Ketamine and MDMA are different in many ways, but both may have uses in treating severe depression and other mental health conditions.

The side-by-side chemical structures of ketamine and MDMA. Share on Pinterest
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Many psychedelic drugs exist — of which ketamine and MDMA (also known as Ecstasy or Molly) are two of the most well-known. Both drugs have been around for decades, with MDMA developed in 1912 and ketamine slightly more recently, in 1956.

Ketamine and MDMA are often used recreationally due to their stimulant effects. However, scientists have also been exploring the potential of these drugs in treating medical concerns like chronic pain, PTSD, and depression.

There are similarities between the two psychedelics — but they also have some notable differences. Let’s take a closer look at how the two compare.

Both ketamine and MDMA affect receptors in the brain, which aid in sending and receiving “messages.”

As such, the drugs “have primarily neurologic effects,” says Dr. Ryan Marino, a medical toxicologist, addiction medicine specialist, emergency physician, and assistant professor at Case Western Reserve University School of Medicine.


Ketamine influences NMDA receptors, which are associated with memory. Although some people take it for its psychedelic effects, the drug was created for a calmer purpose.

“[It] was initially developed as a dissociative anesthetic that is still used in veterinary medicine,” shares Lauren Purington, PhD, associate professor with a focus in neuropharmacology at Albany College of Pharmacy and Health Sciences.

In clinical settings, ketamine is “currently approved for intravenous or intramuscular injection, and in the form of an intranasal spray,” says Marino.

He adds that when used illicitly for recreational purposes, it’s primarily taken orally or by snorting.


MDMA — short for 3,4-Methyl​enedioxy​methamphetamine — impacts two different receptors: serotonin and adrenergic.

Serotonin is linked to mood, while adrenergic is associated with adrenaline and the body’s natural “fight or flight” response.

Chemically, MDMA is “structurally similar to methamphetamine,” reveals Purington. Methamphetamine is a type of stimulant that’s often used illegally and has the potential to be highly addictive.

However, Purington says that while MDMA is often called a psychedelic, it “is better classified as an ‘empathogen’ or ‘entactogen,’ as it increases empathy and feelings of connection with others.”

The drug is typically taken orally in both recreational and medical research settings.

MDMA is primarily a hallucinogen and stimulant, while ketamine is considered an anesthetic that can have stimulant properties. This means some effects of the two drugs differ, and others overlap.

It’s also worth noting that how severe the effects are can vary depending on the dose.

Common potential side effects

anxietyfeeling happy and extroverted
nausea or vomitingincreased senses
increased heart ratehigh blood pressure
confusionincreased body temperature
double visionconfusion
feeling “separate” from your body (dissociation)nausea
hallucinationstingling feelings in the body
feelings of calm dilated pupils
numbness tightening of jaw muscles

How to recognize an emergency

With such a wide range of effects occurring with both drugs, how can you tell when these have progressed to emergency status and indicate an overdose?

“The most obvious indicator of toxicity or overdose from either substance would be significant changes in mental status,” Marino says.

When taking ketamine, this would entail responding to stimuli that aren’t there or not responding at all to external stimuli that are present.

With MDMA, behaviors become more bizarre, and the individual may begin hallucinating. “MDMA overdose can also lead to an extremely stimulated state with agitation and hyperactivity, which is less commonly seen with ketamine,” adds Marino.

Physical reactions can also signal that a person has overdosed on either drug. Some of the main ones include decreased breathing and changes in heart rate or rhythm. Purington notes that seizures can also occur.

If someone overdoses on either drug, call 911 or take them to the emergency room immediately and “ensure their airway remains open,” says Purington. Treatments can vary, she adds, especially if the patient also has other drugs (including alcohol) in their system.

In cases of both MDMA and ketamine fatalities, a large number are linked to multi-drug toxicity.

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Neither ketamine nor MDMA is currently approved by the Food and Drug Administration (FDA) for medical use — aside from a nasal spray form of ketamine (esketamine), which was approved in 2019 for use alongside oral antidepressants in treating treatment-resistant depression.

As a Schedule I controlled substance, MDMA is considered illegal in all settings. Meanwhile, ketamine is legal when taken for medicinal purposes and supervised by a qualified health professional.


Doctors use ketamine to help treat various physical and mental health conditions, including depression and anxiety, bipolar disorder, substance use, and chronic pain. Numerous studies have explored its potential benefits, too.

Research reveals that ketamine may aid in reducing pain, particularly when other “standard” medications (such as nonsteroidal anti-inflammatory drugs) aren’t effective. For instance, it has been shown to lower pain-related symptoms in those with chronic neuropathic pain, fibromyalgia, and arthritis.

Numerous research suggests that ketamine may benefit people with depression, with positive effects on symptoms starting just 40 minutes after administration. Thanks to its antidepressant effects, ketamine has also been noted as effective in significantly reducing symptoms of bipolar disorder — including in treatment-resistant cases.

While more trials are needed, 2018 research suggests that ketamine can aid abstinence and reduce cravings in people with addictions to alcohol, heroin, and cocaine.

Notably, “a use that has received a significant amount of controversy is as a ‘chemical restraint’ to sedate and restrain agitated or violent persons,” adds Marino.


Until the 1980s, “MDMA was previously used to enhance psychotherapy sessions,” reveals Marino. Since then, the drug has not been legally used in clinical settings — but this could be about to change.

In 2017, the FDA granted MDMA “Breakthrough Therapy Designation” (BTD) status in relation to post-traumatic stress disorder (PTSD). BTD status is given to expedite the development of drugs that early clinical research suggests may be significantly beneficial (compared to existing therapies) in treating severe health conditions.

MDMA is currently undergoing a series of phase 3 trials to obtain FDA approval for PTSD treatment, with studies suggesting that MDMA is “highly efficacious” in treating cases of severe PTSD.

The Multidisciplinary Association for Psychedelic Studies (MAPS), which is sponsoring the current trials, believes the drug will become FDA-approved for PTSD treatment in late 2023 or early 2024.

Additional studies have also explored the potential benefits of MDMA on other health concerns.

For example, a 2018 study of adults with autism found that taking the drug aided in reducing symptoms of social anxiety. Meanwhile, the drug also reduced anxiety symptoms in a small 2020 trial of participants experiencing life threatening illnesses.

Get involved

If you’re interested in exploring mental health treatments involving ketamine or MDMA, you should first reach out to your doctor or psychologist. They may know about local trials you could take part in.

You can also check out to learn about trials that are currently looking for participants.

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Although ketamine and MDMA are both labeled as psychedelics, their effects can vary from each other. Ketamine leads to more of a dissociative state, whereas MDMA is more of a stimulant.

Neither drug has FDA approval for medical use, and MDMA is a Schedule I controlled substance.

While illegal for recreational use, ketamine is legalized for treating some medical concerns, such as depression, when taken under supervision.

Clinical trials are ongoing for the medicinal use of MDMA, although it’s believed the drug may soon receive approval for treating PTSD.