MDMA: From Ecstasy’s Party Origins to Modern Therapeutic Potential

• By Sam Woolfe
• Medically approved by Dr. Jonathann Kuo
• July 15, 2022January 31, 2024
• MDMA MDMA articles mdma therapy
• With 0 comments

MDMA, also known as “ecstasy”, is one of the most commonly used recreational drugs. It is a popular drug of choice in club, rave, or party settings. Because it provides users with heightened euphoria, more prosocial feelings, and a greater appreciation for music. However, MDMA – before it entered the club scene – had also been studied as an adjunct to psychotherapy. This is known as MDMA-assisted psychotherapy, or MDMA therapy for short. 

There is a growing body of research on the therapeutic potential of MDMA. But there are also some risks around the drug. MDMA is currently a highly controlled substance in most countries around the world. (It is a Schedule I drug in the United States). This means it can be studied but it is not yet legal for medical or recreational use. 

But legalization of MDMA therapy on the horizon in several countries. Which would give people struggling with various forms of emotional distress a new potential treatment option. Moreover, the drug continues to proliferate in the black market, which entails some risks. Both these situations mean that patients and recreational users require the most up-to-date information on MDMA. Giving them the ability to make informed decisions about using the substance.

RELATED: Here’s How Clinics are Getting Ready for MDMA and Psilocybin

What Is MDMA?

There are several ways we can describe the substance.

MDMA As A Stimulant

Firstly, MDMA is a stimulant. Which refers to a class of drugs that increase the activity of the central nervous system and the body. These drugs have pleasurable and invigorating effects. 

Like other stimulants, MDMA is a sympathomimetic drug. Which means that it mimics the effects of endogenous agonists of the sympathetic nervous system. Epinephrine (adrenaline) and dopamine would be examples of such endogenous agonists. As with these agonists, MDMA increases heart rate, energy, wakefulness, and positive mood. This is why it’s a popular choice for raves and parties since you can feel energized and in positive spirits late into the night. Although like other stimulants, MDMA is associated with a comedown as well.

READ NEXT: These pet owners are considering giving MDMA to their dogs.

MDMA As A Phenethylamine

MDMA is also a phenethylamine. This refers to a class of substances with documented psychoactive and stimulant effects. Which includes not just popular stimulant drugs such as amphetamine and methamphetamine but also psychedelics like mescaline and 2C compounds (e.g. 2CB). 

Phenethylamines stimulate the release of the neurotransmitters norepinephrine, dopamine, and serotonin. Phenethylamine drugs such as MDMA and mescaline are known to release dopamine to a greater degree than tryptamines (e.g. psilocybin and DMT) and ergolines (e.g. LSD and LSA). For this reason, MDMA (as well as mescaline) tends to be more physically and mentally euphoric than psilocybin, for example. These different classes of drugs are based on differences in basic chemical structure.

MDMA As An Empathogen

This drug is also classed as an empathogen (or entactogen). This is because it reliably increases feelings of empathy, friendliness, and benevolence toward others, as well as feelings of being socially accepted and connected.

The drug is more typically referred to as an empathogen than a psychedelic.

MDMA As A Synthetic Drug

MDMA is a completely synthetic drug. It does not occur in nature like mescaline – another phenethylamine – does. This means that you won’t discover (and therefore be able to extract) the compound in any plant, mushroom, or animal. 

However, safrole (a naturally-occuring compound found in Sassafras root) can be used in the illegal manufacturing of MDMA. There are, nonetheless, many methods available for synthesizing MDMA.

As a synthetic drug, MDMA contrasts with many tryptamines (e.g. psilocybin, DMT, 5-MeO-DMT), which are found in the natural world. It is also distinct from the popular psychedelic LSD. Which is semi-synthetic (it is derived from lysergic acid, which is found on a fungus that grows on rye, but the compound is still produced in a lab through chemical synthesis). 

Is MDMA A Psychedelic?

When considering definitions of ecstasy, one area where researchers and users disagree is with respect to the question, “is MDMA a psychedelic?” 

The term psychedelic means “mind-manifesting”. This might encourage some to class MDMA under this category since it is a substance that can reveal more of the mind to the user. In addition, MDMA can alter someone’s perspective on themselves, events in their life, and other people. Often in a way that is therapeutic.

Psychedelics are also known to produce a range of perceptual effects. And MDMA can do to a certain extent. Especially if the dose is high enough, or if it is combined with other substances, such as cannabis. However, perceptual effects are not considered a classic part of the MDMA experience. Visual effects tend to be mild if they should occur. This is why many don’t consider the drug a psychedelic. 

Moreover, MDMA can elicit intense emotional effects like other psychedelics. But it does not tend to lead to other classic psychedelic effects, such as the mystical experience and ego death. 

Nonetheless, researchers and users may refer to MDMA as a “mild psychedelic”, a label also sometimes given to cannabis. This is because the MDMA experience may be like a psychedelic experience in some ways but not others. Or because psychedelic effects can occur but they do so in a weaker way or less reliably than with classic psychedelics like LSD. In addition, some researchers refer to MDMA as a “non-classical psychedelic”, a term used to describe ketamine as well.

A Popular Recreational Drug

As already mentioned, MDMA is a popular recreational drug. It more reliably produces a positive emotional experience compared to classic psychedelics.

When bought for recreational purposes (from a dealer or the dark web), the drug will come either in the form of MDMA powder or crystals (known as Molly) or as pills (known as ecstasy). In the latter case, other drugs may be added, such as amphetamine (“speed”) or caffeine. Which leads to a more stimulating experience. 

It is also possible, however, for harmful adulterants to be added to the pills. While some pills may contain no MDMA whatsoever but dangerous substances like PMA and PMMA. This is why using an MDMA test kit is a crucial harm reduction strategy. This simple test can tell you whether the drug you have is, in fact, legitimate MDMA and whether the product contains other substances you don’t want to ingest.

While MDMA crystals are known as “pure MDMA”, the product may also contain fillers or other drugs. You should test crystalline MDMA as well, then, and not just assume it is 100% pure.

Provided someone does have (and then take) real MDMA, he or she can typically expect a euphoric experience. When taking MDMA with others, it is common to experience greater emotional openness and closeness. Since the drug also increases energy and wakefulness, and enhances one’s appreciation for music, it’s no wonder its use exploded in the rave scene in the late 80s and 90s. It remains a popular drug of choice today for the same reasons. Many users, though, also take MDMA at parties or at home with friends.

RELATED: How Long Does MDMA Stay in Your System? Here’s a Complete Overview

A Therapeutic Agent

Because MDMA can increase empathy, emotional honesty, trust, and intimacy – while reducing fear in the face of traumatic memories – it has become a promising drug to use in the alleviation of psychological distress. 

MDMA has been most studied as a treatment for post-traumatic stress disorder (PTSD). And will first be legalized for this purpose. However, the compound may also be helpful in treating a range of other issues. Including, but not limited to, relationship problems, alcoholism, and eating disorders. 

MDMA is, therefore, no longer thought of simply as a recreational drug that will make you dance for hours on end and become best friends with complete strangers. Research supported by the Multidisciplinary Association for Psychedelic Studies has helped to illuminate the unique benefits of MDMA as a tool for psychotherapy.

MDMA Dosage And Microdosing MDMA

If you want to take MDMA safely, you need to know what the different dosages are for this substance. It is crucial to be aware of these ranges, as fatal reactions are possible when taking too high a dose. This can occur due to overexertion, dehydration, hyperthermia, or – on rare occasions – overdose. 

Unfortunately, because MDMA exists unregulated in a black market, there has been a trend of dealers selling pills containing unusually high amounts of MDMA. Pills have been seized containing over 400 mg of the compound, which is five times the usual dose. If someone is not aware of this and takes the whole pill, serious harm could result.

Some people may also try microdosing MDMA (taking tiny amounts of classic and non-classic psychedelics). But even though smaller doses are involved, this doesn’t mean that regularly taking MDMA this way is without its risks. These are worth exploring as well.

MDMA Dosages

Let’s now take a look at the dosages for pure MDMA HCl (the most common crystalline form), which you would take orally. These MDMA dosages reflect the intensity of experience you can expect, although these are not hard and fast rules. After all, people may have differing levels of sensitivity to the drug.

• Threshold: 30 mg
• Light: 40-75 mg
• Common: 60-150 mg
• Strong: 150-200 mg
• Heavy: 200+ mg

It is common for people to redose. A common practice is to take a full recreational dose (e.g. 100 mg) and then take half that amount later in the night to extend the experience. It is not unheard of for people to take 250+ mg of MDMA over the course of a night.

In clinical trials investigating the effects of MDMA therapy, participants will take 80 mg or 120 mg of MDMA. And then followed 1.5 to 2 hours later by an optional supplemental half-dose (40 mg or 60 mg). The highest dose of MDMA someone would take in such a trial, then, would be 180 mg. 

Researchers have concluded that these doses are safe. With some noting the treatment is safer (and more effective) than commonly prescribed antidepressants.

Microdosing MDMA

When people microdose (that is, take tiny, sub-perceptual doses of psychedelics), they will usually opt for psilocybin mushrooms or LSD. Other people, however, may use drugs like mescaline, DMT, or cannabis. Microdosing MDMA is an even less common practice, but it exists. 

But is microdosing MDMA to deal with mental health issues both safe and effective? 

A Lack Of Research On Microdosing MDMA

We have studies looking at the effects of microdosing LSD and psilocybin mushrooms but none when it comes to MDMA. Microdoses of MDMA are doses so small that you don’t have the classic MDMA experience (strong feelings of euphoria, empathy, and love). Or physical effects like bruxism (teeth grinding, jaw clenching) and sweating.

There are multiple studies on the effects of low doses of MDMA: 50 mg. In a later study, researchers have also given participants 40 mg of MDMA. Nevertheless, these doses are not quite low enough to be considered microdoses. If a microdose is a tenth to a twentieth of the normal recreational dose of a drug, then a microdose of MDMA would be roughly 5-10 mg. 40-50 mg is high enough to induce noticeable classic MDMA effects.

Researchers have not (yet) studied the subjective effects, safety, or long-term effects of regularly taking microdoses of MDMA.

Research On The Safety Of Macrodosing MDMA

While there is a dearth of research on microdosing MDMA, we have plenty of evidence on larger doses of MDMA. 

The first randomized controlled study on MDMA as an adjunct to psychotherapy found that the compound is safe and effective for patients with treatment-resistant PTSD. Further research has found that MDMA-assisted psychotherapy involving doses of 40 mg, 100 mg, and 125 mg is safe.

But we shouldn’t necessarily take this as a sign that microdosing MDMA is equally safe or without risks. These clinical trials – and MDMA therapy more generally – are different from microdosing in some crucial ways. 

Firstly, participants in these trials often have only two sessions with MDMA. When microdosing MDMA, in contrast, people will typically take MDMA two to three times a week, potentially for months at a time. We simply don’t know how this regimen impacts people’s physical health, mental well-being, or cognitive function in the long run.

Is MDMA Neurotoxic?

When it comes to the question of MDMA being neurotoxic (damaging to the brain), the evidence is mixed. We have some research showing that MDMA can damage serotonin receptors in the brain. (These receptors play an important role in functions such as cognition, learning, memory, mood, and sleep.) 

This effect on serotonin receptors has been implicated in certain negative long-term effects observed in regular MDMA users. And includes worsened mental health and cognitive function.

However, you should be aware that many studies on the neurotoxic effects of MDMA involve mice, not humans. Moreover, studies finding these effects often look at people who have heavy use patterns.

In fact, there is some research suggesting that repeated low doses of MDMA can provide neuroprotection against a subsequent neurotoxic dose of MDMA.

Factors believed to contribute to the neurotoxicity of MDMA include taking high doses, taking high doses frequently, and taking MDMA in a hot environment. 

You might think that microdosing MDMA avoids these issues since it involves taking tiny doses and typically not in a way that could lead to overheating (i.e. in a poorly ventilated club, dancing for hours on end). But this conclusion is premature. We don’t have research showing that repeated tiny doses of MDMA are definitively not neurotoxic. 

“We cannot exclude that MDMA even in low doses is neurotoxic to the brain.”

Maartje de Win, MD, PhD

Now, it’s possible that microdoses (since they are much smaller than low doses) pose a smaller risk. But we need rigorous research to actually establish this.

Due to concerns about possible neurotoxicity, MDMA is not the go-to choice as a drug for microdosing. Both psilocybin and LSD have better safety profiles than MDMA, which is why users feel more comfortable microdosing with them. Many people might microdose MDMA without reporting any noticeable issues. But this doesn’t mean very low doses of MDMA entail no risks.

Can Microdosing MDMA Improve Your Mental Health?

Several studies indicate that MDMA therapy is highly effective in the treatment of PTSD. This form of treatment may also be helpful for people struggling with a range of other conditions and issues. Which we will explore in greater depth later on. 

Based on the promising results of clinical trials, people might try microdosing MDMA as a way to alleviate conditions like depression, generalized anxiety, or social anxiety. Just as people report these benefits after microdosing psilocybin mushrooms or LSD, some users may find similar results with microdoses of MDMA.

Nevertheless, the mental health benefits of macrodoses of MDMA do not necessarily mean that microdoses of MDMA will lead to similar, significant, or even minimal improvements in mental health. 

If you are hoping to improve your mental health and personal relationships with MDMA, then the evidence so far suggests that two or three moderate doses of the drug, taken in a therapeutic setting, will lead to significant and sustained improvements. It is not clear that microdosing MDMA – or even microdosing in general – can offer these sorts of long-term benefits.

MDMA Abuse And Tolerance

MDMA may be perceived as generally safe by many. But it is still a substance that has the potential for abuse. This same risk of abuse does not really apply to the classic psychedelics that people commonly microdose, such as psilocybin mushrooms or LSD. These psychedelics have a low potential for abuse.

Taking MDMA causes a surge of dopamine. Which is a reward chemical that motivates you to repeat the same action that caused that surge. For certain individuals, taking drugs or engaging in other behaviors that have this effect may turn into an addiction. 

Classic psychedelics do not affect dopamine in the same way. A phenethylamine psychedelic like mescaline, which increases levels of dopamine to a greater degree than other psychedelics, has “probably a modest influence” on dopaminergic activity, as a paper in Current Molecular Pharmacology puts it. The researchers behind this paper add, “In accordance, there is no evidence to support addiction and dependence to mescaline.”

It may be argued that microdosing MDMA, in contrast to recreational doses, involves doses so low that you won’t get the kind of surge in dopamine that could lead to abuse or addiction. However, taking MDMA routinely over time tends to increase tolerance. This means you’ll require a higher dosage to achieve the desired effect. 

There is a potential risk, then, that microdosing might turn into MDMA abuse. For example, if you microdose MDMA and experience benefits like reduced anxiety and increased social confidence and positive mood, you might take higher doses to achieve these effects when your tolerance increases. Taking these higher doses frequently may then increase certain risks.

Harm Reduction Tips for Microdosing MDMA

Based on the available information, we would not recommend microdosing MDMA. There are just so many unknowns still. While we still don’t know whether microdosing classic psychedelics is safe (concerns have been raised about the heart risks), we have more reason to think that opting for microdoses of psilocybin over MDMA would be the wiser decision.

Nonetheless, if you plan on microdosing MDMA, or are doing so currently, it’s vital to follow some essential harm reduction practices:

• Test your batch: If you buy MDMA, you may end up with a different and more harmful drug, or MDMA adulterated with other harmful substances. This is why you should invest in an MDMA testing kit, offered by providers such as DanceSafe.
• Stick to very low doses: If you try a twentieth of the normal dose of MDMA and feel a benefit, then you don’t need to dose any higher. Research generally finds that low doses of MDMA are safe, so microdoses could be even safer. Nonetheless, as we have seen, no studies have yet demonstrated this to be the case.
• Regulate your dosing: If you experience no effects from MDMA after a two-day break between dosing days (typical with microdosing regimens), then your tolerance may have increased. In this case, you shouldn’t be microdosing that frequently.
• Be mindful of the effects: If you notice any negative effects on your mental health from microdosing MDMA, then you should stop.

How Long Does MDMA Stay In Your System?

When you take a dose of MDMA, how long does it stay in your system? Traces of the drug will typically stay in a person’s system for several days. Although the exact length of time depends on several factors, including:

• The amount they took
• The time of their last dose
• Their overall health
• The rate of their metabolism (influenced by factors such as age, weight, liver health, and kidney health)
• Whether or not they are taking any medications
• When they last ate a meal
• The purity of the drug

A 2011 study found that MDMA is detectable for 24-72 hours. But it can remain in trace amounts for up to five days or more. However, this period of detectability can vary depending on the drug test used:

• Blood test: 1-2 days
• Saliva test: 1-2 days
• Urine test: 2-4 days
• Hair test: Up to 3 months

MDMA Effects

MDMA has a range of effects, spanning the experience itself, after effects, and possible long-term effects.

The MDMA Experience

MDMA produces an array of physical, emotional, cognitive, visual, and even transpersonal effects.

Physical Effects

• Stimulation
• Physical euphoria
• Tactile enhancement
• Increased blood pressure
• Increased heart rate
• Increase bodily temperature
• Muscle contractions
• Increased sweating
• Dry mouth
• Difficulty urinating
• Nystagmus (involuntary, rapid eye movement, causing vibrating vision)
• Nausea during the come up phase of the experience
• Appetite suppression
• Excessive yawning
• Pupil dilation
• Temporary erectile dysfunction
• Bruxism (teeth grinding, known as “gurning”)

Emotional Effects

MDMA can increase feelings of:

• Euphoria
• Empathy
• Trust
• Intimacy
• Affection
• Friendliness
• Self-compassion
• Benevolence toward others
• Connection
• Emotional warmth
• Sociability
• Relaxation

The drug can also decrease feelings of:

• Anxiety
• Fear
• Negative mood

Cognitive Effects

• Amnesia (especially in higher doses)
• Disinhibition
• Increased music appreciation
• Increased sense of humor
• Wakefulness
• Confusion (typically when taking higher doses)

Transpersonal Effects

MDMA does not tend to cause transpersonal or mystical effects in the way that classic psychedelics can. However, experiences of unity and interconnectedness can still occur. This component may manifest within large crowds at raves and music events in the form of “becoming one with the crowd”, with music intensifying this effect.

The MDMA Comedown

MDMA can produce some after effects, which is known as the comedown phase of the experience. As the saying goes, “what goes up, must come down.”

The MDMA comedown is characterized by a range of undesirable physical, psychological, and cognitive effects. 

Physical symptoms may include:

• Nausea
• Headaches
• Exhaustion
• Appetite suppression
• Brain zaps (these are more likely to occur if you take a high dose)

Psychological symptoms may include:

• Anxiety
• Depressed mood
• Irritability
• Wanting to withdraw socially

Meanwhile, negative cognitive effects can include impaired concentration and memory. Everyday tasks requiring focus such as reading or doing work can feel especially difficult.

MDMA after effects can occur the day after taking the drug. Although many people find that the hangover skips a day (which is known as the Tuesday blues, or “suicide Tuesdays”). 

There is some debate as to whether the so-called MDMA comedown is intrinsic to the drug itself. Or whether other factors are causing it. According to a 2021 study published in the Journal of Psychopharmacology, no declines in mood or cognition occur when participants take MDMA in a clinical context.

It has been suggested that the comedown may be due to various aspects of recreational MDMA use: high doses, lack of sleep, dehydration, drug adulteration, and combining MDMA with drinking and other drugs. Nonetheless, users may still find they experience some negative after effects even when these factors are absent.

How To Minimize The MDMA Comedown

If you’re not one of those lucky people who doesn’t struggle much the days after taking MDMA, you’ll be glad to know you can at least minimize the negative effects. Make sure to:

• Get proper rest. You can increase your chances of getting enough sleep by avoiding taking MDMA too late and eating foods and drinking beverages that can help you sleep.
• Watch your diet. An MDMA crash is associated with low mood. So make sure you eat mood-boosting foods the day after. You also want to avoid foods that can make you feel tired, lethargic, and low. These would include highly processed foods and refined carbohydrates.
• Stay hydrated. Dehydration can contribute to MDMA’s negative after effects. You want to make sure you drink enough water both during the night and the day after. You should be careful not to drink too much water (known as hyponatremia) while on MDMA. As this causes the sodium in the blood to dilute to critically low levels, which can be fatal in some cases.

MDMA users may try using supplements (e.g. 5-HTP, magnesium, vitamin C) to mitigate the dreaded MDMA crash. However, there is no specific evidence that these supplements do, in fact, ease the comedown. 

Short-Term Risks

Using MDMA can involve some short-term risks, depending on how you use the drug. These include:

• Dehydration
• Hyperthermia (if taking MDMA in a hot environment)
• Hyponatremia (drinking too much water)
• Serotonin syndrome (this is when high levels of serotonin accumulate in the body. This can occur if you mix MDMA with other drugs that boost serotonin levels)

Is MDMA Addictive?

There is no simple answer to the question “is MDMA addictive?”

The substance is not inherently addictive, but it is certainly possible to develop an addiction to it, as with other stimulants. 

The risk of becoming addicted to MDMA is certainly not as high compared to other stimulants like cocaine or methamphetamine. But it is still a risk that the classic psychedelics don’t carry. Experiments have shown that animals will self-administer MDMA (an important indicator of a drug’s addictive potential). Although the degree of self-administration is less than with other drugs, such as cocaine, for instance. 

MDMA can produce a surge in dopamine, as well as an alleviation of emotional distress and heightened positive feelings. So it is understandable that some individuals will want to frequently repeat this experience. This could turn into a form of self-medication. Psychedelics can also decrease negative emotions and increase positive ones. But the experience is often so profound, challenging, and mentally tiring that it is less likely to be repeated often. 

As already mentioned in the discussion on microdosing, you can develop a tolerance to MDMA through regular dosing, requiring higher doses to achieve the same effect. Taking high doses frequently has a greater chance of causing harm. And if someone feels compelled to continue taking the drug in spite of this harm, we would call this an addiction.

Data from both human and animal studies suggest that regular MDMA use produces adaptations in the serotonin and dopamine systems that are associated with substance use disorder, such as increased impulsivity. 

The prevalence of MDMA addiction among users is uncertain, based on existing evidence. Nevertheless, some people who use MDMA report symptoms of addiction. Which includes continued use despite negative physical or psychological consequences, tolerance, withdrawal, and craving.

Possible Long-Term Effects Of MDMA

We saw in the section on microdosing MDMA that there is conflicting evidence regarding the negative long-term effects of the drug. There are studies showing that heavy use patterns have been tied to persisting issues related to mental health and cognition. In particular, heavy or chronic users may be at a heightened risk of developing depression and deficits in memory and concentration. Researchers have linked these effects to MDMA-induced neurotoxicity. 

On the other hand, taking MDMA in a clinical context (one or two times, at a moderate dose) appears to be safe. Furthermore, if you opt for MDMA therapy as a way to alleviate chronic emotional distress, then you may experience long-term benefits from the experience. Indeed, MDMA-assisted psychotherapy can provide sustained improvements to mental health for people living with PTSD.

MDMA Therapy

Let’s now delve into the many aspects of MDMA-assisted psychotherapy. This form of treatment is showing great promise for those struggling with severe, chronic, hard-to-treat, and treatment-resistant PTSD, as well as a host of other mental health conditions and life problems. 

But while research and media reporting on MDMA therapy has generally been positive and encouraging, it’s important to highlight the risks of this treatment as well. Of particular concern are therapists crossing boundaries with patients and engaging in sexual abuse.

The Benefits Of MDMA

MDMA-assisted psychotherapy holds the potential to effectively treat a number of mental health conditions. Let’s explore each of these in turn, highlighting what the research tells us about the effectiveness of this treatment. 

PTSD And MDMA

PTSD develops after experiencing or witnessing major trauma. These traumas include a life-threatening event, a natural disaster, a car accident, or sexual assault. The severity and duration of the trauma, previous traumatic exposure, age, gender, and even genetics can all play a role in developing PTSD. 

If you are repeatedly exposed to traumatic events, such as violence, neglect, or abuse, this can develop into complex PTSD. 

Whatever form the condition takes, it is known to be hard to treat and can often be treatment-resistant, an issue that many war veterans face.

People who suffer from PTSD report symptoms such as:

• Depression
• Anxiety
• Feeling unsafe
• Sleep problems
• Disturbing dreams and nightmares
• Upsetting memories and triggered flashbacks
• Fear of social events
• Random feelings of anger

Conventional treatments for PTSD include trauma-focused psychotherapies, such as prolonged exposure (PE), cognitive processing therapy (CPT), and eye movement desensitization and reprocessing (EMDR). Medication can also be helpful, including SSRI and SNRI antidepressants.

MDMA-assisted psychotherapy works differently from these options. The MDMA experience helps to decrease defensiveness and anxiety while increasing relaxation and trust. All of which drastically enhances the efficacy of psychotherapy itself. 

In 2017, based on the results of clinical trials, the Food and Drug Administration (FDA) granted Breakthrough Therapy Designation for MDMA-assisted therapy for PTSD. A breakthrough therapy is a drug that alone or in combination with one or more other drugs can treat a serious or life-threatening condition. With evidence suggesting the drug may demonstrate substantial improvement over existing treatments.

In 2021, the results from a phase 3 clinical trial on the treatment were published. A phase 3 trial is when a new treatment (MDMA therapy in this case) is compared against the current standard treatment in terms of safety and efficacy. The researchers behind this study concluded:

“These data indicate that, compared with manualized therapy with inactive placebo, MDMA-assisted therapy is highly efficacious in individuals with severe PTSD, and treatment is safe and well-tolerated, even in those with comorbidities. We conclude that MDMA-assisted therapy represents a potential breakthrough treatment that merits expedited clinical evaluation.”

MDMA therapy for PTSD is on track for FDA approval in 2023. When this occurs, patients with the condition (not just those enrolled in clinical trials) will be able to legally access the treatment.

Social Anxiety And PTSD

Social anxiety is a condition in which the symptoms of anxiety manifest in the context of social situations. This can include anxiety before, during, and after social events. People with this condition can experience intense and debilitating feelings of worry, nervousness, and tension when in crowds.

Since MDMA helps to reduce anxiety and fear, it would make sense that the drug would alleviate much of the distress that people with social anxiety experience. And indeed, this is what studies have indicated. A 2018 Multidisciplinary Association for Psychedelic Studies-funded study found that MDMA therapy helped to reduce social anxiety symptoms (social fear and avoidance) in adults with autism.

Researchers have proposed that MDMA-assisted psychotherapy can alleviate social anxiety more generally (not just in those with autism) by:

• Enhancing motivation to connect with others
• Altering perceptions of social reward
• Enhancing experiences of affiliation and safety when interacting with others
• Reducing feelings of shame
• Improving social skills, which can elicit positive interpersonal responses from others, creating a greater sense of belonging, acceptance, and social efficacy

Alcoholism And MDMA

Alcoholism or alcohol addiction is a condition in which a person struggles to give up a heavy drinking habit, despite the negative repercussions. If someone with alcoholism stops using, intense cravings, as well as physical and psychological withdrawal symptoms, typically follow. This drinking problem can cause serious issues at home, at work, with one’s finances, and in one’s relationships. It often leads to declining physical and mental health as well.

In 2017, a study led by British psychiatrist Ben Sessa became the very first clinical study of MDMA-assisted psychotherapy for alcohol addiction. Participants took the drug in two supervised sessions with a psychiatrist present. These are people who had tried to give up drinking before but had relapsed, despite using other treatments. The full results were published in 2021, with the authors stating:

“MDMA treatment was well tolerated by all participants. No unexpected adverse events were observed. Psychosocial functioning improved across the cohort. Regarding alcohol use, at nine months post detox, the average units of alcohol consumption by participants was 18.7 units per week compared to 130.6 units per week before the detox.”

MDMA-Assisted Couples Therapy

When couples experience a rough patch in their relationship and it seems no progress can be made. And it is common for both people to attend couples therapy sessions. During these sessions with a psychotherapist or counselor, common issues can be addressed, including:

• Differences of opinion
• Negative life events that both are struggling with
• Big life changes affecting the relationship
• Sex and intimacy issues
• Difficulties with communication

Conventional couples therapy can sometimes help save strained or fraying relationships and marriages. However, this option doesn’t work for many couples, with partners struggling to connect with each other, work things out, and maintain the affection and intimacy they previously felt.

MDMA-assisted couples therapy is one option for couples struggling to mend their relationship.

It’s no wonder, then, that MDMA has become famed as the “love drug”.

These effects of MDMA can be extremely useful in the context of couples therapy. For instance, a 2018 study found that MDMA therapy was effective at reducing PTSD symptoms in the majority of couples while also improving relationship satisfaction. 

Katie Anderson, a lecturer in psychology at Middlesex University in London, has also researched couples who take MDMA together. She’s found that these couples rate their MDMA experiences as significantly important and meaningful. Which lead to an enduring increase in closeness. Many other couples have found success in using the drug.

A 2020 study published in the European Journal of Psychotraumatology looked at the safety and feasibility of incorporating two MDMA sessions into couples therapy. The trial recruited six couples, in which one member had a pre-existing PTSD diagnosis. The MDMA experiences were combined with a previously established PTSD therapeutic regime known as cognitive-behavioral conjoint therapy (CBCT). CBCT is a couple-based treatment designed to both improve individual PTSD symptoms and enhance relationship functioning. Candice Monson, one of the authors of the study, remarked:

“PTSD in one partner can cause distress in the relationship and barriers to understanding each other. It seems that MDMA-assisted psychotherapy can engender empathy and connection. And opens a pathway to remembering why came together in the first place and a desire to understand the other.”

She added:

“The literature that inspired this study suggests that MDMA may allow people to talk about painful experiences without experiencing the pain again. The therapist can guide couples to talk about very difficult things that they’ve either experienced themselves or experienced together—against the other or with the other—with a greater sense of understanding, openness, connection, and empathy.”

The study found that the addition of MDMA to the couples therapy protocol resulted in benefits that were “on par with, or greater than, those achieved with CBCT alone.” These effects were improvements in both individual PTSD symptoms and relationship outcomes, which were most significant at the six-month follow-up, suggesting that the MDMA therapy offers strong long-term benefits.

It is important to note that the study was uncontrolled. So any efficacy comparisons to CBCT alone can only be shown by examining prior CBCT studies. Nonetheless, this study did establish that the addition of MDMA to the pre-existing therapeutic protocol was safe and did not negatively interfere with other PTSD treatments.

MDMA and Eating Disorders

Eating disorders refer to a range of psychological conditions that cause unhealthy eating habits to develop. Various eating disorders include:

• Anorexia nervosa: feeling the need to keep your weight as low as possible
• Bulimia: a vicious cycle of binging (eating large amounts of food with a loss of control over the eating) and purging (vomiting, so as to get rid of the extra calories)
• Binge eating disorder: feeling compelled to overeat on a regular basis

Many eating disorders are associated with a variety of physical and mental health conditions, including anxiety and depression, as well as lower health-related quality of life. Remission rates for eating disorders vary widely from 27-85%, with many existing treatments being relatively ineffective for many patients. 

Anorexia is one of the hardest mental health conditions to treat and it’s also the deadliest (people with anorexia are 18 times more likely to die by suicide, for example). This is why new and effective treatments are desperately needed.

There are some studies showing that MDMA can help those struggling with an eating disorder. A 2022 study found that MDMA therapy significantly reduces eating disorder symptoms in adults with severe PTSD.

A Multidisciplinary Association for Psychedelic Studies-sponsored phase 2 clinical trial is also underway, which is looking at the safety and feasibility of MDMA-assisted psychotherapy in the treatment of 18 participants with eating disorders. 12 of the participants have anorexia nervosa restricting-type, while six have binge eating disorder. 

It is widely accepted that problems with emotion processing are central to the development and maintenance of eating disorder symptoms. MDMA may be particularly helpful in improving emotional dysregulation and poor self-esteem, issues that underlie eating disorders. The drug may also create a desirable psychological state that will enhance the therapeutic process, as seen with trial participants who have severe, chronic, and treatment-resistant PTSD.

MDA Vs. MDMA (Sally Vs. Molly)

Both MDA and MDMA belong to the phenethylamine class of drugs. The chemist Alexander Shulgin, known as the “godfather of ecstasy”, first started to synthesize molecules like MDMA after trying mescaline. He described the process of synthesizing various phenethylamine compounds (and his experiences taking them) in his book PiKHAL (1990), which stands for Phenethylamines I Have Known and Loved. 

As phenethylamines, MDA and MDMA are similar in chemical structure. Like other phenethylamines, they also have stimulating effects. Beyond the basic phenethylamine backbone, the compounds have a similar chemical structure in other ways, which translates into other similar effects, such as euphoria.

However, there are many important differences between MDA and MDMA, which you should be aware of.

MDA And MDMA Are Known By Different Names

MDMA is known by different names, which often vary depending on the country the user is from. It is also called ecstasy, Molly, Mandy, E, X, pingers, and the love drug. 

Some people also call MDA the “love drug”, although its more common names are Sally, Sass, and Sassafras. These names refer to the fact that MDA, like MDMA, is derived from the oil of the sassafras plant in the illicit manufacturing of the drug.

Differences In Chemical Structure

MDA is 3,4-Methylenedioxyamphetamine while MDMA is 3,4-Methyl​enedioxy​methamphetamine. MDA, then, lacks the methyl group that MDMA has, which is attached to the nitrogen atom. 

In a chapter in Jullie Holland’s book Ecstasy: The Complete Guide (2001), chemist David Nichols writes:

“The methyl group does not profoundly change the chemical properties or the base strength of MDMA when compared with MDA. It does have consequences in terms of the biological effects, however. First, adding a methyl group to the nitrogen atom makes the molecule more lipid (fat) soluble. This means that because the brain is made largely of lipids, MDMA has a greater solubility in brain tissue. In general, drugs that have greater solubility in lipids and an action in the brain also have a faster onset of action but a shorter duration of action. Based only on this observation, one could predict that MDMA should produce its effects faster than MDA but have a shorter action than MDA. This is in fact what is observed.”

This chemical difference between the two drugs does not result in only this variation in effects. Nichols adds that the MDMA molecule is, “too large to fit comfortably into the brain serotonin 5-HT2A receptor that is responsible for LSD-like actions. That receptor is only minimally activated by MDMA; hence MDMA lacks significant LSD-like effects.”

MDA And MDMA Have Different Subjective Effects

Both MDA and MDMA are empathogens (or entactogens). So they can both induce feelings of empathy, emotional openness, close interpersonal connection, and affection. Yet they are not empathogenic to the same degree. Moreover, to reiterate Nichols’ point, MDMA is not as psychedelic as MDA.

Let’s examine these differences in subjective effects in greater detail.

MDMA Is More Empathogenic Than MDA

Many people find that MDMA offers a more empathogenic experience than MDA. This means when you take MDMA, you’re more likely to experience a “loved up” feeling, feelings of sociability and talkativeness, heartfelt conversations with others, and greater empathy toward others. 

MDA Is More Psychedelic Than MDMA

Due to the fact that MDA more easily binds to 5-HT2A receptors, this drug tends to result in more psychedelic effects compared to MDMA. Most noticeably, MDA is more likely to produce visual effects, including:

• Visual acuity enhancement 
• Color enhancement
• Tracers
• After images
• Seeing geometric patterns
• Visual hallucinations (in high to heavy doses)

Chemist and pharmacologist Gordon Alles described the visual effects of MDA when he experimented with the drug in 1930:

“Forty-five minutes after the second dosage, an abundance of curling gray smoke rings was readily observed in the environment whenever a relaxed approach to subjective observation was used. Perceptually, these had complete reality. It seemed quite unnecessary to test their properties because it was at the same time surely known and fully appreciated that the source of the visual phenomena could not be external to the body. Concentration of attention on the details of the gray curling forms, by trying to note how they would be affected by passing a finger through their apparent field, caused them to melt away with the fixing of attention.”

MDMA can produce visual effects, but you would need a higher dose to experience them. Many users also find that MDMA becomes noticeably psychedelic if combined with cannabis.

MDA Is More Stimulating Than MDMA

Many people also find that MDA is more stimulating than MDMA, providing them with greater energy levels. You may feel perfectly happy sitting or lying down on MDMA, talking with others, and listening to music. But MDA may make you want to move around more.

The common perception of ecstasy is that it gives users the energy to dance non-stop, although this may be because ecstasy pills are often not pure MDMA; they can also contain amphetamine (speed), which has strong stimulating effects.

The Effects Of MDA Last Longer Than Those of MDMA

As Nichols underscored, the effects of MDA last longer than those of MDMA. An MDMA experience can last 3-6 hours, whereas if you take MDA, the effects can last 5-8 hours. For this reason, if you take MDA, you should be prepared for a slightly longer experience. The longer-lasting effects of MDA may also mean you won’t feel the need to redose, which many users do with MDMA.

Therapeutic Applications

We have seen how MDMA can be useful in treating a variety of mental health conditions, particularly PTSD. In contrast, MDA is not being scientifically investigated as a tool for psychotherapy. Researchers in the 1960s and 1970s did investigate this potential of MDA, but MDA-assisted psychotherapy has not been studied and promoted like MDMA therapy has in the past decade (known as the “psychedelic renaissance”). 

This is not to say that MDA cannot also induce therapeutic and meaningful experiences. Many anecdotal reports suggest that it can.

Differences in Popularity

MDA is available in the illicit drug market, but not to the same extent as MDMA. The latter also has a rich cultural history (it’s been an essential part of rave culture), which does not apply to the former. 

Differences in popularity make sense if we compare the subjective effects of the drugs. MDMA is shorter-lasting, less psychedelic, and produces stronger empathogenic effects.