Summary: Motherboard outlines the bureaucratic process for obtaining pharmaceutical grade MDMA for research by examining MAPS’ ongoing clinical trials to make MDMA-assisted psychotherapy into an FDA-approved prescription medicine. “In MAPS’s trials, researchers dose PTSD patients with MDMA before guiding them through a psychotherapy session—they’ve found evidence the drug helps patients tap into the trauma at the core of their disorder without having to relive it in the same visceral, terrifying way they would if they were sober,” reports Kaleigh Rogers of Motherboard.
Originally appearing here.
Inside a nondescript building in a quiet town in Massachusetts, there sits nearly a kilogram of 99.9 percent pure, powdered MDMA. That’s enough Molly to get all 10,000 attendees of the annual Baals music festival rolling pretty hard.
The MDMA belongs to the Multidisciplinary Association for Psychedelic Studies (aka MAPS), a nonprofit research organization that does exactly what it sounds like: studies the potential medical benefits of psychedelic drugs. MAPS has investigated LSD, ayahuasca, and ibogaine, too, but the MDMA is specifically used in its ongoing trials of psychedelic-assisted, post-traumatic stress disorder psychotherapy.
Unfortunately, MAPS can’t do much with this stash of Molly. In order for MAPS to move into phase three of its therapy trials in 2017, the Food and Drug Administration requires it to use MDMA that is certified under Good Manufacturing Practices (GMP), which this original batch is not. That means it has to source a brand new kilo of pure MDMA.
Getting your hands on illicit drugs illegally is easy—as simple as firing off a text. But legally acquiring a massive quantity of certified GMP, 99 percent pure, high yield MDMA? That requires a long journey through a labyrinth of regulation, oversight, and bureaucracy.
It all starts with asking the government if you can please buy some psychedelics.
Step One: Getting Permission
“It’s important to remember that they’re not illicit drugs when they’re used in research,” said Dr. John Halpern, a Harvard psychiatrist who has studied the effects of peyote and LSD. He noted that the difference between a Schedule I drug (like LSD) and a Schedule II drug (like OxyContin) is simply that the latter has been identified for a specific medical purpose. “Otherwise there’s no difference. They’re both equally dangerous,” he said.
But that small difference means research on Schedule I drugs requires a few extra hoops that research on other drugs don’t. The first step is to pen a protocol for a study: a plan for how the researchers intend to conduct their investigation. This protocol is judged by an institutional review board, an independent group that reviews any clinical trials involving humans. If a study involves a Schedule I drug, once the board approves the protocol as ethical, the researchers have to apply for an investigational new drug (IND) number from the FDA.
“Depending on the substance, to get that IND number could be quite a bit of work,” Halpern said.
That’s because the application requires researchers to reference a drug master file: a comprehensive dossier of everything ever published about that drug, from its chemical breakdown to its known risk factors. If this is the first time anyone has studied the drug, it’s a massive undertaking: drug master files are easily hundreds of pages. Luckily for MAPS, the FDA already has a drug master file on hand, submitted by MAPS back in 1986 and updated annually.
The application also needs to include an investigator’s brochure, which outlines the details of how the study will operate: not just how much of the drug will be used, but why and with what other methods. In MAPS’s trials, researchers dose PTSD patients with MDMA before guiding them through a psychotherapy session—they’ve found evidence the drug helps patients tap into the trauma at the core of their disorder without having to relive it in the same visceral, terrifying way they would if they were sober. MAPS would need to include the details of this therapy in its investigator’s brochure. After sending in the application, the FDA decides whether or not the study would be in the public interest. If it deems the study worthy, you get your IND number.
These steps are necessary for any drug trials on humans, but research involving Schedule I drugs have additional requirements through the Drug Enforcement Administration. Medical doctors are licensed to administer Schedule II, III, IV, and V drugs, but not Schedule I, so they have to apply to the DEA for special permission to administer a Schedule I drug specifically in the context of the study, Halpern said.
In MAPS’s case, the doctor involved is Dr. Michael Mithoefer, a psychiatrist based out of Charleston, North Carolina who has been researching MDMA-assisted therapy for more than a decade. Mithoefer already has a Schedule I license granted back when the trials began. That license means only Mithoefer is able to actually handle and distribute the MDMA. The DEA has specific requirements for Schedule I registration, including a criminal background check, and a site inspection of the clinic where the drugs will be kept and administered. These requirements transformed Mithoefer’s office from a typical therapist’s office into a veritable bank vault.
“We have to have a 2,000 pound safe, and it has to be alarmed, and the doors of the room where the safe is have to be alarmed, and then the building has to be alarmed,” said Amy Emerson, the executive director and director of clinical research at MAPS Public Benefit Corporation, a wholly owned subsidiary of MAPS. “So that’s the security part of it.”
With the paperwork squared away and the therapist office cum Mission: ImpossibleCIA vault ready for its first deposit, all that’s left is to get the goods. But MAPS obviously can’t just call up the Walter White of Molly and ask for a particularly large order. The government has its own library of drugs available for researchers, but limits access to scientists investigating the harmful effects of drugs and addiction, not the possible benefits. Luckily there is at least one pharmaceutical company willing, and legally able, to cook up a batch.
Step Two: A Recipe for Molly
Somewhere in the English countryside, off the coast of the North Sea, there’s a pharmaceutical company contracted to make MAPS’s MDMA. An expert at the company was more than happy to talk to me, but we had to keep some details secret, including the company’s name and location, and name of the person I interviewed. When you’re about to make 1,000 grams of an exceptionally high quality, 99 percent pure version of a popular party drug, you want to take some precautions.
“It might attract some unwanted attention,” my source told me.
The pharmaceutical manufacturer—let’s call them Company X, for the hell of it—won’t be producing MDMA tablets. This isn’t like a hit of Molly you buy off a girl wearing white fuzzy boots at an outdoor concert in the middle of summer. Company X will be making the active pharmaceutical ingredient, or API: the 99 percent pure, powdered form of the drug. Just like a Tylenol pill isn’t pure acetaminophen, a Molly tablet isn’t pure MDMA. There are fillers and binders (and in the case of street Molly, a whole host of other possible ingredients) to turn the pure API powder into something that’s easy to pop.
The basic “recipe” for making MDMA is available in chemistry literature: reaction schemes that let t
he company’s chemists know which ingredients to combine in which way to create the target molecule. In fact, the basics of this information can be found through a simple Google search. But to make MDMA that meets GMP standards, the company needs more detail than just the basics.
If you were trying to make MDMA for the first time, even following the “recipe” exactly, the yield and quality would be much lower than what MAPS needs: one kilogram of MDMA that is as pure as possible, ideally 99.5 percent or higher. This is because there are details that can’t be captured in the reaction schemes, so it takes time to refine the process, my source explained. Luckily, other companies with experience making MDMA have already refined the process and are willing to share their knowledge for a price, so MAPS purchased this “annotated recipe,” giving the Company X a head start on concocting the perfect, GMP MDMA recipe.
Certified GMP basically means you can prove that every step in making the drug, from the facility producing the source chemicals to the final packaging process, follows strict procedures that are known to result in a safe and consistent drug. This requires careful documentation and oversight from the drug manufacturer. An inspector could come to the manufacturer and demand to see something as specific as the procedure for ensuring a beaker is clean before a chemical is poured into it, according to Company X. It’s a very precise endeavor. But that precision means that not only will MAPS’s new kilo of MDMA be pure and safe, but that every batch after that will be identical to it.
There are lots of security steps on this end of the process as well: Company X has a license to handle Schedule I drugs already, but also needed to meet certain requirements to hold the raw ingredients to make MDMA. Company X needed to prove its facility was equipped with security systems and provide the UK government with a thorough outline of what the company is making, where that products are going, and what the product will be used for. And since the MDMA is going across the US border, the company needed special permission from the FDA and DEA to ship it stateside, too.
Company X is currently in the process of nailing down the MDMA GMP production by experimenting with small batches. Once the product meets all the standards, it will produce the kilo and send it to MAPS some time in the next year.
But even with the MDMA in MAPS’s possession, getting it into patients’ hands—and heads—requires leaping through a few more hoops.
Step Three: Dosing
Even with its layers of security and vault-like safe stuffed with ecstasy, the MAPS clinic where its MDMA trials take place is quite unassuming. It’s no cold, sterile laboratory: the consultation rooms more closely resemble an upscale retirement home, with plush chairs, neutral carpeting, and cheery paintings. During a session, a PTSD patient takes a dose of Molly (without knowing how much), sits back, and waits for the roll. It’s a deeply personalized process, the trip enabling the patient to reel back to traumatic moments in their memory with the psychedelic effects as a gentle buffer. A session, which lasts several hours and requires an overnight stay at the clinic, flows between guided therapy and quiet reflection. It’s all part of a process intended to heal deep psychic wounds, with the help of the MDMA.
The bulk of the MDMA API (remember, this is a pure powdered form of the drug) can’t all physically be stored in Mithoefer’s office. (It’s a lot of Molly.) Right now, MAPS stores its MDMA with a company called Organix—that’s the nondescript Massachusetts building—which has a license to store and ship the pure, powdered drug. But to dole it out to patients, it’s better to have a pill.Powders are unwieldy and difficult to distribute to patients with precision, which is needed for a study. The dose of MDMA given to PTSD patients in MAPS’s study—previous phases in the study doled out 30, 75, and 125 milligram doses to different patients—needs to be compressed and encapsulated into an easy-to-pop pill.
Emerson told me MAPS is looking for a company that can pre-package the MDMA doses for the study, but in the meantime researchers have found a workaround. When it’s time to conduct a trial, MAPS orders a small amount of the raw powder from the holding facility at Organix, which, in spite of all the intensive security requirements, ultimately ships the MDMA in a plain, old cardboard Fedex box directly to Mithoefer’s office. There, it has to be received by Mithoefer himself and immediately tucked away in that 2,000-lb safe.
This is where it gets really tricky. While Mithoefer has a license to dole out the MDMA, he can’t package it himself, so a pharmacist has to come to the office to make the pills. Since MAPS is doing a double-blind trial, Mithoefer also can’t know which dose each patient is getting. But his license dictates that he can’t leave the room when the MDMA isn’t locked up. So MAPS needed to find a way to have a pharmacist turn the powder into pills with Mithoefer in the room but without him knowing how much powder was going into each pill.
The solution to this conundrum is actually pretty simple: the pharmacist follows specific directions from MAPS to create the doses with Mithoefer in the room, but hidden from view by a cardboard partition, Emerson said. Since the trials have been small so far, this process has worked well, but Emerson said if MAPS wants to do more expansive trials, it’ll need a facility that can pre-package all the doses ahead of time.
With the doses packaged and labelled by the pharmacist, Mithoefer is finally able to administer a dose to a patient and begin the therapy.
The End Goal
Though the protocols required to conduct this kind of research may seem onerous, none of the individuals I spoke to who have to adhere to these regulations expressed any frustration over them.
“It can take several months sometimes to get it done, but I don’t believe researchers will shy away from doing Schedule I research because of the requirements if it fascinates them,” Halpern told me.
MAPS is one group that is certainly fascinated. It has invested almost 30 years and earmarked nearly $20 million to work toward its goal of making MDMA an FDA-approved prescription drug by 2021. If it reaches that goal, doctors and scientists will have to jump through much fewer hoops to get their hands on MDMA for trials, or to help patients who they think could benefit from trip-assisted therapy. But for now, the hoops remain, and researchers will happily clear them if it means advancing our understanding of these mind-expanding drugs.