Clinical trial NCT00957359
Conditions: Cancer
Keywords: Cancer Anxiety Depression Hallucinogens
Sponsor: NYU Langone Health
Start date: 2009-02-01; Completion date: 2018-09-06
Enrollment: 29 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
The primary objective of this double-blind, placebo-controlled pilot study is to assess the efficacy of psilocybin administration (4-phosphoryloxy-N,N-dimethyltryptamine), a serotonergic psychoactive agent, on psychosocial distress, with the specific primary outcome variable being anxiety associated with cancer. Secondary outcome measures will look at the effect of psilocybin on symptoms of pain perception, depression, existential/psychospiritual distress, attitudes towards disease progression and death, quality of life, and spiritual/mystical states of consciousness. In addition, a secondary objective of the study is to determine the feasibility of administering psilocybin to this patient population, with regards to the following issues: safety, patient recruitment, consent for treatment, and retention. The duration of the proposed investigation will be long enough to administer the drug one time to each of thirty-two patients and to conduct follow-up assessments. This study is separate but similar to a recently completed study at the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, run by a psychiatrist, Dr. Charles Grob. Although the outcomes measures would be similar to those used as in the Grob study, the proposed dose of psilocybin is higher at 0.3mg/kg and the total subjects for the study would be 32 instead of 12. The study utilizes a cross-over design at 7 weeks and includes prospective follow-up of 6 months duration. This study has been approved by the Bellevue Psychiatry Research Committee, the NYU Oncology PRMC Committee, the Food and Drug Administration (FDA) through the issuance of an IND (77,138), the New York University School of Medicine Institutional Review Board (NYU IRB), the Health and Hospitals Corporation (HHC)-New York University (NYU) Clinical Translational Science Institute (CTSI), the NYU Bluestone Center for Clinical Research, and the Drug Enforcement Agency (DEA) through the issuance of a schedule I license.

It is hypothesized that a one time experience with psilocybin will occasion dramatic shifts in consciousness and awareness that will lead to short-term (ie hours to days) and long-term (up to 6 months in this study, following the administration of the second dosing, either psilocybin or placebo) improvement in anxiety, depression, and pain associated with advanced cancer. The exact mechanism of action is unclear but based on studies done in the 60's using serotonergic hallucinogens in patients with advanced cancer, improvements in anxiety levels, mood and pain were reported. However, a treatment model developed by the famous British psychiatrist Humphrey Osmond, offers one possibility. In this model, serotonergic hallucinogens' therapeutic mechanism lies in their ability to allow the individual to access novel dimensions of consciousness and their efficacy or lack thereof relies on whether a transcendent and mystical state of awareness is attained. Another possible mechanism relates to what Dobkin de Rios and Grob have described as 'managed altered states of consciousness,' where the power of suggestibility, occurring in a safe setting, allows one to transcend a particular state of consciousness (i.e. anxiety and depression associated with advanced illness) as a means to facilitate emotional discharge and to manage irreconcilable conflict.

Detailed description:

Arms: arm 1: Drug intervention arm 2: Active control
Interventions: intervention 1: Psilocybin intervention 2: Niacin
Intervention descriptions: intervention 1: Psilocybin is a serotonergic hallucinogen that will be administered once at a dose of 0.3mg/kg intervention 2: Psilocybin and niacin will be administered in identically appearing opaque, size 0 gelatin capsules with approximately 180ml of water. The niacin dose will be 250mg

Protocol documents:
Prot_SAP_000.pdf: 
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Effects of Psilocybin on Anxiety and Psychosocial Distress in Cancer Patients
Principal Investigator: 
Stephen Ross MD 
R#:06-954
Assistant Professor of Psychiatry, Child & Adolescent Psychiatry and Oral & Maxillofacial Pathology, 
Radiology and Medicine
Director, Division of Alcoholism and Drug Abuse, Bellevue Hospital
Director, Clinical Core, NYU Langone Center of Excellence on Addiction
Director, NYU Addiction Psychiatry Fellowship 
NYU School of Medicine
NYU College of Dentistry
(212) 562-4097; fax (212) 562-2041
Co-Principal Investigator:
Anthony Bossis PhD
Clinical Psychologist
Clinical Assistant Professor 
Departments of Psychiatry and Anesthesiology
NYU School of Medicine
Co-Principal Investigator:
Jeffrey Guss, MD
Assistant Professor of Clinical Psychiatry
Department of Psychiatry
NYU School of Medicine
Co-Principal Investigator:
Mary-Lynn Nierodzik MD
Assistant Professor
Director, Bellevue Cancer Center
Department of Medicine (Hematology)
NYU School of Medicine
Co-Principal Investigator:
Brian L. Schmidt, MD, DDS, PhD
Professor, Department of Physiology and Neuroscience, and Oral and Maxillofacial Surgery
Director, Bluestone Center for Clinical Research
Director, NYU Oral Cancer Prevention and Treatment Center
Co-Leader, Epidemiology and Cancer Control Program, NYU Cancer Center
NYU School of Medicine
NYU College of Dentistry


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Objective:
The primary objective of this double-blind, placebo-controlled pilot study is to assess the efficacy of 
psilocybin administration (4-phosphoryloxy-N,N-dimethyltryptamine), a serotonergic psychoactive agent, on 
psychosocial distress, with the specific  primary outcome variable being anxiety associated with cancer. 
Secondary outcome measures will look at the effect of psilocybin on symptoms of pain perception, depression, 
existential/psychospiritual distress, attitudes toward disease progression, quality of life, and spiritual/mystical 
states of consciousness. In addition, a secondary objective of the study is to determine the feasibility of 
administering psilocybin to this patient population, with regards to the following issues:  safety, patient 
recruitment, consent for treatment, and retention. The duration of the proposed investigation will be long 
enough to administer the drug one time to each of thirty-two patients and to conduct follow-up assessments. 
This study would be separate but similar to a completed study at the Los Angeles Biomedical Research Institute 
at Harbor-UCLA Medical Center, run by a psychiatrist, Dr. Charles Grob, and an oncologist, Dr. Rowan 
Chlebowski. Although the outcomes measures would be similar to those used as in the Grob study, the proposed 
dose of psilocybin would be somewhat higher at 0.3mg/kg and the total number of subjects randomized for the 
study would be 31 instead of 12 (see below explanation and justification). This study has been approved by the 
Bellevue Psychiatry Research Committee, the Oncology PRMC Committee, the Food and Drug Administration 
(FDA) through the issuance of an IND (77,138), the NYU IRB and the NYU-HHC Clinical and Translational 
Science Institute (CTSI) (previously known as the Bellevue General Clinical Research Center GCRC). 
Hypothesis/Potential Mechanism of Action:
It is hypothesized that a one time experience with psilocybin will occasion significant shifts in 
consciousness and awareness that will lead to short-term (i.e. hours to days) and long-term (up to 5 years in this 
study following the second experimental session) improvement in anxiety, depression, and pain associated with 
cancer. The exact mechanism of action is unclear but based on studies conducted with similar serotonergic 
agents in patients with advanced cancer, improvements in anxiety levels, mood and pain were reported (Grof 
and Halifax 1977; Kast 1970). However, a treatment model developed by the British psychiatrist, Humphrey 
Osmond, offers one possibility. In this model, serotonergic hallucinogens’ therapeutic mechanism lies in their 
ability to allow the individual to access novel dimensions of consciousness and their efficacy or lack thereof 
relies on whether a significant reappraisal or alteration in perception is attained (Osmond 1957). Another 
possible mechanism relates to what Dobkin de Rios and Grob have described as ‘managed altered states of 
consciousness,’ where the power of suggestibility, occurring in a safe setting, allows one to transcend a 
particular state of consciousness (i.e. anxiety and depression associated with cancer) as a means to facilitate 
emotional discharge and to manage irreconcilable conflict (Dobkin de Rios, Grob, & Baker 2002). 
Rationale and Background:
Despite improvements in the understanding and treatment of cancers within the last several decades that 
has led to increases in survival rates, addressing the physical and psychological needs of cancer patients remains 
an inadequately understood and understudied area of focus. In addition to the physical pain associated with 
cancer, a diagnosis of a potentially life threatening illness often provokes considerable psychological and 
existential distress for many patients that can involve anxiety, depression, anger, denial and social isolation.  
These psychological symptoms, in addition to issues such as loss of perceived self-worth, hopelessness, 
helplessness and loss of independence, have been associated with significant suffering for the patient coping 
with cancer.  Indeed, psychosocial issues, specifically depression and hopelessness rather than pain and 
discomfort have been found to be the strongest predictors of desire for hastened death in an advanced cancer 
population (Breitbart et al 2000). The current system of care for patients with advanced cancer is often 
successful in increasing the amount of time the patient has to live, but very little is customarily done to enhance 
the quality of intrapsychic and interpersonal experiences during the patient's final months. This led the National 
Cancer Policy Board of the Institute and the National Research Council to issue a report in 2001 calling for 


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more research to develop novel therapies aimed at palliative treatment in patients with advanced cancer (Foley 
& Gelband 2001). The recent and prominent emergence of the discipline of palliative care has emphasized the 
need for research and clinical therapies to address the severe and debilitating emotional suffering associated 
with advanced illness cancer patients. 
Historically, agents such as psilocybin have been considered and studied as novel therapeutic agents in 
the treatment of patients with advanced cancer. From the late 1950s to the early 1970s, investigators trained and 
authorized to administer serotonergic hallucinogens to carefully selected patients with advanced cancers, 
suffering from significant psychospiritual distress, in highly structured and controlled settings described a 
number of case reports and clinical research studies with promising treatment outcomes. Experimental work 
with these agents in patients with advanced illness began with the use of d-lysergic acid diethylamide (LSD) in 
an attempt to reduce the pain of cancer patients.  Eric Kast, a Chicago internist, published a series of reports in 
the early and mid-1960s reporting on the safety of the use of LSD in patients with advanced cancer and 
describing superior analgesic effects, relief of depression, improved sleep and lessened fear of death. (Kast, 
1966; Kast, 1970; Kast & Collins, 1964). In one study, 100mg of LSD was compared with two short acting 
opiate mu agonists, hydromorphone and meperidine on 50 patients with cancer and gangrene, who were in 
severe pain. LSD was more effective at pain relief compared to the opiates in that the pain relief lasted several 
days as opposed to the opiates where the pain relief was short lived, on the order of several hours. (Kast & 
Collins 1964). Kast believed that the mechanism of pain management was mediated by “attenuation of 
anticipation,” a diminution of the anxiety associated with perceived loss of control in the process of having a 
potentially life threatening illness. (Kast 1970).  In addition to the analgesic properties of LSD, Kast concluded 
that the treatment was capable of not only improving the psychological adjustments of patients with advanced 
illness by making them more responsive to their environments and families, but also of enhancing their ability 
to appreciate the aesthetic satisfaction associated with the subtleties of everyday life. 
In an effort to systematically examine the effects of serotonergic hallucinogens on patients with 
advanced medical illness, Walter Pahnke and Stanislav Grof of the Maryland Psychiatric Research Institute at 
Spring Grove State Hospital in Maryland conducted a series of experiments from the mid 60s to the mid 70s. 
Advanced cancer patients were treated with either LSD or dipropyltryptamine (DPT). It was determined that 
both agents were safe to use in this patient population across a spectrum of patients with advanced cancer, 
including those with central nervous system involvement. Regarding overall quality of life measures, 29% of 
the subjects reported dramatic improvement, and another 41.9% had sustained moderate improvement, with 
22.6% essentially unchanged and only 6.4% with an apparent deterioration of status.  A reduced need for 
narcotic analgesia was also observed. (Grof, et al, 1973; Richards et al, 1972, Grof & Halifax, 1977).  
One early and prolific hallucinogen investigator, Sidney Cohen of UCLA published a moving account of 
his views of the potential value of this treatment model in Harper's Magazine entitled “LSD And The Anguish 
Of Dying.”  Cohen in the mid-1960s was sufficiently impressed with the medical administration of 
hallucinogens under highly structured conditions to speculate on the implications of what he had observed: 
“Death must become a more human experience.  To preserve the dignity of death and prevent the living from 
abandoning or distancing themselves from the dying is one of the great dilemmas of modern medicine... LSD 
(and other hallucinogens) may one day provide a technique for altering the experience of dying." (Cohen, 1965).
The first attempt to re-study the safety and efficacy of psilocybin in patients with potentially life 
threatening cancer began in 2004 in a study that is now completed  at the Los Angeles Biomedical Research 
Institute at Harbor-UCLA Medical Center, run by a psychiatrist, Dr. Charles Grob, and an oncologist, Dr. 
Rowan Chlebowski. It was a double-blind placebo-controlled study that included patients with Stage IV cancer 
and anxiety. The approved oral dosage given of psilocybin was 0.2mg/kg and a total of 12 patients were 
studied. There were several medical exclusion criteria including renal disease, abnormal liver function tests, 
epilepsy, and cardiovascular illness, as well as psychiatric exclusion criteria including the presence of major 
mental illness and active substance abuse. This study was funded by the Heffter Research Institute and was 
FDA approved. The study had a prospective follow-up arm that followed patients for up to 6 months post-
treatment of psilocybin. The study was recently published in the Archives of General Psychiatry in September 


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2010 (Grob 2010). The results were as follows: ‘Safe physiological and psychological responses were 
documented during treatment sessions. There were no clinically significant adverse events with psilocybin. The 
State-Trait Anxiety Inventory train anxiety subscale demonstrated a significant reduction in anxiety at 1 and 3 
months after treatment. The Beck Depression Inventory revealed an improvement of mood that reached 
significance at 6 months; the Profile of Mood States identified mood improvement after treatment with 
psilocybin that approached but did not reach significance.’ This study established the safety and feasibility of 
administering a moderate dose of psilocybin to patients with advanced cancer and anxiety. Some of the data 
suggested a treatment effect with reduction in anxiety and depressive symptoms. 
In addition to the above study by Dr. Grob, another recent study conducted at Johns Hopkins by Roland 
Griffiths and colleagues showed that psilocybin can safely be given to normal volunteers without prior 
experience with serotonergic hallucinogens in a highly supervised setting (Griffiths 2006). The study was a 
double-blind design where 0.43 mg/kg of oral psilocybin was compared with 0.57mg/kg of oral 
methylphenidate, where both agents were given to subjects in counterbalanced order. Significantly, 67% of the 
subjects rated the experience with psilocybin as either the single most meaningful experience of his or her life 
or among the top five most meaningful experiences of his or her life. Also, sixty-one percent of subjects who 
received psilocybin met criteria for a ‘complete’ mystical experience, significantly increased compared to only 
11% who received methylphenidate. Prospectively, at the two month follow-up period, compared to the 
methylphenidate experience, the psilocybin experience was significantly associated with subjective reports of 
greater improvement in the following domains: positive attitudes about life and oneself, positive mood, 
altruistic/positive social effects, and positive behavioral changes. These subjective reports were confirmed by 
community observer ratings of changes in the subjects’ behavior and attitudes.  In a long-term follow-up to this 
2006 study, Griffiths et al. reported in a 2008 published article that at 14 months later subjects reported a 
persistent and statistically significant sense of well-being and life satisfaction (Griffiths, Richards, Johnson, 
McCann and Jesse, 2008). As part of future implications for further research with psilocybin, Dr. Griffiths cites 
two patient populations as potentially benefiting from psilocybin: those with potentially life threatening illness 
and addicted patients. In fact, Dr. Griffiths is currently conducting a study testing the use of psilocybin in 
patients with medium to advanced stage cancer (Griffiths Personal Communication 2007, 2010). 
PROTOCOL
Objectives and Purpose of the Study:
This is a pilot study of a single treatment designed to preliminarily evaluate the effect of psilocybin in 
patients with cancer and anxiety. Secondary outcome measures will be pain perception, depression, and 
existential / psychospiritual distress. Also, issues related to the feasibility of using psilocybin in patients with 
cancer and anxiety will be described.  The study will look at both short-term, immediate effects as well longer-
term effects. We plan to collect and analyze data up to 6-months post the second drug administration for all 
enrolled participants. Participants who complete a psilocybin dosing session and agree to be contacted will be 
invited to partake in two optional data collection time points, which will look at long-term psychological effects 
of psilocybin-assisted psychotherapy.. Subjects’ participation in these two additional longitudinal timepoints 
will be optional and will not affect their previous study involvement as research participants. Study participants 
who opt out or who do not have the option to participate (for example, if they are deceased) will be classified (ie 
study completers, withdrawn, treatment dropout, etc.) as they were in the main portion of the study.  
Participants do not need to complete all questionnaires given at previous time points to be eligible to participate 
in optional time points T13 and T14. 
Criteria for patient selection (Inclusion/Exclusion Criteria)
The proposed project will involve up to 47 subjects 18-76 years of age.  Subjects will have a current or 
historical diagnosis of cancer with a projected life expectancy of approximately 6 months or more and a DSM-
IV psychiatric diagnosis, as determined by the Structural Clinical Interview for DSM-IV (SCID), of one of the 
following Anxiety Disorders:  Acute Stress Disorder, Generalized Anxiety Disorder, Anxiety Disorder Due to 
cancer, or Adjustment Disorder with Anxiety. The cancer could be: at any stage of active illness; potentially life 


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threatening, advanced, or recurrent; or the participant could have a history of a cancer diagnosis and currently 
be in remission or considered ‘cured’ as long as they continue to have anxiety related to the historical diagnosis 
of cancer. Subject’s life expectancy of approximately 6 months or more will be verified by the study’s 
oncologist Dr Nierodzik through the review of medical records. However, it is expected that some subjects will 
not complete the study due to rapid progression of their pre-existing diagnosis of cancer or death due to cancer.
Patients with epilepsy, renal disease, diabetes, abnormal liver function, severe cardiovascular disease 
(i.e. coronary artery disease, congestive heart failure) and uncontrolled hypertension will be excluded from the 
study. Subjects with a history of migraine headaches may be excluded based on severity of the migraines per 
evaluation of the principal investigator. 
Cardiovascular screening: There will be at least four blood pressure assessment occasions over at least 
two separate days.  Within a day, assessment occasions will be separated by at least 15 minutes.  Each 
assessment occasion will involve two or more blood pressure readings.  To qualify for the study, the mean 
blood pressure (mm Hg) of the four or more assessment occasions will not exceed 140 systolic and 90 diastolic.  
Blood pressure will be measured while subjects are at rest and have been seated or supine for at least 5 
minutes.  As recommended by the Joint National Committee on Prevention, Detection, Evaluation and 
Treatment of High Blood Pressure, these assessments will involve the average of 2 or more readings separated 
by two minutes.  If the first 2 readings differ by more than 5 mm Hg, additional readings will be obtained and 
averaged.  On one or more of the blood pressure measurement occasions, the subject will be acclimated to the 
automated blood pressure monitoring equipment by repeatedly having  blood pressure measured (at least 3 
readings) with the device.  It has been our experience that time-to-time blood pressure readings with the 
automated equipment can be variable due to measurement artifact, therefore any reading that initially exceeds 
the protocol’s threshold value will be reassessed twice within 4 minutes to assure accuracy.
Psychiatric exclusion criteria are as follows: those with a personal history, as determined by the SCID, 
or an immediate family history of schizophrenia, bipolar affective disorder, delusional disorder, paranoid 
disorder, or schizoaffective disorder.  Subjects with a current substance abuse disorder will be excluded.  
Medication contraindications will include anti-seizure medications, insulin, certain hypertension 
medications (clonidine, and aldomet specifically), cardiovascular medications and the following psychotropic 
medications: anti-psychotics (first and second generation agents), anti-depressants and mood stabilizers. 
Psychotropic medications cannot be taken in the previous two weeks, with prozac (fluoxetine) not being taken 
within the last 5 weeks prior to receiving any study agents. Subjects may only take prn (as needed) 
benzodiazepines (i.e. lorazepam) up to three days before the session. If subjects are taking an oral hypoglycemic 
agent (i.e. metformin as an anti-cancer treatment), then they must have no history of hypoglycemia. In this case, 
participants will refrain from taking the medication 24 hours prior to the dosing sessions. Subjects will refrain 
from taking any medications the day of either the experimental or placebo treatment session, except they may 
take ongoing adjuvant chemotherapy as prescribed, prescribed opiate pain medication or over-the-counter non-
narcotic pain medication at any time. It will also be necessary to refrain from alcohol the day before, the day of, 
and the day after each experimental session. 
The effects of psilocybin on an unborn child are not known, and it is not known whether receiving 
psilocybin can now have effects on unborn children in the future. Therefore, pregnant or lactating (breast-
feeding) females or females of childbearing potential, not using an acceptable method of birth control, cannot 
take part in this study. You must tell the study doctor if you are pregnant or think that you might be pregnant at 
any time while you are taking part in this study. Acceptable methods of birth control include tubal ligation or 
removal of the uterus (hysterectomy), the use of oral contraceptives (birth control pills for at least 2 months), an 
intrauterine device (IUD), hormonal implants (Norplant), hormonal injections (Depo-Provera) and abstaining 
from sexual intercourse. Women of childbearing potential will have a pregnancy test (urine) during the 
screening process and before each session of the study to make sure female subjects are not pregnant.
Subjects will be excluded if they have a score of less than 8 on the Hospital Anxiety and Depression 
(HAD) scale administered at baseline (T0—see below).


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Materials and Methods
This pilot investigation is a double-blind, randomized, placebo controlled study of the effects of 
psilocybin on the anxiety associated with cancer. The study will compare psilocybin and niacin using a 
crossover design where treatment with single session, one-time administration of the active agent versus 
placebo will occur 7 (+ 1 week) weeks apart, and the sequence of treatments will be randomized among 
patients. 
Participants: Recruitment and Screening
The study is open to anyone with a history of or current diagnosis of cancer throughout the country. 
However, it is most likely that the majority of patients will come from New York City or the Tri-State Area. 
Advertisements in newspapers as well as using contacts in oncology, pain, and palliative care services at local 
hospitals will be the primary methods used to recruit patients. 
In addition to the above-mentioned inclusion and exclusion criteria, Dr. Nierodzik, the Director of the 
Bellevue Cancer Center and one of the co-PIs, will screen all patients to determine if they have a history of or 
current diagnosis of cancer with a life expectancy of approximately 6 months or more. Moreover, the other co-
PI in the study, Dr. Anthony Bossis will assess patients for pain and issues relating to palliative care. Dr. Bossis 
will coordinate all activities related to palliative and supportive care services. 
Meetings with Monitors Before Treatment Sessions:
Following screening acceptance into the study, subjects will be provided with several brief 
psychoeducational   sessions (at least 3 sessions for a total minimum of 6 hours) over a period of 2-4 weeks 
prior to the first  experimental session to review the purpose and intention of participation in the study, the 
treatment goals, the structure of the experimental treatment session, the range of effects of the drug, the pre-
selected music and personal items to assist in creating a comfortable and familiar setting, and critical issues to 
be examined during the course of the psilocybin experience.  Additional goals of the sessions will be to 
establish a comfortable level of rapport and trust between the patient and research personnel, and to review 
significant issues in the patient’s life history, and the nature and status of present relationships and concerns.  It 
is expected that the time required to establish such trust will vary among subjects.  Establishing and maintaining 
rapport between the monitors and participant is important to minimize the risk of adverse reactions to psilocybin 
(Metzner et al. 1965). If sufficient rapport has not been established, as determined by the clinical judgment of 
Dr. Ross,  the subject will be dropped from the study.  This procedure could allow for investigator bias in 
subject selection, but the protection of the psychological wellbeing of the subjects is an overriding factor.  The 
study doctor and the assigned monitors (as a dyad treatment team) will meet each participant on at least 3 
sessions for a total minimum of 6 hours prior to the first experimental session.
Meetings with Study Staff and Monitors Following Treatment Sessions:
In the first six weeks following the experimental treatment sessions, several follow-up meetings (at least 
3 for a total minimum of 6 hours) in person between the subject, the study staff and the monitors will be 
arranged to facilitate psychological integration of the psilocybin experience, as well as to administer the 
research measures. Additional meetings in person or on the telephone will be held at least monthly intervals for 
further follow-up for six months.  The principal investigator will be the primary contact person for the subjects.
Communication with community observers (i.e. family members, friends, co-workers) will be part of 
follow-up as a way to get an objective measure of patient outcome in addition to self-report.  
Drug Conditions
Psilocybin and niacin will be administered in identically appearing opaque, size 0 gelatin capsules with 
approximately 180ml of water. The dose of psilocybin will be 0.3mg/kg and the niacin dose will be 250mg. 
Each subject will participate in two experimental treatment sessions. In the study, approximately half of the 
subjects will be randomized to receive psilocybin (n=15 or 16) or the placebo, niacin (n=15 or 16). Following 


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the first treatment session of either the active agent or placebo, a cross-over design will be instituted with the 
alternative drug administered on the second session. Subjects and treatment personnel will be blinded for each 
experimental drug administration. The time interval between the two experimental treatment sessions will be 7 
weeks (+ 1 week).
For both experimental treatment  sessions, patients will be weighed  as close as possible to the day 
before the session, and the dose of psilocybin will be mixed and compounded the day prior to the drug 
administration session at 0.3mg/kg (- 4 day window). Regarding niacin, it too will be mixed and compounded 
the day before the drug administration session (- 4 day window). 
Justification for 0.3mg/kg dose of psilocybin
As mentioned above, one of the possible mechanisms of action of psilocybin relates to the extent to 
which it is able to produce a shift in consciousness or awareness, often labeled a mystical or spiritual experience 
that can have transformative properties to alter perception, specifically anxiety, pain, and depression associated 
with  cancer in this instance. According to Dr. Grob, several of the patients in his study at UCLA reported a 
partial response to the dose of 0.2mg and had hoped for the experience to have been more profound (Grob- 
personal communication 2007). Given this and data indicating that psilocybin is safe to be given at a dose of 
0.3mg/kg (see below in ‘Safety Considerations’ Section), this study proposes to use 0.3mg/kg of psilocybin. 
The FDA has approved this dose.
Drug Sessions:
Experimental treatment sessions will take place in a specially prepared room at the NYU Bluestone 
Center for Clinical Research (BCCR). Subjects will arrive at BCCR at approximately 08:00 a.m. the day of the 
session. They may eat only a light breakfast of hot cereal or bread/toast on the day of the session. Caffeinated 
clear liquids or juices will be permitted, but no milk as drug absorption might be affected. 
The experimental medicine will be administered between 09:00 and 10:00 hours.  Subjects will be asked 
to remain in the treatment room at the BCCR until both the subject and investigator agree that their perception, 
cognition, functioning and judgment are no longer impaired by the drug.  The procedure will follow the method 
utilized by Dr. Stanislav Grof in treating advanced cancer patients with LSD (Grof, et al, 1973; Grof, et al, 1977 
& Richards, Grof, et al, 1972), as described here:  
Subjects will be encouraged to lie comfortably in bed wearing eye shades during the first few hours of 
the experience and to listen to pre-selected music chosen by the study staff. The treatment team will remain 
with the subject throughout this time, and be available for any processing of intrapsychic material made 
manifest by the treatment.  In addition, the continued need for conventional medications (e.g. narcotics) to 
alleviate pain will be monitored in a systematized, ongoing manner.  Subjects will be allowed to remain at 
BCCR for the night, but, based on the clinical judgment of the principal investigator, may have the option of 
returning home with a responsible adult.  Driving will be performed by a family member or friend, but not the 
subject.  Alternatively, a car service can be provided to the subject, as long as a family member or a friend 
accompanies the subject home.
Immunologic Measures:
The field of psycho-neuro-immunology is predicated on reliable findings that one’s psychological state 
of mind directly affects immune function. One of the hypotheses of this study is that treatment with psilocybin 
may lead to improvements in psychological well-being. If this were to happen, we would want to include 
immune measures to correlate this finding. Alternatively, if one’s psychological state deteriorates, a similar 
correlation would provide useful information. The specific immune measures to be included are: Cortisol, 
ACTH, IL-4, IL-6, IL-10, INF-gamma, TNF-alpha, and Natural Killer (NK) Cell activity. These immune 
measures would be collected by venipuncture at screening, 1-week (+/- 4 days) post sessions (of both placebo 
and the active agent), and at 6-month (+/- 4 days) follow-up.
Observations and Measurements to be used to fulfill study objectives (See Table 1):
Measures Assessed 2-4 weeks prior to the First Experimental Session (T0):


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Anxiety and Depression
Treatment efficacy for anxiety and depression will be assessed by the State-Trait Anxiety Inventory 
(STAI), Hospital Anxiety and Depression (HAD) scale, Brief Profile of Mood States (POMS-SR), Beck 
Depression Inventory (BDI), and Brief Symptom Inventory (BSI). The STAI, HAD, POMS-SR, BDI, and BSI 
will also be re-administered at the following time points: T1, T4-T12. In addition, regarding a broad assessment 
of affective states, the Positive and Negative Affect Schedule Expanded Form (PANAS-X), a 60-item 
questionnaire, will be administered to assess for positive and negative affect. This scale will be re-administered 
at the following time points: T6 (2-weeks after drug administration) and T12 (26-weeks after drug 
administration). The STAI, HAD and BDI will be re-administered at T13 and T14. 
Pain
Treatment efficacy for pain perception will be assessed by the Brief Pain Inventory – Short Form (BPI-SF), and 
the Memorial Symptom Assessment Scale (MSAS) (only questions relevant to anxiety, depression or pain 
symptoms) will be administered two weeks prior to the experimental treatment session, the day before, 7-hours 
after each drug administration session, the day after, two weeks after the session, and then every month for the 
next six months.  In addition, the Memorial Sloan Kettering Pain Card (MSKCC) will be self-administered by 
the subjects every day from two weeks before the treatment session until six weeks after, including just before 
psilocybin administration and at four and seven hours afterward. Subjects’ use of pain medications will be 
closely monitored throughout the study duration. 
Attitudes towards disease progression and death
Attitudes towards disease progression and death will be measured at baseline with the following 
measures: Death Transcendence Scale (DTS), Demoralization Scale (DEM), Death Anxiety Scale (DAS), and 
the Hopelessness Assessment and Illness (HAI) scale. These measures will also be obtained at the following 
time points: T6 (2-weeks after drug administration) and T12 (26-weeks after drug administration). The DEM, 
DAS and HAI will be re-administered at T13 and T14. 
Quality of Life/Spirituality:
Quality of Life (QoL) and spirituality assessments will be made with the Functional Assessment of 
Chronic Illness Therapy (FACIT), the Purpose in Life (PIL) scale, the World Health Organization Quality of 
Life scale, Brief Version (WHO-Bref), and the World Health Organization Quality of Life, Spiritual, Religious 
and Personal Beliefs (WHO-SRPB), with more questions relating to the spiritual importance to their overall 
QOL. An additional Forgiveness questionnaire (FORGIVE), assessing issues relating to forgiveness and 
spirituality, will be administered at baseline. These measures will also be obtained at the following time points: 
T6 (2-weeks after drug administration), and T12 (26-weeks after drug administration). The FACIT and WHO-
BREF will be re-administered at T13 and T14. 
Spiritual/Mystical States
Regarding the assessment of spiritual/mystical states, The Mysticism Scale-Lifetime (Hood et al 2001; 
Spilka et al. 2005), will be administered, instructing patients to answer questions relating to their total life 
experience, and the Spiritual Transcendence Scale (STS), a 24-item questionnaire, will be administered to 
assess an individual’s effort to create a sense of personal meaning in his or her life (Piedmont 1999). These 
scales will also be administered at time points: T6 and T12. The Mysticism Scale-Lifetime will be re-
administered at T13 and T14.
Community observer ratings of changes in subjects’ behavior and attitudes (COM-R):
After acceptance into the study, each subject will designate 2-3 adults who are expected to have 
continuing contact with the subject (i.e., spouse or other family members, friends, co-workers) who can observe 
changes in the subjects’ behavior and attitudes over time. The structured interview consists of asking the 
community rater to rate the subject’s behavior and attitudes using a 10-point scale (from 1=not at all to 
10=extremely) on 11 dimensions: inner peace, patience, good-natured humor/playfulness, mental flexibility, 
optimism, anxiety, interpersonal perceptiveness and caring, negative expression of anger, compassion/social 


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concern, expression of positive emotions, and self-confidence (Griffiths et al. 2006). The COM-R will also be 
assessed at the following time points: T7, and T12. Due to observers’ availability, it is expected that the 
administration of the COM-R may not occur on the exact scheduled time point. However, every effort will be 
made to conduct this assessment as close to the required time points as possible.
Measures assessed 1 day before the sessions (T1):
The STAI, HAD, POMS-SR, BDI, and BSI will be administered to assess for anxiety and depressive 
symptoms. As mentioned above, regarding pain assessment, the BPI-SF, MSAS, and MSKCC will be 
administered one day prior to the sessions as well. 
Measures assessed just before drug administration (T2):
The only measure to be administered will be the MSKCC to assess for pain. 
Measures assessed throughout the sessions:
Ten minutes before and 30,60,90,120,180,240,300, and 360 minutes after capsule administration, 
monitor ratings, blood pressure, and heart rate will be obtained. 
Blood pressure and heart rate:
Blood pressure (systolic, diastolic, and mean arterial pressure) and heart rate will be monitored.
Monitor rating questionnaire:
At the same points in time in which the above physiological measures will be obtained, the two session 
monitors will complete the Monitor Rating Questionnaire, which involves rating 20 dimensions of the subject’s 
mood or behavior on a five-point Likert scale from 0 to 4.
Measure assessed 4 hours after drug administration (T3):
The only measure to be administered will be the MSKCC to assess for pain.
Measures assessed 7 hours after drug administration (T4):
The STAI, HAD, POMS-SR, BDI, and BSI will be administered to assess for anxiety and depression, 
and the BPI-SF, MSAS, and MSKCC will be administered to assess for pain.
Changes in state of consciousness will be assessed with the altered states of consciousness rating scale 
5D-ASC (Dittrich 1998; Dittrich, Lamparter et al. 1999), which is a scale suited to depict alterations in waking 
consciousness — including changes in mood, perception, experience of self and environment, and thought 
disorders — regardless of the inducing factor(s) (Dittrich 1996; Dittrich 1998). In addition, the Hallucinogen 
Rating Scale (HRS) will be administered, a 100-item scale used to assess altered states of consciousness 
produced by serotonergic hallucinogens such as psilocybin (Strassman 1994; Riba 2001).  
The following measures will be used to assess for mystical/spiritual experiences: The Mysticism Scale, 
a 32-item questionnaire (Hood et al 2001; Spilka et al. 2005), and the Pahnke-Richards Mystical Experience 
Questionnaire (PRMEQ) consisting of 100 questions (Pahnke 1969; Richards 1975).
Assessment of adverse psychiatric symptoms will be made by administration of the Brief Psychiatric 
Rating Scale (BPRS) seven hours after drug administration.
 The Kast questionnaire assessing the quality of the experience will be administered at 7 hours after 
study medication administration. This questionnaire will be re-administered at T6 (2-weeks after drug 
administration).
Subjects will be requested to write or record their experience after the session, for possible further 
discussion or analysis. This written record can occur at the 7-hour period following drug administration sessions 
or can be done before the next assessment point (T5) the following day, or during the T5 assessment The Post-
Sessions Subjective Experience Questionnaire (PSEQ) will include a question asking the subject to describe 
their subjective experience of the session in general and in particular to describe what were the most 


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memorable, the most challenging or difficult, and the most spiritually significant aspects of the experience, if 
there were any. 
Measures assessed 1 day after drug administration (T5):
The STAI, HAD, POMS-SR, BDI, and BSI will be administered to assess for anxiety and depression, 
and the BPI-SF, MSAS, and MSKCC will be administered to assess for pain. 
Measures assessed 2 weeks after drug administration (T6):
The STAI, HAD, POMS-SR, BDI, and BSI will be administered to assess for anxiety and depression, 
and the BPI-SF, MSAS, and MSKCC will be administered to assess for pain.
Regarding the assessment of enduring spiritual/mystical states, The Mysticism Scale-Lifetime and STS 
will be re-administered. 
Regarding the assessment of enduring changes in attitudes and affect, the Persisting Effects 
Questionnaire (PEQ), an 89-item questionnaire, will be administered to assess changes in attitudes, moods, 
behavior, and spiritual experience (Pahnke 1969; Richards 1977). The categories of inquiry from this 
questionnaire include: positive attitudes about life and/or self, negative attitudes about life and/or self, positive 
mood changes, negative mood changes, altruistic/positive social effects, and antisocial/negative social effects. 
In addition, regarding a broad assessment of affective states, the Positive and Negative Affect Schedule 
Expanded Form (PANAS-X), a 60-item questionnaire, will be re-administered.
Measures relating to quality of life, spirituality and forgiveness will be re-assessed with the FACIT, PIL, 
WHO-Bref, WHO-SPRB, and the Forgiveness Questionnaire. 
The Kast questionnaire will be re-administered to assess for the quality of the drug administration 
experience.
The DTS, DEM, DAS, and HAI will be re-administered to assess for attitudes towards disease 
progression and death.
Measures assessed 6 weeks after drug administration (T7):
The STAI, HAD, POMS-SR, BDI, and BSI will be administered to assess for anxiety and depression, 
and the BPI-SF, MSAS, and MSKCC will be administered to assess for pain.
 
Regarding community observer ratings of changes in subjects’ behavior and attitudes, the above-
mentioned structured interview (COM-R) will be re-administered.
Measures assessed 10 weeks after drug administration (T8):
The STAI, HAD, POMS-SR, BDI, and BSI will be administered to assess for anxiety and depression, 
and the BPI-SF, and MSAS, will be administered to assess for pain.
 
Measures assessed 14 weeks after drug administration (T9):
The STAI, HAD, POMS-SR, BDI, and BSI will be administered to assess for anxiety and depression, 
and the BPI-SF, and MSAS, will be administered to assess for pain.
Measures assessed 18 weeks after drug administration (T10):
The STAI, HAD, POMS-SR, BDI, and BSI will be administered to assess for anxiety and depression, 
and the BPI-SF, and MSAS, will be administered to assess for pain.
Measures assessed 22 weeks after drug administration (T11):
The STAI, HAD, POMS-SR, BDI, and BSI will be administered to assess for anxiety and depression, 
and the BPI-SF, and MSAS, will be administered to assess for pain.
Measures assessed 26 weeks after drug administration (T12):
The STAI, HAD, POMS-SR, BDI, and BSI will be administered to assess for anxiety and depression, 
and the BPI-SF, and MSAS, will be administered to assess for pain.


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To re-assess for spiritual/mystical measures, the Mysticism Scale-Lifetime, PRMEQ retrospective scale, 
and STS will be re-administered.
To re-assess for enduring changes in attitudes, moods, behavior and spiritual experience, the PEQ and 
PANAS-X will be re-administered.
Measures relating to quality of life, spirituality and forgiveness will be re-assessed with the FACIT, PIL, 
WHO-Bref, WHO-SPRB, and the Forgiveness Questionnaire. 
The DTS, DEM, DAS, and HAI will be re-administered to assess for attitudes towards disease 
progression and death.
Regarding community observer ratings of changes in subjects’ behavior and attitudes, the above-
mentioned structured interview (COM-R) will be re-administered.
A Retrospective Subjective Experience Questionnaire (RSEQ) will be administered to capture the 
subjective experience of the subject during the drug-administration session that may have produced or resulted 
in the most profound changes or alterations in emotional or mental states and/or changes in ordinary 
consciousness. The questions will inquire about possible changes in emotions, thoughts, states of consciousness, 
meaningfulness, and spirituality.
Measures assessed at T13 and T14: 
The STAI, HADS and BDI will be re-administered to assess for anxiety and depression.
           Persisting Effects Questionnaire (PEQ), an 89-item questionnaire, will be re-administered to assess 
changes in attitudes, moods, behavior, and spiritual experience (Pahnke 1969; Richards 1977).
The Mysticism Scale-Lifetime will be re-administered, instructing patients to answer questions relating 
to their total life experience. Measures relating to quality of life, spirituality and forgiveness will be re-assessed 
with the FACIT and the WHO-Bref. 
The DEM, DAS, and HAI will be re-administered for this indication.
A short open-ended questionnaire will also be administered to capture the subjective experience of the 
participant that may be sustained at the T13 and T14 time points.
Optional, Additional Time points
Study participants who completed a psilocybin dosing session and agreed to be contacted in the future 
(as indicated on their written Informed Consent Document that was signed at the beginning of the primary 
phase of the study) will be approached by the study team member via phone or email to offer them participation 
in the optional, additional time points. If the study subjects are interested in participating in these two time 
points, a designated study-team member will read a telephone consent to the interested volunteer over the 
phone. The telephone consent discusses the additional study procedures that the volunteer would have to 
participate in and all risks involved. If the volunteer wants to participate in these optional and additional 
timepoints, a designated study-team member will send the interested participant a link to 
openredcap.nyumc.org. This link will include all of the assessments that are to be completed at each additional 
timepoint. The ability to complete these questionnaires online eliminates the need for the participant to come to 
an in-person visit at the study site. The T13 and T14 optional time points will occur approximately one year 
apart. The T13 time point will occur as soon as possible to the time at which verbal telephone reconsent is 
obtained, and the T14 will occur approximately one year after T13.
Because these timepoints are optional and participants only needed to undergo an active-medication session in 
order to be eligible, study participants who opt out or who do not have the option to participate (for example, if 
they are deceased) will be classified (ie study completers, withdrawn, treatment dropout, etc.) as they were in 
the main portion of the study
 
For example:

Participant XYZ completed both medication sessions, active & placebo, as well as all questionnaire 
timepoints. He has been considered a “study completer” up until this point. If his consent endorses 
having the study team reach out to him regarding future research, he will be contacted. If he denies 


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wanting to participant in the optional & additional timepoints, this will not affect his status as a study 
completer.

Participant ABC completed both medication sessions & all questionnaire timepoints but is deceased. She 
will still be considered a study completer even though she obviously cannot be given the choice to 
participate in T13 & T14.

Participant LMN completed only 1 medication session but it was her active medication session. She 
withdrew from the study before her second medication session. However, since the protocol states that 
in order to be eligible for the optional & additional timepoints, participants must have only completed a 
psilocybin medication session, she would eligible to participate in these additional and optional 
timepoints. If her consent endorsed having the study team reach out to her regarding future research, th 
study team will do so regarding these optional and additional questionnaire timepoints. 
 
For documentation purposes, the study team will keep a log that includes all participants enrolled in the main 
portion of the trial and note whether or not they are deceased. Any and all information that the study team has 
regarding the death of a past participant in this trial will be noted. 
                                                                                                                                                
Statistical Analyses (Including Power Analysis): Done in conjunction with Dr. Chi-Hong Tseng of 
Biostatistics and Approved on 1/24/07
Descriptive statistics (means, medians, standard deviations, frequency distributions) and graphic 
displays will be generated for demographics and baseline clinical presentations to characterize study subjects, 
and to describe the distribution of adverse events, patient dropout, study compliance and all outcome measures.
One of the objectives of this pilot study is to determine the feasibility of giving psilocybin to patients 
with advanced cancer. Although the safety of giving psilocybin to normal, healthy volunteers has been 
established within the last decade (Hasler 2004, Griffiths 2006, Moreno 1998), and although the safety of its use 
in patients with advanced cancer was established in the 1960s, it has not been established in patients with cancer 
using modern research designs (i.e. double-blind, placebo controlled, prospective methodology). In addition to 
safety determination considerations, summary statistics will be used to describe the consent and drop out rates 
as part of patient recruitment and retention. The adverse events associated with study treatments will be 
tabulated, and percent adverse event and its 95% confidence interval will be calculated.  
According to a recent study by Moreno and colleagues, published in 2006, in patients with refractory 
Obsessive Compulsive Disorder (OCD), an anxiety spectrum disorder, it was found that, with psilocybin, 
subject’s mean YBOCS scores were reduced to 10.67 at 24 hours from 24.11 +/- 6.3 at baseline (Moreno 2006). 
This represents a reduction of 2 in effect size (assuming a 0.5 correlation between baseline and 24 hours). If we 
assume placebo has no effect on anxiety, depression and pain, a sample size of 16 subjects in each group (in the 
first treatment session) will provide 75% power to detect a reduction of 1 effect size, and > 99% power at 2 
effect sizes, at the 5% level. This power analysis shows that even if patients dropout before the second cross-
over session, the total of 31 patients in the first session will have adequate power for the study endpoints.  
Regarding the effect of psilocybin on the outcome variables measuring anxiety, the STAI and HAD 
scale, analyses will be conducted using a paired t-test to evaluate the effect of treatment over time. The 
comparisons will be between the following time points: (T0 & T1)-T4, (T0 & T1)-T5, (T0 &T1)-T6, and (T0 & 
T1)-T7. The comparisons between the active agent and placebo groups will be conducted using an independent 
sample t-test to look at differences on the STAI and HAD scale measures. Similar analyses will be conducted 
both within and between groups for the other outcome measures, assessing for depression (POMS-SR, BSI and 
BDI scales) and pain (BPI-SF, MSAS, and MSKCC scales).
To assess the interaction between drug and time, a series of repeated measures multivariate analyses of 
variance (MANOVA) will be used to compare the active drug and placebo study arms across time in terms of 
the major outcome variables during the first and second randomized experimental treatment sessions.  Both 
treatment main effects across time and interactions of treatment with time will be assessed in the repeated 
measures MANOVA.    


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Longer-term effects will be measured in two ways looking at the outcome measures of anxiety, 
depression, and pain. First the effect of time will be assessed with a MANOVA analysis from baseline relative 
to T7-T12. Also, MANOVA will be used to look at the effect of sequencing of getting the active agent vs. 
placebo in a sequence x time analysis from baseline relative to T7-T12.
Data Management and Statistics:
A data manager will be recruited and appointed prior to the initiation of the study. The funding for this 
study from the Heffter Research Institute includes monies to pay for a data manager.
Monitoring for Risk Minimization:
A physical examination will be performed which will include an EKG, urinalysis, and blood chemistry 
panels (liver and renal function tests and CBCs). An admission urine drug screen will be done for patient safety 
and protocol compliance. During each experimental treatment session, vital signs, including blood pressure and 
heart rate, will be taken 10 minutes before and 30,60,90,120,180,240,300, and 360 minutes after drug 
administration. Body temperature will be measured up to 30 minutes before and at six hours after drug 
administration. For these measurements, a window of ±10 mins from the allocated time will facilitate the study 
flow.
Cardiovascular monitoring during a session:  
1. Vital Signs are checked ten minutes before and 30,60,90,120,180,240,300, and 360 minutes after capsule 
administration and monitor ratings (blood pressure and heart rate) will be serially assessed. 
2. Monitor Ratings: Blood pressure (systolic, diastolic, and mean arterial pressure) and heart rate will be 
monitored with an automated blood pressure machine.
3. If Systolic BP is > 160 or Diastolic is > 100 or Heart Rate is >110,vital signs will be checked every 5 minutes 
until systolic pressure is <160, diastolic pressure <100, and heart rate <110 
4. If Systolic BP is > 200 or Diastolic BP is > 110 for three readings (i.e. 15 minutes), the subject will receive 
sublingual Nitroglycerin 0.4 mg. If blood pressure readings do not decrease below these thresholds after 5 
minutes of receiving the first dose of Nitroglycerin, the same dose of Nitroglycerin will be administered. A third 
dose of nitroglycerin will be given after another 5 minutes, if readings remain elevated above these levels 
(maximum dose is 0.4mg x 3 doses).   
5.  If blood pressure remains >200 systolic or >110 diastolic, at the judgment of the treating physician (Dr. 
Ross), the subject will be immediately transported to the nearby Bellevue Hospital Center Adult Emergency 
Room (AES) for further evaluation and treatment.
Aversive reactions to sublingual nitroglycerin:  
The following effects have occurred in clinical trials:  headache, hypotension, cutaneous vasodilation with 
flushing, dizziness and weakness, as well as other signs of cerebral ischemia associated with postural 
hypotension.  Also possible are nausea, vomiting, restlessness, pallor, perspiration and collapse, drug rash 
and/or exfoliative dermatitis, paresthesia, rhinitis, peripheral edema, asthenia, and abdominal pain.
PROCEDURE FOR MEDICAL EMERGENCIES:
      NEW YORK UNIVERSITY COLLEGE OF DENTISTRY MEDICAL EMERGENCY  
MANAGEMENT PROTOCOL INCLUDING BLUESTONE CENTER FOR CLINICAL RESEARCH 
(BCCR):
The Department of Oral and Maxillofacial Surgery (OMS) faculty are trained in managing medical emergencies 
and will respond to the presentation of medical emergencies at the College of Dentistry.


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In a medical emergency security will be called at 89828 and they will dispatch the OMS faculty.  Staff members 
who report the emergency must remain with the subject and administer supportive therapy.  Emergency supplies 
and oxygen is available from the code cart located next to the nurse’s station in BCCR.
The OMS team will assess the situation, stabilize the subject, and notify the Emergency Medical Service 
(EMS), should an ambulance be required to transport the subject to the hospital if this has not been done by 
BCCR staff.  The OMS team will stay with the subject until the emergency has subsided or additional assistance 
has been obtained.
Other emergency numbers:

Poison Control: (800) 222-1222

Bellevue Emergency Room: (212) 562-3015

New York University Emergency Room: (212) 263-5550
If an excessive rise in BP occurs, SBP >200 and/or DBP >140, it will be reported to the IRB and 
BCCR within 72 hrs. In addition the number of subjects in whom SBP >150 occurs will be reported as 
individuals in a special AE Table. 
In the event that a subject experiences distressing anxious or psychotic symptoms during the 
experimental or control session, the clinical personnel in attendance (the principal investigator and treatment 
team) will initiate verbal communication designed to reorient and reassure the subject.  If that does not 
effectively alleviate the signs of an anxious or psychotic reaction, a benzodiazepine (diazepam 5-10mg given 
orally or intramuscularly) will be administered to lower anxiety.  Only if that is ineffective will an antipsychotic 
be administered, olanzapine (5-15mg given orally or intramuscularly). 
Chemistry, manufacturing, and control information:
After the FDA has approved the content of the protocol, the psilocybin will be manufactured by 
Organix, Inc., 240 Salem St, Woburn, MA 01801, who will provide this information as a supplement to this 
IND application.
Safety Considerations
Storage, safeguarding, and regulatory aspects of the drug psilocybin:
Using a 222 DEA form, the psilocybin will be shipped from Organix, Inc. to be stored in a secure are 
within the NYU Bluestone Center for Clinical Research. To safeguard the psilocybin, a special storage safe will 
be provided to store only the psilocybin. Designated staff will be the only personnel with access to the 
psilocybin. Both the active agent and placebo will be prepared by designated study staff by a compounding 
process. A log of the psilocybin accountability, compounding, and dispensing will be kept by designated study 
staff in designated NYUSoM space located within Bellevue Hospital Center. This will provide strict 
safeguarding and accounting of the agent both for internal and external regulatory agencies.
Data Safety & Monitoring Plan (DSMP)
Given the nature of this study, it is important to have individuals who have expertise in general 
psychiatry, addiction psychiatry, and addiction medicine. In addition, it is important to have individuals who are 
actively involved in IRB approved research. All regulatory and study-related documents will be kept in 
accordance with NYUSoM IRB policies and procedures. After this study is closed with the IRB, the study will 
be closed and archived appropriately according to NYUSoM IRB policies and procedures. 
The data safety monitoring board (DSMB) will consist of the following individuals:
1) John Rotrosen MD- chair of the DSMB
Professor of Psychiatry


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Director, NYU Langone Center of Excellence on Addiction
Department of Psychiatry, Manhattan VA
NYU Langone School of Medicine
423 East 23 Street
VET 17 17014W
 New York NY 10010
John.Rotrosen@nyumc.org 
Phone: +1 212 951 3294 
Fax: +1 212 951 6891 
2)Jennifer McNeely, MD, MS
Assistant Professor of Medicine
NYU School of Medicine
Jennifer.Mcneely@nyumc.org
Phone: (212) 263-4975
227 East 30th Room 623
NY, NY 10016
3)Paul Casadonte MD
Clinical Associate Professor of Psychiatry
Director, Substance Abuse Services, Manhattan VA
Department of Psychiatry, Manhattan VA
VET 17
423 East 23 Street
New York NY 10010
Paul.Casadonte@nyumc.org
Phone: +1 212 263 7260
Fax: +1 212 951 3356
4)Donald Goff, MD
Professor of Psychiatry
Vice Chair, Department of Psychiatry
1 Park Avenue, 8th Fl.
New York, NY 10016
Donald.Goff@nyumc.org
Phone: 212-263-7419
C. Designation of responsibilities for data and safety monitoring 
Tara Malone
Research Coordinator
Division of Alcoholism & Drug Abuse
Department of Psychiatry, NYU School of Medicine
462 First Avenue & 27th Street
New York, NY 10016
E-mail: Tara.Malone@nyumc.org
Phone: (646) 501-4206
Study role: Study Coordinator 
1) Responsible for data collection and confidential storage in conjunction with designated staff at the Bluestone 
Center for Clinical Research (BCCR). 


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Dr. Stephen Ross MD (Principal Investigator) will be responsible for the following tasks:
1) Responsible for monitoring the data collected
2) Responsible for monitoring all adverse events, serious adverse events, and unanticipated problems
3) Responsible for communication with internal (i.e. IRB) and external regulatory bodies (i.e. FDA, DEA)
4) Responsible for coordinating meeting and review of data and safety monitoring with the DSMB
Dr. John Rotrosen
1) Chair of the DSMB 
2) Review of psychiatric and addiction related data
Dr. Jennifer McNeely
1) DSMB member
2) Review of internal medicine related data
Dr. Paul Casadonte
1) DSMB member
2) Review of psychiatric and addiction related data
Dr. Donald Goff
1) DSMB member
2) Review of psychiatric data & protocol adherence 
D. Planned DSMB Review
1) Number of subjects screened and enrolled
2) Assessment of dropout rate
3) Assessment of outcomes: An interim analysis will be performed after a cohort of 5 patients has completed the 
study
-Efficacy parameters will be analyzed for anxiety and depression 
4) Assessment of safety information including vital signs, clinical labs, physical examination, medication 
history, and adverse events  
5) Categorization of adverse events using:
-The General Severity Scale to determine the adverse event/serious adverse event grade of severity
-The General Attribution Scale to determine the relationship of the event with the study drug
6) Determination by DSMB regarding continuation, modification or termination of study
7) Other, per DSMB or PI.
E. Reporting of Adverse Events
a. Anticipated adverse events (AEs) will be reported to the DSMB after every 5 subjects have completed the 
study or on a quarterly basis, whichever is more frequent, and will be reported to the IRB and BCCR as part of 
the annual report.  
b. Events and Information requiring reporting to the NYU IRB and FDA in clinical trials of drug and 
biological products conducted under IND regulations (under Title21 of the Code of Federal Regulations 
{21 CFR} part 56 {Institutional Review Boards}, part 312 {Investigational New Drug Application}:
Unanticipated Problems involving risks to participants or others (UAPS)
UAPS are events (including internal or external events, deaths1, life-threatening experiences1, injuries, breaches 
of confidentiality or other problems) that occur any time during or after the research study, which in the opinion 
of the DSMB or the PI are:


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a)Unanticipated (unexpected)- not in the consent form, investigator brochure, protocol, package insert, 
or label; or unanticipated in its frequency, severity or specificity,
AND
b)Harmful –caused harm to participants or others, or placed them at increased risk of harm
AND
c)Serious- resulting in death or injury requiring hospitalization (admission)
AND
d)Related to the research procedures- caused by, or probably caused by research activity
1Unanticipated deaths or life-threatening experiences related to the research will be reported to the NYU IRB, 
BCCR and the FDA in a written INDS safety report of ‘any adverse experience associated with the use of the 
drug that is both serious and unexpected (§ 312.32(c)(1)(i)(A),(B)) within 24 hours. Otherwise, all other UAPS 
will be reported to the NYU IRB and FDA within 5 days.
Other reportable events and information 
1)A single occurrence, or small number of occurrences of a serious, unexpected event that is not commonly 
associated with drug exposure, but uncommon in the study population
2)Multiple occurrences of an AE that, based on an aggregate analysis, is determined to be an unanticipated 
problem. There should be a determination that the series of AEs represents a signal that the AEs were not just 
isolated occurrences and involve risk to human subjects
3)An AE that is described or addressed in the investigator’s brochure, protocol, or inform consent documents, 
but occurs at a specificity or severity that is inconsistent with prior observations.
4)New Information indicating a change to the risks of potential benefits of the research, in terms of severity or 
frequency (i.e. Analysis indicates lower than expected response rate or a more severe or frequent side effect; 
Other research finds arms of study has no therapeutic value; FDA labeling change or withdrawal from 
marketing)
5)Protocol Deviation or Violation. Only if:
a. Intended to eliminate apparent immediate hazard to a research participant, or
b. Harmful (caused harm to participants or others, or placed them at increased risk of harm, or
c.
Possible serious or continued noncompliance
6)Complaint
a. Unresolved by the research team, or
b. That indicates increased or unexpected risks
7)Incarceration when in the opinion of the PI it is in the best interest of the participant to remain on the study
F. Frequency of Review and Rationale for Recommended Frequency
1)At a minimum the DSMB will meet quarterly or after a cohort of 5 patients has completed the study, 
whichever is more frequent.
2)The DSMB will meet more regularly as necessary to review any AEs, serious AEs, UAPs, or new information 
that in the opinion of the PI or DSMB may impact risks or study continuation. 
Pharmacology and toxicology information:
Please refer to IND No. 56,530, submitted by Dr. Francisco Moreno, M.D. of the University of Arizona.
Previous human experience with the investigational drug (Safety Profile):
Psilocybin is 4-hydroxy-N,N-dimethltryptamine, and occurs in nature in many species of mushrooms, 
including the genera Psilocybe, Conocybe, Gymnopilus, Panaeolus and Stropharia.  As is the case with LSD 
and mescaline, psilocybin is an extremely potent agonist at 5-HT(2A) and 5-HT(2C) receptors, and their 


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binding potency to these receptors is directly correlated with their human potency as hallucinogens. (Delgado & 
Moreno, 1998)  Although not provided the extensive degree of investigation received by the prototype 
hallucinogen, LSD, psilocybin was subjected to a variety of research studies during the 1960s employed to 
establish its psychopharmacological profile of action.  Psilocybin was determined to be active and generally 
safe in the 100 to 300 µg/Kg range (Moreno, 1998).  The experience lasts from 4 to 6 hours.  
Research with psilocybin has resumed within the last several years and has been safely given to normal 
volunteers, regarding physiological parameters, at doses ranging from 0.045mg/kg to 0.43mg/kg (Hasler et al. 
2004; Griffiths et al. 2006). It has also been safely administered, again regarding physiological parameters, to 
patients with OCD at doses ranging from 0.025mg/kg to 0.3mg/kg (Moreno et al. 2006). Moreover, a completed 
double-blind, placebo-controlled (niacin as the control), Phase I study with a cross-over design at Harbor-
UCLA Medical was conducted by Dr. Charles Grob, where patients with advanced cancer and anxiety received 
a single dose of 0.2mg/kg of psilocybin. In total, 12 out of 12 patients were enrolled and completed the study. 
As mentioned above, the study established the safety and feasibility of administering a  moderate dose of 
psilocybin to patients with advanced cancer and anxiety. Some of the data suggested a treatment effect with 
reduction in anxiety and depressive symptoms (Grob 2010).  
Regarding the issue of potential adverse psychological effects, these include the relative risks associated 
with alterations of perception, flashbacks and the low probability of dizziness, nausea, vomiting, headaches, 
increased pulse, transient moderate to severe elevation in blood pressure, dilated pupils and slightly elevated 
temperature. Actual reports of psilocybin induced psychosis are very rare. Although psychosis has been 
associated with the use of hallucinogens, the vast majority of cases are from uncontrolled, recreational use. 
Sidney Cohen, a distinguished psychiatric researcher at the UCLA School of medicine from the 1950s to 1980s, 
examined the use of hallucinogens in research settings and estimated the incidence of hallucinogen related 
psychosis to be about 0.8/1000 experimental subjects (Cohen, 1960). Harvard Medical School psychiatrist 
Lester Grinspoon has described the risks of hallucinogens within treatment settings: “The main danger in 
psychedelic drug therapy is the same as the danger of any deep-probing psychotherapy: if the unconscious 
material that comes can be neither accepted and integrated nor totally repressed, symptoms may become worse, 
and even psychosis or suicide is possible.  But the potential for harm has been exaggerated, for two reasons. 
First, much irrational fear and hostility is left over from the cultural wars of the sixties. More generally, we tend 
to misconceive drugs as something utterly different from and almost by definition more dangerous than other 
ways of changing mental processes; actually the dangers in work with LSD do not seem obviously greater than 
in comparable forms of therapy aimed at emotional insight” (Grinspoon and Bakalar, 1979). From the 1950s to 
1970s an extensive literature emerged from experimentation into the controlled use of hallucinogens in the 
treatment of psychiatric patients. Lester Grinspoon has described that “between 1950 and the mid-1960s there 
were more than a thousand clinical papers discussing 40,000 patients, several dozen books and six international 
conferences on psychedelic drug therapy…many people remember vaguely that LSD and other psychedelic 
drugs were once used. This was not a quickly rejected and forgotten fad” (Grinspoon and Bakakar, 1979). The 
model identified as being most efficacious, involving careful attention to developing optimal set (preparation, 
intention and underlying psychological predisposition) and setting (environmental and interpersonal context), 
often involved the administration of the active agent on only one occasion. It is important to point out, however, 
that the one-time hallucinogen facilitated experience occurred within the context of an ongoing 
psychotherapeutic process. The long-term effects of this single dose experience when utilized in optimal context 
were often therapeutic.
Potential Side Effects from Placebo agent: Niacin
Side effects from niacin include mild and brief flushing (for example, warmth, redness, itching, and/or 
tingling). Occasionally, dizziness and increased heart rate and shortness of breath may occur.
Additional information.
Previous INDs


Version date: 3.21.18
19
Please refer to IND No. 56,530, submitted by Dr. Francisco Moreno, M.D. of the University of Arizona 
and IND No. 64,052 submitted by Dr. Charles Grob of UCLA. 
 
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