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Will These Psychedelic Drugs Soon Be Legal?

by Anna Marrian  

Last year, we reported on the use of the hallucinogenic drugs MDMA and psilocybin to ease symptoms in people with post-traumatic stress disorder (PTSD) and treatment-resistant depression. Since then, evidence has continued to mount that these drugs, when administered in controlled therapeutic settings, may be able to succeed where traditional pharmaceuticals have fallen short in the treatment of each condition. One of them, in fact—MDMA—is currently on track for FDA approval.

Unlike research on traditional drug studies, research on psychedelics is funded mainly by academic institutions and nonprofit organizations, such as the Multidisciplinary Association of Psychedelic Studies (MAPS) and the Heffter Research Institute. As nonprofits, these entities don't have the same shareholder pressure and economic interests as pharmaceutical companies might have in the studies’ outcomes. Indeed, both MDMA (full name 3,4-methylenedioxy-methamphetamine), also known as ecstasy, and psilocybin, the active ingredient in magic mushrooms, are off-patent substances that exist in the public domain. So if approved, they’re not likely to be of interest to profit-based, patent-driven pharmaceutical companies—meaning prices could potentially remain low compared with new, patented treatments. Here’s a look at the research on each drug and where they stand in the legalization pipeline.

MDMA-assisted psychotherapy: nearing FDA approval

MDMA’s ability to increase feelings of trust and compassionhas made it a popular party drug, and that attribute may also make it an unusually effective complement to psychotherapy in people with PTSD. In a small, placebo-controlled study of PTSD suffererspublished in the Journal of Psychopharmacology, for instance, researchers found that the drug, administered during two eight-hour psychotherapy sessions spaced about a month apart, reduced symptoms for the majority of participants; a follow-up study in the same journal found that the effects lasted up to six years in some cases. That’s especially significant because PTSD is notoriously difficult to treat; experts estimate that 30 to 40 percentof people who have it get no relief from current therapies,including cognitive behavioral therapy, group therapy, and antidepressants. PTSD affects 8 percent of Americans—nearly 25 millionpeople—and is twice as common among veterans compared with the general population. In 2016, about 868,000 veterans received disability benefits for PTSD, at a cost of $17 billionto the Veterans Administration.

The toll of PTSD and the efficacy of MDMA-assisted psychotherapy could explain why the FDA in August 2017 granted the treatment a Breakthrough Therapy designation, which fast-tracks a drug’s path to approval. Phase III clinical trials on MDMA, the final hurdle to approval, will begin in 2018, conducted by 80 licensed therapists throughout the county. Leading the effort to legalize MDMA for this purpose is MAPS, which has invested 35 years and $60 millionin MDMA-assisted psychotherapy research. (While that may sound like a lot, it takes the average drug company more than $1 billionto bring a drug to approval.) If the Phase III studies confirm its effectiveness, MDMA could gain FDA approval as early as 2021.

Although there were no serious drug-related adverse effects in the original pilot study of 20 people, some minor physical effects were observed on the day of the experimental sessions, according to the researchers, including elevations of blood pressure, pulse, and body temperature, which returned to normal at the session’s end. Jaw tightness, nausea, feeling cold, dizziness, loss of appetite, and impaired balance were also reported.It’s important to note, of course, that the drug was administered in a controlled clinical setting, where the clinicians probably made sure the participants drank plenty of water and otherwise facilitated their physical safety. This isn’t always the case when people use MDMA as a party drug, often in hot clubs where they’re at risk of overheating and dehydration from hours of dancing and inadequate fluid intake.

Once approved,MAPS says the drug will be administered in an inpatient setting at DEA-certified clinics by licensed therapists who have been specifically trained to conduct MDMA-assisted therapy for the treatment of PTSD. It will not be available as a prescription at local pharmacies, the organization says. MAPS is also studying MDMA-assisted psychotherapy for autistic adults with social anxiety and for anxiety related to life-threatening illness.

Psilocybin: for depression and beyond

Compared to MDMA, research on psilocybin is a few steps behind in terms of FDA approval. But it’s also being studied for a broader range of applications. The Heffter Research Institute, a nonprofit scientific organization in Santa Fe, New Mexico, is planning a phase III study of psilocybin to treat distress in end-stage cancer patients. Heffter previously funded two separate studies, conducted by researchers at New York University and Johns Hopkins, which showed decreased depression and anxiety in cancer patients for 8 months following a single dose of psilocybin, compared with a placebo. The psilocybin and placebo were both administered along with psychotherapy. The findings were published in 2016 in The Journal of Psychopharmacology.

An article published in 2017 in Nature may help explain the mechanism by which psilocybin reduces depression symptoms. Researchers from Imperial College London measured the physiologic effect of psilocybin on the brains of 19 adults with treatment-resistant depression. The small study used MRI imaging of the amygdala, an area of the brain associated with emotional regulation. Researchers observed reduced blood flow to the amygdala, which they correlated with a decrease in depressive symptoms in all 19 subjects one week after treatment, and in nearly half of participants five weeks later. (Untreated patients with depression generally experience increased blood flow to the amygdala.) Researchers say the findings fill a knowledge gap on how psilocybin achieves an antidepressant effect, positing that a “reset” therapeutic mechanism occurs in the brain following a high-dose psychedelic experience. The same researchers are now planning a head-to-head study of psilocybin against an existing standard-of-care antidepressantmedication, due to start this year.

The wave of research on psilocybin has broadened into its effect on alcoholism, a significant problem in the U.S. Nearly 13 percent of American adults have an alcohol use disorder, and 88,000 Americans die of alcohol-related causes annually—making it the third leading cause of preventable death, according to the National Institute on Alcohol Abuse and Alcoholism.

Researchers at NYU recently began a phase II trial of 180 participantsto evaluate the effect of psilocybin, with accompanying behavioral therapy, on alcohol dependence, following a positive preliminary study published in The Journal of Psychopharmacology in 2015. The new trial is expected to conclude in 2020 and, if successful, could lead to a larger study designed for FDA approval—following a similar trajectory to the MDMA trial process. Sponsors and collaborators are either academic or nonprofit and include the University of New Mexico and The Heffter Institute. Researchers are also looking into the use of psilocybin in combination with cognitive behavioral therapy for smoking cessation, and possibly as part of treatment for other substance-abuse disorders.

A caution:While both MDMA and psilocybin show promise for hard-to-treat psychiatric disorders, it’s important to keep in mind that the conditions in these studies were strictly controlled and the patients meticulously monitored during treatment. As we warned previously, these drugs should never be tried outside of medical monitoring. MDMA in particular has been linked to numerous adverse health effects, according to the NIH’s National Institute on Drug Abuse.

Also see Recognizing and Treating PTSD.