Psilocybin-Assisted Psychotherapy for Anxiety in People With Stage IV Melanoma

Melanoma is a cancer arising from pigment-producing cells, or melanocytes. These cells are
chiefly located in the skin, but they can also be found in other parts of the body,
including eyes, ears and GI tract. A diagnosis of stage IV melanoma can create great stress
and anxiety for an individual and his or her caregivers. Psilocybin (4-phosphoryloxy-
N,N-dimethyl-tryptamine) is a psychedelic (hallucinogenic) compound found in certain species
of mushrooms that can produce spiritual or mystical experiences and that has been used in
psychotherapy prior to being made illegal. This study will be a randomized, active-placebo
controlled pilot study of the safety and efficacy of psilocybin-assisted psychotherapy as a
means of managing anxiety in association with stage IV melanoma. This study will examine
whether two sessions of psilocybin-assisted psychotherapy scheduled seen to 14 days apart
will reduce anxiety, improve quality of life and be safe in people with stage IV melanoma.

Subjects in this study will have a 66% chance of receiving the full dose of 25 mg psilocybin
and a 33% of receiving 4 mg psilocybin. The first dose is expected to change how people
feel, think and see the world, while the lower dose is expected to have only slight effects.
Each subject will receive these conditions at random, as if by coin-toss. The researchers,
including the therapists, and the subject will not know whether they are assigned to get 25
or 4 mg psilocybin.

The entire study can last up to three and a half months (14 weeks) but the main part of the
study lasts six weeks. After the researchers determine that a person with stage IV melanoma
and anxiety can be in the study, there will be two introductory psychotherapy sessions with
the therapist-investigators. They will prepare the participant for psilocybin-assisted
psychotherapy. The subject will have a day-long psilocybin-assisted psychotherapy session
after introductory sessions, and he or she will remain overnight at the clinic. There will
be a psychotherapy follow-up scheduled the day after each psilocybin-assisted session to
help people work with the psilocybin-assisted psychotherapy, and there will be a
psychotherapy session in between the first and second psilocybin-assisted psychotherapy
sessions. Two weeks after the second psilocybin-assisted psychotherapy session, subjects
will return for another follow-up visit. The subjects will answer questions or fill out
questionnaires about anxiety, depression, quality of life, spirituality and sense of self at
the start of the study, two weeks after the second psilocybin-assisted session and at least
once during the study. Subjects will have blood draws to assess liver function before each
psilocybin-assisted session and they will have a blood draw to assess natural killer (NK)
cells the day after each psilocybin-assisted session. On the day after each
psilocybin-assisted session, subjects will also complete a questionnaire about their
experiences during the psilocybin-assisted session.

Two weeks after the second experimental psilocybin-assisted session, subjects will learn if
they got the full or active placebo dose of psilocybin. Any of the three subjects who
receive the active placebo dose can take part in an "open-label" study phase that will last
another six weeks. The open-label phase will be nearly identical to those used in the first
study phase except that there will be one, and not two, introductory psychotherapy sessions,
and the subject and therapists will know that the subject will be receiving 25 mg
psilocybin. People who got the full dose of 25 mg psilocybin will not take part in the
open-label study phase.

If they are well enough to do so, subjects who received the full dose of psilocybin will
have anxiety, depression, quality of life and spirituality measured again two months after
the second experimental session. Subjects who received active placebo psilocybin will have
anxiety, depression, quality of life and spirituality measured two months after the second
open-label psilocybin-assisted session.