Psilocybin and Depression: Exploring New Treatments for Depression

Can Psilocybin help with depression?

Psilocybin, the naturally occurring compound found in Psilocybe cubensis and other species of psychedelic mushrooms, has recently garnered significant attention for its potential to treat depression, especially in individuals who haven’t responded to traditional therapies. The early results from clinical research are promising, suggesting that psilocybin could become a game-changing tool in the treatment of major depressive disorder (MDD) and treatment-resistant depression (TRD). In this post, we’ll explore how psilocybin works, Micro-dosing to combat depression, what the research says, and what the future holds for this potentially transformative therapy.

How Psilocybin Works in the Brain

Psilocybin works primarily by affecting serotonin receptors in the brain, specifically the 5-HT2A receptor, which plays a key role in mood regulation, cognition, and perception. Here’s how it impacts the brain in ways that may help with depression:

• Neuroplasticity: Psilocybin enhances neuroplasticity, meaning it encourages the brain to create new neural connections. This is critical for people suffering from depression, where rigid, negative thinking patterns often dominate. By promoting new pathways, psilocybin may help patients “reboot” their thought processes and develop healthier patterns of thinking.
• Default Mode Network (DMN): Psilocybin reduces activity in the default mode network, a part of the brain associated with self-referential thought, rumination, and worry—common characteristics of depression. Reduced DMN activity is believed to allow the brain to break free from repetitive, negative thinking patterns, offering a sense of relief from depressive symptoms.
• Altered States of Consciousness: Psilocybin induces a temporary, altered state of consciousness that can bring powerful insights and a sense of connectedness, often leading to emotional breakthroughs. These experiences, when guided by a therapist, can be highly therapeutic.

Clinical Research and Findings

Several studies over the past decade have explored psilocybin’s potential in treating depression, with many focusing on treatment-resistant depression (TRD) and major depressive disorder (MDD). Some key findings include:

1. Johns Hopkins University Study (2020)

A groundbreaking study conducted at Johns Hopkins University found that psilocybin produced substantial reductions in depressive symptoms in patients with major depressive disorder. Notably, 67% of participants experienced a more than 50% reduction in symptoms after just two sessions of psilocybin-assisted therapy. Moreover, 54% of the participants were in remission at the four-week follow-up mark, indicating that the effects of the treatment were both rapid and lasting. Imperial College London Study (2016)

Research from Imperial College London also demonstrated the efficacy of psilocybin in treating depression, particularly TRD. In this study, 12 patients with TRD received two doses of psilocybin alongside therapy. All participants showed reductions in depression severity one week after treatment, and 67% remained depression-free after three months .

Pathways Clinical Trials**

COMPASS Pathways, a mental health care company, has conducted some of the most rigorous clinical trials on psilocybin for TRD. Their Phase II trial results, published in 2021, demonstrated that a single 25 mg dose of psilocybin significantly reduced depressive symptoms compared to a control group, with effects lasting up to three months for some participants.

The dosing used by Compass was 25mg of synthetic Psilocybin – if using a 1% psilocybin content, this equates to 2.5g of dried fruit.

Psilocybin vs. Tradtidepressants

Traditional antidepressants like SSRIs (Selective Serotonin Reuptake Inhibitors) usually take weeks to show effects and must be taken daily. Psilocybin, on the other hand, has shown benefits after just one or two sessions, with effects lasting for months in many cases.

Moreover, antidepressants often come with side effects such as weight gain, sexual dysfunction, and emotional blunting. Psilocybin, when administered in a controlled environment, appears to have minimal long-term side effects, though the experience itself can be emotionally intense and, in some cases, lead to temporary anxiety or discomfort.

Micro-dosing to Combat Depression

At present, most of the evidence supporting microdosing is anecdotal or based on self-reported data. However, small-scale studies and surveys have begun to examine the effects of microdosing on mental health:

• A 2021 study published in the journal Nature-Scientific Reports collected data from over 8,500 participants who microdosed psychedelics, including psilocybin. The researchers found that individuals who microdosed reported lower levels of depression and anxiety, along with improvements in mood, mindfulness, and creativity.
• Another study from the University of British Columbia looked at the mental health effects of microdosing and found that participants showed significant reductions in depression and stress after six weeks of regular microdosing.

However, it’s important to note that most of the current studies on microdosing are observational and rely on self-reporting, which can introduce bias. Controlled clinical trials on the efficacy of microdosing for depression are still limited, and more rigorous research is needed to fully understand its therapeutic potential and safety.

Psilocybin Therapy: More Than Just the Drug

It’s important to note that psilocybin therapy isn’t simply about taking the substance. It is usually part of a broader psychotherapeutic process that includes:

• Pre-treatment counseling: Patients are prepared for the experience and guided through any fears or uncertainties they may have.
• The psychedelic session: In a controlled environment, patients ingest psilocybin under the supervision of trained professionals. The session can last several hours and is often accompanied by calming music or other supportive measures.
• Integration therapy: After the psychedelic experience, patients work with therapists to integrate the insights and emotions they experienced during the session into their everyday lives.

The combination of psilocybin and therapy is thought to amplify the treatment’s effects by helping patients process emotions and reframe their thought patterns in a supportive setting.

Safety and Risks

When administered in a controlled, clinical setting, psilocybin is considered to have a low risk of harm. However, unsupervised use can carry risks, particularly for individuals with a personal or family history of psychosis or schizophrenia, as psilocybin can exacerbate these conditions.

For those not prone to mental health risks, potential side effects during a session might include anxiety, nausea, or difficult emotional experiences, though these are typically temporary and subside after the session ends. In clinical trials, these challenging moments have been framed as part of the therapeutic process, often leading to breakthroughs when properly guided.

Legal Status and Future Directions

While psilocybin remains illegal at the federal level in most countries, there has been growing momentum toward decriminalization and medical legalization. In 2020, Oregon became the first U.S. state to legalize psilocybin for therapeutic use under strict regulation. Cities like Denver, Oakland, and Santa Cruz have decriminalized the personal use of psilocybin, signaling a shift in public perception.

The FDA has also granted psilocybin Breakthrough Therapy Designation for treatment-resistant depression, a designation aimed at expediting the development of treatments that show significant advantages over existing options. With ongoing research, there is potential that psilocybin-assisted therapy could be available as a treatment for depression within the next several years.

Conclusion: A New Hope for Depression Treatment

For individuals battling depression—especially those who have not responded to traditional treatments—psilocybin therapy offers a new frontier of hope. The combination of its rapid onset, long-lasting effects, and minimal side effects in a controlled therapeutic setting makes it a promising alternative to conventional antidepressants.

Though more research is needed, the evidence thus far suggests that psilocybin has the potential to significantly improve the lives of people living with depression, opening the door to new possibilities for mental health treatment.

Sources:

1. Johns Hopkins Medicine (2020). “Study shows psilocybin treatment for major depression effective for up to a year.” Johns Hopkins Medicine
2. Carhart-Harris, R. L., et al. (2016). “Psilocybin with psychological support for treatment-resistant depression: six-month follow-up.” The Lancet Psychiatry. The Lancet Psychiatry
3. COMPASS Pathways (2021). “Psilocybin therapy for depression: Phase II results.” COMPASS Pathways
4. Polito, V., & Stevenson, R. J. (2019). “A systematic study of microdosing psychedelics.” PLOS One. PLOS One
5. Anderson, T., et al. (2021). “Microdosing psychedelics: Personality, mental health, and creativity differences in microdosers.” Nature-Scientific Reports. Nature-Scientific Reports
6. Hutten, N., et al. (2020). “Low dose psychedelics in the general population: An evaluation of microdosing and associated impact on mental health.” Psychopharmacology. Psychopharmacology