From Microdosing to Executive Order: Are We Still Chasing the Same Chemical Fix?

By Elizabeth Curley

A new executive order (EO) is making headlines, “Accelerating Medical Treatments for Serious Mental Illness.” This EO focuses on expediting clinical trials, emergency access, and possible rescheduling of psychedelics. Priority vouchers will be given to Psilocybin and Methylone; Ibogaine compounds, LSD, and other compounds may benefit later. 

This EO is responding to a real and urgent problem: millions of Americans suffer from serious mental health challenges, including veterans with severe PTSD, who have received no relief from current pharmacological options and standard treatment. 

It is important to address one of the rhetorical hinges of the door this EO is hanging: so-called treatment-resistant depression. The most used definition of this term is inadequate response to a minimum of two antidepressants despite adequacy of treatment trial and adherence to treatment. 

Setting aside the sticky question of “adherence,” it’s important to note that this definition equates “treatment” with medication, despite non-drug options like exercise often performing better than antidepressants alone. None of this is to dismiss the very real suffering of people who have tried multiple medications without success; desperation is understandable and the search for better options is valid. 

The landscape of mental health treatment is so vast that equivocating “treatment” to “medication” is a very sneaky false premise, similar to the effects of calling adverse or negative effects from drugs “side effects” to prime us to expect them to be minimally impactful. Additionally, “treatment-resistant depression” is a somewhat misleading label, as antidepressants are often ineffective for many people. What looks like resistance might simply be the ordinary failure rate of a treatment with limited overall efficacy. 

The EO orders the FDA Commissioner to award Commissioner’s National Priority Vouchers (CNPV) to psychedelic drugs that have already received FDA “breakthrough therapy” designation for serious mental illness and meet the pilot program criteria. This speeds up the paperwork and review but does not guarantee approval. 

It also creates a pathway, through the existing Right to Try Act, for people with severe cases of serious mental health struggles to access these substances while in investigational proceedings. It instructs the U.S. Department of Health and Human Services (HHS) to set aside $50 million from existing funds to match money that the states are already allocating to psychedelic research for serious mental illness. 

The HHS and FDA will also work with the Department of Veterans Affairs (VA) to recruit more patients into trials, share data, and generate more “real world evidence” on these treatment options. Finally, once these psychedelic drugs finish their Phase 3 clinical trials and get FDA approval, they will be fast-tracked for an immediate review and possible rescheduling under the Controlled Substances Act.

This order is effectively the theme-park fast-pass of drug trials; instead of waiting in the normal multi-month or multi-year bureaucratic line at the FDA, qualifying candidates jump to the front to enter the full ride of clinical trials. It does, additionally, open up a limited “express lane” of Right to Try for people designated to have high or imminent suicide risk as defined by their treating doctor. 

This new push continues a trend of alternative pharmaceutical treatment in the mental health space. A simple Google search reveals a whole landscape of at-home ketamine treatment companies, post-2020 saw a boom of people declaring their life-changing experiences with microdosing, and recent online trends shows a viral surge of people taking Pepcid and Allegra together to self-manage PMS and PMDD symptoms. 

A perfect storm of skyrocketing mental health crises, eroded trust in traditional (Western) medicine, and easy access to varying quality information has triggered a patient-driven boom in alternative pharmaceuticals. When patient’s faith in the industry faltered, they searched for alternative treatments in their immediate reach. What ties them together is the same DIY ethos: cheap, accessible, often already-on-the-shelf options that people discovered through TikTok, Reddit, and patient forums when standard treatments fell short. 

Credit where credit is due, though; the research on psilocybin for depression is promising. One review from 2024 analyzed 9 studies and a total of 436 participants found moderate to large positive effects of psilocybin for depression treatment. Another 2024 review on psychedelic use for various mental health conditions found similar results, with the most studies done on psilocybin, followed by ayahuasca and LSD. The researchers found that there were positive results for psilocybin, ayahuasca, MDMA, and LSD for improving mood, with some evidence of benefit for tobacco addiction, sleep disorders, eating disorders, and other mental health struggles. 

While psilocybin still leads the pack in clinical progress, methylone is quickly emerging as a serious contender in the announcements around this new executive order.

Methylone appears to have less research available regarding its usage. One preclinical study from 2023, conducted by researchers at Transcend Therapeutics, (the company developing Methylone for PTSD) was done in collaboration with Yale and VA scientists. In this rat study, methylone showed antidepressant and anxiolytic (anti-anxiety) effects in forced swim and open field tests. 

Notably, the authors specifically examined whether methylone could be used as a companion treatment alongside SSRIs and concluded that co-administration did not reduce its efficacy. Transcend is now actively marketing this finding as a major advantage over MDMA-assisted therapy, which typically required patients to stop SSRIs because of reduced efficacy or safety concerns with interactions.   

It’s telling that when scientists acknowledge the limited efficacy of antidepressants, the reaction is either muted or zealously outraged. Yet, when TikTok ads and pharmaceutical companies make the exact same point to market things like at-home ketamine subscriptions, it suddenly becomes a palatable selling point. 

Rather than racing to the next pharmaceutical fix, what if we paused to absorb the deeper revelation? The industry itself is finally admitting that psychiatric medications simply aren’t working for a great many people.

Although much of the research on psychedelics report no lasting adverse effects on participants (or only minimal ones such as headaches) some studies document possible acute psychological risks and lingering harms. Hallucinogen persisting perception disorder, psychotic symptoms, mood disturbances, and anxiety remain possible outcomes. 

We still do not fully understand the conditions that separate those that benefit from those who suffer. 

We hope that the research process will reveal the safest ways to harness benefits of these substances while minimizing potential harms. But history shows that even widely used medicines can later prove dangerously unsafe, as with Vioxx, a pain reliever withdrawn after it was found to markedly increase the risk of heart attack and stroke. 

Although this EO may fast track psychedelics for meaningful research and clinical trials, it is important to still center them within the systems that have given us many other promising treatments that have multiple edges. We, as a culture, may still be buying into the “silver bullet” belief in pharmacology, but maybe we’re just loosening the reins on which substances we believe will do the fixing.

This EO has the potential to reinvigorate trust in the pharmaceutical industry through a classic sleight of hand; same medical model, different substance. They can swap the drug name, but the belief structure stays untouched: the chemical topography of your brain is where your mind will find relief. 

The point isn’t that these new therapies are doomed to repeat past mistakes. But it does suggest we should approach them with clear-eyed caution, rigorous long-term monitoring, and a willingness to question whether we’re once again betting everything on the next chemical fix. 

While this EO may be more than mere marketing, a genuine attempt to address the suffering of millions who seem to have run out of options, we should pay close attention to whether it ultimately breaks new ground or quietly gets folded back into the same medical-model machinery. If these therapies ultimately prove safe and effective under rigorous and real-world conditions, they could represent a genuine step forward for the many people who are searching for help.