How first-ever FDA compliant cGMP MDMA production can save a forest



Reporters frequently document the smuggling of sassafras trees out of Southeast Asian jungles; lumber has been seen occasionally packed out in the back of family sedans. One reason includes MDMA production which partially depends on safrole oil. But the trees used to produce the chemical are not sustainable. Saving a forest is one reason to develop a new method for the sustainable large-scale production of cGMP compliant MDMA.

Before cGMP and Shulgin, there was Merk

3,4-Methylenedioxymethamphetamine (MDMA) was patented by Merk in 1912. The pharmaceutical giant was the first to test the compound, alongside the US Army. Coincidentally, MDMA was rebirthed by chemists in the 1960s using the same production method as Merk.

The first synthesis of MDMA used safrole oil as a starting agent, converted with methylamine. Piperonal was eventually used as a starting agent as well, reduced with iron in hydrochloric acid. Alexander Shulgin utilized the latter synthesis in 1986. And while MDMA can be made from other starting materials. No documented process has complied with pharmaceutical standards until the release of a research project funded by MAPS. (1)

Shulgin was a proficient chemist, but the law forbade his syntheses from any cGMP or FDA compliant process.
The late Dr. Alexander Sasha Shulgin in his clandestine lab.

cGMP MDMA, an industry first

Phase 3 clinical trials effectively wiped MDMA from Schedule 1 of the Controlled Substances Act by proving its medicinal viability. Clinical results drew the need for therapeutically viable MDMA for patients treating PTSD, social anxiety from Autism Spectrum disorder, and even alcoholism.

While the Food and Drug Agency oversees controlled Good Manufacturing (cGMP) Policies. The FDA was founded only 6 years after Merk established its early MDMA patent. cGMP certification implies that the entire production process, not just the final product, follows a set protocol.

Modern MDMA synthesis

The cGMP synthesis starts with a molecule containing a derivative of a six-membered carbon ring found in nature, but not derived from safrole oil or piperine. Further opposing the use of sassafras, other reagents also deviate from conventional syntheses.

Two impurities in the starting material, succinimide and a different derivative of the same moiety are removed during a later novel reaction. It was admitted this particular synthesis is slower, although the methodology is viable for producing multiple kilograms of cGMP MDMA according to MAPS.

Purity at scale

The MDMA produced in the final stage was 99.26% purity — a good grade for the cartel. But recrystallization in isopropanol alcohol produced a 99.96% purity with an 85.5-82.6% yield, for a Heisenberg, cGMP grade MDMA-salt.

Residual solvents account for much of the left behind impurities. 2-proponal was identified as the most abundant residual by HPLC analysis — but less than 0.05% remained. Some solvents and residuals have strict tolerance limits and any impurity above 0.1% is a cause for further quantification.

Two more impurities were identified after following the cGMP process. One of these occurs from overcharged bleach (chlorine) and another after a reaction with bromine. Both impurities were detected but below 0.3%.

Crystal structures and the future

Two new crystal structures of MDMA-HCL were identified. The third is the least stable, converting spontaneously to the first already known structure. And the second is reproducible, albeit the first crystal structure of the salt is the most stable of the three. Now, a fully stable MDMA-salt will be ready if the FDA approves the substance and its benefits.

But will safe standards for synthetic compounds, especially for substances carrying a medical and psychedelic calibre, remain wholesome? Or will the pharmaceutical-minded FDA use the chance to further starve economic viability in foreign countries?

Until that becomes visible, though, pharmaceutical production of psychedelics and MDMA at least grants patients a sustainable option. And with Phase 3 trials underway, it’s at least evident the American Drug War has failed.

Let us know what you think of pharmaceutical MDMA in the comments? Will the process save a forest and provide a sustainable option, or starve a potential foreign industry?

Sources

  1. Nair, J. B., Hakes, L., Yazar-Klosinski, B., & Paisner, K. (2021). Fully Validated, Multi-Kilogram cGMP Synthesis of MDMA. ACS omega7(1), 900–907.





Source link

Previous Does Cannabis Cause Heart Disease? - Cannabis News, Lifestyle
Next Quebec's Love For Cannabis - Cannabis News, Lifestyle