A presentation I gave to University of New Mexico medical students on Feb 7, 2022.

1. A New Era in Psychiatry:
Paradigms & Protocols for Difficult to
Treat Mental Health Conditions Using
Psychedelics
For UNM Psychedelic Interest Group
Reid Robison, MD MBA
Chief Medical Officer, Novamind
Feb 7th, 2022

2. How I came to study psychedelics…
● Ketamine clinical work & research since 2011
○ Facilitated thousands of sessions since then, including >5000 Spravato doses since its approval
in 2019, >5000 ketamine sessions
○ First research study in 2011 (Intermountain Foundation grant)
○ Led Janssen’s IV ketamine study for treatment-resistant depression in SLC from 2011 - 2012
○ Group-based Ketamine-Assisted Psychotherapy pilot in 2018-2019 at Center for Change
○ Co-developed Emotion-focused Ketamine-Assisted Psychotherapy (EF-KAP) with Dr. Adele Lafrance
■ Completed Anorexia study in 2020, depression case series, & family-based retreat work
● Ayahuasca retreat work since 2019
○ Found it while exploring new potential ED treatments -- got more than I bargained for
● MDMA research since 2018
○ Coordinating investigator for MAPS MED1 study of MDMA-assisted psychotherapy for eating
disorders
○ Collaborating with MAPS on MDMA IIT for gender minority trauma (Utah & Portland sites)
● Psilocybin research now active in Utah
○ MDD study now recruiting
○ Psilocybin + IFS for eating disorders study plans
○ Psilocybin or cancer-related depression study plans (ongoing in collaboration with Univ of Utah)

3. Psychedelic
Medicines

4. Mainstream treatments fall short for too many people.
Say you’re in a room with 400 adults, chances are nearly 100 of them are going to
develop a diagnosable mental health condition (and only 50 of them will receive
adequate treatment)
The rate of antidepressant use in the US increased by 400% between 1980 to
2000 -- and these things don’t even work that well (i.e. 20-30% attain remission)
Psychedelic medicines, when properly used, and coupled with psychotherapy, are
showing unprecedented promise for those who are suffering.

5. Current Biology 32, R55–R71, January 24, 2022 © 2021 Elsevier Inc

6. Timeline of Psychedelic “Discoveries”
DMT
Synthesized in 1931
MDMA
Synthesized in 1912
LSD
Synthesized in 1938
Psilocybin
Synthesized in 1955
Mescaline
Discovered in 1897
Synthesized in 1918

7. Favorable Safety Profiles
Cases of mental health complications following a
psychedelic are rare (<0.1%), even in vulnerable populations
(<0.2%), and rarer still with proper screening.
No evidence of increased rates of mental health problems,
and psychedelic use has been associated with reduced
psychological distress and suicidality.
Studies examining use patterns in humans & self-administration
in animals suggest that classic psychedelics possess little or no
abuse liability, and may even be anti-addictive.
(Studerus et al., 2011)
(Krebs et al., 2013; Hendricks et al., 2015; Sexton et al., 2019)
(Heal et al., 2018; Winkelman 2014)

8. Tryptamines:
(chemically similar to l-tryptophan, an essential amino acid and serotonin precursor)
● Psilocybin
● DMT
● Ibogaine
Phenethylamines:
● Mescaline
● MDMA
● The 2-C’s
Ergolines:
● LSD
Three Main Classes of Psychedelics

9. 3 Brain Pathways to Induce Hallucinations
1) Activation of dopamine D2 receptors (D2Rs) with psychostimulants
2) Activation of serotonin 5HT2A receptors (HT2ARs) with psychedelics
3) Blockage of glutamate NMDA receptors (NMDARs) with dissociative anesthetics
Psychostimulants
(cocaine, amphetamine)
Dissociative anesthetics
(PCP, ketamine)
Psychedelics
(LSD, psilocybin)
Schizophrenia
(paranoid)
Mechanism D2R activation NMDAR blockage 5HT2AR activation D2R activation &
NMDAR blockage
Main type of hallucination Auditory Visual Visual Auditory
Main type of delusion Paranoid Mixed Mystical Paranoid
Behavior Agitation Social withdrawal Mystical feelings Variable
Insight No Some Yes No
(Pang 2016)

10. SSRIs
5-HT1A receptor signaling -->
reduced limbic responsiveness, aka
emotional blunting.
Psychedelics
5HT2AR signaling → enhanced
sensitivity + emotional release,
combined with psychological
support = therapeutically potent
The serotonin 5-HT2AR receptor is expressed all over the brain, particularly in regions associated with cognitive functions and
social interactions. Stimulation of this receptor has been directly linked to cognitive flexibility, enhanced imagination, and
creative thinking.
Psychedelics vs. SSRIs
The therapeutic potential of psychedelic drugs
RL Carhart-Harris and GM Goodwin

11. Initial blast of serotonin yields
the short term “psychotomimetic”
effects (i.e. trippin’)
The longer-term effects produce a
“loosening” of the mind, and a
general increase in optimism and
well-being.

12. The Paradoxical Properties of Psychedelics
● When Albert Hoffman ingested 250 µg of LSD in 1943:
○ Initially unpleasant experience: altered perception, fear, paranoia
■ Next-door neighbor turned into a ‘malevolent, insidious witch with a coloured mask’
■ He sensed a ‘disintegration of the outer world’, a ‘dissolution of his ego’ and was
‘seized by a dreadful fear of going insane’ (Hofmann 1980)
○ “I then slept, to awake the next morning with a clear head… A sensation of wellbeing and
renewed life flowed through me. Breakfast tasted delicious and gave me extraordinary
pleasure. When I later walked out into the garden, in which the sun shone now after a
spring rain, everything glistened and sparkled in a fresh light. The world was as if newly
created.’
● When LSD was first distributed by Sandoz in 1948, the guidelines stipulated two main
applications:
1) Analytical psychotherapy (LSD could elicit the release of repressed material and
provide mental relaxation for anxiety & obsessional neuroses)
2) Experimental studies on psychosis

13. REBUS: RElaxed Beliefs Under pSychedelics
● How the brain works (aka the hierarchical predictive coding model of cognition).
○ The brain generates mental models that predict upcoming sensory input (“priors”
or “prior beliefs”)
○ These predictive models are layered on top of eachother in a hierarchy
■ The higher levels send predictions down the hierarchy
■ The lower levels report sensory input data up the hierarchy
○ When the top down predictions don’t match the bottom-up sensory input, the
model either:
■ Updates its “priors” based on the new sensory information, or
■ Ignores the sensory inputs and maintains its “prior beliefs”
● Initial ‘blast’ of 5-HT2AR stimulation has a residual influence on brain network dynamics
and associated cognition.
○ This is thought to have a ‘loosening’ or ‘lubricating’ influence on rigid thinking and
this is hypothesized to be conducive to improved psychological wellbeing (Carhart-
Harris 2016)

14. REBUS & How Psychedelics “Relax” Tightly-held Prior Beliefs
● Psychedelics relax the weight of held beliefs/rules/restrictions, allowing them to be more readily
changed
○ Psychedelics “heat up” the brain, increasing plasticity and weakening the influence of prior
beliefs
○ As the brain “cools”, the hierarchy re-forms, though perhaps in a new configuration than
before
■ Explains how lasting changes may persist after the substance is gone
● Psychedelics show particular promise for conditions associated with too-rigid thought patterns
○ i.e. "disorders that may rest on particularly rigid high-level priors that dominate cognition."
○ In these conditions, new information can't revise the existing story of how things are,
because strong priors suppress the new info before it can update anything.
● Psychedelics relax the strong top-down “prior beliefs” (i.e. ‘I can’t eat that because it will make
me fat’) and boost the bottom-up sensory inputs (i.e. intuitive, mindful eating)

15. 15
Psychedelics are like fresh coat of powder. They
provide a break from the everyday patterns, and
let the brain reset the ruts, so we get to choose the
next set of tracks, and end up consciously
arriving at new destinations.

16. Ketamine & Esketamine
in Clinical Practice
at Novamind

17. First – What is ketamine?
1962 Developed by Calvin Stevens at Parke Davis Labs
1965 Professor Edward Domino conducts 1st human studies
Calls ketamine a potent psychedelic; coins the term “dissociative anesthetic”
1970 Approved for human use by the US FDA in 1970 for anesthesia
Widely used in Vietnam war as a battlefield anesthetic
2000 First controlled study of ketamine for major depressive disorder (MDD)
2019 Spravato (esketamine) nasal spray FDA approved for treatment-resistant depression
(TRD)

18. NMDA Receptor Blockade
Mechanism
Blocks NMDA
receptors, leading
to GABAergic
inhibition and a
surge of glutamate
release.
Effect
Rapid
improvements in
mood by restoring
glutamatergic
signaling
Analogy
Wakes up dormant
neurons like jump starting
a car battery; lets them
communicate freely

19. Brain Activity is Reduced
During Depression
Depressed Non- Depressed

20. Lateral Habenular Burst Mode
Mechanism
Turns off “burst
mode” in the lateral
habenula (the “anti-
reward” center)
Effect
A break from
stress mode:
facilitates emotion
processing, reduces
avoidance of negative
affective states
Analogy
Giving a dose of ketamine
is like extinguishing the
“fire” of stress in the brain

21. BDNF & Neuroplasticity
Mechanism
Stimulates BDNF,
leading to
neurogenesis & new
connections
Effect
Neuron growth & a
window of opportunity for
deep therapeutic work*
(neuroplasticity),
including: making new
connections and
strengthening
connections.
Analogy
Ketamine is like fertilizer
for neurons
*Ideally done during the 24-48 hour window of optimal
neuroplasticity after ketamine dosing

22. Limbic/Cortical Interruption
Mechanism
Interrupts connection
between cortex &
limbic system
Effect
Time out from ordinary
mind (decreased
rumination), down
regulation of default
mode network (DMN),
increased cognitive
flexibility
Analogy
Rebooting your
computer

23. Three main ways we work with ketamine at Novamind
Psychedelic
Ketamine-Assisted Psychotherapy
(KAP)
IM (or IV) journeys in the ketamine
room, with brief therapy before and
after, and psychotherapeutic
integration sessions in between
Psycholytic
Ketamine-Assisted Psychotherapy
(KAP)
Lozenges or nasal spray taken
before the session to facilitate
openness & deeper work, with the
therapist present the whole time.
Psychiatric
Ketamine or Spravato as a
medical intervention.
In office, usually starting at twice a
week then decreasing frequency as
tolerated. Optional home dosing for
maintenance (lozenge or nasal spray).

24. Components of Ketamine-Assisted Psychotherapy
● Preparatory Session
○ Medical/Psychiatry screening (if not done previously)
○ Establish rapport, consent & psycheducation
○ Treatment goals
● Dosing session (4-6 sessions)
○ Intention setting prior to dosing
○ Brief/limited processing afterwards
● Integration sessions
○ Ideally within 1-2 days of dosing session
○ Explore material that emerged / draw connections, insights, meaning related to
intentions and day-to-day life

25. Set & Setting

26. Set
Refers to mindset during the experience.

27. Optimizing Mindset for Psychedelic Experiences
● Psychedelic medicines are non-specific amplifiers of what’s in our subconscious
○ If you go in anxious, there’s a risk of this getting ‘amplified’
● Important to note that we are not trying to completely control or direct the experience when we
try to optimize mindset. We want to get out of the way of the medicine and the inner healing
intelligence.
○ Educate about what to expect
○ Make sure they understand the logistics
○ Give them a sense for what it will feel like
■ This will help reduce distracting thoughts, fear, and uncertainty.
● Prime the mind with meditative practices / inner work
● When in doubt, curiosity/surrender/let go. “If there’s a door, open it… etc.”

28. The WHY of Intention Setting
➔ A way to empower you and your experience; individualize the treatment
➔ Important that you really connect with the intention; own it; write it down
➔ An anchor for you in the moment and as you reflect after
➔ The intention often crosses over to an intention in life
➔ An anchor for the meaning making process, especially with the stance that the ketamine
unlocks the inner healer

29. Formula for Intention Setting
First choose one of the following verbs:
➔ Help me with
➔ Teach me about
➔ Show me
Combine it with:
➔ A difficult emotion (fear, anger, guilt, sadness, shame, joy) or
➔ An essential quality (peace, love, compassion, connection – essential human qualities the we might
have become disconnected from, through challenging life experiences)
Examples:
➔ Show me – my fear
➔ Teach me – about love
➔ Help me – experience joy

30. Setting
Refers to the environment during the experience.

31. How to Optimize the SETTING for Psychedelic Experiences
● Setting can shape the experience vs. but we also want it to get out of the way of the medicine
○ Physical comfort:
○ Comfortable clothing, layers and a blanket for temp control
○ Access to bathroom, food, water.
○ chair / couch they are on
○ Eyeshades promote journey inward, but not required.
● Social presence. Private room is great, but not necessary. Everybody in there needs to be
mindful of the energy/noise/attitude they bring into the room.
● Feng Shui: lighting, decor, furniture
● Music.
○ Recommend non-lyrical. Instrumental, chanting, ceremonial drums, ambient nature sounds. A song
change can alter the experience for good or for ill. If they use their own phone they need to turn off
notifications. If they use a music service that inserts ads, they may want to find another way (like use
ours). Playlists on Spotify.
● Clinical presence. You as the facilitator are part of the setting.
○ If their mindset seems to take a turn for the worse, support with safe touch, reminders that they are safe,
coach through relaxation breathing.

32. The Role of Ceremony & Ritual

33. Ceremony & Ritual
● The uncertainty of life can be quite uncomfortable at times
● You can “punctuate” the chaos of life with ceremony / ritual
○ Essentially, you are “sacramentalizing” the mystery of life
○ Collapses chaos into something more predictable / comforting
■ A place of more order, a place of worrying about less, a place for thinking less and feeling
more
● Rituals themselves can be “difficult” at times (like a sweat lodge or vision quest)
○ However, when done with intention / purpose / meaning, we get out of our heads and into our
experience
○ We start to be more accepting of the uncertainty

34. “In the sunlight of awareness,
everything becomes sacred.”
Thich Nhat Hanh

35. Emotion-Focused Ketamine-Assisted Psychotherapy
(EF-KAP, Lafrance & Robison, 2020, efkap.org)
Emotion-Focused Ketamine-Assisted Psychotherapy is an extension of KAP / a treatment
model informed by emotion-focused theory and techniques to facilitate healing and growth
Every aspect of the treatment is guided by two principles:
1. Supporting the emotional health of the patient (inspired by elements of Emotion-Focused Therapy)
a. By focusing on the development of skill and confidence with emotion processing
b. By focusing on transforming emotion with emotion
2. Leveraging the healing power of family (inspired by elements of Emotion-Focused Family Therapy)
a. By providing education and skills to a support person thereby:
b. Strengthening meaningful relationships
c. Creating a recovery-friendly environment outside of the therapy office
d. Extending healing beyond the individual

36. Sample Outline of
Family-Based
Ketamine-Assisted
Psychotherapy
“Intensive Retreat”
Day 1 AM Orientation, goals & intention setting
PM Family & individual psychotherapy
Day 2 AM Intention setting
Ketamine #1
Post-ketamine processing
PM Recovery
Personal integration practices
Day 3 AM Family & individual psychotherapy
PM Family activity
Personal integration practices
Day 4 AM Intention setting
Ketamine #2
Post-ketamine processing
PM Recovery
Personal integration practices
Day 5 AM Family & individual psychotherapy
PM Closing session
Recommendations /Treatment Planning

37. A real-world retrospective study evaluating safety,
efficacy and cost of Spravato
Clinical outcomes of Spravato for treatment resistant depression across multiple clinics.

38. Growing the evidence base for ketamine
A retrospective look at our IM ketamine data

39. Group-based ketamine-assisted psychotherapy pilot
program for COVID-19 frontline workers
● A novel psychedelic therapy protocol offering
critical mental health care for a timely need
● Depression & anxiety scores were measured
weekly
● Mystical experience & emotional
breakthrough scores were measured after
each dosing session
● From the psychedelic literature, and our real-
world data, we know that the mystical
experience can be a predictor of positive
changes

40. MDMA

41. How does MDMA work?
● MDMA, while not a “classic psychedelic”, is unique among consciousness-altering
substances in its ability to promote acceptance of and empathy for self and others.
○ In addition to elevating oxytocin levels, MDMA stimulates the release
of the monoamines serotonin, norepinephrine and dopamine,
resulting in an improved mood and increased sociability.
○ Brain imaging after administering MDMA shows
decreased amygdala activation, and the reduced fear
response that follows allows the client to emotionally
engage in therapy without becoming overwhelmed by
anxiety or negative affective states.

42. Post 3rd
Experimental Session
Post 2nd
Experimental Session
Up to 12 months after treatment,
67% of individuals treated with MDMA-assisted psychotherapy
no longer met criteria for PTSD.
Mithoefer et al., 2019
High
Medium
Low
Baseline
Active (75-125 mg)
Control (0-40 mg)
PTSD Level

44. More on MDMA Expanded Access (aka Compassionate Use)
After obtaining FDA approval, the protocol will be
submitted for DEA and IRB approvals.
The basic requirements of a qualified site include:
1. Treatment Facility conducive to MDMA-
assisted psychotherapy,
2. Therapy Team qualified and able to complete
required training, made up of at least two
therapy providers, and
3. Prescribing Physician who can obtain a DEA
Schedule 1 license for MDMA.

45. If clinical trials are not an option, drug manufacturers may
consider providing access to unapproved investigational
medicines under very specific circumstances.
Most common way for people to
access medicines before they are
approved by the FDA

46. MDMA-assisted psychotherapy for Anorexia Nervosa &
Binge Eating Disorder
● MED1: An Open-Label, Multi-Site Phase 2 Study of the Safety and Feasibility of MDMA-
Assisted Psychotherapy for Eating Disorders
● 12 participants with Anorexia Nervosa
● 6 participants with Binge Eating Disorder
● Protocol:
● Weeks 1-3: three participant preparatory sessions (individual and with caregiver)
● Weeks 4-12:
● Three 8-hour experimental sessions
● Six individual integration sessions
● Three individual + caregiver integration sessions

47. Why MDMA for eating disorders?
TRUST: MDMA increases oxytocin levels, which may
strengthen the therapeutic alliance
FEAR REDUCTION: MDMA increases ventromedial prefrontal
activity and decreases amygdala activity, which may improve
emotional regulation and decrease avoidance
EMOTIONAL ENGAGEMENT: MDMA increases norepinephrine
release and circulating cortisol levels, which may facilitate
emotional engagement and enhance extinction of learned
fear association
1
2
3

48. 48
"I’m tempted to say MDMA gave me ‘hope,’ but that word
isn’t right: the insight was more substantive than hope.
I’d held the sensation in my body; I understood, at a
visceral level, what might someday be mine: the sense
of peace and joy within my body. For me, the therapeutic
process could unfurl from there.”
MDMA Study Participant

49. Group MDMA for Gender Minority Trauma (a multi-site
IIT)
Rationale:
1) Gender diverse people (e.g., anyone not identifying as either cisgender male or cisgender
female) experience trauma & PTSD at higher rates than the general population, yet they have
not been adequately represented in clinical research aimed at investigating new PTSD
treatments. Research shows that gender diverse people experience high levels of stigma &
discrimination, including from healthcare providers, and also experience high rates of
depression & suicidality.
2) Group therapy offers unique healing opportunities and has the capacity to uncover the
resilience of community. Individuals with shared trauma experiences from systemic
oppression may especially benefit from group therapy. In addition, group therapy may act to
reduce cost and increase access to MDMA-assisted psychotherapy, although more research is
needed.

50. Group MDMA for Gender Minority Trauma: Protocol
Protocol synopsis:
● A total of 24 gender diverse individuals (4 cohorts of 6) will be enrolled in the study across two
sites: Portland and Salt Lake City.
● Our group therapy model involves 4 therapists (2 primary and 2 adjunct) for each cohort and
greatly reduces the number of therapist hours compared to standard individual treatment.
● Our team consists of equal numbers of gender diverse therapists and
cisgender therapists trained to conduct MDMA-assisted psychotherapy.
Clinical outcomes to measure:
● PTSD symptoms
● Markers of minority stress
● Symptoms of depression
● Suicidality

51. Psilocybin

52. Maria Sabina, Mazatec Curandera (healer)
● In 1955, R. Gordon Wasson, amateur mycologist (and VP at JP
morgan) and his wife (Valentina Wasson, a pediatrician) to see a
woman named Maria sabina, who was healing the community with
powerful mushroom rituals
● She welcomed Wasson in to one of the rituals, in good faith, allowing
him to take pictures but taking his word that he wouldn't publish
them.
○ She called in the mushroom spirits for healing, and Wasson’s
life was transformed
● In 1957, Wasson published an article in Life Magazine about magic
mushrooms, altered states, and this shamanic lineage
● Americans flocked to Mexico in search of healing and spirituality
● Then the university studies began

53. Psilocybin Research is Back
● Year 2000, psilocybin research began again, after a multi-decade hiatus
● Psilocybin is sometimes called ‘Orally active DMT’
○ Similar chemical structure
● Serotonin mimicking is the hallmark of psychedelic neuroscience .
○ Serotonin allows human consciousness to assemble consensus reality that we inhabit,
and
○ Break down the walls around normal waking consciousness.
● Turns down the default mode network (DMN) -- the neurobiological seat of the ego
○ Which is very active during conditions of vigilance, and depression
○ The DMN is down-regulated in long term meditators.
○ The DMN is very rapidly down-regulated on psilocybin.
■ This may account for some of the antidepressant effects (“a wandering mind is an
unhappy mind”)

54. Psilocybin Dose Finding Study (Griffiths 2016 @ Hopkins)
● 18 healthy volunteers were given four tiers of psilocybin doses and encouraged to lie down in a comfortable
environment with headphones.
○ The study’s aim was to evaluate volunteers’ subjective experiences—positive and negative—at different
doses.
● The highest dose tested was 30 mg of psilocybin per 70 kg participant weight
○ This is roughly equivalent to a 155 lb individual taking ~5 g of dried psilocybe cubensis
● Four out of five volunteers receiving this dose reported the experience was one of the top five most spiritually
significant events of their lives
○ A third of participants also reported a significant psychological struggle.
○ At this higher dose, experiencing fear, anxiety, and stress was more likely.
● At a dose of 20 mg per 70 kg (equivalent to ~3 g of dried psilocybe cubensis), all volunteers reported positive
experiences, and only one experienced any negativity.
● This trend continued for lower doses, with slightly less profundity of experience but still significant, long-lasting
effects.
○ Even the lowest dose of 5mg/70kg found long-lasting positive effects on behavior/attitude/outlook
● Over a year later, the researchers followed up with volunteers and found that 94% still thought that their
experiences were in the top five most spiritually significant of their lives.

55. More on Psilocybin Dosing
● Terence McKenna called a heroic dose 5g (5DGISD= 5 dried grams in silent darkness)
○ Enough to elicit a profound spiritual experience in most
● The doses in Rick Strassman’s studies were almost 8g
○ The doses that we now consider high were just barely threshold in earlier psychedelic studies
● The probability of salient experiences increases with dose, but so does the probability of difficult
experiences.
○ But very often, it’s those deeply uncomfortable experiences that provide a window of opportunity,
through which, if people can investigate and go through, open up into larger experiences.
● The experiences that people describe as difficult, are among the most meaningful and beneficial.
Low dose: Problem solving
Medium dose: Therapy
High dose: Spirituality

56. In a treatment-resistant depression study,
2 doses of psilocybin plus psychological support lead to
improvements in mood within 1 week, with lasting benefits still
seen at 3 and 6 months.
Carhart-Harris et al., 2016
0
Baseline 1 Week
QIDS Score
5
10
15
20
25
2 Weeks 3 Weeks 5 Weeks 3 Months
Hedges’ g
3.1
p=0.002
Hedges’ g
3.2
p=0.002
Hedges’ g
3.2
p=0.002
Hedges’ g
2.7
p=0.003
Hedges’ g
2.0
p=0.003

57. IFS + Psilocybin
● It’s not about the food
● Disordered eating thoughts & behaviors are often ways to deal with the experiences in our life
that overwhelm us with fear, grief, shame and other emotional pain.
● IFS is a form of psychotherapy developed by Richard Schwartz in his therapy sessions with
individuals with eating disorders.
● It acknowledges the innate multiplicity of the mind and starts from the premise that the mind
is composed of relatively distinct subpersonalities or "parts“, i.e. self critical voices, pessimism…
● There are 3 categories of parts
● Exiles: Hold onto the burdens of trauma
● Managers: Take proactive measures to prevent activation of exiles and encounters with similar
painful situations. ex parts that "manage" food intake, sleep, public perceptions, self critical
voices, pessimism etc.
● Firefighters: Soothe exiles when they are activated. They use tools like food, drugs, meditation,
exercise, sex etc. to sooth activated or disrupted systems.

58. Planned feasibility study:
IFS + psilocybin for eating disorders
● Study Design:
● Group therapy preparation, dosing, integration, and follow-up
● Outcome measures:
● Safety and tolerability (vitals, ECG, adverse events)
● Exploring preliminary eating disorders outcomes & changes in functioning

60. ● 10 healthy psychedelic-naive volunteers were given a single oral dose of 0.2-0.3mg/kg psilocybin
○ Anyone with any history of DSM diagnosis was excluded, as was anyone with a first degree
relative with a DSM diagnosis
○ Psychedelic-naive volunteers were chosen because of the potentially long-lasting effects
on 5-HT2AR that one or more past psilocybin doses might have
○ No placebo group
● Neuroimaging:
○ PET neuroimaging of 5-HT2AR (with the area of interest being the neocortex) at baseline
and 1 week later (using radioligand [11C]Cimbi-36, which has great test-retest reliability)
○ This was based on their assumption from past literature that 5-HT2AR levels would have
stabilized 1 week post-dose, and plasma psilocin levels would be zero
○ MRI done at BL and 1 week post-dose as well
Psilocybin Neuroscience (from the Madsen 2019 study)

61. ● Results
○ 8/10 had a “complete mystical experience” (MEQ>60% of max on all 4 sub scales)EDI mean score of 58.2
(range 36.7-79.7)
● Imaging:
○ They did NOT observe a direction-specific change in [11C]Cimbi-36 across individuals
○ They did, however, observe a negative correlation between change in [11C]Cimbi-36 at one-week and change
in mindfulness at three-months.
○ This suggests that psilocybin may indeed affect [11C]Cimbi- 36 levels, but that this effect varies between
individuals and possibly shapes the long-term outcome on mindfulness
● Assessments:
○ NEO-PI-R showed increased openness at 3 mo follow-up (127.0 at BL, 131.2 at 3mo, p=0.04)
○ MAAS scores, which are generally quite stable over time, increased at 3 mo follow-up from 4.2 to 4.6
(p=0.004)
○ The effect size of this is comparable to MBSR mindfulness training
○ Consistent with the findings of the Smigielski et al 2019 paper showing increased mindfulness on
psilocybin as compared to placebo in retreat participants, 1 day post retreat
○ Of note, this study did not include any mindfulness training
● PEQ scores indicated that the psilocybin session enhanced mood, spirituality and outlook on life and self
(consistent with previous studies, i.e. Griffiths 2011)
Psilocybin Study Results

62. ● They replicated the previous finding of long lasting increases in trait Openness after
psilocybin administration
● They showed an increase in mindfulness at 3 mo follow-up, which they point out may
constitute an important part of psilocybin therapy
● On a group level in this study, no differences were found on PET imaging (neocortical 5-
HT2AR binding), however, their finding of a negative correlation between individual change
in 5-HT2AR and mindfulness suggests a possible mechanism for psilocybin’s long term
effects on mindfulness
Psilocybin Study: Take Home Messages