MDMA and the Brain: Is Ecstasy Neurotoxic?

by Ruthie Poizner

MDMA, ecstasy, molly, E (Sharifimonfared & Hammersley, 2020) – no matter what it’s called, this popular club drug has found its way into our collective vocabulary. Ecstasy, which has been a mainstay on the party scene since the early 1990s, is now one of the most commonly used illegal drugs. In fact, over 18 million Americans have reported using MDMA at least once in their lifetime (SAMHSA, 2017). Since this drug has become so widespread, it is important from an individual and public health standpoint to understand both the short- and long-term effects of its use. This article will explore these issues, as well as providing resources for safer ecstasy consumption.

How Does MDMA Affect the Brain and Body?

People mostly use ecstasy because it can produce enjoyable short-term effects. MDMA stimulates the release of neurotransmitters like dopamine and serotonin, which can produce euphoric feelings such as heightening of the five senses and increased empathy (Mustafa et al., 2018). On the flip side, however, it can also cause insomnia, appetite loss, restlessness, jaw clenching, and in rare cases, overdose and death (Curran, 2000).

Ecstasy is generally not considered physically addictive, meaning that although people may crave the high, their bodies will not become dependent on the substance and experience painful withdrawals when they stop using it. For this reason, people rarely require psychological treatment for their use (Sharifimonfared & Hammersley, 2020). But does this mean we don’t have to worry about its long-term effects?

Although researchers have been studying ecstasy toxicity for years, some of the evidence is mixed (Mustafa et al., 2018). This issue is a bit confusing, but it may be more relevant now than ever: not only is MDMA a drug of choice for millions, it is also a potential medicine of the future. While notorious for its recreational use, MDMA was actually first studied as a treatment for psychological disorders (Müller et al., 2019). In recent years, researchers have been taking a second look at this possibility, and are specifically interested in whether it could be an effective treatment for post traumatic stress disorder (PTSD) (Mustafa et al., 2018). This makes it even more important to understand how this drug affects the brain and body. Though MDMA neurotoxicity studies aren’t perfect, they can still provide valuable insight into the possible risks of this drug and how they can be reduced. With that in mind, let’s take a look at what the research says and why these findings are so important.

What is Neurotoxicity?

Neurotoxicity describes a given substance’s harmful effects on the brain and the rest of the nervous system. This can include damage to nerves and neurons, which are responsible for communicating signals (messages) in the brain. Neurotoxins can be found in a variety of substances such as heavy metals, pesticides, and drugs. The severity of neurotoxicity depends on the substance and how it is consumed. There is a significant range in how these neurotoxins affect us, and how much they harm our bodies and functioning (Robertson, 2019).

Is MDMA Neurotoxic?

The short answer is yes, most research suggests that this drug is neurotoxic. MDMA is thought to cause damage to brain cells by disrupting the flow of neurotransmitters, the messengers that allow cells to communicate with one another. It also causes an overflow of free radicals: molecules with an unstable structure that eat away at cells. These molecules can kill brain cells by limiting the cell’s ability to produce energy. Although our bodies are built to flush out free radicals, ecstasy can overload the detoxification process, which puts a strain on the system (Mustafa et al., 2018). Free radicals are possibly linked to the development and/or worsening of a variety of diseases, such as cancer and Alzheimer’s (Halliwell, 2001).

Examining the Evidence

Most of the evidence on MDMA neurotoxicity comes from either animal studies or correlational research, which looks at whether there is an association between two variables. In animal studies, MDMA has consistently shown to be toxic to serotonin structures. This has been observed in every animal tested, and while some animals recover normal serotonin function over time, many suffer lasting effects (Curran, 2000). Additionally, correlational research has found associations between MDMA use and neurotoxicity in humans. This means that MDMA use can predict changes to the brain.

In most correlational studies, researchers use something called SERT (serotonin transporter) density to measure MDMA neurotoxicity. Serotonin is a neurotransmitter that plays a key role in mood regulation, and is often described as producing feelings of wellness and happiness. Studies have shown that ecstasy use can reduce SERT in many parts of the brain, such as the hippocampus and temporal lobe (both of which are associated with memory function) (Müller et al, 2019). There is also evidence that MDMA users have less 5-HT, a receptor that is responsible for binding to serotonin and receiving its signals. This decrease seems to be linked with the amount of MDMA use: in other words, the more MDMA a person has done, the fewer 5-HT receptors they seem to have (Curran, 2000).

What Does this Mean?

If MDMA is technically neurotoxic, does this mean it affects people’s thoughts, behaviour, and daily life? Some research, as described by Mustafa and colleagues (2018), suggests that people who have used ecstasy over long periods of time perform worse on memory tasks (Wunderli et al., 2017). It is also believed that ecstasy can negatively affect the working memory, the system that allows us to pay attention to and manipulate information before we commit it to our long-term memories. In a 2013 study, Potter, Downey, & Stough found that MDMA users performed significantly worse than non-drug users on spatial working memory tasks, which required them to remember visual information. The MDMA group averaged a score of 0.85, while the non-drug group averaged a score of 0.96. The MDMA group also had longer reaction times across tasks, averaging 302.47 milliseconds compared to 286.00 milliseconds in the non-drug group.

Psychological Impact

It is possible that these changes to the brain also have psychological consequences. Even though relatively few people require psychological treatment for their MDMA use, this does not necessarily represent a lack of impact on mental health. In a turn-of-the-millennium study on ecstasy users in the UK, researchers found that 83% reported midweek “low mood”, and 80% reported concentration or memory problems. which are often related to low mood (Curran, 2000). These changes in mood and functioning could be linked to serotonin toxicity, as well as damage to brain regions involved in key tasks such as learning and memory. Interestingly, Potter and colleagues found that the average depression level (as measured by the Beck Depression Inventory) was 13.35 in people who used MDMA, 7 points higher than that of non-drug users (2013). Although this difference was not large enough to be significant, it is still important to note since MDMA users commonly report low mood.

Is the Damage Permanent?

The good news is that the effects of MDMA neurotoxicity might be reversible over time. Researchers have found a link between SERT density and the length of abstinence, a period where the drug is not being used. This means that, without MDMA, serotonin and 5-HT levels may be restored in the brain (Müller et al., 2019), which in turn could possibly lead to improved mood and memory.

What Else Should We Know?

Although these studies share important findings about how MDMA interacts with the brain, there are limits to their design and how well their results can be applied to real life. Let’s explore some of these limitations:

  • Most researchers study heavy or long-term ecstasy use, but are unable to describe the long-term effects of the drug on people who use it occasionally and moderately. It’s currently believed that the more severe neurotoxic effects are linked to binges, which requires taking lots of ecstasy at once (Müller et al., 2019)
  • It’s extremely difficult to determine a cause-and-effect relationship between MDMA and neurotoxicity in the human brain, because there could be a variety of other factors that cause these changes. Human participants have unique and complicated lifestyle factors that can be difficult to control for in experiments. For example, many people who use ecstasy also use other recreational drugs that could be responsible for cell damage
  • The findings from animal studies do not necessarily apply directly to humans, since each animal’s brain functions differently
  • It is impossible to compare dosage between participants, since it’s unlikely they know the exact amount of ecstasy they have taken in their lifetime (Curran, 2000)
  • The drugs used in labs are very different from street drugs. Street ecstasy has developed a reputation for its impurity, since it is often cut with drugs like methamphetamine, cocaine, and bath salts (Curran, 2000). Sometimes it doesn’t contain any MDMA at all! This makes it even harder for people using the drug to get a sense of what they’re taking and how it might affect them in the short- and long-term

What Can I Do with This Information?

Like any recreational drug, there are significant risks to using MDMA. Neurotoxicity studies can help us understand how common and severe these risks are in the long run. Since MDMA may soon become legal as a treatment for PTSD, it is also helpful to learn more about how different types of use have different effects. Therapeutic MDMA would be used differently than recreational ecstasy (for example, doses would be small and given by a psychiatrist or doctor), so it is very unlikely that it would have concerning neurotoxic consequences (Müller et al., 2019).

If you do decide to use ecstasy, researchers Sharifimonfared and Hammersley (2020) have outlined some helpful harm reduction tips:

  • Stay informed about this drug and its effects- it is important that you are making an informed decision, and that you can create harm reduction strategies that best suit you. This can also help you prepare for unwanted side effects
  • Test your drugs- since ecstasy is often mixed with other substances, it’s important to ensure that you know what you’re putting into your body to prevent a bad trip or accidental overdose
  • Drink a healthy amount of water while using ecstasy- sweating will cause you to lose fluid, so it’s important to stay hydrated- but make sure not to overcompensate by drinking too much, as this is also dangerous
  • Don’t mix ecstasy with other drugs- this could increase the risk of a negative outcome
  • Don’t use too much at once, and don’t use the drug too often

In addition, websites such as www.rollsafe.org provide nonjudgmental advice that helps ecstasy users stay updated and educated. If you are struggling with ecstasy use, strategies such as tapering off the drug, making positive lifestyle changes, or seeking professional help may be useful. Helplines such as ConnexOntario (1-866-531-2600) and therapy providers such as the Centre for Addiction and Mental Health (https://www.camh.ca/) are valuable resources for individuals struggling with their own or a loved one’s drug use.

References

Business Tech. (2015). Ecstasy [Stock image]. Businesstech. https://businesstech.co.za/news/lifestyle/96707/96707/

Camh. https://www.camh.ca/

Canadian Centre on Substance Use and Addiction. https://ccsa.ca/addictions-treatment-helplines-canada

Center for Behavioral Health Statistics and Quality (2017). 2016 National Survey on Drug Use and Health: Detailed Tables. Substance Abuse and Mental Health Services Administration. 1-2889.

Curran, H. V. (2000). Is MDMA (‘ecstasy’) neurotoxic in humans? An overview of evidence and of methodological problems in research. Neuropsychobiology, 42(1), 34-41. 10.1159/000026668

Halliwell, B. (2001). Role of free radicals in the neurodegenerative diseases: therapeutic implications for antioxidant treatment. Drugs & Aging, 18(9), 685-716. 10.2165/00002512-200118090-00004

Müller, F., Brändle, R., Liechti, M. E., Borgwardt, S. (2019). Neuroimaging of chronic MDMA (“ecstasy”) effects: A meta-analysis. Neuroscience and Biobehavioral Reviews, 96, 10-20. https://doi.org/10.1016.j.neubiorev.2018.11.004

Mustafa, N. S., Bakar, N. H. A., Mohamad, N., Adnan, L. H. M., Fauzi, N. F. A., Thoarlim, A., Omar, S. H. S., Hamzah, M. S., Yusoff, Z., Jufir, M., Ahmad, R. (2020). MDMA and the brain: A short review of the role of neurotransmitters in neurotoxicity. Basic and Clinical Neuroscience, 11(4), 381-388. http://dx.doi.org/10.32598/bcn.9.10.485

Potter, A., Downey, L., Stough, C. (2013). Cognitive function in ecstasy naïve abstinent drug dependants and MDMA users. Current Drug Abuse Reviews, 6(1), 71-76. 10.2174/1874473711306010008

Robertson, S. (2019, September 16). What is neurotoxicity? News-Medical Life Sciences. https://www.news-medical.net/health/What-is-Neurotoxicity.aspx

Rollsafe.org. https://rollsafe.org/

Sharifimonfared, G., Hammersley, R. (2020). Harm reduction and quitting techniques used by heavy MDMA (ecstasy) users. Addiction Research & Theory, 28(3), 222-230. https://doi.org/10.1080/16066359.2019.1622684

Vectormine. (2018). Serotonin vector illustration [Stock image]. iStock. https://www.istockphoto.com/vector/serototin-vector-illustration-labeled-diagram-with-gut-brain-axis-and-cns-gm1053647528-281517929

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