Summary: Gizmodo explores ongoing clinical research into the development of MDMA-assisted psychotherapy into an FDA-approved prescription treatment for posttraumatic stress disorder (PTSD). MAPS Founder Rick Doblin, Ph.D., speaks about the politics surrounding MDMA research, the pathway to prescription approval of MDMA-assisted psychotherapy, and the importance of increased funding for scientific research.
Originally appearing here.
Not long ago, the idea of walking up to a clerk behind a counter and getting a baggie of weed seemed ludicrous. Now, in states where recreational or medical marijuana is approved and regulated, it’s a routine, mundane part of life. Are psychedelics next?
It may seem like a similar scenario isn’t far off for MDMA and other psychedelic drugs, like LSD (acid), psilocybin (mushrooms), and even DMT (ayahuasca); every few months news seems to break of another successful study on this or that psychedelic for the treatment of everything from alcoholism to post-traumatic stress disorder. But in truth, psychedelics will probably never be available by prescription at your corner pharmacy—if they even make it to the commercial market at all. Here’s why.
What Are Psychedelics?
A drug counts as a psychedelic if it affects the user’s cognition or self perception. This umbrella categorization includes everything from marijuana to ketamine. However, classic psychedelics like LSD and psilocybin are those that alter the user’s sensory experience and promote hallucinations by masquerading as serotonin. MDMA, in contrast, causes the brain to release its own stores of serotonin to promote feelings of empathy, euphoria, and love. These are the drugs that have most intrigued psychiatrists with their potential therapeutic value.
When these drugs were first discovered, psychologists of the 60s (LSD) and 70s (MDMA) were quick to note and document their usefulness in conjunction with psychotherapy. But with the proliferation of these same drugs on the street and in clubs, the Drug Enforcement Agency was quick to list them as schedule 1: substances with a high potential for abuse and no legitimate medical value.
Scheduling these drugs effectively halted all research.
“I thought that was a terrible mistake and an overreaction,” Rick Doblin, founder of the nonprofit Multidisciplinary Association for the Study of Psychedelics (MAPS) told Gizmodo.
In his early career, Doblin dodged the draft for the Vietnam War and decided to devote his life to the study of psychedelics instead. “Because I was anticipating going to jail for being a draft resister, I figured I wouldn’t be able to become a doctor or a lawyer, so I would try to become an underground psychedelic therapist instead.”
Over time, Doblin managed to start MAPS, get funding, and begin the long and arduous process of developing a new medical drug. MAPS runs several studies looking into different drugs for different diseases, but we’re going to focus on their work with MDMA for the treatment of PTSD.
From the Lab Bench to the Pharmacy
Once a drug has passed all the “preclinical” testing—animal and other small scale studies to prove it may work for a particular disease—the compound begins the process of obtaining FDA approval.
Clinical trials happen in three phases. The first phase tests safety, dosing, and looks for how the drug is metabolized and excreted by the body in healthy individuals. Drugs that move on to phase two trials continue to look at the safety profile and efficacy in a small group of people with the disease.
The main reason drugs fail between phase two and three is that they simply aren’t effective enough at treating the disease they’re supposed to treat. If there are already drugs on the market for the disease—like Zoloft and Paxil for PTSD—new compounds are held to an even higher standard. If the drugs being tested don’t surpass the current available drugs, then they will likely be dropped.
This is because phase three trials take considerably more time, resources, and money to perform than the previous phases. Phase three trials are much larger, usually take place in several locations, and have more rigorous statistical benchmarks to meet in order to prove efficacy, Kenneth Kaitin, the director of the Tufts Center for the Study of Drug Development told Gizmodo. “On average, about 33 percent of drugs that end phase two testing will move onto phase three.”
And because of those more rigorous benchmarks, most of the drugs that do make it to phase three don’t ever make it out. Kaitin said he expects experimental psychedelics to “struggle” in phase three of testing for this reason.
But when it comes to psychedelics, there are more factors at play — particularly money (we’ll get to that) and social stigma. “The FDA is extremely sensitive to the public view of the use and availability of certain drugs,” Kaitin said. “[Psychedelics], I would be willing to guess, have a somewhat higher hurdle because the public’s view of the type of drugs these are.”
But is public perception really that bad? It’s hard to tell. Two stories about MDMA—one about its ability to restore lives, and another about its ability to destroy them—hit the mass media within a month of each other. Though some are pushing for the legalization of all drugs, such organizations like Law Enforcement Against Prohibition (LEAP) remain in the peripheral vision of the public eye.
Regardless of public perception, the Food and Drug Administration is remarkably amenable to psychedelic research. Michael Mithoefer heads the research of MDMA as a treatment for PTSD at MAPS. He said when he first proposed his research to the FDA in 2000, the agency was quick to approve. It was the Drug Enforcement Agency—which must sign off on the research of any schedule 1 drug—that was slow to approve. (However, once Mithoefer cleared that hurdle for the initial study, obtaining approval from both agencies was relatively easy.)
Mithoefer and his group have now completed the phase two studies of MDMA. As you may have heard, the popular party drug has performed incredibly well. In the initial pilot study, which tested MDMA against a placebo in a group of 20 patients, the participants that received MDMA enjoyed a reduction of 30 points (out of 120) in the Clinician Administered PTSD Scale. More importantly, 10 out of the 12 patients who received MDMA in the trial no longer met the criteria for diagnosis for PTSD by the end of the study.
But phase two is just child’s play compared to phase three studies, especially when it comes to cost.
The Cost of Bringing a Drug to Market
Most of the research and development for new drugs is paid for by big pharmaceutical companies. These companies are notoriously secretive about how much money truly goes into research and development, as well as how that factors into drug pricing. However, according to Doblin, the average cost of drug development is upwards of $1 billion.
And pharmaceutical companies aren’t interested in developing psychedelics, for a number of reasons. First, they’re not very profitable. As MAPS is proposing them, psychedelic drugs would only be administered a few times in a patient’s life. Compared to an antidepressant, which needs to be taken daily, psychedelics aren’t too lucrative. Drug companies often use patents to maintain their proprietary hold on a drug for as long as possible, thus maximizing their profits. But Doblin has gone to great lengths to make sure psychedelic drugs can’t be patented.
So psychedelic research has
h
ad to rely mostly on private donations from wealthy individuals and organizations, and some funding from government agencies like the National Science Foundation. But psychedelics have one major leg up on the funding front: previous research.
Before the DEA scheduled classic psychedelics in the 70s and MDMA in the 80s, psychiatrists had performed many studies examining safety, mechanism of action, and dosage—laying the groundwork for the clinical trials MAPS is performing today. “We estimate that those studies have been produced at a cost somewhere in excess of 300 million dollars taken together,” Doblin said.
The phase two trials cost MAPS roughly 5 million. Now the nonprofit is shooting for 22 million for phase three; they’ve raised about 7 million so far. Doblin said he expects phase three trials to be completed by 2021, though pinning an exact date on clinical trial completion is difficult.
So How About That Prescription?
Presuming MDMA does pass phase three with flying colors, the process still isn’t over. At that point, MAPS will have to submit a New Drug Application (NDA) to the FDA. The FDA reviews the application, decides on how it will be labeled, and inspects the facility where it will be manufactured. This can take anywhere between six months to two years.
But the road doesn’t end there. Because MDMA is at high risk for abuse, MAPS expects it will go through painstaking lengths to prove they have an effective risk management strategy in order for the FDA to give it the green light for commercial use.
Mithoefer told Gizmodo the current plan is that MDMA will only be made available to therapists who pass MAPS training program. It will be administered by a team of two therapists in an office where the patient will be monitored overnight. MDMA will never be available as a take-home drug, Mithoefer said, because it’s not just MDMA that’s subject to the FDA approval. The FDA needs to approve the drug and the therapy protocol proposed and tested by MAPS in their clinical trials.
Lastly, in order for MDMA to be used by anyone in a therapeutic context, the DEA will have to change its legal status from schedule 1 to one of the “medical schedules” — statuses afforded to controlled substances which have proven medically useful. The FDA will suggest a new status for the drug, but ultimately the decision about scheduling lies in the hands of the DEA. According to an agent within the DEA, this process can take up to 12 months.
Sean Dunagan, a former senior intelligence research specialist at the DEA and current member of LEAP told Gizmodo that he expects the DEA will be willing to reschedule MDMA if it shows medical value. However, its status as a medical drug will not change the criminality of selling and possessing the drug outside of its approved medical uses, Dunagan warned. The MDMA on the street will also still have all the same problems as it does now—with mystery adulterants and dosages.
While MDMA and other psychedelics may never be available at the corner pharmacy, their development into medical drugs provides a ray of hope to those whose suffering hasn’t been alleviated by the current options.
