Psychedelics

in Addiction Treatment

Chris Stauffer, MDUCSF & SFVAMC, Dept of Psychiatry

Matthew Johnson, PhDJohns Hopkins, Dept of Psychiatry & Behavioral Sciences

Mary Cosimano, MSWJohns Hopkins, Behavioral Pharmacology Research Unit

Boston | November 8, 2019

Disclosure

• No classic psychedelic (e.g., psilocybin, LSD, mescaline) nor MDMA have a current FDA-approved indication for medical use

What is a ”PSYCHEDELIC”?

• Classic Psychedelics (5HT2A agonists)• Psilocybin • LSD (lysergic acid diethylamide)• Mescaline • DMT (N,N-Dimethyltryptamine)

• Empathogen-Entactogen• MDMA• MDA

• Dissociatives• Ketamine

Why PSILOCYBIN?

PsilocybinPsilocybe cubensis(+ >200 other species

of mushroom) Caffeine

Coffee

Maria Sabina, Mazatec curandera

Robert Gordon WassonPsilocybe mexicana

Pharmaceutical Psilocybin

1959: Isolated from P. Mexicana

1960s: Produced by Sandoz, 100’s of legal administrations worldwide

Brown RT, et al. Clin Pharmacokinet. 2017;56(12):1543-1554. Passie T, et al. Addict Biol. 2002;7(4):357-364.

1970: Controlled Substances Act Psilocybin - DEA Schedule 1 substance

1980’s: animal work

1990’s: FDA approves human dose-response study (UNM)

2001: First modern-day psilocybin clinical trial (OCD, UArizona)

Relative Harm of Drugs of Potential Misuse

Nutt D, et. al. The Lancet 2007, 369:1047-1053

van Amsterdam J, et. al. Eur Addict Res 2010;16:202–207

National Survey on Drug Use & HealthThe Substance Abuse & Mental Health Services Administration (SAMHSA)

• Pooled 2008-2012, n > 191,832 (7,550 lifetime psilocybin use)

• Respondents ≥18yo

Lifetime Hx Psilocybin Use vs No Hx Psychedelic Use

weighted odds ratios (95% confidence intervals), *p<.05, **p<.01, ***p<.0001

Psychological distress

Suicidal thinking

Suicidal planning

Suicide attempt

past month past year past year past year

.70 (.60-.81)*** .76 (.64-.90)** .54 (.36-.82)** .58 (.35-.94)*

Hendricks, Johnson, & Griffiths. J Psychopharmacol. 2015; 29(9):1041-1043.

Petri G, Expert P, Turkheimer F, Carhart-Harris R, Nutt D, Hellyer J, & Vaccarino F. (2014) Homological scaffolds of brain functional networks. J. R. Soc. Interface. 11:20140873.

Placebo Psilocybin

•Major Depressive Disorder•Cancer-related anxiety•Migraine/Cluster Headache•OCD•Anorexia•Substance Use Disorders (Nicotine, Alcohol, Cocaine)

PSILOCYBIN –Current Clinical Trials (33)

Psychedelics in Addiction Treatment

Matthew W. Johnson, Ph.D.Associate ProfessorBehavioral Pharmacology Research UnitDepartment of Psychiatry and Behavioral SciencesJohns Hopkins University School of Medicine

• Psilocybin in >100 mushroom species

• “Classic psychedelic”– Psilocybin

– LSD

– Mescaline (peyote)

– DMT (ayahuasca)

1940s – 1970s

• Psychedelics were intensely investigated as research tools and therapeutics

• Promising findings for:

– Cancer-related distress

– Alcoholism

The Dark Ages

• Despite promising preliminary findings, human research with psychedelics became largely dormant

• Dormancy largely a reaction to the association of LSD with the 1960s counterculture

Abuse liability & Risks 2018

• Can cause harm in people with psychosis or predisposition

• For anybody, can cause fear, panic, confusion and potentially dangerous behavior

• Moderate elevations in pulse & blood pressure

• Headaches in day following use

• Persisting perceptual changes

• No addiction

Safety Guidelines 2008• Assisted in the approval of

psychedelic studies by new scientists and universities

• Screening, preparation, monitoring, follow-up

Mystical Experiences & Lasting Benefit 2006 & 2008• Safe in this structured setting• Among the 5 most meaningful life

experiences for majority of people• Improvements in mood and quality

of life >1 year after sessions

Psilocybin Dose Effects 2011• Increasing psilocybin dose has an

orderly effect on mystical experience, challenging experience, and long term positive attribution

Mystical Experience

• About 60% of participants in both studies met criteria for a “complete” mystical experience

• Unity• Noetic quality• Sacredness• Sense of transcending time and space• Positive mood• Ineffability

Psilocybin Increases Openness 2011

• First experimental study to change a personality dimension

• Driven by mystical experience

Driven by Mystical Experience

Addiction Treatment• Classic psychedelics can be misused but are not addictive

Krebs & Johansen (2012)Across studies, LSD nearly doubled the odds that

alcoholic patients would be improved at the 1st follow up (N=536)

Smoking Cessation Pilot 2014

• Feasibility and safety

Pilot Study Timeline

• 15 week protocol with weekly meetings• Cognitive behavioral therapy• 3 psilocybin sessions over 8 weeks (20-30 mg/70 kg)• 1st Psilocybin session on target quit date

Success Rates Substantially Higher than Typical

(Hughes et., 2003; Jorenby et al., 2006; Sykes & Marks, 2001)

Mystical Experience in Smoking Cessation 2015• Greater success in those who

had mystical experience• Mystical experience associated

with craving reduction

Alcohol Dependence Pilot

• 10 alcohol-dependent participants

• Motivational Enhancement Therapy

• 2 sessions of .3 mg/kg and .4 mg/kg psilocybin

Survey Study of Alcohol Cessation

• 343 people claiming to have quit or reduced smoking as the result of a psychedelic experience

• 83% no longer qualified as having a alcohol use disorder

Randomized Comparative Efficacy Trial

• 80 treatment-resistant smokers• Randomized to psilocybin or nicotine patch• Same cognitive behavior therapy• 1 psilocybin session

“Matt Johnson believes that psychedelics can be used to change all sorts of behaviors, not just addiction. The key, in his view, is their power to occasion a sufficiently dramatic experience to ‘dope-slap people out of their story...’ Psychedelics open a window of mental flexibility in which people can let go of the mental models we use to organize reality.’”

The Dope Slap Effect

AcknowledgmentsRoland Griffiths, Ph.D.

Bill Richards, Ph.D.

Mary Cosimano, M.S.W.

Albert Garcia-Romeu, Ph.D.

Brian Richards, Psy.D.

Frederick Barrett, Ph.D.

Maggie Klinedinst

Robert Jesse

Annie Umbricht, M.D

Chad Reissig, Ph.D.

Peter Hendricks, Ph.D.

Katherine MacLean, Ph.D.

Haley Sweet

Samantha Gebhart

Toni White

Fred Reinholdt, M.A.

Leticia Nanda, N.P.

Eric Richter

Grant Glatfelter

Janna Bonesteel

Crystal Barnhouser

Theresa Carbonaro, Ph.D.

Patrick Johnson, Ph.D.

Jenna Cohen

Marylyn Clark

Daniel Emory

Eric Jackson

Heather Cronin

Una McCann, M.D.

Debbie Allan

Kim Nelson

T. Cody Swift, M.A.

Lilian Salinas

Laura Doyle

Nathan Sepeda

John Clifton

Nora Belblidia

Dan Evatt, Ph.D.

David Nichols, Ph.D.

Charles Nichols, Ph.D.

Tehseen Noorani, Ph.D.

FundingHeffter Research Institute

Beckley Foundation

Counsel on Spiritual Practices

Betsy Gordon Foundation

William Harrison

National Institute on Drug Abuse

https://hopkinspsychedelic.orgEmail: mwj@jhu.edu

Psychedelics in Addiction Treatment

Mary Cosimano, MSWBehavioral Pharmacology Research UnitDepartment of Psychiatry and Behavioral SciencesJohns Hopkins University School of Medicine

Johns Hopkins Center for Psychedelic & Consciousness Research

Conducting Psychedelic-Assisted Treatment

Mary Cosimano, MSW Director of Clinical Services

Are Psychedelic Drugs a Panacea?

• Smoking cessation, end-of-life, depression, beginner and long-term meditators

• Tom Insel former director of NIMH• Different symptoms - Same mental formations • Excess rigidity in brain• Destructive narratives• Psychedelics work on locked-in conditions

The Role of the Guide

• Similar for all studies• Each participant assigned 2 guides• Preparation meetings• Psilocybin sessions • Integration meetings

Preparatory Meetings

• 6 to 8 hours - few days to weeks• Developing trust and rapport • Session logistics• Managing high-dose psilocybin sessions• Set: participant’s internal mental state• Setting: external environment

Volunteer on Value of Preparation

“Had it not been for the two experienced researchers in the room, I probably would have had a full- blown panic attack and lost the larger experience.”

Psilocybin Session

⚫ 8 hour day – Lying on sofa – eyeshades - headphones

⚫ Relax and Let go - Expansion of Consciousness⚫ The onset of revelatory experiences seems to

correspond to my success in remaining relaxed.”⚫ Majority have Mystical Experience -

Interconnectedness⚫ Difficult experiences not uncommon⚫ Important and meaningful

Integration Meetings

• Incorporate experiences into daily life• Key Component of Studies• Easy to dismiss• “Integration is weaving the mystical into the practical.”

My Perspective as Guide

• Who am I? What is meaning of my life?• Our Connections – to everything – to life• Love is connection - relationships• Love: true nature, authentic self• Guide – exploration with participant• Each a unique exploration – same method

Personal Belief

• I believe this exploration in combination with the psilocybin sessions and integration, is what leads to reconnection to our true, authentic self— and that helps to find meaning to our lives-

• THAT appears to me to be one of the main outcomes of our psilocybin studies.

Volunteer Quote

• “My single strongest memory will be from the first session when I found myself chasing something that had been eluding me. When I caught it, I discovered that it was me. The subsequent embrace and rejoining seems to me to be the single most powerful event in my life. I feel whole for the first time and able to cope with anything. Apart, “I” was weak and directionless. Listless, really. But together, I’m strong, capable of anything, and just happier.”

Tom “Comfortable and Cozy”

• 59 year old male

• Professional artist

• 41 years smoking a pack a day

• Multiple quit attempts

Tom’s Reasons to Quit

• More energy• More money• More oxygen in his body• Sleep better• Procrastinate less – more productive

• Be healthier

Tom’s Mantra

• “I am confident and content and free to be who I am.”

Tom’s Reasons to Continue Smoking

• Great with coffee• Helped him get away from it all• Helped him focus. • Social aspects important, “It was a way of really bonding with

others – a communion with others.” • An integral part in Tom’s life.

Tom’s First Session

“This is like being present where anything feels possible. I am comfortable to wait and see. I want to share this feeling of being held here, coddled and cozy, just simply being is so unique. It holds me without effort. I am so grateful to be here.”

Tom’s Second Session

“It was one of exultation, fun, joy, and it was child-like. I was taken care of so I was able to expand and see with new eyes.”

“I was made comfortable and cozy, safe and secure.”

Tom’s Third Session

“I felt comfortable and cozy physically, and confident and content mentally. To have both together is a sense of the eternal.”

• Registered a “zero” on Cotinine and CO• who am I going to be in the next 30-40 years• So many possibilities as non-smoker

6 and 12 month follow –up and Beyond…

Another Smoking Volunteer

• Felt hopeless she could quit smoking.• Felt trapped and unhappy in many areas of life.• Successfully quit smoking• Made major changes in her life• Realized smoking masked her depression

6 month follow up report

• “I do feel like the study helped me remember who I was outside of what my life had become. I believe I was depressed, and that is the reason I went back to smoking in the first place. The study allowed me to look at the feelings of depression and process them instead of distracting myself from them by using nicotine.”

• She felt she had gotten her “old” (true) self” back.

Johns Hopkins Session Room

Study Team Funders

⚫ Roland R. Griffiths, Ph.D ⚫ Matthew W. Johnson, Ph.D⚫ Fred Barrett, Ph.D⚫ William A. Richards, Ph.D.⚫ Albert Garcia-Romeu, Ph.D.⚫ Natalie Gukasyan, M.D.⚫ Alan Davis Ph.D⚫ Annie Umbricht, M.D.⚫ Manoj Dos, Ph.D.⚫ Nathan Sepeda⚫ Nora Belblidia⚫ Ian Geithner⚫ Anna Stern⚫ Jessica Lombardi⚫ Brian Winston⚫ BPRU Faculty and Staff

Heffter Research InstituteCouncil on Spiritual PracticesRiverstyx FoundationBetsy Gordon FoundationBeckley FoundationFetzer InstiituteMcCormick FamilyTim FerrissMatt MullenwegCraig Nerenberg,Blake MycosjieStephen and Alexandra Cohen

FoundationNIDA