological mechanism

• Spiritual experiences

• Scrooge effect, i.e. quantum change – one or two treatment sessions

• Ideas to explore• Virtual reality => safer than

going outdoors

• Post-treatment: cultivation of awe in nature, art, etc.

Epilogue• 2017 Conference on

Psychedelics – 3,000 attendees

• Panel on Future with Paul Summergrad, frmrhead of Amer PsychiatAssoc, and Tom Insel, frmr head of NIMH

• I’ve added psilocybin to my bucket list ;)

References / more info

• Google talk by Pollan

• ITV News interview – Michael Pollan: Magic mushrooms and LSD could help solve mental health crisis (ITV – UK, second to BBC)

• MAPS (Multidisciplinary Association for Psychedelic Studies)

• Heffter Research Institute Promotes and funds high quality clinical research on psychedelics, founded by David Nichols, now @ UNC, semi-retired.

• Book, with personal stories of healing: “Acid Test: LSD, Ecstasy, and the Power to Heal,” by Tom Shroder, 2014.