MAPS1-03-077

9/25/03

SUBJECT INFORMATION AND CONSENT FORM

Study TitleA TEST OF MDMA-ASSISTED PSYCHOTHERAPY IN SUBJECTS WITH CHRONIC POSTTRAUMATIC STRESS DISORDER (PTSD)

Company and FundingMultidisciplinary Association for Psychedelic Studies

(MAPS)

3 Francis St., Belmont, MA 02478

Phone: 617 484-8711 Fax: 617 484-8427

Investigator Michael C. Mithoefer, MD

Daytime telephone number:

24 hour contact number:

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PURPOSE OF THE SUBJECT INFORMATION AND CONSENT FORM

This consent form describes a research study and your role as a participant. Please read this form carefully. Do not hesitate to ask anything about the information provided; it should stimulate your questions. The investigator will describe the study and answer your questions. After reading the consent form, the investigators will give you a short quiz to spot any parts of the study that need to be explained even further or in a better way than in the consent form. You will not be excluded from being in the study on the basis of your answers to this quiz.

This consent form may contain words that you do not understand. Please ask the researchers or the study staff to explain any words or information that you do not clearly understand. You may take home an unsigned copy of this consent form to think about or discuss with family or friends before making your decision.

PURPOSE AND BACKGROUND

This small, early study is designed to gather preliminary information about whether MDMA-assisted psychotherapy is safe and helpful for subjects with posttraumatic stress disorder (PTSD). The researchers plan to use the results of this study to design further studies.

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 is sometimes known as "Ecstasy" (which is supposed to contain MDMA but often contains other drugs instead of or in addition to MDMA).

MDMA has already been used legally in research and illegally in uncontrolled environments, such as nightclubs. While much is known about MDMA and its risks, there remains much that is unknown.

This study will compare use of MDMA (125 milligrams) with a placebo (an inactive substance or a “sugar pill”).

You are being asked to participate in this research study because you have been diagnosed with posttraumatic stress disorder (PTSD) as a result of being the victim of a crime, and because your symptoms have failed to go away after receiving treatment for PTSD.

Length

Participation in this study will take approximately 3 to 4 months and will involve 17 visits. Most visits will last for no more than 90 minutes (an hour and a half). The first two visits might last two to four hours, and the two MDMA or placebo- assisted psychotherapy visits could last for six to eight hours or more. You will also be required to spend the night in the clinic after each experimental session, returning home after the 90 minute non-drug psychotherapy session the next morning.

Conduct

If you and Dr. Mithoefer agree that you should be in the study, you will be asked to agree to the following:

  1. To come to all medication, psychotherapy and evaluation sessions.
  2. To avoid taking any psychiatric medications from the beginning of the study until the last follow-up session. You will be off any psychiatric drug for up to 17 weeks.
  3. If you are currently on any psychiatric medications, you should discuss this with Dr. Mithoefer. You will be required to give Dr. Mithoefer permission to talk to your doctor about your withdrawing from (not taking) medication during the study. We encourage you to talk to your doctor as well if you wish.
  4. If you are currently seeing a psychotherapist you may continue to do so. You may not begin any new psychotherapy, or increase the frequency or length of visits with your psychotherapist until after the final evaluation session.
  1. You must be able to spend the night after each experimental (MDMA or placebo) session at the office where the session will be held and remain until after the non-drug psychotherapy session the next morning. A private bedroom will be available for you. If you request and if Dr. Mithoefer agrees, you may have one other person stay with you, such as your spouse or partner, or a friend.
  2. You must be willing to have an attendant, who will be the same sex as you, stay in the clinic from the time after you are done with the experimental (MDMA or placebo) sessions until the non-drug session on the next day. The attendant will be a registered nurse (RN) and will be trained to be part of this study. The attendant will offer dinner and breakfast, assist you with any physical needs if requested, and contact Dr. Mithoefer to speak with him or to return to the clinic at your request or if the attendant considers it necessary. You will meet the attendant at one of the non-drug psychotherapy sessions prior to the experimental sessions.
  3. You must find someone who will take you home from the non-drug session scheduled for the morning after the experimental session because we cannot predict with certainty how MDMA might affect your driving. You might feel tired or feel less alert than usual.
  4. You must be willing to speak with one of the researchers over the telephone every day from the day following each experimental (MDMA or placebo) session up until seven days later. One of the researchers will contact you every day to determine if you are experiencing any physical or emotional distress that would require Dr. Mithoefer's attention.
  5. If you are a female and are able to get pregnant, you must use an effective method of birth control.

Importance of Honesty

Many of the procedures and tests are designed to reduce the chance of your being hurt by being in this study. It is important that you do your best to fully describe your general medical and psychiatric history as well as your recent and past drug use. If you accidentally break one of the study rules (such as taking a drug that was not approved by the researchers), it is important that you tell the researchers.

Please, if in doubt, discuss this with the researchers.

PROCEDURES/WHAT WILL HAPPEN TO YOU

Screening (Evaluation):

Before you can be in the research study, the researchers must first make sure that you qualify for the study and that you are generally physically healthy. This evaluation will be done during several office visits.

The tests will include the following:

  • Questions about your medical history, including questions about your emotional and psychiatric history. This may include any previous medical or psychiatric problems or treatment and may include questions about difficult experiences you may have had during childhood or at other times of your life.
  • A questionnaire about your posttraumatic stress symptoms and how you deal with them in your everyday life. Your score on this questionnaire will be used to decide if you can be in the study.
  • A physical examination that will include measures of your blood pressure, pulse, temperature, and body weight.
  • A study doctor (someone other than the researchers) will listen to your heart and lungs and examine your body for any signs of disease.
  • An ECG (electrocardiogram) will also be taken, which is a recording of the electrical activity of your heart.
  • You will be asked to provide a blood sample (about 2 tablespoons) and a urine sample for routine laboratory testing.
  • Your urine will also be tested for drugs of abuse.
  • If you are a woman and are able to get pregnant, a pregnancy test will be done on the urine sample. Your urine drug screen and pregnancy test must both 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 the results of positive tests for HIV be reported to a local health agency. This is the legal obligation of the medical personnel.

Beginning of Study

If you have decided that you want to be in the study and if the doctors find that you are eligible to be in the study, you will then take some more psychological tests. Within approximately two weeks after the preliminary testing, you will have a two to four hour visit. During this visit, you will be given three different types of evaluation. Each will be given again at the end of the study to compare your results before and after. They include:

  1. Three questionnaires about symptoms of posttraumatic stress disorder and how you deal with them in your life.
  2. A personality test that measures the way you tend to think and feel about the world, and how you tend to interact with other people.
  3. A series of tests of attention, memory and different types of problem solving. These are not tests of intelligence. They are measures of skills and processes we use in thinking and problem-solving.

You will not be taken out of the study as a result of how you do on any of these three groups of questionnaires or tests.

schedule of events

Time is counted from the first study visit after you are selected to be in the study. Screening will be done approximately two weeks before you start the study.

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Time:
d=days
w=week
m=month / 1 to 3 visits within two weeks before / +2 w / +2w, 1d / +2w, 4d / +3w / +4w / +5 w / +6w / +6w, 1d / +6w, 4d / +7w / +8w / +9w / + 3.5 m
Visit / Screen/Start / Therapy and Evaluation / Therapy and Evaluation
Screening / x
Personality Tests / x
Psycho
Therapy only / x / x / x / x / x / x / x / x / x / x / x
MDMA and therapy / x / x
PTSD
Symptom Measures / x / x / x / x
Medical Exam / x / x
Memory, Problem Solving Tests / x / x

Most visits will last for no more than 90 minutes (an hour and a half). The first two visits might last two to four hours, and the two experimental sessions (MDMA or placebo-assisted psychotherapy visits) could last six to eight hours or more. You will also be required to spend the night in the clinic after each experimental session, returning home after the 90 minute non-drug psychotherapy session the next morning.

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Introductory Psychotherapy Sessions:

You will meet with the researchers on two occasions before the experimental session. These visits will last about 90 minutes. During each of the two introductory sessions, you will discuss thetraumatic incidents that led to your PTSD, the ways PTSD symptoms are affecting your life and what you would like to achieve during these sessions. You will also learn more about what to expect during the MDMA or placebo sessions, and you will meet the attendant who will work at the clinic on the evening after each experimental session until the non-drug psychotherapy session the next morning.

Selection of Drug – MDMA or Placebo?

Each subject will be randomly assigned (by chance, as if by flipping a coin) to get either MDMA or placebo (a capsule containing the type of sugar found in milk but no active drug). There will be twenty subjects. Eight will receive placebos (a 40% chance) and twelve will receive MDMA (a 60% chance). Whatever you are assigned, MDMA or placebo, you will take on two occasions, as there are two separate experimental sessions scheduled three to five weeks apart.

Neither you nor the researchers will know who is getting MDMA or placebo until after the study is completed. However, this information is available if needed in an emergency. You will be told after the study is over whether you received the MDMA or the placebo.

Experimental Session:

There will be two MDMA/placebo sessions. The first will occur at about week 2 and the next between week 5 and 7.

First, you and the researchers will discuss your goals, 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 this session. 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.
  • 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 in the clinic 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.
  • You will also complete a very brief, simple test of how comfortable or distressed you feel. This will involve marking a number on a sheet of paper that coincides with the way you feel at that moment. You will complete the same short test every 60 to 90 minutes throughout each experimental session. This will allow the researchers to know how you are feeling throughout the session and to see whether your feelings of comfort or distress change after receiving MDMA or placebo.
  • 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 test is positive, the session may be delayed or cancelled.
  • The attendant will arrive during the last hour of the experimental session. If you choose, a significant other such as a close friend or a family member can also come at this point in the session.

The experimental session will be audiotaped, so that the researchers will have accurate records of the session and so that they can gather more information about drug-assisted psychotherapy sessions.

In addition to the doctor and nurse you will work with during the experimental session, a board-certified emergency room doctor and emergency room nurse will be in the adjacent room to provide medical assistance or opinions if the researchers request it. They will not generally be in the room with you and the researchers. Unless they are in the room, they will not hear anything that takes place during the sessions. If they do overhear anything, they will keep it in confidence.

After the preliminary tests you will receive a capsule that will either contain 125 mg MDMA or a placebo. After taking the capsule, you will sit or lie down in a comfortable position. You can ask for an eye shade 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 bring out emotional thoughts and feelings, including thoughts and feelings about the trauma. Both researchers will remain with you, and they will help you if you need them to help you. 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 inner experience (your inner thoughts and feelings). There will be juices or Gatorade available, and you will be encouraged to drink an adequate amount of fluid. You can drink it whenever you wish to do so, within the limits of the amount that is safe for your body. 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. Temperature will also be measured, but slightly less often. You will be monitored for any side effects, which will be treated if they occur. If this should occur, the researchers will explain what they are doing at all times.

The attendant will arrive during the last hour of the experimental session. If you have asignificant other who you would like to be with after your session, he/she can also come at this time.

If you are still 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 have you stay in East Cooper Medical Center 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 clinic with the attendant in charge. If you or the attendant considers it necessary, the attendant will call Dr. Mithoefer and request that he return to the clinic, which should take him only 10-20 minutes.