The Potential of Psychedelics in Treating Depression

The State of Depression Treatment

Depression affects over 260 million people worldwide, a number that has likely increased in the wake of the COVID-19 pandemic. Traditional treatments for depression, including various forms of psychotherapy and medications like SSRIs, SNRIs, TCAs, and MAOIs, often fall short for many individuals, leaving them with persistent symptoms and unwanted side effects. This has led to an urgent need for alternative treatments, and psychedelics are emerging as a promising option.

Depression affects over 260 million people worldwide, a number that has likely increased in the wake of the COVID-19 pandemic, which exacerbated many of the social, economic, and personal stressors that contribute to depression. Traditional treatments for depression, including various forms of psychotherapy and medications like SSRIs (Selective Serotonin Reuptake Inhibitors), SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors), TCAs (Tricyclic Antidepressants), and MAOIs (Monoamine Oxidase Inhibitors), are effective for some, but frequently fall short for many. These treatments can been criticized for leaving patients with persistent symptoms, such as chronic sadness, fatigue, and a lack of motivation, which are then often accompanied by unwanted side effects like weight gain, sexual dysfunction, and emotional numbness.

Most antidepressants work by altering the levels of neurotransmitters in the brain, such as serotonin and norepinephrine, which play a role in mood regulation. However, these medications are intended to manage symptoms and do not address the underlying causes of depression, such as trauma, unresolved emotional issues, or maladaptive thought patterns. They typically require several weeks to take effect, and even then, many patients do not achieve full remission.

Psychedelics are emerging as a promising alternative option. Psychedelics, such as psilocybin (found in magic mushrooms) and LSD (lysergic acid diethylamide) are being studied for their potential to treat depression in a fundamentally different way. Unlike antidepressants, which are taken daily over long periods, psychedelic therapies have been known to lead to breakthroughs even after a single session. When accompanied by psychotherapy, treatments are known as psychedelic-assisted therapy.

Remember, negative emotions in response to adverse circumstances is a natural and justified human experience, not necessarily indicative of clinical depression. These emotions are vital for our learning and growth, helping us navigate and respond appropriately to life's challenges. Distinguishing between normal emotional responses and clinical depression is crucial to ensure that treatments are targeted correctly.

Psychedelics a Hopeful Option

Research into psychedelics for treating depression is not new, but recent years have seen a resurgence of interest and progress in this field. Psychedelics like psilocybin, ketamine, ayahuasca, LSD, and DMT are being studied extensively, with many clinical trials showing promising results.

Psilocybin

Known for its use in psychedelic mushrooms, psilocybin has been found to significantly reduce depressive symptoms when administered in controlled, therapeutic settings. This compound, when ingested, is metabolized into psilocin, which acts on serotonin receptors in the brain, particularly the 5-HT2A receptor. This interaction is believed to lead to altered states of consciousness, which can facilitate deep psychological insights and emotional breakthroughs—critical for therapeutic progress.

Research from institutions like Johns Hopkins University and Imperial College London has consistently demonstrated the potential to produce rapid and sustained improvements in mood and mental health. Studies have shown that a single dose of psilocybin, in conjunction with psychological support, can lead to significant reductions in depressive symptoms, with the effects lasting for months after treatment.

One notable study, "Psilocybin with Psychological Support for Treatment-Resistant Depression: An Open-Label Feasibility Study" by Carhart-Harris et al., published in 2016 in The Lancet Psychiatry involved patients with treatment-resistant depression who received two doses of psilocybin. All participants showed some reduction in depressive symptoms at one week, and 67% of participants went into complete remission. At the three-month follow-up, 42% of participants continued to experience significant improvements in their symptoms. The study also highlighted the safety of psilocybin, noting that while some participants experienced temporary anxiety during the peak effects, there were no serious or long term adverse events.

In 2018, due to the growing body of evidence psilocybin was granted "breakthrough therapy" status by the U.S. Food and Drug Administration (FDA) for the treatment of major depressive disorder. This designation helps to expedite the further development and review of drugs that show substantial improvement over existing therapies.

Ayahuasca

Refered to as the “big brother” of psilocybin because of the notably more challenging physical experience, this traditional Amazonian brew, containing the psychoactive compound DMT (dimethyltryptamine) and an MAOI (monoamine oxidase inhibitor) typically derived from the Banisteriopsis caapi vine, has been used for centuries by indigenous tribes in ceremonies. It’s known for inducing intense, often visionary experiences that are integral to its use in healing rituals and spiritual practices. Now in recent years, Ayahuasca has gained attention in the scientific community for its potential therapeutic benefits, particularly in the treatment of depression.

The brew's combination of DMT and MAOIs is believed to work in tandem. The MAOIs prevent the breakdown of DMT in the digestive system, allowing it to cross the blood-brain barrier and exert its psychoactive effects. These effects are thought to promote neuroplasticity, enhance connectivity within brain networks associated with mood regulation, and lead to profound insights. Its ability to foster emotional release has been often cited as a key factor in its effect.

One study, "Rapid Antidepressant Effects of the Psychedelic Ayahuasca in Treatment-Resistant Depression: A Randomized Placebo-Controlled Trial" by Palhano-Fontes et al., published in 2019 in Psychological Medicine, showed that Ayahuasca led to a significant reduction in depressive symptoms, with effects observed just 24 hours after administration and sustained for up to three weeks post-treatment.

LSD (Lysergic Acid Diethylamide)

Despite its cultural baggage and the stigma that emerged during the countercultural movements of the 1960s, LSD has been revisited by researchers for its potential to treat mood disorders. Early studies then suggested that LSD could be effective in treating a variety of mental health conditions, including depression, anxiety, and alcoholism and could help patients achieve significant psychological insights.

LSD has been shown to influence the brain's default mode network (DMN), a network of interconnected brain regions that is often overactive in individuals with depression. In the study, "Psychological Flexibility Mediates the Relations Between Acute Psychedelic Effects and Subjective Decreases in Depression and Anxiety" by Davis et al., published in 2020 in Frontiers in Psychology, it was found that one of the mechanisms by which LSD may increase psychological flexibility—the ability to adapt to changing circumstances, shift perspectives, and embrace new ways of thinking and behaving—qualities that are often impaired in individuals with mood disorders. Those that reported this effect also reported significant reductions in depression and anxiety symptoms, helping individuals reframe negative thought patterns, reduce rumination, and foster a greater sense of connection and meaning in their lives.

DMT (N,N-Dimethyltryptamine)

Synthetic DMT is a powerful and short-acting psychedelic compound with trips typically lasting 30 minutes or less. Injected or inhaled from a vaporizer, experiences are known for their intensity intensity. This short and intense approach has been gaining DMT attention in the scientific community for its potential.

In the world’s first trial study, conducted by Small Pharma in collaboration with Imperial College London, titled "A Phase I/IIa Trial of DMT for Major Depressive Disorder,” it was found that DMT combined with psychotherapy led to significant reduction in depressive symptoms of MDD.

DMT also has an effect of interrupting the Default Mode Network, which is often hyperactive in individuals with depression. This allows for a temporary disruption of entrenched thought patterns. This disruption, combined with the intensity of experiences induced by DMT, can facilitate significant shifts and help individuals gain new perspectives into their depression.

Unlike naturally occurring DMT, which is found in various plants and is a key ingredient in the traditional Amazonian brew Ayahuasca, synthetic DMT can be precisely dosed and administered in controlled clinical settings, offering a more standardized approach to studying its effects.

Psychedelic experiences may have a profound impact on depressive symptoms.

It is important that you are in the right mindset and setting for your psychedelic experience. Stable Pathways Group and Lucid Cradle will assure your support and comfort with your experience using Psilocybin.

The Path Forward

Several companies and research institutions are at the forefront of developing psychedelic treatments for depression. One of the leaders, COMPASS Pathways, is conducting extensive clinical trials using synthetic psilocybin for treatment-resistant depression (TRD). Their synthetic psilocybin compound, COMP360, is now being investigated in larger-scale, Phase 2B clinical trials. Similarly, Atai Life Sciences is exploring DMT and other synthetic compounds, leveraging advances in biotechnology to optimize the delivery and efficacy of these treatments.

The growing acceptance and integration of psychedelics into mainstream mental health treatment are also evident in policy changes. Oregon has emerged as a leader in this field, becoming the first U.S. state to legalize the supervised use of psilocybin for adults age 21 and over. They have developed the first modern regulatory framework that supports the safe and effective use of psychedelics in mental care.

Within Oregon’s legal framework, Lucid Cradle has established itself as leaders in providing psilocybin services, offering primarily one-on-one experiences designed to help individuals navigate their depressive issues safely and effectively. To support individuals traveling to Oregon, Stable Pathways Group offers comprehensive destination management services, ensuring that clients receive top-notch care and support throughout their travels, including logistical planning, on-the-ground assistance, and private transportation, creating a seamless and supportive environment for those seeking psilocybin treatment in Bend, Oregon.

These advancements reflect a broader trend toward integrating psychedelics into the mainstream mental health treatment. With ongoing research, regulatory progress, and the establishment of specialized clinics and services, the future of mental health care may be profoundly transformed by these once-stigmatized substances.

If you’re ready to embark upon your personal journey, contact Stable Pathways Group for your consultation.