Effects of Psilocybin on Behavior, Psychology and Brain Function in Long-term Meditators

This study will use questionnaires and functional magnetic resonance imaging (fMRI) to
examine the acute and persisting effects of psilocybin on brain function, meditation,
spirituality, and psychology. The majority of the study procedures -- including screening,
preparatory meetings, placebo and psilocybin sessions, and a large battery of behavioral and
psychological measures -- will be conducted at the investigator's laboratory at the
Behavioral Pharmacology Research Unit (BPRU) on the Johns Hopkins Bayview campus. The brain
imaging procedures will be conducted at F.M. Kirby Research Center at the Kennedy Krieger
Institute (KKI).

Inclusion criteria:

- Have given written informed consent

- Some college-level education (college degree preferred)

- Be healthy and psychologically stable as determined by screening for medical and
psychiatric problems via a personal interview, a medical questionnaire, a physical
examination, an electrocardiogram (ECG), and routine medical blood and urinalysis
laboratory tests

- Agree to consume approximately the same amount of caffeine-containing beverage (e.g.,
coffee, tea) that he/she consumes on a usual morning, before arriving at the research
unit on the mornings of drug session days. If the participant does not routinely
consume caffeinated beverages, he/she must agree not to do so on session days.

- Agree to refrain from using any psychoactive drugs, including alcoholic beverages and
nicotine, within 24 hours of each drug administration. The exception is caffeine.
Participants will be required to be non-smokers.

- Agree not to take any Pro re-nata (PRN) medications on the mornings of drug sessions

- Agree not to take sildenafil (Viagra®), tadalafil, or similar medications within 72
hours of each drug administration.

- Agree that for one week before each drug session, he/she will refrain from taking any
nonprescription medication, nutritional supplement, or herbal supplement except when
approved by the study investigators. Exceptions will be evaluated by the study
investigators and will include acetaminophen, non-steroidal anti-inflammatory drugs,
and common doses of vitamins and minerals.

- Live within driving distance of Baltimore - out-of-State residents may be eligible if
they can provide their own transportation and lodging.

- Have a long-term meditation practice, ideally in a Buddhist tradition, with good
familiarity with breath meditation and loving kindness meditation; preference given to
those with very long-term practices

Exclusion criteria:

- Women who are pregnant (as indicated by a positive urine pregnancy test assessed at
intake and before each drug session) or nursing; women who are of child-bearing
potential and sexually active who are not practicing an effective means of birth
control.

- Cardiovascular conditions: coronary artery disease, stroke, angina, uncontrolled
hypertension, a clinically significant ECG abnormality (e.g., atrial fibrilation), or
Transient Ischemic Attack (TIA) in the past year

- Epilepsy with history of seizures

- Insulin-dependent diabetes; if taking oral hypoglycemic agent, then no history of
hypoglycemia

- Currently taking psychoactive prescription medication on a regular (e.g., daily) basis

- Currently taking on a regular (e.g., daily) basis any medications having a primary
centrally-acting pharmacological effect on serotonin neurons or medications that are
Monoamine Oxidase (MAO) inhibitors. For individuals who have intermittent or PRN use
of such medications, psilocybin sessions will not be conducted until at least 5
half-lives of the agent have elapsed after the last dose.

- More than 20% outside the upper or lower range of ideal body weight according to
Metropolitan Life height and weight table

- Head trauma

- Claustrophobia

- Cardiac pacemaker

- Implanted cardiac defibrillator

- Aneurysm brain clip

- Inner ear implant

- Artificial heart valve (last 6 weeks)

- Prior history as a metal worker and/or certain metallic objects in the body

Psychiatric Exclusion Criteria:

- Current or past history of meeting Diagnostic and Statistical Manual (DSM)-IV criteria
for Schizophrenia, Psychotic Disorder (unless substance-induced or due to a medical
condition), or Bipolar I or II Disorder

- Current or past history within the last 5 years of meeting DSM-IV criteria for alcohol
or drug dependence (excluding caffeine and nicotine) or severe major depression

- Have a first or second-degree relative with Schizophrenia, Psychotic Disorder (unless
substance induced or due to a medical condition), or Bipolar I or II Disorder

- Has a psychiatric condition judged to be incompatible with establishment of rapport or
safe exposure to psilocybin