Originally published on Blossom Analysis.

Ecstasy: The Complete Guide edited by Julie Holland gives a solid and near-complete overview of the scientific and therapeutic knowledge about Ecstasy (MDMA, XTC, Adam, Molly). Although the book dates back to 2001, it’s more complete than one would expect, as much was then already known about Ecstasy. Next to chapters by Julie Holland herself, other contributors are from Ralph Metzner, Andrew Weil, Rick Doblin (MAPS), Sasha & Ann Shulgin, and David Nichols.


Introduction: Medicine for a New Millennium (Julie Holland, M.D.)

The book starts with an overview of the recreational and widespread use of MDMA, the punishing laws, and the lack of (therapeutic) research that was possible in the decades leading up to 2001. “This book is about the importance of bringing MDMA back into the fold of medicine.” Julie wants MDMA to be researched again, and to become available to the people who need it the most.

Part I: Let X = MDMA

Chapter 1 – The History of MDMA (Julie Holland, M.D.)

  • MDMA was first synthesized somewhere before 1912 by Merck (pharma company)
  • The mention of MDMA was only as a intermediary chemical
  • MDA (more psychedelic-like experience) became popular before MDMA
    • Later on, it’s learned that (bad) research on this substance was used (in part) to ban MDMA
  • Sasha Shulgin didn’t invent MDMA but did synthesize it in 1976
  • In 1985 it was discussed that the therapeutic use of MDMA exceeded 1000 sessions
  • Only in the 1980s did the recreational use of MDMA take off
  • After some legal back-and-forth, MDMA was banned on July 1st, 1985 (and finally again on March 23rd, 1988)
    • Therapists argued that it should be in Schedule III (with medical uses approved), but it was placed in Schedule I, next to cocaine and heroin)
  • The consequent crackdown on MDMA, of course, made it more popular than ever before
  • Currently, based on self-reported data on drug use, 33% of participants used MDMA in the last year (GDS, 2019)

Chapter 2 – What Does MDMA Feel Like? (Gary Bravo, M.D.)

Although MDMA’s effects are dependent on the set and setting, there are distinct features of the experience:

  • Reduces or eliminates the neurophysiological fear response to a perceived threat to one’s emotional integrity
  • Loving and forgiving awareness
  • Powerful empathy towards others (feelings of closeness)
  • Insight into personal patterns or problems (improved self-examination)
  • Jaw tension, teeth clenching, insomnia, fatigue, decreased appetite
  • Elevated blood pressure, pulse rate, and pupillary dilatation

The chapter lists more effects from different surveys and studies. It also notes that multiple doses (2-3 hours later) lead to less desired outcomes (less empathy, more amphetamine-like side effects). The same is true for repeated use over multiple occasions.

Chapter 3 – How MDMA Works in the Brain (Jessica Malberg, Ph.D., and Katherine R. Bonson, Ph.D.)

MDMA acts in the brain through three main neurochemical mechanisms: blockade of serotonin reuptake, induction of serotonin release, and induction of dopamine release... MDMA can directly interact with receptors in a variety of neurotransmitter systems and can act as a monoamine (MAO) inhibitor.

The rest of the chapter explains the exact mechanisms behind these processes (and that the combination of them is needed to create the distinct MDMA effects). It also notes the interaction with other drugs. SSRIs may (completely or partially) block the effects of MDMA. Dextromethorphan (DXM) and MDMA together may lead to serotonin syndrome. The combination with MAO-A inhibitors is dangerous. The combination with hallucinogens (e.g. LSD) may lead to combination effects that can be positively perceived.

Chapter 4 – The Chemistry of MDMA (David Nichols, Ph.D.)

This chapter explains the chemistry of MDMA in layman terms. It explains how MDMA is an organic base (versus acid), and looks very similar to MDA (but with a methyl group added). MDMA is derived from safrole, which comes from sassafras root. You can have two types/mirror images of MDMA, (+)-MDMA and (-)-MDMA, and if your mix consists of both in the same quantities, you have a racemate or racemic mixture. Because MDMA is more lipd (fat) soluble (than MDA), the onset is quicker and the duration is shorter. The added methyl group also mean MDMA doesn’t fit in the 5-HT2a receptor, which produces LSD-like effects. The (-)-MDMA is thus not ‘active’.

Chapter 5 – MDMA Myths and Rumors Dispelled (Julie Holland, M.D.)

There are many crazy myths about MDMA and this short chapter dispels them.

Chapter 6 – The Godparents of MDMA: An Interview with Ann and Sasha Shulgin (Julie Holland, M.D.)

Some quotes from the interview with two legends of the psychedelic world:

  • It is an insight drug. That’s its main use. The effect of MDMA, for most people, is that it allows insight without fear.”
  • MDMA is also great for marital therapy. It enables two people to step out of the negative patterns that they might set up between themselves so that they can’t communicate openly anymore.”
  • “[MDMA] is the kind of drug that cannot be used frequently.”
  • The Shulgins note the positive effect of MDMA on rave culture and even football culture

Part II: Risks of MDMA Use


The table at the end of the introduction does a good job of grounding the next few chapters:

prescription drugs100.000
aspirin and over-the-counter-painkillers7.600
Estimated U.S. Deaths in 1998 attributed to

Chapter 7 – Medical Risks Associated with MDMA Use (John Henry, M.D., and Joe Rella, M.D.)

It’s difficult to say how many deaths have been caused by MDMA as in many cases users did other drugs two, were dancing all night, and pills might have contained adulterants. Without saying it, the introduction might also have said that prohibition is the most likely killer when it comes to MDMA.

Hyperthermia is an effect that has been shown to occur occasionally in recreational (club/rave) use, but hasn’t been found in therapeutic settings. Hyponatremia (low plasma sodium level) has also been seen, and is caused by dilution of the blood by drinking too much water. The serotonin syndrome is again mentioned, as are cardiac conditions and liber abnormalities. One interesting fact about the latter is a genetic difference (polymorphism) where the specific enzyme that breaks down MDMA (CPY2D6) is inactive in 5-10% of the Caucasian population. This is, however, only a theory as to this being the reason why some first time users at reasonable dosages have adverse events.

Neurologically MDMA may have negative effects. Studying that with animal models has led to some results, but also highlights that it’s very difficult to make a direct link between e.g. rats and humans (very different (drug) metabolism).

The chapter ends with the following precautions:

  • Do not take more than one pill
  • Avoid dancing for prolonged periods of time
  • Drink electrolyte-rich fluids (sports water), but don’t overdo it, and only drink more if you’re dancing
  • Wear light loose clothes (to dissipate heat)
  • Seek medical help early

Chapter 8 – Mental Health Problems Associated with MDMA Use (Karl L. R. Jansen, M.D., Ph.D.)

This chapter also highlights the trouble with researching the negative effects of MDMA use. Adverse psychological effects discussed are psychosis, anxiety disorders and panic attacks, depersonalization and derealization, depression and mania, cognitive deficits, the Pandora’s Box Syndrome, flashbacks and PTSD, and sleep disturbance. Each with limited to no widespread occurance.

The rest of the chapter discussed the ways of treating people with acute or long-term problems resulting from MDMA use. Discussed are psychotherapy, medication, meditation and other calming activities, and antioxidants and food supplements (sources of tryptophan – e.g. banana, chocolate, milk, turkey).

Chapter 9 – Does MDMA Cause Brain Damage? (Matthew Baggot and John Mendelson, M.D.)

There have been limited findings of neurotoxicity in behavioral and animal studies. But for the user who does MDMA a handful of times per year, one should not expect any adverse effects. The chapter mentions the serotonergic changes, and oxidative stress resulting from MDMA use and studies that compare MDMA and non-MDMA users. What is most notable is that in 2001, much more research was needed to establish the specific effects MDMA has (especially long-term) on the brain.

Chapter 10 – The Legal Status of MDMA around the World (Julie Holland, M.D.)

Alas, this chapter is not as outdated as one would hope in 2020. MDMA is still illegal in most countries and only some countries don’t have penalties if someone is caught with an amount for personal use.

See for the latest, the MDMA wikipedia page.

Chapter 11 – Minimizing Risks in the Dance Community: An Interview with Emanuel Sferios (Julie Holland, M.D.)

Emanuel Sferios is the founder and executive director of DanceSafe, a drug abuse prevention program/organization. The organization does pill testing and other harm reduction services (e.g. chill-out areas), mostly related to clubbing/festivals. The interview talks about this work and the causes of deaths related to MDMA (adulterants, hyperthermia).

The good thing is that the focus is on harm reduction and not the prevention of drug use (‘just say no’) and DanceSafe seems to be giving honest and reasonable advice that helps save lives.

Part III: MDMA-assisted Psychotherapy


MDMA acts as a catalyst to the psychotherapeutic process in four ways:

  • Connection: it enhances the therapeutic alliance (doctor-patient relationship)
  • Recall: lowering barriers to remembering childhood or traumatizing events
  • Insight: able to draw conclusions and make decisions (partially based on the recall)
  • Acceptance: able to develop compassion and forgiveness for others and self

Chapter 12 – Using MDMA in Healing, Psychotherapy, and Spiritual Practice (Ralph Metzner, Ph.D., and Sophia Adamson)

It is the primary thesis of this chapter that the empathogenic substances induce an experience that has the potential for dissolving the defensive intrapsychic separation between spirit, mind, and body and that therefore physical healing, psychological problem solving, and spiritual awareness can, and usually do, occur at the same time in the same experience.”

The chapter recounts how MDMA is able to open the heart center/chakra and offers guidelins for sacramental use of empathogenic substances (MDMA being one of them). One key point of individual sessions is the recalling (see introduction), for group sessions there are two possibilities where there is (ritualized) communication or none (inward journey) during the session.

Chapter 13 – Experience with the Interpersonal Psychedelics (Claudio Naranjo, M.D.)

This chapter recounts Claudio Naranjo’s extensive experience with MDA, MMDA, and MDMA and their use in therapy.

Chapter 14 – Clinical Experience with MDMA-assisted Psychotherapy: An Interview with George Greer, M.D. (Julie Holland, M.D.)

George Greer used psychedelics in his private practice when this was still legal and this chapter recounts his experience. He is also involved with the Heffter Institute as a medical director, secretary, and treasurer.

Part IV: Potential Clinical Uses for MDMA


MDMA is a unique medication … that works in an hour to enhance feelings of happiness and relaxation…”

There are many possible clinical uses of MDMA and as of now (2020) some of the uses are going through FDA approval (e.g. PTSD, Phase 3). But it is believed by many that MDMA could be used for most mental disorders. Some of these are laid out in the next few chapters.

Chapter 15 – Using MDMA in the Treatment of Post-traumatic Stress Disorder (José Carlos Bouso)

José Carlos Bouso was one of the first to do research (again) with MDMA, but after the first six patients, the program was shut down again (this took place right after the book was published). The chapter itself talks about the characteristics of PTSD, how it could be treated, and how MDMA could help. Both recall and acceptance are two very important points for people suffering from PTSD.

Chapter 16 – Using MDMA in the Treatment of Depression (June Riedlinger, R.Ph., Pharm. D., and Michael Montagne, Ph.D.)

Depression is very prevalent in the population (between 10-25% and 5-12% for women and men respectively, lifetime prevalence). The underlying (biological) problems of depression may be changed by MDMA (as a serotogenic agent), but most of the research for depression with psychedelics is focused on psilocybin and ketamine.

Chapter 17 – Using MDMA in the Treatment of Schizophrenia (Julie Holland, M.D.)

Schizophrenia and MDMA use has not been rigorously studied, but this chapter does recount some anecdotal findings. Most of the chapter is dedicated to explaining schizophrenia and the two sides (active/passive) that possibly indicate the imbalance of chemicals in the brain.

Chapter 18 – Using MDMA in Alternative Medicine: An Interview with Andrew Weil, M.D. (Julie Holland, M.D.)

Julie Holland interviews Andrew Weil, an author and alternative medicine proponent. It offer some insight in how MDMA is viewed from his perspective and how it could match with (other) alternative healing protocols.

Part IV: MDMA Research

Chapter 19 – Clinical Research with MDMA: A Worldwide Review (Andrew Kleiman, M.D., and Julie Holland, M.D.)

Chapter 20 – Giving MDMA to Human Volunteers in Switzerland (Alex Gamma, Ph.D., Matthias E. Liechti, M.D., and Franz X. Vollenweider, M.D.)

Chapter 21 – Giving MDMA to Human Volunteers in the United States: An Interview with Charles Grob, M.D. (Julie Holland, M.D.)

These three chapters about the research ongoing with MDMA are a good snapshot of what was known at the turn of the century.

For an overview of the MDMA research one could best go to the MAPS website.

Some common findings from the research at that time are:

  • Increase in certain cardiac parameters (blood pressure, heart rate)
  • Subjective effects are caused by an enhancement of serotonergic neurotransmission through an interaction with the presynaptic 5-HT uptake site
  • Women show a bigger response to MDMA
    • This is in correlation with bigger mood disorders prevalence in women, implicating the same 5-HT system

Part V: MDMA and Society

Chapter 22 – Ecstasy: Prescription for Cultural Renaissance (Douglas Rushkoff, Ph.D.)

Douglas Rushkoff offers his esoteric view on how MDMA is leading/can be used as a catalyst for a cultural renaissance.

Chapter 23 – MDMA and Spirituality: An Interview with Rabbi Zalman Schachter (Julie Holland, M.D.)

Rabbi Zalham Schachter offers his perspective on MDMA as a rabbi and as someone who has used MDMA and other psychedelics.

Chapter 24 – MDMA’s Promise as a Prescription Medicine: An Interview with Rick Doblin, Ph.D. (Julie Holland, M.D.)

The book ends where the rest of the last two decades have remained, with an interview with Rick Doblin. He recounts his personal history with MDMA research and advocacy and the uphill battle that is still being fought. He recounts how he (and the community at large) wasn’t surprised when it got put in Class I, but of course still deeply saddened by it. And how he, with MAPS, is hoping to have MDMA available as a therapeutic agent as soon as humanely possible.