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Therapeutic Uses of MDMA1
George Greer, M.D. & Requa Tolbert, R.N., M.S.N.
[from Psychedelic Medicine, ed. MJ Winkelman and TB Roberts, 141-153. Westport, CT:
Praeger Publishers (2007)]
There have been several scientifically controlled studies of the psychological and physiological
effects of MDMA (methylenedioxymethamphetamine) in humans, and books and media reports
have told many stories about the use of MDMA in healing. However, no scientifically controlled
studies of MDMA in treatment have ever been published or completed. The first such study is
underway at present and is described by Michael Mithoefer, M.D. in these volumes (Mithoefer,
2007). At the time of this writing in mid-2006, other therapeutic projects in the US, Israel, Spain
and Switzerland are beginning. Other than small studies using ketamine for depression (Berman,
et al, 2000) and studies by Evgeny Krupitsky, M.D. (Krupitsky, 2007) for addiction as described
in these volumes, as of this writing in mid-2006, no controlled studies on the therapeutic use of
any psychedelic drug have been published since the early 1970s (Mangini, 1998).
MDMA has been used therapeutically since the late 1970s, and there have been two systematic
follow-up studies. However, these studies employed only customized questionnaires
administered before and after the MDMA sessions. All of this work was done in the context of
purely clinical psychiatric practice, and there were no control groups or sessions, or standardized
or quantitative assessments. The first study (Greer & Tolbert, 1986) reported on the first 29
people administered MDMA from 1980 to 1983, before it became a controlled substance in the
US in 1985. The second report, by Swiss psychiatrist Peter Gasser. (Gasser, 1995) describes the
results of courses of treatment involving both MDMA and LSD (lysergic acid diethylamide) in
the same patients conducted by a small, organized group of Swiss psychiatrists from 1988 until
1993, when all psychedelic therapy was halted by the Swiss government. This chapter will
summarize and comment on the findings of these two studies.
Greer and Tolbert Research
For our study, Greer synthesized MDMA in the laboratory of Alexander Shulgin, a biochemist
who with David Nichols first reported on the subjective effects of MDMA (Shulgin & Nichols,
1978), comparing it to low doses of MDA (methylenedioxyamphetamine), which had been used
therapeutically (Yensen et al, 1976). The ethical context for this work included informed
consent and peer review, utilizing all scientific information available at the time. Because the
primary purpose of the project was to assist the subjects in achieving their particular and varied
goals for having the sessions, only vital signs during sessions and phenomenological descriptions
of the therapists' observations and of the subjects' experiences before, during and after the
sessions were recorded.
All subjects were referred by psychotherapists or friends specifically for the purpose of having
an MDMA session for various reasons, and none were referred from the author's (Greer) private
psychiatric practice. A questionnaire1 designed for screening and preparing the subjects for
Greer, Therapeutic Uses of MDMA, page 2
MDMA sessions was filled out, and lengthy informed consent information about the possible
side effects that could occur was explained both verbally and in writing. Subjects with any
known medical conditions that might be worsened by MDMA—such as hypertension, heart
disease, hyperthyroidism, diabetes mellitus, hypoglycemia, seizure disorder, glaucoma, liver
disease and pregnancy—were excluded, as were subjects who had ever had functional problems
resulting from a psychiatric disorder, other than substance intoxication. Of the 29 subjects, 14
reported relatively mild psychological problems before the sessions.
The treatment model utilized was derived from the method established by psychiatrist Stanislav
Grof for LSD psychotherapy (Grof, 2001) and psychologist Leo Zeff. for MDMA psychotherapy
(Stolaroff, 2004). To optimize the therapeutic alliance and mindset of everyone involved in the
sessions, the life histories of the subjects were discussed as well as their intentions and goals for
the session. This is the same general model being employed in the current therapeutic trials with
MDMA and psychedelic drugs, including the Mithoefer MDMA study.
An extensive preparatory session was held to establish a close relationship with the subjects. At
that time, subjects were told that they should not take MDMA unless they were certain that they
were willing to deal with any disturbing experience they might have, including but not limited to
previous psychological difficulties. Following Zeff’s method, the following agreements were
made with the therapists before the session to ensure an atmosphere of psychological security
and physical safety during the session:
1) Everyone agreed to remain on the premises until the session was over, and the therapists
determined that it was safe to leave;
2) The subjects agreed to refrain from any destructive activity to self, others, or property;
3) All agreed that there would be no sexual activity between the therapists and the subjects;
and
4) The subjects agreed to follow any instructions given by a therapist when explicitly stated
as part of the structure of the session.
Sessions were conducted with individuals, couples and small groups, usually at the homes of the
subjects or sometimes the facilitators. A 6-hour fast was instituted to ensure rapid absorption of
the MDMA and to prevent nausea. Before the dose was administered, there was time to
reestablish contact with the therapists and to answer questions. A dose of 75-150 mg of MDMA
was then given by mouth. Lower doses were used in interpersonal sessions, and higher doses
were given to heavier people. During individual sessions, the subjects listened to instrumental
music—with or without headphones and/or eyeshades—to facilitate an internal experience.
During interpersonal sessions, music was usually played in the background. The therapists were
attentive and available to respond to requests or needs, to receive and record communications,
and to interact with subjects as was deemed appropriate.
When subjects noticed that the effect of MDMA was beginning to subside, usually before 2
hours, they were offered a second dose of 50 mg or, rarely, 75 mg. The purpose of the second
dose was to prolong the session and to provide a more gradual return to their usual state of
consciousness. Some subjects were offered diazepam/Valium, 5 mg, at the beginning of the
session, or propranolol/Inderal, 20-40 mg, every 3½ to 4 hours to reduce unwanted
Greer, Therapeutic Uses of MDMA, page 3
sympathomimetic side-effects such as muscle tension. Others received l-tryptophan 500 mg to
help reduce various emotional discomforts occurring late in the sessions.
When the sessions were over, the subjects’ ability to drive was assessed before they were
allowed to drive a car. The usual duration of sessions was 5-8 hours, depending on the dosage
and setting. Follow-up was conducted verbally soon after the session, and much later by written
questionnaire. DSM-III (Diagnostic and Statistical Manual of Mental Disorders, Third Edition)
psychiatric diagnoses were made retrospectively. Subjects completed the follow-up between two
months and two years after the last session with most around 9 months, though one subject wrote
a letter two years later instead of the questionnaire.
Side Effects and Complications
These subjects (19 of 29) reported undesirable emotional symptoms:
• anxiety or nervousness during the session (5)
• mild depression the day after (2)
• mildly distracting thoughts for a few days (4)
• panic attacks a few weeks later; that subject had had panic attacks before (1)
• guilt around men for a while, related to an insight about the childhood death of her
brother (1)
• miscellaneous emotional symptoms (6)
All 29 of the subjects reported some undesirable physical symptoms:
• jaw tension or shaking, or teeth clenching (22)
• fatigue (23)
• some insomnia the night after the session (11)
Benefits
Twenty-eight of the subjects had a specific purpose for the session. Of these, 16 had their
purposes completely realized and 11 had them partially realized, as indicated in the following:
A more cognitive understanding of themselves (of the 9, 3 were fully realized and 2, partially
realized)
A peak experience or a sense of wholeness, connectedness, or enlightenment (of the 8, 6
were realized)
A personal or spiritual growth or self-exploration (all 5 were realized)
Increased communication with spouse or someone else taking MDMA with them (of these, 5
were fully satisfied and 1, partially realized)
To facilitate creative writing (all 5, who took 50 mg, were satisfied)
Greer, Therapeutic Uses of MDMA, page 4
Fun, enjoyment or increased awareness (all 6 were achieved)
A change in their personality or behavior patterns in some lasting way (of the 3, 2 were
satisfied and 1, partially satisfied)
To experience a different state of consciousness (both of the 2 were satisfied)
More awareness of their feelings (both of the 2 were satisfied)
The 9 subjects with formal DSM diagnoses reported significant relief from their problems. They
include:
2 with full and lasting remissions (1, dysthymic disorder and 1, simple phobia),
4 with improvement of depressive disorders, and
3 with improvement of personality disorders.
All 29 reported benefits during sessions, including positive changes in their attitudes or feelings:
• felt closer and more intimate with anyone present (27)
• all 21 who had sessions in couples or groups experienced more closeness and/or
enhanced communication
• various cognitive benefits (22)
All 29 reported improvements in relationships:
• (spouses present but not using MDMA) - more closeness and/or improved
communication with spouses, 2 briefly and the other still at follow-up after 10½ months
(3)
• closeness and enhanced communication with people other than their mates (14)
• resolved conflicts with others after the session, 5 with partners not at the session (10)
• increase in the interpersonal expression of feelings afterwards (7)
• increase in acceptance and/or tolerance of others afterwards (6)
Of the 5 couples who had sessions with their partners:
• closeness and enhanced communication present during sessions continued for a few
days to 2 years, at follow-up(3 couples)
• resolved prior conflicts after the session (2 couples)
• enhanced sexual enjoyment afterwards—partly due to delayed orgasm (1 couple)
• more awareness of their prior sexual problems (1 couple)
15 subjects changed some of their life goals after sessions, all implying that they were positive:
• sought more positive kinds of experiences in life (9)
• avoided negative experiences in life more (9)
Greer, Therapeutic Uses of MDMA, page 5
• improved self-actualization, with insight into psychological problems, and less guilt and
limiting beliefs (13)
Of the 28 subjects who answered follow-up questionnaires, 14 reported a decrease in the use of
mind- or mood-altering substances, and 3 reported increase:
Alcohol (6 decreased and 1 increased)
Marijuana (6 decreased and 1 increased)
Caffeine (5 decreased and 1 increased much later)
Tobacco (2 decreased and 1 increased urge to smoke)
Cocaine (only 2 users in the study; 1 stopped and 1 had less desire)
LSD (1 decreased)
Psychedelics (1 desired less and 1 desired more)
There were also a variety of miscellaneous changes reported by the 29 subjects, such as:
• positive attitude lasting from a week to a follow-up time of 2 years (23)
• positive mood or emotional state, lasting from several hours to several weeks and
averaging about 1 week (18)
• positive beliefs about themselves and/or their relations to others or the world, including
self-confidence and ability to pursue spiritual growth (16)
• positive at work since their sessions (16)
• more spiritual or physical practice (14)
• see dying as less fearful or not an end (4)
• eventual termination of relationships that were failing before the sessions; partners were
not at the sessions (4)
MDMA was administered to approximately 50 more individuals with similar results before being
placed in Schedule 1 by the Drug Enforcement Administration in 1985. To provide a window
into what MDMA therapy is like for someone, a case report follows of the person who, among
the total of 80 people administered MDMA, experienced the most dramatic improvement in
emotional and physical health and quality of life.
Case Study
A married man in his early seventies, father to an adult son and daughter, had had successful
careers as a geophysicist and farmer. At the time of his sessions, he had been told that he was
among the longest-lived survivors with multiple myeloma to date. This metastatic, cancerous
condition of the bone marrow, had been diagnosed about 10 years earlier. For two years before
his cancer diagnosis, he had had group therapy to help with depression over family problems.
On being diagnosed with cancer, he began a different type of therapy in a group format in which
he learned deep relaxation, meditation, and visualization to combat his cancer and assist in pain
control. He was able to achieve states where his pain was as reduced as well as it was with
narcotics, but he still endured much pain.
Greer, Therapeutic Uses of MDMA, page 6
At the time of our first meeting, his main complaint was “movement pain” from four collapsing
vertebrae due to the cancer. Over the prior months the pain had increased, decreasing his
physical and sexual activity and his ability to go fishing and to fly his plane. He also was
troubled by depression that usually followed the numerous fractures of his spine, which
necessitated confinement to bed. The goal for his session with MDMA, which he wished to take
with his wife, was to cope with his pain in a better way and to receive help in adjusting to his
current life changes.
During his first session, he and his wife remained in separate rooms listening to music with
eyeshades and headphones on for five hours. He hummed along with the classical music being
played. Shortly after an extra dose of 50 mg of MDMA, he announced ecstatically that he was
free of pain and began singing aloud with the music, repeatedly proclaiming his love for his wife
and family. He spent several hours in this elated state. Afterwards he said it was the first time
he had been completely pain free in the four years of the current relapse of his myeloma. He
described his beautiful experience of being inside his vertebrae, straightening out the nerves, and
“gluing” fractured splinters back together. In a letter two weeks after his session he stated that
his pain had returned, but that his ability to hypnotically “re-anchor” his pain-free experience
greatly assisted him in reducing the pain by himself.
He had four MDMA sessions spaced over the course of nine months, and each time he achieved
relief from his physical pain and had greater success in controlling painful episodes in the
interims by returning himself to an approximation of the MDMA state. He noted in particular
that the feelings of “cosmic love,” and especially forgiveness of himself and others, would
usually precede the relief of physical pain. He describes an episode from his second session:
As I was finishing the meditation, time ceased to exist, my ego fell away,
and I became one with the cosmos. I then started my visualization of my
body’s immune system fighting my cancer, of the chemo[therapy] joining
with my immune system to kill the cancer cells in my vertebrae and of
positive forces coming from the cosmos to fight my cancer. Gradually I
went deeper in to where the feeling of love, peace and joy were
overwhelming. Although I had heard the new age music before, many
details of the music became clear and more beautiful.
His sessions stopped when MDMA was placed in Schedule I by the Drug Enforcement
Administration in 1985, and the Food and Drug Administration denied permission to continue
the treatment pending further animal studies. He remained quite functional and mostly pain free
for a few months after the last session, but eventually his pain began to return. He died very
peacefully in his wife’s presence soon afterwards.
Swiss Research
Between 1988 and 1993 the Swiss Federal Office for Public Health gave permission to five
psychiatrist members of the Swiss Medical Society for Psycholytic Therapy to conduct
psychotherapy with MDMA and LSD in private practice. Among the five, Jurai Styk, M.D. and
Greer, Therapeutic Uses of MDMA, page 7
Samuel Widmer, M.D. administered both MDMA and LSD to their patients, and Dr Marianne
Bloch, M.D. administered only MDMA, and Gasser reported the combined results for all three,
without reporting the results of sessions or patients with MDMA and LSD separately.
There were 171 patients who completed treatment with one of the three psychiatrists by the end
of the period. All were sent a standardized questionnaire about the patients’ reasons for
treatment, social situation, other treatments, self-evaluation of improvement during and after
treatment, summary of the sessions, and life situation after treatment. Diagnosis, duration of
therapy, number of non-drug and drug sessions, and duration of the follow-up were obtained
from the medical records. There were 121 follow-up questionnaires completed.
The MDMA and LSD sessions were conducted in small groups, combining elements of the
psycholytic therapy of Dr. Hanscarl Leuner, M.D.—low to medium dosage, group setting and
continuous verbal therapy—with those of the psychedelic therapy of Grof—high dosage,
individual session and use of music and silence as a therapeutic method. A dose of 125mg of
MDMA or 100-400 mcg of LSD was used in the sessions. Average duration of therapy was
three years and average follow-up was two years. Non-drug sessions occurred an average of
every two weeks, with an average of seven drug sessions per patient, or a session about every
five months after ten non-drug sessions.
Two-thirds of the patients sought treatment for interpersonal problems and two-thirds for
psychological symptoms. About 30% wanted help for somatic symptoms, and 57% wanted the
treatment for self-exploration. About 20% sought help for non-drug addictive behaviors such as
“need to be used (co-dependency) and excessive sexual or workaholic behavior.” Patients were
diagnosed only by their presenting problem: 38% had a personality disorder, 26% an adjustment
disorder, 25% an affective disorder, 7% eating disorders. “Addiction, Psychosis and Sexual
Deviation” affected just under 2% each.
Results
Eighty-five percent of the patients reported good to slight improvement during treatment and
91% at follow-up. The treatment was helpful emotionally to 65% of the patients and
interpersonally to 56%. Forty-nine percent said they had important biographical insights.
Thirty-six percent said the sessions helped them make important life decisions, such as about
their careers and relationships. Five percent had spiritual and religious experiences, 7% reported
improved self-esteem and self-confidence, and 3% reported more creativity and awareness.
As for important experiences during the sessions, 71% reported important experiences of unity
and/or love, 45% reported religious or spiritual experiences, and 40% reported visions, though it
there is no determination as to whether MDMA or LSD was involved.
Most (84%) said their quality of life was improved, but 3% said it worsened. Most (82%)
reported more self-acceptance and 3% less. Sixty-eight reported more autonomy and only 3%
less. Eighty-one percent had better relationships with family members and 3% had worse. Work
involvement was better for most (57%) and worse for 3%. Seventy-four percent reported “a
Greer, Therapeutic Uses of MDMA, page 8
better approach to the Divine” and 1% worse. Fifty-eight percent had less fear of death and 2%
more fear. These changes were attributed to the drug sessions with LSD or MDMA.
Gasser (1995, pp. 6-7) concludes:
Nine out of ten patients declared themselves to have experienced good improvement or
slight improvement concerning the problems that brought them to therapy.
The feedback of the ex-patients permits us to say that psycholytic psychotherapy is a safe
treatment. In the personal notes, only one patient complained of persistent depression
that appeared three months after his last psycholytic session. During psycholytic therapy
[which lasted an average of three years], none of the patients committed suicide, were
hospitalized in a psychiatric hospital, or had a psychotic episode for more than 48 hours.
This result is consistent with other studies. In a 1960 paper by Cohen, the complication
rate from 44 therapists with about 5,000 patients and 25,000 applications of LSD or
Mescaline was 0.04% for suicide and 0.18% for the risk of a psychosis longer lasting
than 48 hours. In a 1971 study by Malleson, the complication rate for 4,300 patients and
49,500 applications of LSD was 0.07% for suicide and 0.9% for a longer psychotic crisis.
Psychological Mechanism of Action
It appears that in the right circumstances MDMA reduces or somehow eliminates the
neurophysiological fear response to a perceived threat to one's emotional integrity. The main
neurotransmitter effects of MDMA are the release of serotonin, norepinephrine and dopamine
(Vollenweider, et al, 2002). Therefore, this release is likely the reason why MDMA reduces the
primary somatic symptoms of fear: the tightness and nervous feelings in the throat, chest,
abdomen and skeletal musculature. There is also a moderate anesthesia to pain (but not to touch)
in the skin during the acute effect, which may parallel the anesthesia to emotional pain or fear
without reducing emotional sensitivity.
With this experience of fear eliminated, a loving and forgiving awareness seems to occur quite
naturally and spontaneously. Subjects found it comfortable to be aware of, to communicate, and
to remember thoughts and feelings that are usually accompanied by fear and anxiety. Alcohol,
anti-anxiety drugs and beta sympathetic nervous system blockers also can reduce fear. However,
they have no effect after the pharmacological effects have ended, and they do not facilitate
intimate and emotional communication, access to repressed memories or feelings, or the learning
of new attitudes and beliefs or social behaviors.
Unresolved emotional conflicts from the past perpetuate conditioned fear responses, which drive
people to avoid having certain feelings or thoughts symbolically associated with those conflicts.
Without the conditioned fear, access to the information contained in these thoughts, feelings or
memories is enhanced, allowing value judgments about the past, relationships and self-worth to
be based on more accurate interpretations of experiential data. A corrective emotional
experience then can occur once psychological defenses are no longer needed. One can then
Greer, Therapeutic Uses of MDMA, page 9
reassess their life and relationships from a broader perspective of security and love rather from
one of vulnerability and fear. It then becomes easier to trust the validity of one’s own feelings
without fear, as well as those of a significant other who is experiencing the same state with them.
As the subjects reported, they can then remember and integrate these healthier psychological
processes into their everyday lives.
Couples who had a session together frequently reported basing their relationships much more on
love and trust than on fear and suspicion after their MDMA sessions. These results were
achieved by the patients making decisions based on what they learned during their MDMA
experience, and by their cognitively and emotionally remembering and applying those decisions
after the session was over.
Because MDMA did not significantly distort perception, thinking or memory (except in doses
well over 100 to 150 mg), new insights and behaviors can be carried over into everyday life.
Therapeutic learning occurs with the normal structure of the ego and personality intact, unlike an
experience with a psychedelic drug such as LSD, psilocybin or mescaline.
Potential Applications of MDMA for Healing
MDMA's use as an adjunct to insight-oriented psychotherapy for a variety of problems was
specifically recommended by 6 subjects in the Greer and Tolbert study. Many felt that MDMA
enhanced self-understanding and was useful in their personal and spiritual growth. Given the
consistently positive experience that people have and the lack of complications, many psychiatric
conditions could be helped by MDMA-assisted treatment.
Anxiety Disorders. Given the improvements in mood, attitude and self-confidence,
treatment for anxiety disorders, such as in terminal illness and posttraumatic stress, is already
being pursued through controlled studies internationally.
Relationship disorders. The enhancement of emotional intimacy and communication that
occurs with MDMA therapy could dramatically improve treatment for dysfunctional
relationships. Regardless of the mechanism, most subjects expressed a greater ease in relating to
their partners, friends, and co-workers for days to months after their sessions. Once a
therapeutically motivated person has experienced the lack of true risk involved in direct and open
communication, it can be practiced without the assistance of MDMA. This ability can help
resolve existing conflicts and prevent future ones from occurring due to unexpressed fears or
misunderstandings.
Substance use disorders. A value in treating at least mild alcohol and other drug abuse
disorders was indicated by the decreased use of substances that have psychological dependence
potential. Some subjects mentioned that these substances seemed less appealing after
experiencing MDMA. The ability not only to feel free of conflict—which can be provided by
many drugs of abuse—but to learn how to prevent conflicts in everyday life seems unique to
MDMA as a therapeutic adjunct. Inadequate parenting, with its traumas and deprivations, is a
major factor in the development of both addictive behaviors and the codependency of family
Greer, Therapeutic Uses of MDMA, page 10
members that helps sustain the addiction. If those at risk can acquire the skills of becoming
aware of and communicating their deepest feelings to family members who can learn to receive
and accept them, it could prevent the transmission of dysfunctional family relationships from one
generation to the next. Such potential benefits of the careful therapeutic use of MDMA should
be considered when evaluating the potential medical risks.
In addition, MDMA's diminished pleasurable effects and markedly increased side effects when
taken in either larger doses or with greater frequency distinguish it from most drugs of abuse,
though cases of frequent and abusive use of MDMA at high doses do occur. Two subjects took
four 50 mg supplements after their initial dose and found the fourth to cause only more agitation
and confusion without any pleasant effects at all. Some subjects reported using MDMA on their
own, but only one used it twice in the same week. The second experience was therapeutically
useful but left her depressed and exhausted for about two days. Therefore, both the positive
experience of MDMA and the relative impracticality of using it frequently can motivate people
to find other ways to achieve a desirable state of mind in everyday life. Sixteen subjects began
or increased their meditation practices or exercise programs, supporting this conclusion.
Concluding Thoughts
Double-blind controlled experiments of treatment with MDMA are necessary to prove the
efficacy of MDMA under current scientific standards, and the Mithoefer study is the first of this
type to occur. However, it is important to keep in mind that double-blind, placebo-controlled
conditions necessarily change the mindset of the subject and facilitator because it requires that
the neither the client and therapist both know that MDMA is being ingested. The knowledge that
there is only a chance that a subject is actually receiving MDMA could result in less motivation
to prepare for the session and less hopefulness about its outcome, on the part of both therapist
and subject.
Therefore, changing the purpose of the session from treatment to treatment research can have an
important influence on the outcome of a session. Also, motivation could be affected if therapists
and clients believe that the primary goal of the session was to study the therapeutic effects of the
drug to help others, rather than for the patients to receive benefit mainly for themselves. Just the
difference of a patient paying the therapist for the drug and their service during a session or not
can change the mindset of both.
Because the therapeutic method is not fully separable from the ingestion of MDMA, a carefully
considered compromise is necessary in research design. This is exemplified in the Mithoefer
study, involving a combination of sessions for which some sessions it is known that MDMA will
be administered, and others for which it is not known. Hopefully this will generate valuable data
about how the variable of blindness to drug vs. non-drug session affects therapeutic outcome.
Endnotes
Greer, Therapeutic Uses of MDMA, page 11
Portions of this chapter have been excerpted from the following articles with permission from the
Journal of Psychoactive Drugs:
Greer, G., & Tolbert, R. (1986). Subjective reports of the effects of MDMA in a clinical setting.
Journal of Psychoactive Drugs, 18(4), 319-327. [Full text at:
http://www.heffter.org/pages/subjrep.html]
Greer, G., & Tolbert, R. (1998). A Method of Conducting Therapeutic Sessions with MDMA.
Journal of Psychoactive Drugs, 30(4), 371-379. [Full text at:
http://www.heffter.org/pages/sessions.html]
1. The data from the questionnaires before and after the session are reflected in the Results
section.
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