MDMA is a synthetic compound that has a chemical structure similar to that of methamphetamine and the psychoactive hallucinogen mescaline. However, it is pharmacologically distinct from both drugs and has a different tolerance and addiction profile.
For the purpose of clarity, it is important to differentiate between MDMA and ecstasy. Although the names are often used interchangeably, studies have shown that illicitly purchased ecstasy or “molly” often contains no MDMA at all. News stories that implicate MDMA in deaths or adverse health and social effects are nearly always later found to be rightfully attributable to methamphetamine, “bath salts,” heroin and other profoundly dangerous drugs.
Is it Possible to Develop a Tolerance to MDMA?
Initial studies on the mechanisms of MDMA action and tolerance found it to be “neurochemically messy,” and a complete understanding of MDMA actions has not yet been described.
Unfortunately, there are onerous federal restrictions that significantly hamper research on the effects of MDMA, so scientists must rely on self-reports from people who have used illicitly purchased ecstasy to evaluate the drug. Because a significant portion of illegally obtained ecstasy has no MDMA at all, it is impossible to be confident that studies on ecstasy tolerance are actually relevant to MDMA. However, researchers have learned a great deal about ecstasy and MDMA from interviewing people who report that they have used it in the past.
One study categorized people who took illicitly purchased ecstasy into three groups: novice (up to nine occasions of use), moderate (10 to 99 occasions of use) and heavy (more than 100 occasions of use). They found that the people who used the most were more likely to take more ecstasy pills than people who used novice or moderate amounts, suggesting that ecstasy tolerance (and probably MDMA tolerance) occurs with repeated use.
A study of MDMA tolerance in rats found that prior exposure to low-dose MDMA did not affect future neurochemical response to MDMA, but that high-dose (“binge”) MDMA exposure reduced subsequent responses to MDMA administration. It is difficult to directly translate these findings to humans “because humans take much lower doses than those given to rats.” In spite of translational challenges, the authors of this study believe that MDMA tolerance is likely to occur in humans who regularly consume ecstasy and MDMA.
Although far from conclusive, data suggests that MDMA tolerance exists in humans who regularly take ecstasy and MDMA. However, a great deal is unknown and research into the effects of MDMA and tolerance associated with MDMA use remains ongoing.
MDMA Tolerance Symptoms
When someone has developed tolerance to a drug, their brain has become accustomed to its presence and no longer responds as strongly when it is administered. Subsequently, ever-increasing amounts of the drug are required to achieve the desired effect.
While there is some controversy about whether MDMA is addictive, an overwhelming majority of data shows that MDMA does not meet the criteria for dependence or addiction as defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) or the International Statistical Classification of Diseases (ICD-10).
Furthermore, prior to the federal ban on recreational and clinical uses of MDMA, published literature did not identify MDMA as a drug that was associated with tolerance or dependence. However, literature was generally published on people who used MDMA in supervised settings. It is likely that, with repeated exposure in a short amount of time, MDMA would cause tolerance.
A definitive description of symptoms of tolerance requires a valid understanding of the drug of consideration. Because of the lack of published data reporting on chronic MDMA use and the development of tolerance and dependence, any list of MDMA-related tolerance symptoms is purely speculative.
What can be said is that drug tolerance, in general, is associated with several overlapping symptoms that identify tolerance, including the need for ever-increasing doses of the drug to achieve the desired effect, and physical and psychological withdrawal symptoms in the absence of the drug.
Unlike MDMA, methamphetamine is known to be a profoundly addictive drug that has devastating consequences on people who regularly take it. Because methamphetamine is a common adulterant in ecstasy, some people may develop methamphetamine-like dependence and addiction symptoms with ecstasy use. However, it is impossible to attribute these symptoms to MDMA and, in light of a great deal of clinical data from the 1970s and ‘80s — as well as more recent data suggesting that MDMA is a valuable drug with far fewer negative side effects than most modern prescription drugs — it is highly unlikely that MDMA itself is responsible for the methamphetamine-like symptoms attributed to regular ecstasy use.
Causes Of MDMA Tolerance
Tolerance is the consequence of the brain becoming less responsive to a drug when it is administered regularly. Some drugs, notably opioids and benzodiazepines, are notorious for having tolerance after a week or two of regular use.
Empirical evidence that clarifies the addictive capacity of MDMA remains to be published. However, general rules that apply to most drugs exist:
- Dosage: Larger doses cause tolerance to set in rapidly.
- Frequency of use: Frequent use is associated with a rapid tolerance onset.
- Duration of use: Longer time spent using a drug is generally associated with a higher tolerance.
- Interactions with other drugs: The majority of drugs are metabolized using shared pathways in the body; each drug can affect how other drugs are metabolized. The consequences of drug-drug interactions can range from negligible to lethal.
- Other factors: Among the most interesting factors currently being studied in clinical research is the role of genetics in drug metabolism, tolerance, and addiction (“pharmacogenomics”). Other factors include age, metabolic rate, and physical/mental health status.
It should be reiterated that MDMA and ecstasy are not equivalent drugs, and neither can be accurately described in terms of their likelihood to cause tolerance. MDMA is a pharmacologically distinct drug that lacks empirical data; ecstasy is composed of different dangerous chemicals that make a valid description impossible to provide.
Getting Help With MDMA Addiction
Although MDMA and ecstasy are pharmacologically different drugs, the names are often used interchangeably. People who regularly consume MDMA or ecstasy are likely to experience negative consequences including the development of physical and psychological dependence and addiction. If you are concerned that you or someone you know has an MDMA/ecstasy use disorder, help is available. Look for a rehab facility that is equipped to address each stage of recovery, from detox and acute withdrawal to long-term support via aftercare programs.
Contact The Recovery Village Ridgefield to speak with a representative about how professional treatment can help people who struggle with MDMA. Take the first step toward a healthier tomorrow, call today.
Palamar, Joseph. “MDMA Vs. Ecstasy: How They Differ, Risks, And Benefits You Need to Know.” Medical Daily, December 9, 2016. Accessed September 26, 2019.
Parrott, Andrew C. “Chronic tolerance to recreational MDMA (3,4-methylenedioxymethamphetamine) or Ecstasy.” Journal of Psychopharmacology, 2005. Accessed October 3, 2019.
Baumann, Michael H; et al. “Tolerance to 3,4-methylenedioxymethamphetamine in rats exposed to single high-dose binges.” Neuroscience, March 2008. Accessed October 3, 2019.
Sessa, Ben; Higbed, Laurie; Nutt, David. “A Review of 3,4-methylenedioxymethamphetamine (MDMA)-Assisted Psychotherapy.” Frontiers in Psychiatry, March 2019. Accessed September 26, 2019.
National Institute on Drug Abuse. “The Neurobiology of Drug Addiction.” January 2007. Accessed September 26, 2019.
Kalant, Harold. “The pharmacology and toxicology of “ecstasy” (MDMA) and related drugs.” Canadian Medical Association Journal, October 2001. Accessed September 26, 2019.
Ahmed, Shabbir; et al. “Pharmacogenomics of Drug Metabolizing Enzymes and Transporters: Relevance to Precision Medicine.” Genomics, Proteomics & Bioinformatics, October 2016. Accessed September 26, 2019.
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