Introduction
In April of 2016, user Le Junk posed a question to the Bluelight harm reduction message board. Since then, his thread, “What is wrong with the MDMA available today?” has garnered over 6,300 responses and spanned over 320 pages. The thread, which has attracted worldwide contributions, seeks to understand why some MDMA users experience an alternate effects profile even though the product is identified as MDMA by GCMS testing.
Throughout this discussion, two primary lines of thinking have emerged – either something is wrong with the MDMA or something is wrong with the user. “Loss of magic” is a frequently accepted phenomenon amongst MDMA users, where those who engaged in frequent MDMA use/abuse lose the ability to feel the primary effects of the drug. However, both experienced and new MDMA users have complained of experiencing an alternate effects profile from the drug, and some users claim to have access to two types of product with distinctly different effects profiles. This seems to indicate that “loss of magic” is not the reason behind the phenomenon.
Classic or “magic” MDMA produces empathy, elation, euphoria, music enhancement, and tactile enhancement. Some users also experience enhanced sensuality or sexuality. Mydriasis is a commonly observed physical sign of use that is easily witnessed by outside observers. Subpar MDMA, or “meh-DMA” as defined by the forum, fails to produce these effects. Instead, users report a cold and sedate experience that decreases sociability and encourages introspection. Mydriasis is reduced, and the overall effects of the drug feel muted in comparison to typical MDMA effects.
While discussing this phenomenon, users have developed multiple theories in association with published research articles. Although many theories have been discussed, the leading hypotheses involve MDMA contaminants, and/or GCMS inability to accurately differentiate coeluting isobaric derivatives. Contaminant profiles have changed as the result of changing synthesis methods, and these changes may have resulted in the alternate effects profile that users experience. The following research articles establish the basis of these theories.
Presence of Synthesis Byproducts
Although many labs such as Drugs Data in the USA report results of MDMA only, synthesis byproducts are present in MDMA samples. Law enforcement agencies use synthesis byproduct profiles to assist them with identifying the source of MDMA. Complex extraction techniques are sometimes used prior to analysis to separate the byproducts from the MDMA samples. These articles establish that synthesis byproducts are present in MDMA, and that byproducts/impurities vary depending on which synthesis method was used.
- “Synthesis and impurity profiling of MDMA prepared from commonly available starting materials” by Ryan Gallagher, Ronald Shimmon, Andrew M. McDonagh (Gallagher)
- “Impurity profiling of ecstasy tablets seized in Hong Kong by gas chromatography–mass spectrometry” by Jack Yuk Ki Cheng, Man Fai Chan, Tai Wai Chan, Mei Yuen Hung (Yuk Ki Cheng)
- “Basic and neutral route specific impurities in MDMA prepared by different synthesis methods Comparison of impurity profiles” by M. S´wist, J. Wilamowski, A. Parczewski (S'wist)
- “A review of impurity profiling and synthetic route of manufacture of methylamphetamine, 3,4-methylenedioxymethylamphetamine, amphetamine, dimethylamphetamine and p-methoxyamphetamine” by Natasha Stojanovska, Shanlin Fu, Mark Tahtouh, Tamsin Kelly, Alison Beavis, K. Paul Kirkbride (Stojanovska)
- “Optimization of HS-SPME/GC–MS analysis and its use in the profiling of illicit ecstasy tablets” by Federica Bonadio, Pierre Margot, Olivier Dele´mont, Pierre Esseiva (Bonadio)
- “Determination of synthesis method of ecstasy based on the basic impurities” by M. S´wist, J. Wilamowski, A. Parczewski (S'wist, Determination of synthesis method of ecstasy based on the basic impurities)
Interference with Monoamine Transporters
“Pharmacological Characterization of Ecstasy Synthesis Byproducts with Recombinant Human Monoamine Transporters” by Christian Pifl, Gabor Nagy, Sa´ ndor Bere´ nyi, Alexandra Kattinger, Harald Reither, and Sa´ ndor Antus (Pifl)
In the first article, researcher Christian Pifl establishes that some “byproducts of illegal ecstasy synthesis can interact with the primary sites of action of MDMA, the monoamine transporters, and were active with similar potency as MDMA.” In other words, some byproducts can block the action of MDMA.
“Duloxetine Inhibits Effects of MDMA (‘‘Ecstasy’’) In Vitro and in Humans in a Randomized Placebo-Controlled Laboratory Study” by Ce´dric M. Hysek et al. (Hysek)
To better understand what it may look like for monoamine transporters to be blocked in humans, consider this article on how pre-treatment with Duloxetine impacts the MDMA experience in virgin users. “The findings confirm the important role of MDMA-induced 5-HT and NE release in the psychotropic effects of MDMA” (Hysek).
Regioisomers and Isobaric Derivatives
In addition to the presence of potentially active synthesis byproducts, the presence of isobaric derivatives could explain why GCMS testing is inadequate at identifying certain contaminants. Isobaric derivatives are chemicals that are so structurally similar to MDMA that they may appear to be MDMA to GCMS testing. They may “co-elute” which means that the peak of one substance overlaps with another peak, making separation and identification challenging. These articles discuss the regioisomers and isobaric derivatives of MDMA, the advanced testing methodologies needed to successfully separate and identify these compounds, and the presence of these compounds in samples seized by law enforcement.
- “MASS SPECTRAL AND CHROMATOGRAPHIC STUDIES ON A SERIES OF REGIOISOMERS AND ISOBARIC DERIVATIVES RELATED TO METHYLENEDIOXYMETHAMPHETAMINES” by Tamer Awad (Awad)
- “Regioisomers of 3,4-methylenedioxy-N-methylamphetamine in clandestine ecstasy pills” by Inmaculada Fierro et al. (Fierro)
- “Synthesis and Analytical Profiles for Regioisomeric and Isobaric Amines Related to MDMA, MDEA and MBDB: Differentiation of Drug and non-Drug Substances of Mass Spectral Equivalence” by C. Randall Clark (Clark)
- “Mass-Spectrometry-Based Identification of Synthetic Drug Isomers Using Infrared Ion Spectroscopy” by Kranenburg, Ruben F. et al. (Kranenburg)
- “Chromatographic and Mass Spectral Studies on Isobaric and Isomeric Substances Related to 3,4-Methylenedioxymethamphetamine” by Laura Aalberg et al. (Aalberg)
- “GC–MS studies on acylated derivatives of 3-methoxy-4-methyl- and 4-methoxy-3-methyl-phenethylamines: Regioisomers related to 3,4-MDMA” by Tarek Belal, Tamer Awad, Jack DeRuiter, and Randall Clark (Belal)
- “Distinguishing drug isomers in the forensic laboratory: GC–VUV in addition to GC–MS for orthogonal selectivity and the use of library match scores as a new source of information” by Ruben F. Kranenburg (R. e. Kranenburg)
- “Chromatographic and Mass Spectral Studies on Methoxy Methyl Methamphetamines Related to 3,4-Methylenedioxymethamphetamine” by Tamer Awad et al. (T. e. Awad)
- “GC–MS and GC–IRD Studies on the Ring Isomers of N-Methyl-2-Methoxyphenyl-3-Butanamines (MPBA) Related to 3,4-MDMA” by Tamer Awad et al. (T. e. Awad, GC–MS and GC–IRD Studies on the Ring Isomers of N-Methyl-2-Methoxyphenyl-3-Butanamines (MPBA) Related to 3,4-MDMA)
- “The Identification of 3,4-MDMA from Its Mass Equivalent Isomers and Isobaric Substances Using Fast LC–ESI-MS–MS” by Katja Pihlainen et al. (Pihlainen)
New Psychoactive Compounds
Also, of interest are the presence of new psychoactive compounds and analogues that GCMS testing may be incapable of identifying due to the novel nature of the compound.
“Identification of a new M-ALPHA analog and MDMA in an illegal health product” by Ji Hyun Lee et al. (Lee)
Conclusion
Although user tolerance is the most commonly accepted explanation for loss of effects in experienced MDMA users, product quality may also contribute to wide variation in user experience. The presence of undetected synthesis byproducts, inhibition of monoamine transporters, or substitution of an isobaric derivative may explain what is wrong with some MDMA today. In order to fully investigate the question and associated hypotheses, user samples would need to be analyzed with advanced lab techniques beyond simple GCMS imaging, and the results compared to subjective user reports. If you know of a researcher, university, or laboratory willing to assist with this research, please reach out to user indigoaura via the Bluelight harm reduction forum.
Works Cited
Aalberg, Laura et al. "Chromatographic and Mass Spectral Studies on Isobaric and Isomeric Substances Related to 3,4-Methylenedioxymethamphetamine."
Journal of Chromatographic Science (2004): 464-469. Web.
Awad, Tamer et al. "Chromatographic and Mass Spectral Studies on Methoxy Methyl Methamphetamines Related to 3,4-Methylenedioxymethamphetamine."
Journal of Chromatographic Science, (2007): 467-476. Web.
—. "GC–MS and GC–IRD Studies on the Ring Isomers of N-Methyl-2-Methoxyphenyl-3-Butanamines (MPBA) Related to 3,4-MDMA."
Journal of Chromatographic Science, (2011): 345-352. Web.
Awad, Tamer. "MASS SPECTRAL AND CHROMATOGRAPHIC STUDIES ON A SERIES OF REGIOISOMERS AND ISOBARIC DERIVATIVES RELATED TO METHYLENEDIOXYMETHAMPHETAMINES ." 15 December 2006.
Auburn University. Web. 4 January 2021.
Belal, Tarek et al. "GC–MS studies on acylated derivatives of 3-methoxy-4-methyl- and 4-methoxy-3-methyl-phenethylamines: Regioisomers related to 3,4-MDMA."
Forensic Science International (2008): 61-82. Web.
Bonadio, Federica et al. "Optimization of HS-SPME/GC–MS analysis and its use in the profiling of illicit ecstasy tablets."
Forensic Science International (2009): 73–80. Web.
Clark, C. Randall.
Synthesis and Analytical Profiles for Regioisomeric and Isobaric Amines Related to MDMA, MDEA and MBDB: Differentiation of Drug and non-Drug Substances of Mass Spectral Equivalence. Electronic. Auburn, Alabama: Department of Justice, 2011. Web.
Fierro, Inmaculada et al. "Regioisomers of 3,4-methylenedioxy-N-methylamphetamine in clandestine ecstasy pills."
ICADTS 2007. Seattle, 2007. Web.
Gallagher, Ryan et al. "Synthesis and impurity profiling of MDMA prepared from commonly available starting materials."
Forensic Science International (2012): 306-313. Web.
Hysek, Ce'dric et al. "Duloxetine Inhibits Effects of MDMA (‘‘Ecstasy’’) In Vitro and in Humans in a Randomized Placebo-Controlled Laboratory Study."
PLoS ONE (2012). Web.
Kranenburg, Ruben et al. "Distinguishing drug isomers in the forensic laboratory: GC–VUV in addition to GC–MS for orthogonal selectivity and the use of library match scores as a new source of information."
Forensic Science International (2019): 1-13. Web.
Kranenburg, Ruben F. et al. "Mass-Spectrometry-Based Identification of Synthetic Drug Isomers Using Infrared Ion Spectroscopy."
Analytical Chemistry (2020): 7282-7288. Web.
Lee, Ji Hyun et al. "Identification of a new M-ALPHA analog and MDMA in an illegal health product."
Forensic Science International (2020). Web.
Pifl, Christian et al. "Pharmacological Characterization of Ecstasy Synthesis Byproducts with Recombinant Human Monoamine Transporters."
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 314.1 (2005): 346-354. Web.
Pihlainen, Katja et al. "The Identification of 3,4-MDMA from Its Mass Equivalent Isomers and Isobaric Substances Using Fast LC–ESI-MS–MS."
Journal of Chromatographic Science, (2005): 94-97. Web.
Stojanovska, Natasha et al. "A review of impurity profiling and synthetic route of manufacture of methylamphetamine, 3,4-methylenedioxymethylamphetamine, amphetamine, dimethylamphetamine and p-methoxyamphetamine."
Forensic Science International 224 (2013): 8-26. Web.
S'wist, M. et al. "Basic and neutral route specific impurities in MDMA."
Forensic Science International (2005): 100-111. Web.
—. "Determination of synthesis method of ecstasy based on the basic impurities."
Forensic Science International (2005): 175-184. Web.
Yuk Ki Cheng, Jack et al. "Impurity profiling of ecstasy tablets seized in Hong Kong."
Forensic Science International (2006): 87-94. Web.
(and not knowing anything about MDMA):
