Evidence Based
10

MDMA (Ecstasy) Effects, Dangers & PTSD Research

Written by Puya Yazdi, MD | Reviewed by Ana Aleksic, MSc (Pharmacy) | Last updated:
Jonathan Ritter
Medically reviewed by
Jonathan Ritter, PharmD, PhD (Pharmacology) | Written by Puya Yazdi, MD | Reviewed by Ana Aleksic, MSc (Pharmacy) | Last updated:

SelfHacked has the strictest sourcing guidelines in the health industry and we almost exclusively link to medically peer-reviewed studies, usually on PubMed. We believe that the most accurate information is found directly in the scientific source.

We are dedicated to providing the most scientifically valid, unbiased, and comprehensive information on any given topic.

Our team comprises of trained MDs, PhDs, pharmacists, qualified scientists, and certified health and wellness specialists.

All of our content is written by scientists and people with a strong science background.

Our science team is put through the strictest vetting process in the health industry and we often reject applicants who have written articles for many of the largest health websites that are deemed trustworthy. Our science team must pass long technical science tests, difficult logical reasoning and reading comprehension tests. They are continually monitored by our internal peer-review process and if we see anyone making material science errors, we don't let them write for us again.

Our goal is to not have a single piece of inaccurate information on this website. If you feel that any of our content is inaccurate, out-of-date, or otherwise questionable, please leave a comment or contact us at [email protected]

Note that each number in parentheses [1, 2, 3, etc.] is a clickable link to peer-reviewed scientific studies. A plus sign next to the number “[1+, 2+, etc...]” means that the information is found within the full scientific study rather than the abstract.

MDMA

MDMA is a synthetic drug of abuse that is broadly known as “ecstasy” when diluted. It has a wide range of psychoactive (mind-altering) effects that impact energy levels, mood, and socialization. Abuse can be dangerous and even deadly. But some researchers think it has therapeutic potential in safe, medically-supervised settings. Continue reading to understand the full story behind MDMA and its dangers.

Disclaimer: MDMA is classified as a Schedule I substance. This means that it is an illegal drug with high potential for harm and no known medical uses. We highly advise against the use of MDMA until future studies determine its safety and efficacy in safe environments. The only aim of this post is to outline risks and research findings.

What is MDMA?

Overview

3,4-methylenedioxymethamphetamine (MDMA) is an illegal synthetic drug that has psychoactive or mind-altering properties [1].

It is chemically similar to the amphetamine group of drugs like methamphetamine, MDA (3,4-methylenedioxy-amphetamine, a breakdown product of MDMA), and hallucinogens [2].

MDMA is commonly called Ecstasy or Molly and its abuse likely spread with raves and clubs of the late 80s. It also became known for its effects on increasing energy and openness on college campuses. However, MDMA use can cause many adverse effects, addiction, and withdrawal syndrome [3, 4].

Discovery & Legal Status

It was widely believed that this drug was originally developed as an appetite-suppressant or weight-loss chemical by the German pharmaceutical company Merck in 1912. But a recent analysis of the original documents in the company’s archive tells a different tale.

The authors of this analysis concluded that the weight-loss story is a myth. It seems that MDMA was actually only synthesized as an in-between step to other drugs (thus, it served as a so-called precursor) in the pipeline [5].

Later on, in the 70s, researchers got interested in MDMA for psychotherapeutic reasons. It was tested alongside psychotherapy for making people more willing to talk about emotionally-charged or traumatic experiences [6].

However, due to its widespread recreational use in the 1980s, the drug was banned in 1985. Thus, most of the research halted.

Ongoing Research

With the new wave of psychedelic research, some scientists got interested in MDMA again, especially when it comes to its emotionally-disinhibiting effects in psychotherapeutic settings.

The FDA recently granted breakthrough therapy designation for a phase 3 trial of MDMA-assisted psychotherapy for PTSD. This clinical trial is sponsored by the Multidisciplinary Association for Psychedelic Studies (MAPS) [7].

MAPS says their goal is to “develop MDMA-assisted psychotherapy for PTSD into an FDA-approved prescription treatment by the end of 2021” and are investing roughly $26.9 million in this undertaking.

Aside from PTSD research, MDMA is also in clinical trials as a potentially therapeutic aid for stress disorder and anxiety in terminally ill patients, and for social anxiety in autistic adults.

But despite some preliminary findings, trials are still ongoing and we have yet to see large-scale safety and effectiveness data.

Current Abuse & Added Risks

MDMA is currently sold illegally around the world. According to a United Nations report, around 18.8 million people had used MDMA in the year 2015 [8].

The drug is primarily used by young adults in highly-social situations such as festivals and dance parties. MDMA is usually taken orally as a tablet or capsule, although some people prefer to store it in powder form [9].

MDMA is largely combined with other substances such as caffeine, ephedrine, ketamine, and Tylenol. This is extremely dangerous and increases the risk of serious and potentially fatal side effects [10].

MDMA is also said to be available in “pure form” as a crystal powder, with a number of street names including Molly, Adam, or Mandy.

However, this supposedly pure powder may contain other dangerous or illegal drugs instead of or in addition to MDMA.

The National Institute on Drug Abuse warns Molly seized by the police tends to contain cocaine, ketamine, methamphetamine, over-the-counter cough medicine, or synthetic cathinones (“bath salts”). People who take in this mixture with other substances, such as marijuana and alcohol, risk putting themselves at an even higher risk of serious harm [3].

Additionally, MDMA use is associated with risky sexual behaviors and an increased risk of sexually-transmitted diseases like HIV, even in people who considered themselves “low risk” [4].

Mechanism of Action

When administered orally, MDMA absorbs rapidly into the bloodstream and reaches the brain. Effects start within 30-45 minutes following oral ingestion, peaks in 70-120 minutes, and can last for 3-3.4 hours [11, 12].

Once in the brain, MDMA likely increases the release of the neurotransmitters serotonin, norepinephrine, and dopamine. The serotonin effects seem to be more significant than for the other neurotransmitters [13].

The large and rapid release of these neurotransmitters in the brain likely causes psychoactive changes in the body, including emotional excitation, elated mood, increased social behavior, and self-confidence [14].

MDMA is hypothesized to increase neurotransmitter levels by acting as a VMAT2 (DAT, NET, and SERT) inhibitor [15].

VMAT2s are neurotransmitter reuptake transporters and their inhibition by MDMA may result in increased concentrations of the associated neurotransmitter (serotonin, norepinephrine, or dopamine) in neurons, according to cell-based studies. This mechanism hasn’t been explored in humans [15].

MDMA and its byproducts may also have some activity on postsynaptic serotonin receptors 5-HT1 and 5-HT2 receptors, but more research on these pathways is needed [16].

MDMA Effects

Short-term

The desired short-term psychoactive effects of MDMA have been reported to include [17]:

  • Euphoria, described as a sense of general well-being and happiness
  • Increased sociability and feelings of communication being easy or simple
  • Entactogenic effects, such as increased empathy or feelings of closeness with others
  • A sense of inner peace
  • Mild hallucinations
  • Enhanced sensation, perception, or sexuality
  • Altered sense of time

Adverse short-term effects include [3, 4]:

  • nausea
  • muscle cramping
  • involuntary teeth clenching
  • blurred vision
  • chills
  • sweating
  • high blood pressure (hypertension)
  • faintness
  • panic attacks
  • loss of consciousness and seizures

The effects last about 3 to 6 hours, but many users take another dose as the effects of the first dose begin to wear off.

According to the National Institute on Drug Abuse, a person may experience the following after a week of using the drug [3]:

  • irritability
  • impulsiveness and aggression
  • depression
  • sleep problems
  • anxiety
  • memory and attention problems
  • decreased appetite
  • decreased interest in and pleasure from sex

It’s possible that some of these effects are from the combined use of several drugs, including marijuana.

Setting-Dependent Effects

Some researchers have suggested that the experience elicited by MDMA may depend on the setting. For example, MDMA used at parties is associated with high physical activity, reduced sense of self-identity, and poor awareness of one’s background surroundings.

MDMA use in combination with intense physical activity – such as at dance parties and festivals – can lead to dehydration, which often makes people want to drink large amounts of liquids. This may increase the risk of electrolyte imbalances or brain swelling, as MDMA causes the body to retain more water [4].

On the other hand, ongoing research is focusing on its potential value in assisting psychotherapy. Accompanying this type of experimental psychotherapy, MDMA is only given over a couple of spaced sessions, in a safe, medically-supervised, and peaceful environment [7].

Research Areas

The studies listed below are highly experimental. We summarized them with the aim of sharing the latest research with the general population. The existing studies should guide further investigation efforts. They should not be interpreted as supportive of any health benefit.

Remember that MDMA is still an illegal drug with high potential for harm. We highly advise against the use of MDMA until future studies determine its safety and efficacy in medically-supervised and safe settings.

1) Social Behavior & Anxiety

The use of MDMA has been linked to increased prosocial behaviors [18].

Moderate doses (75 mg) have been shown to encourage closeness and strengthen the bond between people [19].

Exposure to MDMA is hypothesized to enhance the level of a chemical known as oxytocin, which plays a key role in bonding [20].

In one small placebo-controlled study of 15 human volunteers, oxytocin increases in the blood were correlated with the subjective social effects of MDMA [20].

This is probably the reason why some therapists initially got interested in MDMA for assisting couple’s therapy and family therapy. However, its effects on these types of therapies specifically is not a topic of ongoing research [21].

MDMA is currently in clinical trials as a potential psychotherapeutic aid for stress disorder and anxiety in terminally ill patients, and for social anxiety in autistic adults.

2) PTSD

FDA-approved clinical trials are investigating MDMA as a potentially novel approach for the treatment of PTSD [22].

In two small pilot trials, the intake of MDMA markedly improved symptoms associated with PTSD [23, 24].

Research on an animal model of PTSD suggests that MDMA exposure may improve some of the brain abnormalities linked to PTSD, but this has yet to be determined in humans [25].

Some scientists have suggested that one possibly useful aspect of MDMA in psychotherapy, is its ability to facilitate self-examination with reduced fear. Such claims have yet to be verified, though.

All in all, we’re still awaiting the results of large clinical trials before we can say whether MDMA is useful for people with PTSD undergoing psychotherapy.

3) Other Aspects of Brain Health

The use of MDMA has been proposed as a new strategy for reducing symptoms of schizophrenia [26] and Parkinson’s disease [27]. However, clinical data are lacking to back up this approach.

Research on an animal model of Parkinson’s disease has suggested that MDMA exposure might improve uncontrollable arm and leg movements, common motor symptoms in Parkinson’s disease [28].

Similarly, some people diagnosed with Schizophrenia had reported that they have experienced an improvement in mental behavior after using MDMA [29].

Human studies have yet to see if MDMA has any value for people with schizophrenia of Parkinson’s disease.

4) Inflammation & Immunity

We don’t yet know how MDMA affects inflammation and immunity in humans. Limited studies suggest it might act as a stressor on the immune system, reducing the immune response. Thus, it has been called an immunosuppressive drug [30].

Many of the physiological changes elicited by MDMA closely resemble those induced by acute stress [30].

In animals, MDMA inhibits the inflammatory cytokines IL-12, IL-1b, and TNF-alpha [31, 30].

In cells, scientists are investigating whether it suppresses neutrophil activity and circulating lymphocyte numbers (more characteristic of a Th2 response) and increases the production of the anti-inflammatory cytokine IL-10 (R, R).

IgG2a levels were decreased following MDMA administration, possibly by reducing the production of the Th1 cytokine, IFNy [30].

In a few human trials, MDMA suppressed the number of circulating CD4+ T cells and increased the number of circulating natural killer cells. However, natural killer cell numbers in MDMA users were reduced to 33% of that seen in control subjects [30].

It was also reported that MDMA promoted a switch to a Th2-type cytokine profile, as indicated by reduced IFNy and IL-2 production, with a concomitant increase in the Th2 cytokines, IL-4, and IL-6, and the T-regulatory (TREG) cytokines, IL-10 and transforming growth factor-β1 (TGF-β1) [30].

These immunosuppressive effects of MDMA were maximal 3-6 hr following drug administration, and in some cases were evident 24 hr later. In some instances, the co-administration of alcohol further enhanced the immunosuppressive effects of MDMA [30].

In humans, repeated administration of MDMA with both a short and a long time interval between doses increases both the magnitude and duration of MDMA-induced immunosuppression [30].

The total number of lymphocytes, CD4+ T cells, and CD19+ B lymphocytes were all significantly reduced even years later in MDMA abusers compared to control subjects [30].

However, it is not possible to ascertain if the suppression of immune parameters observed in the MDMA users is a result of MDMA abuse alone. For instance, the subjects enrolled in the clinical trials were all habitual users of cannabis, with prior experience of cocaine or methamphetamine. These drugs all also have immune-suppressive properties [30].

Most of these immune-suppressive effects are likely not the result of a direct action of the drug on immune cells, but rather caused by the release of chemicals that MDMA releases, which go on to affect immune cells [30].

Dangers of MDMA

Clinical studies on humans and animals reveal that exposure to MDMA alone or in combination with other drugs (e.g., cocaine, cannabis) causes damage to the heart, brain, liver, and kidneys. These abnormalities may potentially lead to death [32, 33, 34, 35].

How MDMA Causes its Toxic Effects

Laboratory research on animals has suggested a mechanism for MDMA’s adverse effects on a cellular level [36].

Inside the cell, MDMA has been shown to disrupt the structural and functional integrity of mitochondria, which are the major energy-producing machines in the cell. Consequently, an energy crisis is hypothesized to develop in the cell [37].

MDMA may also elicit its toxic effects by driving oxidative stress in cells [38].

Increased levels of oxidative stress can cause severe damage to all components of the cell, including proteins, lipids and nucleic acids [39].

Side Effects and Overdose

Adverse effects of MDMA use include addiction, memory problems, paranoia, difficulty sleeping, teeth grinding, blurred vision, sweating, and a rapid heartbeat. Use has also been linked with depression, anxiety, and fatigue. Deaths have been reported due to increased body temperature and dehydration [40, 41, 42].

The use of MDMA can cause muscle aches/headaches, sweating, numbness, dizziness, and dry mouth. In some cases, it may also cause vomiting [43].

Electrolyte Imbalances and Heart Problems

Since MDMA increases vasopressin [44], it may cause electrolyte abnormalities – particularly low sodium. Sweating makes the situation worse. The usual reaction of people is to drink more water, which can be even more dangerous. MDMA retains water, and drinking a lot of fluids can worsen electrolyte imbalance and lead to brain swelling [4]

Two major syndromes are most commonly reported as the immediate cause of death in fatal cases: hyperthermia and hyponatremia (low sodium) [45].

Intake of MDMA is also associated with increased heart rate and blood pressure [46].

Modest oral doses (1.5 mg/kg) of MDMA have been reported to increase heart rate, blood pressure, and oxygen consumption in the heart [47].

The use of MDMA may adversely affect sexual performance [48].

A study conducted on MDMA users (both men and women) has shown that MDMA exposure results in sexual arousal, but with impaired erections in 40% of the men [49].

Cognitive Function

The use of MDMA in higher doses or for a longer period of time has negative effects on cognitive function. A study conducted on abstinent MDMA users revealed that excessive use of MDMA causes impairment in verbal and visual memory [50].

The use of MDMA has also been reported to cause severe short-term memory impairment. In one clinical study, a 21-year-old man, who had a history of taking one or two pills a day of MDMA for 4 months, was reported to develop a sudden memory loss after intake of two pills of MDMA [51].

Administration of MDMA can cause an uncontrolled secretion of the antidiuretic hormone (ADH), which is involved in a condition called hyponatremia (low-level of sodium/salt in the body) [52].

Hyponatremia under severe conditions may lead to drowsiness, seizures, coma, and death [53].

Small but significant deficits for ecstasy users compared to controls were reported in areas relating to attention, memory, psychomotor speed, executive systems functioning, and self-reported depressive symptoms [45].

Ecstasy users performed worse than controls on common measures of immediate and delayed verbal recall (RAVLT, RBMT, digit span). No difference was seen in IQ (NART).

Ecstasy users performed significantly worse than controls in 13/16 cognitive domains (immediate and delayed verbal and visual memory, working memory, two measures of attention, three measures of executive function, perceptual organization, self-rated depression, memory and anxiety, and impulsivity measured objectively and subjectively) [45].

The largest, most consistent exposure effects were seen in meta-analyses of memory (especially verbal and working memory, with less marked effects seen in visual memory). Former ecstasy users frequently showed deficits that matched or exceeded those seen amongst current users.

Overdose Symptoms

MDMA overdose symptoms vary widely due to the involvement of multiple organ systems. Some of the more overt overdose symptoms are listed in the table below.

SystemMinor or moderate overdoseSevere overdose
Cardiovascular
  • Disseminated intravascular coagulation
  • Brain bleeding
  • Severely high or low blood pressure
Central nervous

system

  • Abnormally fast reflexes
  • Agitation
  • Mental confusion
  • Paranoia
  • Stimulant psychosis
  • Cognitive and memory impairment potentially to the point of not remembering anything
  • Coma
  • Convulsions
  • Hallucinations
  • Loss of consciousness
  • Serotonin syndrome
Musculoskeletal
  • Muscle rigidity
  • Rhabdomyolysis (rapid muscle breakdown)
Respiratory
  • Acute respiratory distress syndrome
Urinary
  • Kidney failure
Other
  • Brain swelling
  • Hepatitis
  • Hyperpyrexia (a life-threatening elevation of body temperature)
  • Hyponatremia (Syndrome of inappropriate antidiuretic hormone)

If you have been exposed to MDMA and experience serious side effects or overdose, urgently contact a poison control center near you (call 1-800-222-1222).

Proposed New Drug Classification Systems

Some scientists think that the current drug classification system should be revised. Their propositions remain theoretical and most have been rejected by governmental bodies.

For example, the UK Science and Technology Select Committee published a 2006 report which suggested that the current system of recreational drug classification in the UK was arbitrary and unscientific and that a more scientific measure of harm should be used for classifying drugs.

In the report, the risks of MDMA are not downplayed. It’s mentioned that around 200-250 ecstasy-related deaths have been reported, since the first one was in 1989 [54].

Some have suggested that that heroin, cocaine, alcohol, benzodiazepines, methamphetamine, and tobacco should belong to the most dangerous “class A” drugs, while MDMA may warrant being placed under “class B” drugs, which are still dangerous but slightly less so. This proposition was rejected.

An article published in 2007 in The Lancet, outlines this alternative method for drug classification that was rejected. This system uses a “nine category matrix of harm.” The authors did not evaluate or rate the negative impact of “ecstasy” on the cognitive health of ecstasy users, e.g., impaired memory and concentration [55].

Genetics

The impact of MDMA on genetics – as well as the impact of genetics on MDMA toxicity and breakdown in the body – is unknown. This section is purely theoretical and outlines early scientific research.

These are hypothesized to break down MDMA into the more toxic MDA:

These are related to receptors and transporters affected by MDMA:

Want Better Ways to Improve Your Mood?

If you’re interested in natural and targeted ways of improving your mood, we recommend checking out SelfDecode’s Mood DNA Wellness Report. It gives genetic-based diet, lifestyle and supplement tips that can help improve your mood. The recommendations are personalized based on your genes.

SelfDecode is a sister company of SelfHacked. The proceeds from your purchase of this product are reinvested into our research and development, in order to serve you better. Thanks for your support!

About the Author

Puya Yazdi

Puya Yazdi

MD
Dr. Puya Yazdi is a physician-scientist with 14+ years of experience in clinical medicine, life sciences, biotechnology, and nutraceuticals.
As a physician-scientist with expertise in genomics, biotechnology, and nutraceuticals, he has made it his mission to bring precision medicine to the bedside and help transform healthcare in the 21st century.He received his undergraduate education at the University of California at Irvine, a Medical Doctorate from the University of Southern California, and was a Resident Physician at Stanford University. He then proceeded to serve as a Clinical Fellow of The California Institute of Regenerative Medicine at The University of California at Irvine, where he conducted research of stem cells, epigenetics, and genomics. He was also a Medical Director for Cyvex Nutrition before serving as president of Systomic Health, a biotechnology consulting agency, where he served as an expert on genomics and other high-throughput technologies. His previous clients include Allergan, Caladrius Biosciences, and Omega Protein. He has a history of peer-reviewed publications, intellectual property discoveries (patents, etc.), clinical trial design, and a thorough knowledge of the regulatory landscape in biotechnology.He is leading our entire scientific and medical team in order to ensure accuracy and scientific validity of our content and products.

Click here to subscribe

RATE THIS ARTICLE

1 Star2 Stars3 Stars4 Stars5 Stars
(3 votes, average: 4.33 out of 5)
Loading...

Leave a Reply

Your email address will not be published. Required fields are marked *

This site uses Akismet to reduce spam. Learn how your comment data is processed.