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Transcript of Lindesmith MDMA Seminar, 3/30/00 NYC
Julie Holland, MD

 MDMA, better known as "Ecstasy," is the chemical 3,4 -methylenedioxymethamphetamine. It is chemically related to the family of amphetamines, which includes MDA, and also related to mescaline.  This chemical was discovered in 1912 by Merck.  MDMA was a byproduct of a synthesis of hydrastinin; Merck was looking for a good vasoconstrictive substance to use as a styptic, to stop bleeding, and when they stumbled across this chemical in their synthesis, as any good chemical company would do, they patented their finding.  Of note, at the time of the patent application, there was no use specified for MDMA.  It was never considered for marketing by Merck, and was never marketed as an appetite suppressant by Merck or anyone else.
 The next time we hear about MDMA is in 1953, when the Army did some animal experimentation with MDMA.  No human studies were performed at that time.  The first published study on the effects of MDMA was in 1978, when Sasha Shulgin described the subjective effects in humans.  Dr. Shulgin, who lived in California and had many friends in the scientific community, some of whom were therapists, introduced MDMA to a few of his colleagues.  He had experience with many psychedelics by that time, and felt that this substance in particular may be useful to the psychotherapeutic process.
 One therapist, referred to in Myron Stolaroff's book The Secret Chief as Jacob, was so impressed with the effects of MDMA that he began to introduce other therapists to this drug.  This lead to a slow spread of underground psychotherapeutic work in the late seventies and early eighties.  Then what happened in the early eighties is that small communities in Texas and the Pacific Northwest began to use MDMA in a different context.  In bars in these areas, people were buying MDMA with credit cards. More and more people started to experience MDMA and because it is so euphorogenic, it quickly became quite popular.  In 1984, Senator Lloyd Bentsen of Texas made a formal plea to the DEA that MDMA be placed in Schedule I.  At this time, MDMA was not scheduled, so it was not illegal to consume or distribute.
 In England, in the eighties, MDMA was also experiencing an increase in popularity.  Large, all-night dance parties called raves were being held in underground locations or in clubs, and a growing number of attendees were taking MDMA.  In the United States, our own rave culture, which had its beginnings in the eighties, really grew in popularity in the nineties.  Both rave scenes, in the US and the UK, fed off each other and grew to become a substantial part of the youth culture. Throughout the nineties, raves have become increasingly common, spreading throughout Europe, Spain and Portugal, Australia, and even India.
 In the United States, in the late nineties, government seizures of MDMA have increased by 450 percent.  In 1997 400,000 tablets were seized.  In 1999, 3.3 million.  Projected seizures in the next few years by the US government are 7 to 8 million.  In 2000, Sammy "the bull" Gravano admitted to financing sales of 25,000 tablets of MDMA a week.  A dealer in Miami claimed he could unload 100,000 tablets in 48 hours in that area.  Russian and Israeli organized crime has been implicated, as have Hassidic couriers.
 A recent survey in 1998, 8% of high school seniors had tried ecstasy up from 5.8% the year before.  Another study in NYC reported that 1 in 4 adolescents had tried "Ecstasy."
 When I talk about "Ecstasy" it's important to understand that when somebody buys a tablet called Ecstasy, it may or may not contain MDMA.  When I speak of MDMA-assisted psychotherapy or MDMA research, I am speaking of the pure chemical.
 
 Before July 1, 1985, MDMA was completely legal.  There was no penalty for using it, there were no penalties for giving it to patients;  it was unscheduled.  After Lloyd Bentsen requested that it be placed in Schedule I, doctors, psychiatrists and psychotherapists who had been using MDMA in their practices, as well as some scientists and MDMA researchers, petitioned the DEA against this move.  The DEA then assigned an administrative law judge, Francis Young to hear from the petitioners who argued against the proposal, and from the DEA.  By placing the drug in Schedule I, no clinical work or research could move forward.  This would put a halt to everything we could learn about MDMA.
 On February 1, 1985, the hearings began.  On June 1, 1985, the DEA announced it would emergently place MDMA in Schedule I on July 1, even though the hearings were far from over.  This was in response to fear of widespread underground use, and a fear that MDMA may be neurotoxic, which was based on a study of a different drug, MDA, given to animals in high doses.
 In May of 1986, Judge Young made a recommendation to the DEA, based on all the evidence he had heard from all the doctors, scientists, and government witnesses, that MDMA should be placed in Schedule III.

Schedule I means:
 high potential for abuse
 no currently accepted medical use in treatment
 lack of accepted safety for use under medical supervision
Schedule III means:
 less potential for abuse than Schedule I or II
 is a currently accepted medical use in treatment
 abuse may lead to moderate physical dependence or high   psychological dependence.

A placement into schedule III would capitulate to the fact that MDMA may be abused, but that it has some medical merit.  This would allow physicians to prescribe the drug, and it would allow clinical research to proceed at a much faster pace than placement in Schedule I would allow.
 The DEA received Judge Young's recommendation and ignored it.  In November of 1986, MDMA was permanently placed into Schedule I, where it remains today.  There was a brief period during the appeals process, when it was removed from Schedule I, in December of 1987.  Although the appellate court decided that the Schedule III ruling stood, so did the DEA's decision to ignore the recommendation, which is within its rights. It was returned to Schedule I in March of 1988, and that is where it remains today.
 

 I'd like to go over some of the objective effects of MDMA, what you could see in someone if they had taken MDMA.  Dilated pupils, slightly increased heart rate and blood pressure, possibly increased temperature.  In human studies, no one is getting consistent findings in temperature readings.  In animal studies, the core body temperature is dependent on the ambient temperature of the laboratory.  What may be happening in a rave setting, then, is that high temperatures in the club, combined with increased body temperatures in the dancers, may be causing excessively high temperatures in some Ecstasy users.  There is also reason to believe, based on animal studies, that hyperthermia can exacerbate the neural changes seen in animals given high doses of MDMA.
 Also, there is an initial diuresis, meaning there is an increase in urine output at the beginning of the MDMA experience, but then there is a decrease in urine output later on, which is important.  Jaw clenching, tooth grinding, also known as bruxism or trismus is common at higher doses, which is also a common side effect of amphetamine use.  Abnormal eye movements, little eye wiggles reminiscent of Rapid Eye Movements or nystagmus, are usually only seen at the peak of the MDMA experience.  It is one way to tell if people have taken pure MDMA or not, because it is not a common side effect of other stimulants.  Also seen sometimes are uncontrolled rolling eye movements where the eyes roll around, sometimes towards the back of the head.  It is possible that one of the slang terms of taking ecstasy called "rolling" comes from this phenomenon.
 The subjective effects of MDMA can best be described by having the audience humor me for a minute and take a nice, deep breath and let it out slowly.  Notice that you've got a very mild change of how you're feeling now compared with a moment ago.  The feeling that people get sometimes when they're taking MDMA, especially in a therapeutic situation without a lot of distractions, is that subtle and that mild.  It is a very slight shift --ó a little calmer, a little bit of a feeling of satiety perhaps that there's nothing that you really need, that you've got what you need.  Maybe you have a feeling of an enhanced capacity, that you can handle whatever's coming your way.
 At higher doses, at more of a peak level of MDMA, that feeling of satiety or confidence becomes a feeling of enhanced self-esteem.  Taking that a step further, it becomes euphoria, feelings of increased self worth, feelings of self love and self acceptance.  I think this is very important.  If you're talking about a psychotherapy session, having feelings of satiety and self worth and self acceptance can be invaluable during a therapeutic session.
 There is also enhanced memory for early events, perhaps early traumatic events.  Repressed memories often come to the fore, perhaps not as strongly as with LSD.  The difference is, they become accessible to you, and whether you choose to look at them or not, in general, I would say, you have that option. It's up to you and up to your therapist.  Also, besides enhanced remote memory, your memory for the entire MDMA experience is intact.  This is important, because sometimes with other psychoactives and psychedelics, you may not really remember everything you come across, and with MDMA you typically do and you should have a memory for the entire event.
 People report feeling calm, focused, centered.  Some people take MDMA to help them with meditation practices, other people find that low dose MDMA can assist them in studying, concentrating, making art, or writing, in that MDMA can often help to decrease distractibility.
 Now, the other side of this slide lists decreased defensiveness and decreased anxiety, which I think is very important in a therapeutic context.  To have less anxiety to look at your core issues, or to look at repressed memories, and to feel calm in the face of what would typically be considered threatening, that helps a lot of work get done in therapy.  Not only does the decreased fear and defensiveness allow a lot of progress during the therapeutic session where you are tackling some of these core issues, but you have an increased bond with the therapist.  This feeling of self love tends to flood outward, and you tend to be more accepting and loving of the people around you, and so the therapeutic alliance is strengthened during an MDMA-assisted psychotherapy session.  You are more trusting that this person actually cares about you and is trying to help you.  This enhanced therapeutic alliance carries over into subsequent sessions, and so strengthens the whole psychotherapy process.
 The issue of empathy is crucial.  When MDMA was named "Ecstasy" some people wanted to call it "Empathy," and I guess the joke was that it wasn't as good a marketing tool.  But, most therapists were impressed by the degree of empathy generated during an MDMA-assisted psychotherapy session.  This makes it especially useful for couple's therapy and family therapy, for patients to have an understanding of what their loved ones are going through and to really feel like they can experience it.
 Other subjective effects of MDMA include feeling less hopeless and less socially isolated which are extremely important in terms of working with people who are depressed or acutely suicidal.  Because there is this sense that you can handle what's coming your way and you do feel a little bit stronger in that you have more of a capacity to deal with the problems in your life.  And to feel connected with the people in your life is crucial.  When people are suicidal, there's a couple of issues that routinely come up.  They are hopeless and they are isolated.  They are lonely and they don't have any social connections, so to use MDMA in a person like this, as an acute interrupter of depression and of these feelings, would be a valuable tool.
 There is an increased kinesthetic awareness or body awareness in response to MDMA, focus is shifted more towards posture, deep breathing, and many people find touch and movement in general to be more pleasurable.  This is likely why so many people enjoy dancing and cuddling when taking MDMA, and also why some instructors of the Alexander technique, which focuses on posture and breathing, were having good results when incorporating MDMA into their practices.
 If I had to summarize the subjective effects of MDMA, I'd say that is increases your "love to fear ratio," in that "love is letting go of fear" sort of way.  I think it really enhances your capacity to love yourself, and love others, and it decreases your anxiety about doing just that.

 So, why MDMA research?  First of all, in terms of harm reduction, which I know Lindesmith supports, literally millions of people are taking this drug every week, around the world, no exaggeration, and clinical research and human studies need to happen so we know exactly what these people are doing.
Second of all, I believe this substance is a potent, immediate-acting antidepressant and there is no such thing right now in psychiatry.   Most of the antidepressants take weeks to work, sometimes months, and if you're really lucky you may find a medicine that starts to help you feel better in a few days, but there is nothing that works in an hour and this does.  And I think especially if you're talking about someone who is acutely suicidal and at risk, you don't always want to wait four to six weeks for the prozac to kick in.
 Also, MDMA is a non-sedating anxiolytic.  What does this mean?  It means it completely ablates the anxiety response and the fear response in most people.  I'll tell you from working in the Bellevue psychiatric emergency room, we give anxiolytics all the time to people to calm them down.  They come in anxious and agitated and we need to calm them down, and then what happens is, they're sedated and asleep for eight hours and we can't talk to them.  MDMA is a medication that can calm somebody, and take away the anxiety and the agitation, but it would keep them awake and focused and able to really communicate exactly what is going on in their lives, and again, there is no medication like this in psychiatry at all.  Every anxiolytic is sedating.  Valium, Xanax, Ativan, they all make you sleepy, and they also interfere with memory processing; but here's one that doesn't.
 I believe that MDMA could have potential use as an acutely acting antipsychotic.  I may be alone in this, but I just don't care.  My personal theory is that people with schizophrenia could very likely be helped by MDMA, and it is certainly a theory that is not shared by other people. But in terms of being less defensive, less paranoid, more open, more trusting, having increased insight, it would be a great tool to be able to use with people who were chronically psychotic.  I may be wrong, but the only way we're going to know is if we do clinical research and see.
 Pharmacologically-assisted psychotherapy.  This went on for fifteen years before MDMA became scheduled and I think there is no question, if you talk to any of these therapists who worked with MDMA, if you look at the literature, they all felt like they had a special powerful tool to use in therapy that was a catalyst, that made the therapy more effective, more efficient, much quicker. People said they could get years worth of therapeutic work done in a few hours.  Right now in psychiatry, all we have is the amytal interview, which is basically that you give an anxiolytic.  You give a sedative to someone so that they can be a little less anxious and try to tell you what's going on, but the problem is, you have to carefully titrate the dose so they can talk to you without falling asleep, and it's not the best tool, but it gets used, because we don't have anything else.
 You know, one way to think about this is like surgery and anesthesia.  Good psychotherapy is a little bit like surgery, and if we were allowed to give an anesthetic, we could go deeper, faster, and take out the rotten thing that is in there much quicker, and with a lot less psychic pain.
 The other thing is that MDMA is an extremely potent painkiller.  It is an analgesic.  There are a handful of people who have had cancer or have had chronic pain syndromes and have taken MDMA and discovered that their pain has gone away for five or six hours.  It doesn't go away forever, but for the duration of the MDMA session, they are pain free.  And this is sometimes in cases where the pain was not adequately treated by morphine.  So, to give someone a respite from their pain would be very nice, but also in terms of palliative care, or the care of the dying, we don't have many tools to help people deal with the fact that they're dying, or to help their families to deal with that.  So, this is something that a family can take, or a couple can take, when one member is dying, and there are some great case reports in the MAPS journals and elsewhere, about couples and families who have done just that.
 So, potential psychiatric and medical uses for MDMA are:   individual therapy, couples therapy, family therapy, group therapy, there is also mind/body work, in terms of biofeedback, creative visualization, enhancing hypnotic sessions.
 I also think in terms of eating disorders, it may be helpful for people to get a more realistic impression of their body, a less distorted body image.  Also, many times, people's medical complaints and chronic pain syndromes have a psychosomatic component, and to get at the psychological underpinnings of the symptoms with the help of MDMA would be a huge step in their treatment.
 Again, palliative care, is a huge branch of medicine that is really in its infancy.  We have a long way to go, in this country anyway, to make dying easier for our culture.  I think there are some people here from the Death In America project who would agree with that.  And again, we don't have that many tools at our disposal to assist us in that.  Here is something that has the potential to be quite valuable to patients and their families to alleviate the pain and fear associated with dying, and I think we should make use of it.
 Specific illnesses that have the potential to benefit from MDMA therapeutic research are depression, with MDMA being used as an acute interrupter of depression, feelings of suicidality, hopelessness, isolation.  Anxiety disorders, social phobias, simple phobias.  Especially simple phobias, in one MDMA session, you get to the root cause and symbolic connection of the meaning of the phobia, you discuss it, and it is gone.  I think it is really that simple.  The same thing happens in psychoanalysis, it just takes longer.  There are millions of Americans that have social phobia and simple phobias, and in terms of anxiety disorders, MDMA is useful because it shows the patient what it feels like to be relaxed, and less defended, and they can learn from this experience, and they can anchor themselves in that feeling and tap into it at other times.  And also, for them to understand what triggers are making them feel anxious, to identify the causes of the anxiety, where their fears are coming from, these are all things that can be explored quite easily with the help of MDMA during therapy.
 In terms of Post Traumatic Stress Disorder, I think that rape victims, and people who have been assaulted, and in other countries victims of torture and war, can all be helped immensely by MDMA-assisted psychotherapy.  MDMA allows people to revisit the trauma with much less anxiety than usual, and to process it in a non-threatening manner, and perhaps allows a measure of forgiveness and certainly acceptance to occur for the event.  Uncovering the repressed memories and speaking about them calmly and openly is the first step towards getting better in PTSD.  I am happy to report at least two research teams pursuing clinical research in using MDMA to treat PTSD, and one group in Spain has secured government approval to run these studies with sexual assault survivors.
 In general, with major mental illnesses, if you can enhance the therapeutic alliance between psychiatrist and patient, you will have improved mental health care.  MDMA-assisted psychotherapy affords the opportunity for "break through" sessions where issues of compliance with medication and treatment can be solidified, and insight into the illness can be gained.  Also, their support system can be enlisted more fully, perhaps in a group session or family session, where empathy and openness and acceptance are emphasized, which can improve outpatient care.  For instance, in drug addiction, improving insight into self-destructive behaviors is one of the first steps in changing that behavior.
 So, now the downside.  Morbidity and mortality, these are the physical problems associated with MDMA use.  The first thing I would like to say is that most adverse reactions reported with MDMA are in cases where people are taking more than the therapeutic dose, which is 125 milligrams.  When you're talking about people at raves, I don't know if you're talking about MDMA, and I don't know if you're talking about 125 milligrams, because I don't know exactly what people are taking.
 The big thing is hyperthermia.  Increased body temperature which leads to muscle breakdown which can cause kidney failure, clotting problems called Disseminated Intravascular Coagulopathy (DIC.)  It's very rare, but there have been a few deaths because of this, though less in the US than the UK.  The last year we have emergency room data for right now is 1997, and there were no deaths in the US that year.  The problem is that people are taking this drug, and other drugs, and they are not cooling off and not taking in enough fluids and they are overheating.
 The second problem is abnormal fluid/electrolyte balance.  What's happening here is they some people are drinking too much water, and because MDMA increases water retention by increasing the effect of Anti-Diuretic Hormone (ADH), the balance of water and sodium is off.  Urinating less and keeping more water in the body causes sodium levels to drop, this means you can have seizures, cerebral edema, which is basically "water in the brain," and this is not good.  So, basically, you need to stay cool and drink water but you can't drink too much water.  You should only replace the water you have lost through sweating.
 Abnormal heart rhythms are very rare, also intracerebral hemorrhage (ICH) has been reported though this is also exceedingly rare.  One report of four cases of ICH, when looked at closely, showed one person with a congenital anomaly or birth defect which could account for the diagnosis, another did not actually take MDMA, and the other two people did not have any confirmation that what they took was MDMA, and yet this was titled a case series of four incidences of MDMA causing intracerebral hemorrhage.
 Hepatitis has been reported, though rarely, but one thing I'm concerned about is that the enzyme which metabolizes MDMA in the liver is called CYP2D6.  It is deficient, or totally absent in 5 to 10 percent of Caucasians and African Americans and 1 to 2 percent of Asians.  I think this is one of the places that we're getting into trouble is that some people do not have the capacity to metabolize MDMA and the levels get too high.  Some clinical research studies will not take people into MDMA studies if they don't have this enzyme, and I think that is probably a good idea until we learn more.
 To emphasize how important the context and the behavior of the MDMA user can be, Dr. John Henry reported a case in which a person ingested forty tablets of MDMA, did not engage in vigorous physical activity, nor drank copious amounts of fluid, and never became hyperthermic nor hyponatremic (high temperature, low salt).  Also, no psychotherapist ever came across any problems with temperature or fluid balance in their patients who were given therapeutic doses of MDMA in a clinical setting.
 The neurotoxicity issue is a key issue when discussing morbidity and mortality, and it will be addressed by Dr. John Morgan later in this seminar.
 Adverse psychiatric sequelae is what can go wrong psychiatrically.  I think the most common problem, even though I've told you how calming and soothing the MDMA experience is, is that there are still people who have acute anxiety reactions and acute stress reactions.  Some people are not properly prepared for what they are going to get from MDMA.  Part of the problem is that people have had traumatic experiences in their past which they may be unaware of, or unprepared to revisit, and these memories may come to the foreground in order to be processed, and in the wrong setting, in an unprepared person, they are very threatening and unsettling and lead to a sense of panic.  The other issue is that some people simply panic when taking a drug that leads to any altered state of consciousness, no matter how mild or pleasurable.
 There are definitely reports of depression from post-binge use.  In England, it is very common to take ten or twelve tablets of "Ecstasy" (as opposed to MDMA) over the weekend, and reports of a depressed mood mid-week are common.  There have been a small number of reports of mania, which is basically the opposite of depression occurring, but it should be noted that one percent of the general population has manic depression, so it is hard to say if this person simply had that diagnosis anyway.  There have also been occurrences of sleep disturbances or insomnia.
 There is one report of a brief psychotic episode following administration of MDE (methylene dioxy ethylamphetamine) in a clinical research setting, but I still haven't heard of MDMA causing psychosis.  And in terms of anything occurring in clinical settings with MDMA, there have been no reports like that.
 There have been a few reports of something called de-personalization and de-realization where either you or your surroundings don't quite seem real, and this is something that can happen when you take any psychotropic drug.
 There has been a lot of press lately about cognitive disturbances, about memory problems in chronic "Ecstasy" users.  So far, I'm not particularly impressed by this data.  They give these polydrug users multiple tests and play with the statistics until an abnormality is found, and clinically, none of these subjects are reporting any complaints of memory dysfunction.  There hasn't been any persuasive data that's come out yet in the medical literature, but I'll keep reading it and see.
 I'd like to go over some popular myths associated with MDMA now.  Ecstasy drains your spinal fluid.  This one always kind of tickles me.  Nothing can drain your spinal fluid but a needle inserted into your back.  Unfortunately, this is exactly what happened to MDMA users in the 1980's, because MDMA researchers were examining samples of spinal fluid looking for abnormalities.  I think this is how the rumor got generated.  The drug itself will not drain your spinal fluid, nor will it cause Parkinson's Disease, and I am asked this all the time.  There is a drug called MPTP, which causes Parkinsonism.  In 1985, this phenomenon was hitting the media, with scary pictures of heroin users who had mistakenly injected MPTP and were frozen stiff or shaking, and it made a big impact on television shows, and it was the exact same time as the first big media wave about MDMA, and people got confused.
 MDMA was never "initially marketed as an appetite suppressant."  I read this all the time in news stories about MDMA, and it just gets propagated over and over.  And by the way, did we really need an appetite suppressant in 1912?
 MDMA is an aphrodisiac.  This is a little more complex.  In terms of increased kinesthetic awareness, body awareness, and tactile sensation, then I would say yes.  In terms of mechanics and hydraulics, and orgasm potential, I would say no.  It definitely delays orgasm in men and women during its peak effects, maybe when you "come down," things return to normal.
 MDMA is a "date rape drug."  Every time a new drug comes across the attention of the media it gets labeled as a date rape drug.  It is a real media phenomenon; it happened with rohypnol ("roofies") and with GHB.  I think this just plays on people's fears.  If you take a drug that makes you happy, and if you are ecstatic or blissful, then you may be vulnerable, and if you're vulnerable, then you may be attacked.  But the thing about MDMA is that you are awake and alert.  Your consciousness is not clouded and you retain your memory, so an attack should not occur without your awareness.
 There is heroin in Ecstasy pills.  Of all the pill analyses that I have seen, I don't think anyone has ever discovered heroin in the tablets.  It's a pretty expensive adulterant, and it wouldn't be cost effective to the pill manufacturer.  Also, the effects of MDMA would completely override the effects of heroin and you wouldn't feel it, soóno.
 Irreversible brain damage from a single pill.  Never been proven; I'm not even sure it's ever been reported.  It's just another scary myth circulated by the fried egg mentality, "this is your brain on drugs" propaganda.
 Also, it's not a hallucinogen.  I have a real problem with this and MDMA is often labeled a hallucinogen in the press.  Maybe you could say that feeling good about yourself, and your life, and the people around you is a hallucination, but I wouldn't say that.  It does not cause visual hallucinations, it does not cause a break with reality; reality testing is still intact.  It has its own class, it's called an entactogen, named by David Nichols.  MDMA deserves to have its own class because it is a uniquely acting substance; there is no other drug or medicine like it.
 Thank you.