Science & Health
Millions Of Americans With Depression Could Be Eligible For Psilocybin Therapy If Approved By FDA, Study Shows
As many as 6 in 10 people currently receiving treatment for depression in the U.S. could qualify for psilocybin-assisted therapy if the treatment were approved by the Food and Drug Administration. That’s according to a recent study in the journal Psychedelics that highlights the broad impact that could result from wider clinical availability of the entheogen.
“Our findings suggest that if the FDA gives the green light, psilocybin-assisted therapy has the potential to help millions of Americans who suffer from depression,” Syed Fayzan Rab, an MD candidate at Emory University, and the study’s lead author, said in statement about the report. “This underscores the importance of understanding the practical realities of rolling out this novel treatment on a large scale.”
The study, authored by a three-person team from Emory, the University of Wisconsin and UC Berkeley and published last month, sought to estimate the upper, midrange and lower boundaries of current depression patients—including both major depressive disorder (MDD) and treatment-resistant depression (TRD)—who would likely be eligible for the psychedelic treatment. Its low-end figure is 24 percent, the midrange estimate is 56 percent and the upper boundary is 62 percent of current patients.
Overall, the report gives a range of estimates on the number of depression patients who’d qualify for psilocybin therapy, with between 4.7 million and 6.6 million MDD patients and between 1.4 million and 1.9 million TRD patients potentially eligible.
“These ranges highlight the potential variability in our estimates based on changes in the assumptions underlying comorbidity prevalence, emphasizing both the robustness and the uncertainty inherent in our projections,” the paper says.
Behind the wide range of estimates are open questions about who would be eligible for psilocybin-assisted therapy (PSIL-AT). For example, authors said the variance was “largely influenced by the removal of alcohol and substance use disorders as exclusion criteria” as well as analysis of other comorbidities that may or may not affect patient eligibility.
Other issues involve the degree to which healthcare providers would dispense psilocybin for off-label use (meaning for conditions other than depression), whether treatment is covered by insurance and whether other psychedelics—for example LSD—become available as alternatives to psilocybin.
“Perhaps most importantly, the prospective demand will be shaped by the extent to which insurers, both public and private, include PSIL-AT in their coverage schemes,” authors wrote. Medicaid, the paper points out, is the largest health care payor in the nation, and “18%–20% of its beneficiaries are likely to have clinical depression. Thus, decisions Medicaid makes regarding conditions under which PSIL-AT services are made available and reimbursed will be particularly important in determining effective demand.”
Widespread off-label use of psilocybin after hypothetical FDA approval, meanwhile, “could elevate demand beyond our projections,” the team said, while FDA approval of LSD for generalized anxiety disorder might lead to off-label use for depression, potentially replacing psilocybin in some cases.
“If these other psychedelics are given FDA approval in the future,” authors noted, “the demand estimate would need to be modified to distribute across the relative uptake of all psychedelics that have therapeutic effects on depression.”
Other issues that could affect uptake—and outcomes—around psilocybin include the availability of trained healthcare providers capable of dispensing the drug and supporting its integration into therapy.
“The range of eligibility estimates (24%–62%) highlights the need for flexible healthcare planning and resource allocation strategies,” the paper says. “Policymakers and healthcare providers must prepare for this variability by ensuring that sufficient resources—including trained therapists, facilities, and financial support—are available to meet demand under various scenarios. This flexibility will be crucial as more data becomes available post-FDA approval, allowing for adjustments in resource distributions and ensuring equitable access to PSIL-AT across diverse populations and regions.”
Authors said their analysis strove to capture a realistic picture of who would be eligible for psilocybin-assisted therapy, using federal health data to estimate the number of depression cases in the U.S. They then focused on individuals who received treatment within the past year and “further adjusted to estimate the number of individuals who would qualify as having [treatment-resistant depression].”
“In focusing on individuals currently undergoing treatment for depression, our approach ensures that demand estimates are grounded in real-world clinical settings, where PSIL-AT will likely be administered should they receive FDA approval,” the study says. “This allows us to work with a population whose treatment-seeking behaviors and clinical profiles are well documented, providing a reliable foundation for demand estimation.”
Authors noted the methodology also avoids “speculative assumptions about the future behavior of untreated individuals (acknowledging a potential influx post-FDA approval), ensuring that our projections remain conservative and methodologically consistent.”
Study co-author Charles Raison, who is also the lead investigator on a clinical trial looking at the efficacy of psilocybin for depression, called the team’s analysis “a crucial first step” but said researchers have “only scratched the surface in understanding the true public health impact psilocybin therapy might have.”
“Ultimately, the realizable potential of this treatment rests in the hands of regulatory bodies, policymakers, insurers, and the healthcare community at large,” Raison said in a news release. “It’s our hope that these findings spur productive discussions and proactive preparations to optimize the benefit to patients while minimizing unintended consequences.”
Separately, results of a clinical trial published by the American Medical Association (AMA) last December “suggest efficacy and safety” of psilocybin-assisted psychotherapy for treatment of bipolar II disorder, a mental health condition often associated with debilitating and difficult-to-treat depressive episodes.
AMA also published research last year finding that people with major depression experienced “clinically significant sustained reduction” in their symptoms after just one dose of psilocybin.
Earlier this year, the federal government itself published a web page acknowledging the potential benefits the psychedelic substance might provide—including for treatment of alcohol use disorder, anxiety and depression. The page also highlights psilocybin research being funded by the federal government into the drug’s effects on pain, migraines, psychiatric disorders and various other conditions.
Posted on the website of the National Center for Complementary and Integrative Health (NCCIH), which is part of the National Institutes of Health, the page includes basic information about what psilocybin is, where it comes from, the legal status of the drug and preliminary findings around safety and efficacy. The NCCIH page highlights three possible areas of application: alcohol use disorder, anxiety and existential distress and depression.
Yet another promising application for psychedelics could be pain management. NCCIH notes on its psilocybin page that the agency is currently funding research to study the safety and efficacy of psychedelic-assisted therapy for chronic pain, while other federally funded research is looking into “the effect of psilocybin on people with chronic low-back pain and depression in regard to their emotions and perceptions of pain.”
Separate research published this year on psilocybin found that it’s unlikely that a single experience with the drug changes people’s religious or metaphysical beliefs—though it may affect their perception of whether animals, plants or other objects experience consciousness.
Findings of another recent study suggests that the use of full-spectrum psychedelic mushroom extract has a more powerful effect than chemically synthesized psilocybin alone, which could have implications for psychedelic-assisted therapy. The findings imply that the experience of entheogenic mushrooms may involve a so-called “entourage effect” similar to what’s observed with cannabis and its many components.
A separate study published by the American Medical Association found that single-dose psilocybin use was “not associated with risk of paranoia,” while other adverse effects such as headaches are generally “tolerable and resolved within 48 hours.”
That study, published in JAMA Psychiatry, involved a meta-analysis of double-blind clinical trials where psilocybin was used to treat anxiety and depression from 1966 to last year.
Yet another recent study of emergency first responders suggests that a single self-administered dose of psilocybin can help “to address psychological and stress related symptoms stemming from a challenging work environment, known to contribute to occupational burnout.”
