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The therapeutic use of MDMA

Authors:
  • Heffter Research Institute

Abstract

This chapter describes a method for the therapeutic administration of MDMA ((+/−), 3,4-methylenedioxymethamphetamine) to humans and includes five case reports. Comparisons are made to the approach of “Twelve Step programs” for substance abuse treatment and to sacred rites of passage. The importance of the mental set of the patient and therapist and the psychological preparation of both are emphasized. Screening criteria and informed consent information are also discussed. Results from 80 patients indicate that MDMA seems to decrease the fear response to a perceived threat to a patient’s emotional integrity, leading to a corrective emotional experience that probably diminishes the pathological effects of previous traumatic experiences. The acquisition of effective skills for communicating feelings to family members also occurs. Psychological benefits were lasting up to a two-year follow-up for many patients, and relief from chronic pain and premenstrual symptoms occurred for one patient each. Double-blind controlled experiments utilizing the method presented are not feasible because the mental set is affected and the MDMA effect is easily perceived by patient and therapist. Suggestions for potential applications include the prevention and treatment of dysfunctional family relationships and of substance abuse.
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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... In contrast, R. L. Carhart-Harris and Nutt propose MDMA as an exemplar "passive coping" substance due to its role in releasing endogenous serotonin, which preferentially activates the 5-HT1a receptor system. In humans this is hypothesized to manifest most acutely in the felt sense of equanimity and acceptance that characterizes the unique phenomenology of the MDMA (Greer & Tolbert, 1990;R. L. Carhart-Harris & Nutt, 2017). ...
... The copyright holder for this preprint (which this version posted April 15, 2024. ; https://doi.org/10.1101/2024.04.12.589282 doi: bioRxiv preprint drugs such as MDMA (Greer & Tolbert, 1990). ...
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Serotonergic psychedelics have been identified as promising next-generation therapeutic agents in the treatment of mood and anxiety disorders. While their efficacy has been increasingly validated, the mechanism by which they exert a therapeutic effect is still debated. A popular theoretical account is that excessive 5-HT2a agonism disrupts cortical dynamics, relaxing the precision of maladaptive highlevel beliefs, thus making them more malleable and open to revision. We extend this perspective by developing a theoretical framework and simulations based on predictive processing and an energy-based model of cortical dynamics. We consider the role of both 5-HT2a and 5-HT1a agonism, characterizing 5-HT2a agonism as inducing stochastic perturbations of the energy function underlying cortical dynamics and 5-HT1a agonism as inducing a global smoothing of that function. Within our simulations, we find that while both agonists are able to provide a significant therapeutic effect individually, mixed agonists provide both a more psychologically tolerable acute experience and better therapeutic efficacy than either pure 5HT2a or 5-HT1a agonists alone. This finding provides a potential theoretical basis for the clinical success of LSD, psilocybin, and DMT, all of which are mixed serotonin agonists. Our results furthermore indicate that exploring the design space of biased 5-HT1a agonist psychedelics such as 5-MeO-DMT may prove fruitful in the development of even more effective and tolerable psychotherapeutic agents in the future.
... Early trials with MDMA in patient populations suggested that the drug altered patients' sense of themselves such that they felt they were able to better experience their "true nature" (53,54). A more recent placebo-controlled laboratory study investigated this question with healthy volunteers and showed that MDMA (1.5 mg/kg) increased ratings of authenticity or the degree of congruence between the ideal and real self (15). ...
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There has been renewed interest in the use of 3,4-methylenedioxy-methamphetamine (MDMA) and serotonergic psychedelics in the treatment of multiple psychiatric disorders. Many of these compounds are known to produce prosocial effects, but how these effects relate to therapeutic efficacy and the extent to which prosocial effects are unique to a particular drug class is unknown. In this article, we present a narrative overview and compare evidence for the prosocial effects of MDMA and serotonergic psychedelics to elucidate shared mechanisms that may underlie the therapeutic process. We discuss 4 categories of prosocial effects: altered self-image, responses to social reward, responses to negative social input, and social neuroplasticity. While both categories of drugs alter self-perception, MDMA may do so in a way that is less related to the experience of mystical-type states than serotonergic psychedelics. In the case of social reward, evidence supports the ability of MDMA to enhance responses and suggests that serotonergic psychedelics may also do so, but more research is needed in this area. Both drug classes consistently dampen reactivity to negative social stimuli. Finally, preclinical evidence supports the ability of both drug classes to induce social neuroplasticity, promoting adaptive rewiring of neural circuits, which may be helpful in trauma processing. While both MDMA and serotonergic psychedelics produce prosocial effects, they differ in the mechanisms through which they do this. These differences affect the types of psychosocial interventions that may work best with each compound.
... Past research has primarily focused on negative cognitive and emotional effects e.g. [8][9][10][11] or has highlighted positive effects mainly in therapeutic settings [12][13][14] . Although some research suggests that recreational MDMA use may also have positive long-term effects 15,16 , much remains to be learned about what factors contribute to positive emotional and social outcomes in the long-term. ...
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MDMA is a recreational drug commonly used to enhance euphoria, but it is also used in non-party settings with self-insight or social connection intentions. Yet, little is known about whether distinct consumer groups are formed based on consumption setting and intention. We aimed to characterize different types of recreational MDMA users based on consumption setting and intentions, and to examine their differences in perceptions of long-term social-emotional effects of MDMA use. We analyzed self-reports of 766 individuals (ages 18–61, mostly from Western countries), reporting on their MDMA consumption habits and perceived effects. We used a K-medoids clustering algorithm to identify distinct types of consumption settings and intentions. We identified three setting types – party settings with friends (N = 388), private home settings (N = 132), mixed settings (N = 246) – and three intention types – euphoria and energy (N = 302), self-insight (N = 219), mixed intentions (N = 245). Members of the self-insight and mixed intentions clusters reported considerably more long-term socio-emotional benefits than members of the euphoria and energy cluster. No differences were observed between the setting clusters. In this particular sample, more long-term benefits than harms were reported. Our findings suggest that the long-term social-emotional benefits of MDMA are associated with whether users seek self-insight or have mixed intentions.
... Nesse documento, o psiquiatra George Greer detalhou 29 sessões terapêuticas, devidamente consentidas pelos pacientes, conduzidas usando os métodos originais de Zeff, através dos quais o MDMA era utilizado de forma a induzir um estado alterado de consciência facilmente controlável, facilitando a comunicação ao eliminar a resposta neurofisiológica de medo que normalmente é percecionada como uma ameaça à integridade emocional do paciente. 17 Estas sessões permitiam ao paciente vivenciar intensa autodescoberta, acompanhada de sentimentos de amor e empatia, onde a comunicação era reforçada e uma forte aliança terapêutica cultivada, tendo sido observados resultados terapêuticos duradouros. 16 Paralelamente ao entusiasmo crescente em torno do potencial terapêutico do MDMA, a disseminação desta substância para fora dos ambientes clínicos controlados marcou a década de 1980, na qual o "ecstasy" -assim designados os manipulados contendo MDMA -viu o seu uso recreativo tornar -se progressivamente mais popular enquanto club drug. ...
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A perturbação de stress pós‐traumático (PSPT) é uma doença psiquiátrica comum, geralmente crónica, com severas implicações na qualidade de vida da pessoa afetada e da sua família, e que tem vindo a apresentar um crescente reconhecimento enquanto problema de Saúde Pública. Nas últimas duas décadas, estudos clínicos com 3,4‐metilenodioximetanfetamina (MDMA) têm vindo a demonstrar o seu papel promissor enquanto potencializador psicoterapêutico em doentes com PSPT, tendo a psicoterapia assistida por MDMA inclusivamente recebido em 2017 a designação de breakthrough therapy. Estes estudos têm vindo a ser replicados em vários locais do mundo, segundo estritos protocolos, estando atualmente a sua aprovação para uso clínico prevista para 2023. Em maio de 2021, foram publicados os primeiros resultados de estudos de fase III, nos quais os participantes que receberam psicoterapia assistida por MDMA experienciaram uma redução significativa e duradoura nos sintomas de PSPT. Os efeitos pró‐sociais e interpessoais agudos do MDMA têm demonstrado melhorar significativamente a qualidade da aliança terapêutica, potenciando a adesão ao tratamento da PSPT e o seu outcome. Os clínicos sugerem que o MDMA pode catalisar o processamento terapêutico, permitindo que os pacientes permaneçam emocionalmente envolvidos enquanto revisitam experiências traumáticas sem se tornarem oprimidos. Tendo em conta a prevalência da PSPT e as limitações encontradas com os tratamentos atualmente disponíveis, foi realizada uma revisão narrativa da literatura com o objetivo de examinar a utilização da psicoterapia assistida por MDMA na perturbação de stress pós‐traumático, apresentando uma contextualização histórica desta molécula, os seus potenciais efeitos nos diferentes sintomas desta patologia e identificando áreas prioritárias para intervenção e investigações futuras.
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Background: Neurorehabilitation in military populations is complicated by higher rates of PTSD and unique characteristics of military institutions. These factors can adversely impact the patient-therapist therapeutic alliance and engagement with the rehabilitation process leading to poorer outcomes. MDMA is a non-classical psychedelic with pro-social and fear regulating properties. MDMA-assisted therapy is being explored as a novel treatment for PTSD that potentially offers rapid symptom improvement and enhances therapeutic alliance. Objective: A review of MDMA-assisted therapy for PTSD is provided in the context of neurorehabilitation in military populations. The molecular mechanism of MDMA is outlined and a novel application of MDMA for neurorehabilitation is proposed. Methods: This is an expert review and synthesis of the literature. Results: Results from late-stage clinical trials suggest MDMA-assisted therapy for PTSD would be of particular benefit for military populations with PTSD. The unique pro-social properties of MDMA could be leveraged to enhance the therapeutic alliance and patient engagement during neurorehabilitation. Conclusion: The unique qualities and benefits of MDMA and MDMA-assisted therapy for PTSD suggest relevant application in military personnel undergoing neurorehabilitation. There are many similarities in patient-therapist dynamics in PTSD treatment and neurorehabilitation. The properties of MDMA which enhance therapeutic alliance, downregulate fear, and increase cognitive flexibility would potentially benefit both military personnel with and without PTSD undergoing neurorehabilitation.
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The phenylethylamine, 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’), is the prototypical example of an entactogen. Its original placement in highly restrictive drug usage categories in the US and UK, led to an inevitable restriction on MDMA neuroscience research and treatment. The dominant pharmacological effects of MDMA are its properties of release and inhibition of reuptake of amine neurotransmitter transporters for dopamine, norepinephrine, and serotonin. MDMA is an agonist of a wide range of receptors; its mood-altering effects are mediated via 5-HT2A receptors; this receptor may also mediate its effects on body temperature, analgesia, and anxiolytic properties. The mechanisms underlying MDMA’s entactogenic properties of sociability and interpersonal closeness are not known but release and involvement of oxytocin, a peptide thought by some to be involved in social bonding, has been suggested. Adverse effects of MDMA are mostly transient; acute multiorgan adverse effects occurring during raves or crowded dance gatherings include dehydration, hyperthermia, seizures, rhabdomyolysis, disseminated intravascular coagulation, and acute renal failure. Deaths following MDMA taken by itself are rare compared to fatalities following coadministration with other drugs. A recent FDA-approved phase 3 clinical trial of MDMA for post-traumatic stress disorder (PTSD) led to the conclusion that MDMA-assisted therapy represents a potential breakthrough treatment meriting expedited clinical evaluation. Despite the ongoing deliberations by the FDA and EMA for approval of MDMA treatment of PTSD, the Australian Therapeutic Goods Administration (TGA) recently announced that after an evaluation of the therapeutic value, benefits, and risks of MDMA, it will permit its prescribing for the treatment of PTSD. Further examples of regulatory relaxation toward MDMA-assisted psychotherapy are underway. These include the FDA’s recently approved clinical trial to assess MDMA’s efficacy in the treatment of “asociality” in patients with schizophrenia and an open trial of MDMA treatment for alcohol-use disorder which showed decreased alcohol consumption. There are also ongoing studies on the little understood startle response, anxiety associated with life-threatening illness, and social anxiety in autistic adults.
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There are global concerns about the proliferation and misuse of club drugs and novel psychoactive substances, yet we know little about their harms and research on clinical management and treatment remains limited. This book fills the knowledge gap by providing a detailed overview of the research evidence available to date. The book provides a framework that allows readers to understand this large number of new drugs, using classifications based on primary psychoactive effect. Within this framework, the book provides detailed reviews of the more commonly used drugs. Each chapter explores pharmacology, patterns and mode of use, acute and chronic harms, and clinical interventions supported by research evidence. An invaluable resource for clinical staff, this book will support clinicians working in the emergency department, substance misuse and addiction services, mental health services, primary care, sexual health services and more. It will also be of interest to academics and those developing drug policy.
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In recent years, researchers in the “psychedelic renaissance” have been reinvestigating the therapeutic potential of psychedelic compounds for conditions like post-traumatic stress disorder, clinical anxiety/depression, and addiction. Each of these has treatment-resistant cases, sometimes decades in the making, but studies employing psychedelics to address them are yielding impressive results. Given the evolving legal situation around these substances as well as corporate investment in them, their availability and appeal promise to increase. The question facing Christians is: How do these developments impact the theological significance of psychedelics as a broader phenomenon? This paper argues that since the population standing to benefit from these treatments is likely to include Christians, a thoughtful and rigorous response is necessary. The inquiry proceeds by analyzing some of the pertinent research, showing the insufficiency of previous Christian responses, and considering some hurdles and objections before issuing a call to theologize on this timely and important cultural moment.
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The last two decades have seen a revival of interest in the entactogen 3,4-methylenedioxy-N-methylamphetamine (MDMA) as an adjunct to psychotherapy, particularly for the treatment of post-traumatic stress disorder. While clinical results are highly promising, and MDMA is expected to be approved as a treatment in the near future, it is currently the only compound in its class of action that is being actively investigated as a medicine. This lack of alternatives to MDMA may prove detrimental to patients who do not respond well to the particular mechanism of action of MDMA or whose treatment calls for a modification of MDMA's effects. For instance, patients with existing cardiovascular conditions or with a prolonged history of stimulant drug use may not fit into the current model of MDMA-assisted psychotherapy, and could benefit from alternative drugs. This review examines the existing literature on a host of entactogenic drugs, which may prove to be useful alternatives in the future, paying particularly close attention to any neurotoxic risks, neuropharmacological mechanism of action and entactogenic commonalities with MDMA. The substances examined derive from the 1,3-benzodioxole, cathinone, benzofuran, aminoindane, indole and amphetamine classes. Several compounds from these classes are identified as potential alternatives to MDMA.
Chapter
Seit hunderten, wenn nicht sogar seit tausenden von Jahren werden Psychedelika von Menschen verwendet. Die ernsthafte medizinische Erforschung dieser Substanzen begann im Westen erst im späten 19. Jahrhundert mit der Entdeckung von Meskalin.
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This article is a summary report of data gathered from the first 29 people administered MDMA in a clinical setting. Because the primary purpose of the project was to assist the subjects in achieving their particular and varied goals for having the sessions, the data available for analysis is limited. Only phenomenological descriptions were obtained of the therapists' observations and of the subjects' experiences before, during and after the sessions. Psychological evaluations by independent observers with testing before and after sessions, placebo control group data with double-blind assessment, and laboratory examinations of organ and metabolic functions were not conducted. Providing the reports of these 29 subjects' experiences will hopefully encourage further research into the beneficial effects of MDMA. Presenting evidence establishing the limits of its usefulness should discourage any movement to promote it as a social or psychological panacea.
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( ± )3,4-Methylenedioxymethamphetamine (MDMA) is a popular recreational drug that has been proposed to be useful as an adjunct to psychotherapy. This study assessed the neurotoxic potential of MDMA in nonhuman primates. Monkeys were repeatedly administered doses (2.50, 3.75, and 5.00 mg/kg) of MDMA subcutaneously and analyzed for regional brain content of serotonin and 5-hydroxyindoleacetic acid two weeks later. In all regions of the monkey brain examined, MDMA produced a selective dose-related depletion of serotonin and 5-hydroxyindoleacetic acid. These neurochemical deficits were associated with evidence of structural damage to serotonergic nerve fibers. In addition, MDMA produced pathological changes in nerve cell bodies in the dorsal, but not median, raphe nucleus. These results indicate that MDMA is a selective serotonergic neurotoxin in nonhuman primates and that humans using this drug may be at risk for incurring central serotonergic neuronal damage.(JAMA 1988;260:51-55)
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3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy"), a synthetic analogue of 3,4-methylenedioxyamphetamine, has been the center of recent debate over its potential for abuse vs its use as a psychotherapeutic agent. Following its emergency classification in Schedule 1 by the Drug Enforcement Administration in 1985, 3,4-methylenedioxyethamphetamine (MDEA,”Eve") has appeared as MDMA’s legal replacement. MDMA is thought to be safe by recreational users and by psychotherapists who support its use. The details of five deaths associated with the use of MDMA and MDEA are reported. In three patients, MDMA or MDEA may have contributed to death by the induction of arrhythmias in individuals with underlying natural disease. In another patient, use of MDMA preceded an episode of bizarre and risky behavior that resulted in accidental death. In another patient, MDMA was thought to be the immediate cause of death. Death as a consequence of the use of these drugs appears to be rare, but it does occur; this outcome may be more common in individuals with underlying cardiac disease.
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Ten neurotic patients (five males and five females) were treated over a period of 2 to 6 months (mean, 4.1) as outpatients. The study allowed for a maximum of 75 hours of psychotherapy (mean, 51.55 hours). During the course of treatment, two to four (mean, 3.5) administrations of MDA (3,4-methylenedioxyamphetamine) were employed as adjunctive aids in an effort to enhance the psychotherapeutic process. The mean duration of the drug sessions was 8 hours (range, 6 to 14 hours). The first administration of MDA took place when, in the therapist's judgment, sufficient rapport had been established with the patient. All patients received an initial dose of 75 mg of MDA; subsequent dosage was allowed to range up to 200 mg. On these occasions, the drug appeared to be well tolerated with no serious side effects or complications observed. Psychometric assessments were obtained pre- and post-treatment, employing the Minnesota Multiphasic Personality Inventory (MMPI), Wittenborn Psychiatric Rating Scales (WPRS), and Brief Psychiatric Rating Scale (BPRS). In addition, follow-up evaluations were obtained 6 months after the termination of therapy by the use of the MMPI, WPRS, BPRS, and a Social History Questionnaire (SHQ) which had also been administered before treatment was initiated. Clinically, the impression was obtained that psychotherapy and the adjunctive use of MDA appeared to facilitate improvement in these patients. This impression was substantiated by significant reductions in scores on the psychometric assessments measuring depression, anxiety, and obsessive-compulsive traits. The meaures evaluating the sense of well-being and self-actualization also were encouraging. Although some of the patients were not as responsive as others, there were no observations to suggest that the condition of any of these patients had become worse.
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(+/-)-3,4-Methylenedioxymethylamphetamine (MDMA) was administered s.c. to rats (10, 20 or 40 mg/kg b. wt.) and guinea pigs (20 mg/kg) twice a day for 4 days, 2 weeks before decapitation. Norepinephrine, dopamine and serotonin (5-HT) levels were assayed in the hippocampus, hypothalamus, striatum and neocortex. In rats, MDMA produced dose-dependent reductions in 5-HT in all brain regions examined. The highest dose also reduced norepinephrine and/or dopamine in some regions. The 20-mg/kg dose of MDMA depleted 5-HT in all regions of the guinea pig brain assayed. In both species, repeated administration of 20 mg/kg of MDMA reduced the Vmax but not the Km of 5-HT uptake 2 weeks after administration. A single 40-mg/kg injection of MDMA depleted 5-HT 2 and 8 weeks after administration to rats in all regions of the brain examined except the hypothalamus. Administration of 80 mg/kg of MDMA twice a day for 2 days to rats depleted striatal 5-HT and dopamine. Brain sections from rats injected with MDMA according to this dosage regimen were stained by the Fink-Heimer method. Degenerating axon terminals and cell bodies were observed in the striatum and somatosensory cortex, respectively. These findings suggest that MDMA is toxic to serotonergic and, to a lesser extent, catecholaminergic neurons. Some neurons that do not contain these transmitters (neocortical neurons) are also affected.