Title:	A TEST OF MDMA-ASSISTED PSYCHOTHERAPY IN SUBJECTS WITH ADVANCED-STAGE CANCER AND CANCER-RELATED ANXIETY
Company and Funding:	Multidisciplinary Association for Psychedelic Studies (MAPS)
Principal Investigator:	John H. Halpern, M.D. McLean Hospital
Daytime telephone number:
24 hour contact number:
Co-Investigators:	Umadevi Naidoo, M.D. Todd D. Shuster, M.D. Arthur J. Siegel, M.D.
Subject's Initials:
Version date:	November 17, 2004

Why Have I Been Asked to Take Part in this Research Study and Why is this Study Being Done?
To see if this therapy will be safe and reduce anxiety and improve quality of life, Dr. John Halpern and colleagues are conducting a small, early (pilot) study of an experimental drug, MDMA (3,4-methylenedioxymethamphetamine) taken during two special therapy sessions by people with advanced-stage cancer who are either not helped enough or are not helped at all from anti-anxiety medications or who have declined to take anti-anxiety medications. The effects of a nearly full and a full dose of MDMA will be compared with a low dose of the drug. You have been asked to take part in this study because you have a diagnosis of advanced-stage cancer with less than 12 months of estimated remaining life and because you are experiencing anxiety related to this diagnosis. MDMA is experimental, which means it has not been approved by the US Food and Drug Administration (FDA) for medical use, except within research studies. MDMA is also a controlled drug (illegal to use outside of research) and when sold illicitly is sometimes known as "ecstasy." Ecstasy is supposed to contain MDMA but often contains other drugs instead of or in addition to MDMA. Please read all of the information in this form carefully. Do not hesitate to ask anything about the information provided; it should stimulate your questions. You may take home an unsigned copy of this consent form to think about or discuss with family or friends before making your decision. A copy will also be provided to you after signing this informed consent form.

How Long Will I Be In The Study?
The length of the study is 14 weeks (3 months plus about 2 weeks), and there will be 9 (nine) required visits, including one screening visit before you can take part in the study and two visits that will require an overnight stay at McLean Hospital.

How Many People Will Take Part In The Study?
12 people in total will participate in this study.

Will Everybody Receive the Same Treatment, and How Will this Be Determined?
All people who decide to take part in the study will receive MDMA, but 33% (4 of 12) will receive low doses, and 66% (8 of 12) will receive nearly full and full doses of MDMA. A person will receive low or nearly full and full doses of MDMA by "random assignment" (by chance, as if by flipping a coin).

You will have seven psychotherapy visits with the investigators, each lasting 1 hour.

You will complete questionnaires and take part in interviews during six (6) approximately 90-minute-long sessions. One of these questionnaire and interview sessions happens at the start of the study, and the other five are scheduled to happen before a psychotherapy or experimental session.

The last time when you fill out questionnaires and have psychotherapy with the investigators will be two months after the second experimental session, or about 2.5 months after the start of the study.

On two occasions, you will have a six-to-eight-hour-long experimental session. This is when you will get MDMA (either low dose or experimental intervention dose).

You cannot eat anything after midnight on the day before each experimental session, and you cannot drink alcoholic beverages after midnight on the day before the study.

You can take your usual pain or anti-nausea medication on the day of the experimental session, but if you take extra pain or anti-nausea medications, the investigators may decide to delay or reschedule the experimental session.

You will get one dose of MDMA at the start of each experimental session. If you and the investigators agree that it is safe to do so and you feel well enough to do so, then 2.5 hours after the first dose, you will get another dose of MDMA that is always half the size of the first dose.

You can have a significant other, such as a spouse or partner, a relative, or a close friend, stay with you during part or all of the experimental session, but you do not have to have someone stay with you.

You will have to stay overnight at McLean Hospital after each experimental session, and a psychotherapy session will be scheduled for the next day.

You cannot drive yourself home on the day after each experimental session. You should try to arrange a ride home, but if you cannot do that, the investigators will arrange a ride for you.

There is some risk that MDMA could damage certain parts of serotonin neurons (cells) in your brain. Though these neurons remain living, some of these cells' signaling fibers ("axons") may be destroyed after administration of MDMA. Several scientists have reported these observations in animal studies. The functional significance of these changes has not been clearly established, but some investigators are concerned that these changes may impair memory functioning and alter mood.

Before you can be in the study, the researchers must first make sure that you are eligible to be in the study. Doctors in the group practice of one of the study investigators, Dr. Todd Shuster, will have been able to tell whether you might be a study subject after you have one of your regular medical examinations. You should already have agreed to be screened with a medical examination and a measure of anxiety.

If Dr. Shuster decided that you may be eligible to be in the study and if you have reached and spoken with Dr. John Halpern, and have decided that you want to further consider being in the study, you will have a meeting with Dr. Halpern. This meeting may take up to 3 (three) hours to complete, and will include a semi-structured psychiatric interview and questionnaires on anxiety, quality of life issues, your thoughts about your illness, and your thoughts on suicide. You will have a urine screen for drugs of abuse on this day. Your drug screen must be negative for all drugs except for opiates (often used for pain control).

You will have to undergo further tests that will take place at an hour-long office visit in the Medical Oncology Wing of the Lahey Clinic. These tests are to further evaluate whether you are eligible for study participation. Tests and measurements included during this visit include the following:

You will be asked to provide a blood sample (about 2 tablespoons) and a urine sample for laboratory testing for different hormones, such as thyroid hormone.

An ECG (electrocardiogram) will also be taken, which is a recording of the electrical activity of your heart.

If you are a woman and are able to get pregnant, a pregnancy test will be done on the urine sample. Your urine pregnancy test must be negative for you to take part in the study. The screening process will take about 3 to 4 hours.

You will also be tested for HIV. State law requires that positive HIV test results be reported to a health agency, but your name will not appear on or be connected to the positive results.

Starting at the very beginning of the study (the day of the baseline evaluation) and throughout the study period until you are no longer in the study, you will be required to keep a daily diary of all the medications you are taking each day, and any time during each day when you had to take medications to reduce anxiety or pain. You will also rate your pain level in the daily diary. Completion of the daily diary should take approximately 6 to 8 minutes per day.

SCHEDULE OF EVENTS

Time D = Day	D -1	D 0	D 7	D 14 Session 1	D 15	D 21	D 28 Session 2	D 29	D 35	D 36	D 84
Visit	Screening & Start		Therapy & Evaluation				Therapy & Evaluation
Screening	x	x
Baseline Evaluation		x
Medical Exam	x									x
Questionnaires	x	x		x		x	x		x	x	x
Psychotherapy			x		x	x		x	x		x
MDMA and therapy				x			x
Daily Diary		x	x	x	x	x	x	x	x	x	x
Pain rating		x	x	x	x	x	x	x	x	x	x
Conducted at Lahey Clinic	x									x
Conducted at McLean Hospital		x	x	x	x	x	x	x	x		x

Time is counted from the first study visit (the baseline evaluation visit at McLean Hospital - "Day 0") after you are selected to be in the study. The screening assessment at the Lahey Clinic ("Day -1") should be completed within two weeks before the baseline evaluation. The two experimental (MDMA) sessions are on "Day 14" and "Day 28" of the study.

If you are still undergoing cancer treatments, such as chemotherapy or radiation, you cannot at this time participate in this study, but you may still qualify for participation at a later date. Cancer treatments should have concluded at least two weeks before the first experimental session. If you want to or must start cancer therapy before you have undergone your second experimental session ("Day 28"), you will have to be taken out of the study. If you want to do this, Dr. Halpern and his colleagues will tell you about alternative treatments for your anxiety. You can start cancer treatment after you have undergone the second experimental session ("Day 28") but you should speak with Dr. Todd Shuster, the oncologist investigator, about specific timing.

You will meet with the researchers one week before the first experimental session to fill out the paper-and-pencil measures of anxiety, depression, and quality of life, which will take approximately 90 minutes to complete, and then you will have a 60-minute introductory psychotherapy session with Dr. Halpern and his co-therapist, Dr. Naidoo. During this session, you will discuss your anxiety or distress relating to your cancer diagnosis, and any other feelings you have about your diagnosis that make you upset. You will also learn more about what to expect during the experimental sessions.

Each subject will be randomly assigned (by chance, as if by flipping a coin) to get either a low dose ("sub threshold dose") of MDMA during both experimental sessions, or nearly-full to full doses ("experimental intervention dose") of MDMA on both experimental sessions. For people getting the larger doses, the amount of MDMA given on the second session will be bigger than the amount on the first experimental session.

At the start of each experimental session, you will take one dose of MDMA. Approximately two and a half hours later, you will take another dose of MDMA. The second dose will always be one half the size of the first dose for everyone and in each experimental session, whether the first dose was low, nearly-full, or full. If you or the researchers note problems after the first dose of MDMA, then the second dose of MDMA may not be given to you.

Neither you nor the researchers will know who is getting "Experimental Intervention" (nearly-full or full) doses of MDMA and who is getting low doses of MDMA until after the study is completed. However, this information is available if needed in an emergency.

There will be two experimental sessions. These are the times when you will receive MDMA. The first will occur at about day 14 and the next in two to three weeks (approximately day 28).

First, you and the researchers will discuss your goals and your problems with anxiety, so that all of you will know what you want to achieve during the experimental session. The researchers will also answer any additional questions you may have about the experimental sessions before they occur. Some of the tests done before and during the experimental sessions are meant to make sure you can still be in the study and to spot problems during the experimental session.

You will be asked not to eat anything or drink any alcohol after midnight on the night before each session. You can drink non-alcoholic liquids during this time, such as water or juice.

You can take your usual amount of medication for pain control or for nausea, but if you take extra medication, the investigators may decide to delay or reschedule the session after talking with you.

Each of the two sessions will last for six to eight hours, though the researchers will remain with you for a longer period of time if necessary. You will also spend the night at McLean Hospital and remain until after the non-drug psychotherapy session the next morning.

Your temperature, blood pressure, and pulse will be measured before you receive the medicine.

Before the start of each session, your urine will be tested for drugs of abuse. If you are a woman who can become pregnant, a pregnancy test will also be done on your urine. If either urine test is positive, the session may be delayed or cancelled.

If you choose, a significant other, such as a close friend or a family member, can also remain with you during the experimental session and afterwards. In order to confirm that this individual can serve in this supportive role for you, the researchers must meet this individual prior to the experimental treatment day, and you, the person staying with you, and the researchers will arrange when the person will arrive.

Before taking the study drug (from 9:00 A.M. to 11:00 A.M.), you will complete the questionnaires on anxiety levels, quality of life, your thoughts about your illness, and your thoughts, if any, about suicide. The researchers will look at your responses to see if there are any changes before or after each experimental session.

After the preliminary tests you will receive a capsule (at 11:00 A.M.) that will either contain a low "sub threshold" dose of MDMA or a larger (experimental intervention) doses. During the first experimental session, the initial capsule may contain either 25 or 83.3 mg MDMA. If you received an initial capsule of 25 mg during the first session, then you will receive an initial capsule of 25 mg during the second session. If you received an initial capsule of 83.3 mg during the first session, then you will receive an initial capsule of 125 mg during the second session. After taking the capsule, you will sit or lie down in a comfortable position. You can ask for eyeshades if you wish. You will listen to music through headphones during much of each experimental session. Periodically you will be asked to remove the headphones to talk to the researchers. You may also remove them yourself when you want to talk to the researchers or if you choose to request periods of silence. Lying or sitting in a comfortable position and listening to music are meant to encourage emotional thoughts and feelings, including about your cancer diagnosis and about anxiety. Both researchers will remain with you, and they will help you if you need help. They will speak with you and ask you to talk to them at least once an hour, but you can talk to them whenever you wish. There may be periods of time when, after you have been talking, they will suggest that you stop talking for a while in order to pay attention to your thoughts and feelings. There will be juices and other non-alcoholic beverages available for you, and you will be encouraged to drink an adequate amount of fluid. You can drink up to 12 cups (3 liters) spaced out over the day of the experimental session. Later on, food will also be provided that you can eat if you wish to do so.

The researchers will continue to measure blood pressure and pulse at regular intervals, and they will measure temperature automatically and slightly less often. You will be monitored for any side effects, which will be medically treated, if indicated, and the treatment will be explained to you by the researchers. In addition to Dr. Halpern and Dr. Naidoo, staff will be available to deal with any emergencies that might arise. An internist will also be available throughout an experimental session, in case any concerns are raised about your medical safety during the experimental session.

Approximately two and a half (2.5) hours after ingesting the initial capsule, you will take another capsule that will contain half the dose of MDMA you received at the start of the study. People who got the low dose of 25 mg will therefore have a second dose of 12.5 mg MDMA during the first and the second experimental sessions. People receiving experimental intervention doses will receive a second dose containing 41.7 mg MDMA during the first session and 62.5 mg MDMA during the second experimental session. The experimental session will continue, and Dr. Halpern and Dr. Naidoo will continue to monitor body temperature, blood pressure, and heart rate soon after this second dose of MDMA.

If you are confused or very upset eight or more hours after the start of the experimental session, the researchers will stay with you until you have recovered more fully. If the researchers think you are at risk for hurting yourself or someone else, they will either remain with you all night or transfer you to an appropriate inpatient bed at McLean Hospital until you are no longer at risk of hurting yourself or someone else.

If the researchers determine that the effects of the drug have worn off and you are in an appropriate frame of mind, they will leave the research unit. You can call Dr. Halpern and request that he return to see you if you think it necessary. It should take him only 10 minutes to return to the research unit.

You will be spending the night at McLean Hospital. Other doctors and nurses will be available in case of any problems that develop after each experimental session. There will be a psychiatry resident staying overnight, as well, expressly for your care, should problems arise through the night. An additional bed will also be made available at McLean Hospital for the person you had chosen to stay with you during experimental sessions.

On the next day, you will have a 60-minute psychotherapy session with the researchers. You will need to have someone drive you home after this session because it is possible taking MDMA on the previous day will affect your ability to drive and because some people report feeling tired, less alert, or that they have trouble concentrating a day after having taken MDMA. You should arrange to have someone help get you home ahead of time; the person helping you to get home can be the family member, spouse, or close friend who stayed with you during the experimental session. If you cannot find anyone to take you home, the researchers will pay for a taxi service.

If you need to schedule additional psychotherapy meetings with the researchers besides those that are scheduled as part of the study, then you may do so. There will be no cost to you for any additional meetings with the researchers during your participation in the study.

You can contact the researchers at any time. Dr. Halpern will be on call (reachable by telephone or pager) 24 hours a day throughout the research study, except on occasions when he is out of town. At those times another psychiatrist familiar with the study will be on-call and can be reached through Dr. Halpern's phone number.

If you decide that you do not want to continue in the study during one of the experimental sessions, you will still have to stay at McLean Hospital until the researchers think that you are well enough to go and all the psychoactive effects of the drug have worn off.

If you experience very high blood pressure, an unusual and difficult physical or emotional reaction, or have a significant lasting negative reaction after the first experimental session, you or the researchers may decide that you should not take part in the second experimental session. You may make this decision to stop being in the study for any reason. If the researchers decide to take you out of the study, they will let you know that they are doing this and they will tell you their reasons for taking you out of the study. If you are taken out of the study at this point, or if you decide you do not want to be in the study, the researchers will ask you to complete some final questionnaires. These include questionnaires about your anxiety levels, quality of life, and feelings about your illness and about dying soon, and pain levels. The researchers want to see whether there are any changes in your anxiety levels, quality of life, or pain. If you wish, you can decide not to complete these questionnaires and tests.

There will be two different types of follow-up session: A follow-up psychotherapy to talk about your experiences, thoughts, and feelings during the experimental session, and a research (evaluation) follow-up - to assess your responses before and after the experimental session.

One follow-up psychotherapy session will occur 24 hours after each experimental session ("Day 15" and "Day 29"). These will last for about an hour. During these sessions, you and the researchers will talk about what you experienced during the experimental sessions and what you thought and felt about it afterwards. You and the researchers will also talk about ways to work with this information and to use what you experienced to help you better deal with anxiety. You will be asked to guess whether you received low or experimental intervention doses of MDMA. Asking you to guess which doses you received will allow the researchers to know more about what condition you thought you were in, and whether this belief changed how you felt or thought about the experimental session.

There will also be one research (evaluation) follow-up session seven days after each experimental session ("Day 21" and "Day 35"). During the 60 to 90-minute long research follow-up, you will complete paper and pencil questionnaires on anxiety, quality of life, thoughts about your illness, and thoughts about assisted suicide or early death. Then there will be an additional 60 minutes for further (not drug-assisted) psychotherapy with the researchers. Dr. Halpern and the other researchers will see whether there were any changes in these questionnaire responses over time.

Approximately 36 days from the start of study participation ("Day 36"), you will also receive a second medical examination and some blood tests at the Lahey Clinic Medical Center's Medical Oncology Department. The medical examination will be done again by the co-investigator oncologist Dr. Todd Shuster in order to determine that your health has not changed since the beginning of the study in ways other than expected from the progression of your cancer. If your health status has changed in ways other than expected, we will make treatment available for any study-related condition and will report this finding of a study-related adverse event to the Institutional Review Boards of McLean Hospital and the Lahey Clinic Medical Center and also to the U.S. Food and Drug Administration.

The last follow-up session will occur approximately 84 days after the start of the study (approximately two months after the second experimental session). This final meeting should last for two to three hours. You will fill out the same questionnaires that you have filled out throughout the study, and this should take approximately 90 minutes. You will also have a final meeting with Dr. Halpern and Dr. Naidoo for about one hour to talk about your experiences during the study. This will be the last day that you complete the daily diary.

If you are accepted into the study and you wish to take part in it, you will be asked to agree to the following:

Do I Have to be Part of This Study?
Participation in the study is completely voluntary. You may refuse to participate or withdraw at any time without jeopardy to your medical care. Should you choose to withdraw, you will notify Dr. Halpern or the research staff. You will be encouraged to return for a final visit and complete all safety procedures (blood draw, urinalysis, electrocardiogram, physical exam).

Dr. Halpern and his colleagues, or the sponsoring company (Multidisciplinary Association for Psychedelic Studies (MAPS)) can remove you from the study at any time if it is determined that this is in your best interest or the best interest of the study. For example, if you have a bad reaction to the study drug during the first experimental session, such as very high blood pressure or heart problems, or if you become too ill and need to start taking a medication that might interact with the study drug, then you will be taken out of the study.

What are My Rights as a Study Participant?
You may choose not to be in the study, or, if you agree to be in the study, you may withdraw at any time. Your decision not to participate or to withdraw from the study will not involve any penalty or loss of benefits to which you are entitled, and will not affect your access to health care at Lahey Clinic. If you do decide to withdraw, we ask that you speak with Dr. Halpern at McLean Hospital to let him know that you are withdrawing from the study.

You have the right to review and copy your health information. However, if you decide to be in this study and sign this consent, you may not be allowed to look at or copy your information until after the research is completed.

What Other Options Are There?
The alternative to participating in this study is to choose not to participate. In that case, you will still receive standard care and these alternatives will be discussed with you by your doctor prior to your enrollment in the study. There are other medications and other forms of psychotherapy that you could try to reduce your anxiety related to your cancer diagnosis. These include psychotherapies ("talk therapies") that help you learn to control or manage stress, cognitive (thought related) therapies where you look at patterns of thought that make you more anxious, and exposure therapies where you confront directly the ideas, thoughts and feelings that make you anxious. Anxiety can also be treated by different types of drugs, including drugs such as Xanax, Valium, Ativan, Buspar, and different types of antidepressants.

Are There Benefits to Taking Part in This Study?
The direct benefits to you are as follows: You will receive a psychiatric examination, additional medical tests as part of being screened for being in the study, and one (1) physical examination during the course of the study, and six (6) psychotherapy sessions.

There is no guarantee that your anxiety or quality of life will get better from taking part in this research study. The results of this study may benefit patients who might later be treated with this experimental intervention. You will be helping Dr. Halpern and his colleagues learn more about the safety and efficacy of MDMA-assisted psychotherapy as a way to reduce anxiety in people with advanced-stage cancer.

Will I be Paid to Be In This Study?
You will not be paid any money for taking part in this study.

What are the Costs?
There are no anticipated additional costs for you to bear in connection with this study. However, the researchers, McLean Hospital, and the Sponsor will not cover costs of unanticipated additional costs relating to hospitalization in response to being at risk of harming yourself or others.

What are the Foreseeable Risks and Side Effects to this Study?
Participation in this study may involve some added risks or discomforts. These include risks related to screening and the medical examination, risks and discomforts of psychotherapy, and risks and discomforts related to the experimental drug (MDMA).

RISKS RELATED TO SCREENING
Mild discomfort, and rarely a small arm bruise, clot, or infection may occur at the site of the blood draw. Feeling faint or light-headed, or actual fainting, could also occur.

Having a medical examination can take up a lot of time, and some parts of the examination may be uncomfortable. Having a psychiatric examination can take up a lot of time, and parts of the examination may be distressing or uncomfortable. Some people may be upset by talking about having advanced-stage cancer or other thoughts related to being very sick.

RISKS RELATED TO PSYCHOTHERAPY
People in psychotherapy often talk about memories, events, thoughts, or feelings that make them unhappy (angry, afraid or sad). It is very likely that psychotherapy will make people experience these feelings. Talking about upsetting thoughts or feelings may lead to an increase in feeling angry, frightened, or sad during or immediately after a therapy session.

RISKS RELATED TO THE EXPERIMENTAL DRUG (MDMA)
To date, MDMA has been given in the context of clinical research to a total of about 230 people without emotional disorders and 6 with posttraumatic stress disorder. Some of the risks observed are listed below. There may be unknown side effects or risks from the use of MDMA.

MILD RISKS
These side effects have been reported by 40 to 70% of volunteers in previous studies. Side effects during the MDMA experience that are frequently reported, are

Less commonly, study subjects reported feeling hot or cold, feeling that their heart is racing, sweating, dizziness, drowsiness, upset stomach, anxiety, tenseness, weakness, shaking, headache, or feeling faint. Most human studies of MDMA have used only one dose, and not two on the same day. On the basis of previous reports of people in therapy before MDMA was made illegal, and on the basis of one study of two equal sized doses of MDMA given 24 hours apart, side effects produced by an additional dose of MDMA are predicted to be the same as those produced by the first dose. When any of these side effects occur, they usually last less than four hours, though some people report side effects lasting up to twenty-four hours.

Changes in vision or hearing: In previous research studies, most volunteers reported experiencing minor changes in vision and hearing, such as sounds seeming closer or farther away than usual, or objects seeming brighter than usual, with these changes lasting 2 to 3 hours after one dose.

Anxious or jittery feeling: Some subjects in prior research studies reported feeling over- stimulated or anxious at times. These feelings usually lasted less than 30 minutes but sometimes lasted longer. It is possible that because you have anxiety problems, you may feel intensely anxious during the experimental sessions. Letting yourself accept and feel those emotions deeply can be part of the psychotherapy in the experimental session. If you are not able to deal with these experiences in a way that helps you, the researchers will help you work with these feelings. It is possible that if such periods of heightened emotion have not been adequately resolved during the session, you could be at increased risk for suicide or other self-harm afterwards. You will be encouraged to call the researchers immediately if any thoughts about hurting or killing yourself should occur so they can help you resolve them safely. If necessary, they may prescribe anti-anxiety medication or medication for sleep.

Insomnia & drowsiness: In previous studies, some subjects have reported insomnia (difficulty sleeping), and feeling tired, irritable, or drowsy for as long as 3 days after MDMA.

Mood: Some after-effects of MDMA on mood may be noticeable up to 2 or 3 days later. While some subjects feel that their mood is better, others feel it is worse.

Immune response: You will probably have a less active immune system for up to 2 days after MDMA. This change in immune system activity is similar to what would occur if you had 4 to 5 drinks of alcohol. This may make you more likely to become sick with a cold or other infection during this time, as can happen after some types of chemotherapy.

Interaction with Pain Control Medications: No studies have specifically investigated the effects of MDMA when given with pain control medication. There are past anecdotal reports of people describing no problems with this combination, however, and a study in rats suggests that MDMA will not interfere with the pain reducing effects of pain control medications. It is possible that MDMA might affect how your pain control medications are broken down. Generally, opiate-type drugs have opposite effects on heart rate and breathing as MDMA. The investigators will watch carefully for any problems.

Blood pressure and heart rate. MDMA increases blood pressure and speeds up heart rate. These effects of MDMA usually last 4 to 6 hours, and taking a second dose may make effects last until 3 hours after the second dose. At the doses in this experiment, the increases in blood pressure and heart rate are likely to be moderate, with greater increases happening after higher doses.

Blood pressure increased well above normal rates after MDMA in a few subjects (a little less than 5%) in past research studies, but these subjects did not report any discomfort and did not require any treatment. Although these higher blood pressures are similar to those that occur after vigorous (heavy) exercise, they could cause serious problems in individuals with pre-existing heart or blood vessel defects. These serious problems could include heart failure or stroke. We are going to screen all potential subjects for preexisting heart problems before they are allowed to enter into this study. This doesn't guarantee that no heart problems will occur, but it does greatly reduce the risk of this happening.

Severe Anxiety or Distress: If you are in immediate danger of hurting or killing yourself or hurting someone else, then the researchers may take you to the Crisis Evaluation Center in McLean Hospital for further observation and assessment for the need for further inpatient-level psychiatric care.

Impaired Driving: Some of the effects of MDMA that appear one to three days later could possibly impair driving ability, including increased fatigue and changes in mood. People should be careful driving or using heavy machinery for a few days after each experimental session, since it is not known whether and for how long MDMA could affect driving.

Addiction: There is a small chance that you will become dependent on (addicted to) MDMA. One study found that up to 6% of people using ecstasy for recreational purposes were dependent on it. However, a study of people who had received MDMA for the first time in a legal medical laboratory setting found that they did not want to try it again outside of the laboratory.

You can talk with the researchers about any worries you have about taking a drug with a potential for addiction. People who have had problems with drug abuse in the last 60 should not take part in this study.

Serious problems and Death: There have been some serious problems, and even deaths, associated with the use of ecstasy outside of controlled clinical or laboratory settings. Serious problems have included high fever, drinking too much liquid, convulsions, and liver damage. Some recreational users of ecstasy have become severely anxious, depressed, or paranoid (thinking that other people are against them). These problems have not occurred in research settings to date, and so they are not expected to occur during or after the experimental sessions. If serious problems do occur, the investigators and the staff at the hospital are prepared to respond to reduce the chances that you will experience any long-term consequences.

Possible Brain Damage - Human Recreational Use
Some studies comparing those who have used ecstasy repeatedly with people who do not use ecstasy found ecstasy users were more likely to report feeling generally anxious or depressed. Some scientists think that increased reports of feeling depressed or anxious after ecstasy are signs of brain damage from MDMA. However, other scientists believe that these differences in mood are not related to ecstasy use. For instance, people who repeatedly use ecstasy may have been depressed or anxious before they began taking the drug, and feeling this way might even have led them to use ecstasy. Researchers have also found that feeling depressed or anxious was equally or even more strongly connected to using drugs other than ecstasy.

People receiving one or two doses of MDMA in a legal medical laboratory setting did not notice any lasting increase in feeling depressed or anxious after having taken MDMA. The investigators believe that the doses of MDMA used in this study will not make you more depressed or anxious, but we cannot guarantee that this will not happen.

Some studies found that people who had used ecstasy were not able to recall words, pictures, or patterns as well as people who did not use ecstasy. People who had used ecstasy many times also performed less well on tests of planning and impulse control. These differences are not great, and most ecstasy users do not notice having any trouble in everyday life. When found, these differences have lasted for at least a year after people had stopped taking ecstasy. Some studies have even found that people who had stopped regular use of ecstasy had lower scores on tests of memory than people who were still regularly using the drug. Not all studies have found ecstasy users to have difficulty recalling words or pictures, and some studies have not found differences in impulse control. Other scientists believe that these differences are not due to MDMA.

A number of scientists have found that people who have used ecstasy a moderate number of times, such as on fifty or fewer occasions, do not have the same difficulties with memory or planning. One study also found that people who used ecstasy on 20 or fewer occasions did not have signs of low brain serotonin. Since people in research studies receive fewer doses of MDMA, the likelihood that you might experience the problems that ecstasy users experience is low. To date, no scientists with studies administering MDMA to humans have published on subsequent/follow-up changes in brain function or cognition. All the studies mentioned in this section have been with users of illicit MDMA preparations, or "ecstasy."

Animal studies can point the way to look in human studies. Experiments with rats and monkeys show that some doses of MDMA can damage parts of brain cells that release a chemical called serotonin. Serotonin is one of the "neurotransmitter" messenger compounds released between neurons as a signal to or from neuron cells. MDMA, usually given repeatedly on several days in a row, caused losses of the part of the cell (called "axons") involved in relaying signaling between neurons from different brain areas. Although axons can re-grow, one study detected damage to serotonin cell axons in monkeys seven years after four days of twice-daily injections of MDMA. Re-growth of axons leading from neuron cell bodies have not been found to be in the same pattern of interconnections as prior to MDMA exposure.

Studies have found that animals given doses of MDMA high enough to cause these changes in their brains are affected several weeks later in three ways. These changes include being less sensitive to the effects of MDMA and other drugs, more sensitivity to becoming overheated when placed in a warm room, and worse performance in difficult tests of memory. However, other studies found no changes in animal memory. It is not known if these changes are permanent or reversible or if similar damage occurs in humans.

Effects of MDMA on the growth and development of an unborn baby are not known; exposure to MDMA may involve risks to an embryo or fetus if the subject is or becomes pregnant. While studies in humans are not very clear, studies in rats suggest that some parts of the brain may be changed in fetuses exposed to MDMA. Therefore you will not be allowed to enter the study if you are pregnant.

You will be tested at the start of the study and again before each MDMA or placebo session to see if you are pregnant. If, at any time during the study, you suspect that you may be pregnant or are concerned that you may become pregnant, you must advise Dr. Halpern immediately. If you should become pregnant during the study, the researchers will help you get proper advice and help you and your unborn baby get proper care while you are pregnant.

Will I Hear About New Findings?
If any new information about MDMA that significantly changes our understanding of its risks becomes available while you are participating in this study, the investigators will tell you about it.

What sort of Emergency Coverage is there for This Study?
There is a physician available 24 hours a day in case of emergency or if you become suicidal (have thoughts of killing or severely hurting yourself). You can page Dr. Halpern through the McLean Hospital Operator if you need to speak with him for any reason. You will be given a sheet with this and other emergency contact numbers on it at the beginning of the study.

What About Study-Related Injuries?
If you are injured as a result of participation in this research, McLean Hospital will only provide medical care needed to treat those injuries. This includes only minimal efforts available on grounds and for more serious injuries, arranging (but not paying for) transportation to an acute care center for treatment of injuries. McLean Hospital will not pay for additional medical and hospital costs required for the diagnosis and treatment of any adverse effect caused by tests, drugs, device, or study procedures, or laboratory work required by the protocol. McLean Hospital will not provide any other form of compensation if you are injured. You may call the McLean Hospital Department of Research Administration or the Lahey Office of Research Administration for more information about this or to report research related problems.

In the event of a study-related injury that is not covered or fully covered by McLean Hospital, the physician who treats you will bill your insurance company. If your insurance company denies coverage or insurance is not available, then MAPS will pay for any costs that arise from treating a study-related injury. To reach MAPS, contact Rick Doblin, Ph.D., MAPS President.

Dr. Halpern and researchers working with him have explained this study to you and have answered your questions. If you have other questions or research related problems, you may reach Dr. Halpern or Dr. Shuster. Should you experience any problems arising from participation in this project, you may contact the Research Administration Department of McLean Hospital, the McLean Hospital Research Privacy Office at for assistance between 8:30 a.m. and 5:00 p.m., Monday through Friday, or the Lahey Clinic Office of Research Administration.

How Will Information About Me be Kept Private?
Federal law requires McLean Hospital and its affiliated hospitals, researchers, health care providers, and physician network to protect the privacy of information that identifies you and relates to your past, present, and future physical and mental health conditions ("protected health information"). If you agree to participate in this study, the study information (which does not contain your identity) will be shared with the study sponsor (MAPS), including its agents and contractors, an ethical review board for this study, the U.S. Food and Drug Administration, and regulatory authorities in other countries. This study information (which does not contain your identity) may also be published. "Protected health information" will be used as shared with others as explained below in the "Authorization for Use of Protected Health Information." Medical records that do contain your identity will be treated as confidential information. They may be inspected at McLean Hospital by the above-mentioned parties, but information will not be taken from McLean Hospital (for example, by photocopying) except in the case of an audit by the U.S. Food and Drug Administration. In those cases your identifying information would be accessed and disclosed only to the extent absolutely necessary for the audit.

The records are kept locked in file cabinets, identified by study numbers to preserve confidentiality. Your records or any part thereof can only be legally obtained with your written permission specifying what exact information is to be released or if court ordered by law.

The information obtained in this study will be used for research investigational purposes and that your name will never be publicly disclosed at any time. You will not be identifiable in any publication that may arise from this research.

You should be aware that under certain circumstances, information that you report will not be kept confidential. Pursuant to Massachusetts law, health professionals are mandated to report to the respective agency whenever in their professional capacity they have reasonable cause to believe a child under 18, or an elderly or disabled person is suffering from abuse or neglect. In addition to the above, mental health professionals are mandated to report or protect patients who pose a serious threat of physical harm to themselves or others

Videotapes: The researchers and the sponsor will watch and listen to these recordings, and no identifying information will be written or otherwise attached to the recording. If permission is granted by you, portions of these videotapes may be viewed by other McLean Hospital faculty or other physicians for educational training and supervision purposes.

Federal law required Partners HealthCare System, Inc. and its affiliated hospitals, researchers, healthcare providers, and physician network to protect the privacy of information that identifies you and relates to your past, present, and future physical and mental health conditions (Protected Health Information - PHI). If you enroll in the research described in this consent form, your PHI will be used and shared with others as explained below.

Study: A TEST OF MDMA-ASSISTED PSYCHOTHERAPY IN SUBJECTS WITH ADVANCED-STAGE CANCER AND CANCER-RELATED ANXIETY

It is very important that subjects taking part in this study know what will happen to them during the study and be aware of the possible risks and problems involved as a result of their participation. We know there is a lot to read and keep track of in the informed consent form. We have created this quiz in order to make sure that you are not confused about the study and any problems related to it. Please answer these questions as best as you can. This will let us know if we did not explain a specific part of the study well enough, or if we need to talk more about a part of the study in more detail. Don't worry if you don't get all of the answers right. We will go over the quiz with you, with special attention on any questions that were answered incorrectly.

A TEST OF MDMA-ASSISTED PSYCHOTHERAPY IN SUBJECTS WITH ADVANCED-STAGE CANCER AND CANCER-RELATED ANXIETY STAGE CANCER AND CANCER-RELATED ANXIETY

This research will be conducted and administered in compliance with all state and federal laws.

You have read this consent form and had the opportunity to ask questions. Dr. Halpern or his colleagues have answered all your questions to your satisfaction. You voluntarily agree to participate in this research study. You may refuse to take part in or you may stop taking part in this study at any time. Your decision will not affect your current or future regular medical care or any benefits to which you are entitled at this site.

Subject:
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Principle Investigator:
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Witness:
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TITLE:	A Test of MDMA-Assisted Psychotherapy in Subjects with Advanced-Stage Cancer and Cancer-Related Anxiety: Videotaping of Human Subjects
PRINCIPAL INVESTIGATOR:	John H. Halpern, M.D.
CO-INVESTIGATORS:	Umadevi Naidoo, M.D., Todd D. Shuster, M.D., and Arthur J. Siegel, M.D.
COMPANY AND FUNDING:	Multidisciplinary Association for Psychedelic Studies (MAPS)
PRIMARY CONTACT:	Dr. John Halpern

Dr. John Halpern and colleagues are conducting a small, early (pilot) study of an experimental drug, MDMA (3,4-methylenedioxymethamphetamine) taken during special therapy sessions in people with advanced-stage cancer to see if this therapy will be safe, and to see if it will reduce anxiety and improve quality of life. The effects of a nearly full and a full dose of MDMA will be compared with a very low dose of the drug. In this study, 33% of the subjects will receive the very low dose during both experimental sessions, and 66% of the subjects will receive a nearly full dose on the first experimental session, and a full dose on the second session. There will be two six to eight hour experimental sessions scheduled 2 to 3 weeks apart. In this study, the experimental (MDMA) session will be videotaped, so that the researchers will have accurate records of the session and so that they can gather more information about drug-assisted psychotherapy sessions. The researchers will record the entire experimental session, starting soon after you take MDMA and continuing for the whole six to eight hours of the experimental session. You can stop the recording at any point in time, and you may request that portions of the videotape be erased after they are recorded. A copy of these tapes (edited to remove periods of silence/non-activity or segments you request not to copy) will be provided for your review, as well. All investigators involved in this study and the sponsor of this study may review these videotapes to refine and improve this experimental treatment. In addition, other McLean faculty and/or other physicians may be shown portions of a videotaped session for training and educational purposes. No clearly identifying material will be screened for persons other than the investigators and the sponsor. You may also request that your videotapes be restricted to only being made available to the investigators and sponsor. The videotapes will be stored in a locked cabinet of the Biological Psychiatry Laboratory at McLean Hospital.

This research will be conducted and administered in compliance with all state and federal laws.

Do you request that videotapes be restricted to viewing by the investigators and sponsor only?

Subject:
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Principle Investigator:
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Witness:
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