In an age where mental health matters more than ever, new treatments like psychedelics are pushing the boundaries of traditional psychiatry. Among these new therapies, psilocybin—the psychoactive compound found in some mushrooms—looks like a big deal.

A groundbreaking study in the Journal of Affective Disorders uncovers psilocybin’s potential to help U.S. military veterans with severe treatment-resistant depression (TRD). When other treatments fail, a single dose of psilocybin can provide big relief and maybe even change the face of mental health treatment, especially for the heroes who served.

This article looks at psilocybin in the context of this study, its mechanisms, veterans and complex mental health profiles, and the challenges and future of psychedelic treatments.

What is Psilocybin and its Connection to Mushrooms?

Psilocybin in Nature and Culture

Psilocybin is found in over 200 species of mushrooms, known as “magic mushrooms." Psilocybin mushrooms have a long history of use in spiritual and religious rituals. Indigenous groups in Mesoamerica, like the Mazatec and Mixtec, used psilocybin containing mushrooms in shamanistic rituals where they were used to induce altered states of consciousness believed to give spiritual insight or healing.

In the 20th century, modern science discovered the therapeutic potential of these mushrooms after some controversial but interesting research in the mid-1900s. By the end of the 20th century, psilocybin and other psychedelics were made illegal in the U.S. due to social and political pressure. But now attitudes are changing with renewed scientific interest, especially around psilocybin’s mental health applications.

Molecular and Neurochemical Effects of Psilocybin

When ingested, psilocybin is metabolized in the body into psilocin, the compound that produces the psychedelic effects. Psilocin mainly interacts with serotonin receptors—especially the 5-HT2A receptors—in the brain. These receptors are involved in mood regulation, cognition and perception. Interestingly, serotonin is often called the “happiness hormone” and its depletion or dysfunction is linked to mood disorders like depression.

Psilocin temporarily “rewires” the brain, opens up previously stuck or blocked pathways and gives people new perspectives on entrenched emotional and behavioral patterns. This “reset” can help alleviate the hopelessness of chronic mental health conditions, often called a “mental reboot." For those with treatment-resistant depression, this pharmacological action makes psilocybin worth looking into.

The Mental Health Crisis for Veterans

Statistics and the Scope of the Problem

Veterans are disproportionately affected by mental health issues when they transition back to civilian life. Many veterans experience major depression which adds to the complexity of their mental health challenges. According to the National Institute of Mental Health (NIMH) 13.5% of U.S. veterans have major depressive disorder (MDD), several points higher than the general population average of around 7%. What makes their depression more difficult is that many veterans have “treatment resistant” depression, meaning they have tried multiple treatments—SSRIs, CBT, ECT—and nothing has worked.

Adding to the complexity is the frequent co-occurrence of other disorders like Post-Traumatic Stress Disorder (PTSD) and anxiety disorders from the traumatic and stressful experiences many have during combat and active service. Finding a one-size-fits-all treatment for these intersecting issues has been impossible. Chronic pain, substance abuse and insomnia in many veterans with depression make managing these conditions a huge challenge.

The Need to Address Veteran Depression

The long-term effects of untreated or undertreated depression symptoms in veterans are alarming, especially when you consider the link between depression and suicide rates. Veterans are 13.5% of adult suicides in the U.S. and are only 7% of the population. This is a mental health crisis. Since conventional treatments don’t work, we need innovative solutions. Psilocybin therapy could be part of the solution.

Key Findings from the Pilot Study

Study Overview

The recent open-label pilot study published in the Journal of Affective Disorders was a depression treatment study with 15 U.S. veterans, all with treatment-resistant depression. Each participant received a single dose of 25 mg of psilocybin in a controlled setting with psychological support. After just 3 weeks, 60% of the participants had a 50% reduction in depression scores on the Montgomery-Åsberg Depression Rating Scale (MADRS) a commonly used tool to measure depression severity. 53% of the participants went into full remission, meaning their depression scores were 10 or below, which is considered mild or no depression.

This is huge since a single dose had long-lasting effects. By 12 weeks, 47% of the participants still had their initial improvement and 40% were still in full remission.

Why This Matters

The fact that over 50% of the participants went into remission after a single dose is huge for two reasons. First, conventional treatments require daily medication with inconsistent results. Second, many patients don’t feel significant relief until weeks or months into treatment. The fast-acting nature of psilocybin therapy eliminates these barriers to recovery.

How the Study Was Conducted

Study Methodology

This was an open-label pilot study, a common design used early in testing experimental treatments. The researchers measured changes in depression severity and captured the participants’ mental states at several points: baseline (before the psilocybin dose), 3 weeks post-administration and 12 weeks.

Screening and Baseline Protocol

Participants were selected based on a diagnosis of treatment-resistant depression meaning they had failed at least 5 antidepressant medications. Before receiving the psilocybin, they were tapered off their current medications—important to avoid drug interactions. This was longer than other studies with shorter tapering windows, making the administration of the psychedelic safer.

Psilocybin Session and Psychological Support

The psilocybin sessions were in a calm, controlled environment. Participants lay down, often with eyeshades and soothing music, and had experienced guides or therapists with them throughout the session to support and help integrate emotions or memories that came up during the experience. This integrative approach—combining the psilocybin session with therapy—is believed to amplify the therapeutic effect of psilocybin and catalyze deep emotional breakthroughs that translate into big reductions in depressive symptoms and ease of depression.

How the Psychedelic Experience Affects Treatment Resistant Depression Recovery

The Mystical Experience Hypothesis

One of the interesting findings from the study, which was focused on severe depression was that improvements in depressive symptoms didn’t necessarily correlate with the intensity of the psychedelic experience as measured by the Five-Dimensional Altered States of Consciousness Scale (5D-ASC). Previous studies have suggested that the depth of the “mystical experience” was the key to psilocybin’s antidepressant effects but this study suggests another mechanism is at play.

Challenging the Status Quo: Intensity Isn’t Everything

This departure from previous thinking suggests that there may be chemical or neurobiological processes at play that aren’t related to the participant’s subjective experience. While insights gained during the psychedelic experience certainly help with recovery by allowing patients to reframe emotions and thoughts, the long-lasting neural changes may be the core of psilocybin’s antidepressant effects. The lack of correlation between “intensity” and effect has opened up more possibilities to explore, and it’s important to understand how sub-psychedelic doses or microdosing might also affect depression without inducing a full-blown psychedelic experience.

Can Psilocybin Also Treat Post Traumatic Stress Disorder and Other Comorbidities?

PTSD, Depression and Psychedelics

Many military veterans have depression but also PTSD, a condition characterized by flashbacks, anxiety and a hyperactive stress response. The study found that the benefits of psilocybin were seen in veterans with comorbid PTSD. This doesn’t mean psilocybin treats PTSD directly, but rather that by addressing the underlying depressive symptoms, including treatment-resistant unipolar depression, the overall mental health burden in veterans is reduced.

This raises the question of whether psilocybin could be used in integrative treatments for PTSD. Some studies have already suggested that psychedelics, including MDMA, can be used to treat PTSD. If psychedelics can help a person reprocess and make sense of traumatic memories in a safe therapeutic environment, they might help with the root causes of both PTSD and depression.

Co-Occurring Issues and a Holistic Approach to Healing

Veterans often have other issues such as anxiety, sleep disorders and substance use disorders. A key takeaway from the pilot study is that the therapeutic effects of psilocybin may go beyond just improving depressive symptoms. In fact, the relief from depression can indirectly help with other mental health issues such as insomnia and chronic stress. These findings make psilocybin a multi-tool that can address complex mental and emotional distress in ways that traditional medicine can’t.

Safety and Absence of Adverse Effects

Common Fears about Psychedelics

There has been a stigma around psychedelics for a long time due to safety concerns. Much of this is due to the rise of recreational use in the 1960s and 1970s, which led to widespread prohibition. Psychedelics are often seen as causing psychological breakdowns, dangerous behavior or permanent changes in perception (such as hallucinogen persisting perception disorder (HPPD) often called “flashbacks”).

Safety Findings in the Study

Fortunately, the study with veterans didn’t report any serious adverse psychological effects. No participants had increased suicidal ideation and there were no incidents of distressing psychological reactions. Some participants did report emotional or challenging moments during their psilocybin experience (common in psychedelic therapy), but this was expected and handled properly with the psychological support in place. This is in line with a growing body of evidence that suggests when administered in a controlled therapeutic setting, psychedelics like psilocybin are both safe and effective.

Risks vs. Traditional Treatments

Traditional antidepressants like SSRIs have their own set of risks, especially in long-term use. Side effects like weight gain, sexual dysfunction and emotional numbing are common reasons why many patients stop their medication. No such long-term side effects have been reported with psilocybin-based therapies to date.

Psilocybin vs Other Depression Studies

What the Research Says

Research on psilocybin and depression is growing and the findings are consistent across different demographics and risk factors. For example, studies by Carhart-Harris (2016) and Goodwin (2022) showed similar response rates of 60–70% in individuals with moderate to severe treatment-resistant depression. These studies were done on non-veteran populations and further validated psilocybin’s efficacy and fast-acting antidepressant effects.

Veterans as a Unique Population

The military population has unique challenges, mental health issues related to combat exposure, the adaptive disconnect between military and civilian life and physical injuries. While the research has shown psilocybin’s benefits for depression, this veteran-specific dataset offers insight into what a tailored mental health intervention might look like for this group.

Why Open-Label Studies are Important in Psychedelic Research

Open-Label Trials

Open-label studies where both the participants and researchers know what treatment is being given are often the first step in the research process and are crucial in laying the groundwork for more rigorous randomized controlled trials (RCTs). For an ethically complex and new area of research like psychedelics, open-label trials allow researchers to assess efficacy and safety before moving into larger studies, effectively creating a stepping stone for future research.

Open-Label Limitations

Of course, open-label designs lack placebo control, so there could be bias. Participants may experience a placebo effect where psychological expectations influence outcomes. But in situations where gold standard RCTs can’t be done immediately, open-label studies are a necessary tool to determine if further research is warranted.

Study Limitations

Small N

15 participants is a small sample size, so the study has limited statistical power. For treatment recommendations, larger cohort studies and RCTs will need to replicate these findings.

No Control Group

The lack of a placebo group introduces bias since knowing you are getting a “new” or “exciting” treatment can improve moods and perceptions. Future studies need control groups to separate the drug’s effects from placebo effects.

Long-Term Variability

Another consideration is to look at longer-term follow-ups beyond 12 weeks to see how the results hold up over time. While impressive in the short term, long-term sustainability is key to understanding the real-world potential of psilocybin in treatment.

Implications for Future Mental Health Care

Revolutionizing Psychiatry

Psilocybin and psychedelics in general are a new frontier in psychiatry, especially for treatment-resistant populations like veterans. The value is not just in the relief it provides but in the potential to change the approach to mental health, more holistic individualized treatments that combine medicine, psychology and social reintegration.

Veteran-focused mental health programs may soon include psychedelic-assisted therapy, which will focus not just on treating symptoms but on creating healthier, more sustainable emotional and cognitive frameworks for patients.

Filling the Gaps

One of the biggest advantages of psilocybin research for veterans is that it can fill the huge gaps left by current treatments. Veterans will benefit most from treatments that address depression and also the comorbid conditions that add to the mental health burden.

Funding and Research Independence

Funding from Compass Pathways

Research like this pilot study doesn’t come cheap. While psilocybin looks promising, funding for psychedelic research is scarcer than traditional pharma research. In this case, the support of Compass Pathways—a company developing psilocybin therapy for mental health conditions—made this study possible.

Industry-Funded Research: Ethical Considerations

Industry funding can raise concerns about independence. But without this funding, psychedelic research would be underfunded or rare, if not absent. As the regulatory landscape improves, including FDA approval pathways, industry-funded initiatives will work alongside academic research to ensure the rigor of the studies while maintaining independence.

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Psilocybin and the Mushroom Wellness Revolution

Psilocybin is just one piece of the larger mushroom wellness phenomenon. For example non-psychedelic mushrooms like lion’s mane, reishi and chaga are popular for their claimed benefits like boosting cognitive function, supporting immune health and reducing stress.

As consumers are using functional mushrooms for daily wellness, the social acceptance of psilocybin as a mental health treatment is growing. We are seeing a mushroom renaissance where more people are looking beyond conventional medicine to natural holistic therapies that focus on plant-based and fungus-derived wellness.

Bright Future for Psilocybin Therapy

This pilot study shows psilocybin could be a game changer for veterans with treatment-resistant depression. Psilocybin’s ability to reduce depressive symptoms quickly sometimes in a single session is huge for those who have gotten little relief from conventional treatment.

But there’s more work to be done. Future research should focus on larger placebo-controlled trials to understand the mechanisms, optimal dosing, and experience-based variables that contribute to psilocybin’s success in TRD. Tailoring psychedelic-assisted therapy to the painful and often complex experiences of veterans will ensure that the many mental health struggles of these individuals are addressed.

As the regulatory landscape evolves and becomes more psychedelic-friendly, rigorous and ethical research will be the key to turning these early results into mainstream treatments.

Taking Action: Psychedelic Therapy Advocacy

As psychedelic therapies gain traction, patients, clinicians and advocates should demand more research and awareness. Whether you’re a veteran, a clinician looking for new treatments or an advocate of psychedelic medicine, stay informed and get involved. Check out current studies, attend seminars and advocate for the destigmatization of responsible psychedelic use.

Psychedelic research is in its infancy but the ground is moving. Follow our blog for psilocybin research and mushroom wellness updates.

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Key Takeaways

• Psilocybin origins: Psilocybin found in over 200 mushroom species has spiritual and ritualistic roots and is being researched for medical use.

• Mental health crisis among veterans: Veterans have higher rates of treatment-resistant depression and co-occurring conditions like PTSD so new interventions are needed.

• Study results: A single dose of psilocybin resulted in long-term depression reduction for over 60% of depressed veterans in a pilot study, and nearly 50% achieved full remission.

• Pilot study design: 15 veterans were followed for 12 weeks post-therapy, and improvements in depression were seen regardless of the “intensity” of the psychedelic experience.

• Comorbid PTSD: Psilocybin may be a double whammy for veterans with depression and PTSD; it’s a versatile treatment.

• Safety: Controlled studies show psilocybin, when used responsibly with professional support is safe and free of long-term severe adverse effects.

• Future of psychiatry: Psilocybin therapy could be a game changer for mental health treatment, especially for those who don’t respond to conventional treatments.

• Cultural wellness: As functional mushrooms become more mainstream, psilocybin therapy is becoming more acceptable in the health and wellness space.

Check out our blog or research updates for more on psilocybin and psychiatry.