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Beyond the Veil

How Psychedelics are Reshaping Depression Treatment

Olivia Florence

📅 2023-08-24

The world is currently grappling with a critical spike in mental illness, with depression ranking among the most burdensome social and medical challenges. Affecting approximately 15% of the general population at least once during their lifetime, depression has become a pressing global concern. Over the last decade the UK's need for prescription antidepressants has more than doubled and the demand is starting to exceed the supply (NHS Digital, 2017). The exact cause of depression is not known or fully understood. Conventional approaches to treating depression, such as antidepressant medications and psychotherapy, have faced limitations in providing long-lasting relief. However, the psychedelic renaissance is upon us, challenging the status quo and igniting a profound shift in our understanding and approach to mental health treatment.


As the veils of stigma and outdated paradigms are lifted, swarms of studies have recently resurrected the potential therapeutic value of substances such as LSD, DMT and Psilocybin (Carhart-Harris, et al 2021; Nutt, 2020). A radical collaboration of psychedelic-assisted psychotherapy has been bolstered by mainstream narratives and labelled by the US Food & Drug Administration (FDA) as a break-through therapy (Nutt, 2020).

Unpacking Psychedelic-Assisted Psychotherapy

Psychedelic-Assisted Psychotherapy (PAP) involves administering mind-altering substances such as LSD, DMT, and Psilocybin, in conjunction with psychotherapy sessions. These substances, commonly referred to as psychedelics, have a long history of therapeutic research. The word psychedelic is derived from the Ancient Greek word meaning "mind-manifesting" and was first coined by British psychiatrist, Humphrey Osmond, in 1957. The term psychedelic seemed to serve well as an encompassing term that described the mysterious and mystical effects of mind-altering substances.

Today, most contemporary medications are derivatives of drugs discovered in the 1950s that have been refined through pharmacological modifications. Current selective serotonin-reuptake inhibitors (SSRI) are merely variations of Prozac, first marketed in 1988, meaning nothing substantially new has been produced in the field of psychiatry for decades (Nutt at al., 2020). However, recent years have witnessed a rebirth in psychedelic research, re-examining the potential therapeutic value of substances like Psilocybin (otherwise known as magic mushrooms). PAP represents a radical collaboration that embraces altered states of consciousness in combination with psychotherapy, offering a new and innovative treatment model for mental illness.

How Psychedelic-Assisted Psychotherapy Works

Zooming in at a neurological level, psychedelics are believed to deregulate the default mode network in the brain, which is responsible for encoding habits of thought and behaviour. The default mode network is a part of the brain, where the neural pathways are most associated with introspection, self-awareness and mind-wandering. Psychedelics offer a unique neurological chance to rewire the brain's cross-cortical connections through downstream effects, acting as agonists on the serotonin 2A receptor. This process has been linked to heightened brain activity and enhanced neuroplasticity. A long-recognised critical component of PAP as a treatment model is the context in which the drug has been ingested. This is known as 'set' and 'setting' with 'set' being the mental space the participant brings to the experience and 'setting' the physical environment (Leary et al.,1963). It is vitally important for the participant to feel comfortable and safe in order to get the best therapeutic outcome. In most clinical trials, participants are placed in a comfortable room with peaceful music and were asked to close their eyes and focus on their body, thoughts and emotions.

The brain connectivity on a placebo compared to on Psilocybin
The brain connectivity on a placebo compared to on Psilocybin
(Nutt & Carhart-Harris, 2020)

One significant advantage of psilocybin over anti-depressants is that anti-depressants only work as protectors against the stressors that perpetuate depression, but do not directly access the underlying root cause of the depression. PAP appears to create a neurological window of opportunity in which to harness the psychedelic experience, allowing the patient to explore the deepest recesses of their mind. With the guiding hand of psychotherapy, this transformative journey unlocks sincere insight, offering potential remedies for the root causes of depression through introspection and lifestyle revision (Carhart-Harris & Nutt, 2017). Moreover, the psychedelic experience unveils the enchanting \"afterglow\" phenomenon, originally described by Pahnke (1969) as an 'elevated and energetic mood with a relative freedom from concerns of the past and from guilt and anxiety'. This empowers therapeutic interventions, allowing patients to revisit uncomfortable memories and thoughts without the usual distressing encumbrance.

Cost-Effectiveness and Long-Term Considerations

Magic mushrooms alongside psychotherapy in action at the clinical
trials in London
Magic mushrooms alongside psychotherapy in action at the clinical trials in London.
(Imperial College London / Thomas Angus)

Psychedelic-Assisted Psychotherapy (PAP) shows promise in treating treatment-resistant depression, but its extensive therapy sessions make it a costly and time-consuming option. The current format of PAP involves multiple weekly therapy sessions, often with both male and female therapists present during the psychedelic session, which can last up to six hours (Carhart-Harris & Nutt, 2017). Additionally, integration sessions with the same therapists in the days following the experience form an integral part of PAP to assimilate any newfound outlook into the participant's everyday life. Integration contributes to the treatment's overall cost, making it potentially hard to access and in short supply.

In contrast, cognitive-behavioural therapy (CBT) is the most commonly offered intervention for depression due to its cost-effectiveness (Byford et al., 2007). However, research suggests that CBT's efficacy may diminish over time, leading to the return of depressive symptoms for many patients (Ali et al., 2017; Johnsen & Friborg, 2015). Given the world's current mental health crisis, exacerbated by the global pandemic's impact, adopting a more humane approach with longer-term considerations becomes imperative. Providing patients with multiple effective treatment options, including PAP, could prove beneficial both economically and therapeutically. While there is significant evidence suggesting that PAP is a superior treatment model compared to traditional antidepressants, some conflicting views have recently emerged. A double-blind, randomised, controlled trial by Carhart-Harris et al. (2021) compared the effects of psilocybin (a psychedelic) to escitalopram (an anti-depressant) in patients with long-standing major depressive disorder. Surprisingly, no significant difference was found in the antidepressant effects between psilocybin and escitalopram. However, secondary outcomes favoured psilocybin over the anti-depressant, and considering the lower toxicity and fewer treatment sessions required for PAP, it may still present a compelling alternative (Roberts et al., 2020).

The brain connectivity on a placebo compared to on Psilocybin
Dr Robin Carhart-Harris and the committee of The Psychedelic Research Society at The University of Sussex
(a shamefully obvious plug)

The Power of Qualitative Evidence

When considering new treatment models, assessing the qualitative nature of these treatments becomes paramount for understanding patients' subjective experiences. A six-month follow-up qualitative analysis of participants in Imperial College London's pilot study on psilocybin-assisted therapy revealed two major themes (Watt et al., 2017). Participants reported a transformation from a sense of disconnection to connection and a shift from emotional avoidance to acceptance, nurturing a renewed sense of connectedness to both the outward and inward world. One participant, who underwent a psilocybin session, shared their reflective experience:

"The dose (of psilocybin) helped me realise why I felt the pain in my chest, I saw it visually and felt it emotionally, then I felt so much lighter, like something had been released. It was an emotional purging; the weight and anxiety and depression had been lifted."

Connectedness to the world around us plays a significant role in psychological well-being. It provides us with an intuitive sense of purpose and meaning. Conversely, a sense of disconnection has been associated with and thought to contribute towards mental illnesses, particularly depression. Psychedelics seem to neurologically rekindle an innate desire to change, creating meaning through connection and re-envisioning the world around them.

Call-to-Action: Advocating for a Brighter Mental Health Future

The powerful fusion of psychotherapy with mind-expanding psychedelic drugs paves the way for transformative healing, transcending the limitations of conventional antidepressants. As the evidence supporting psychedelic-assisted psychotherapy remarkable benefits continues to mount and gain peer acceptance, it emerges as a beacon of hope and a viable intervention for severe depression. Embracing this innovative approach not only advances our comprehension of mental illness but also unlocks the door to desperately needed answers, fostering a brighter and more hopeful future for mental health. Collectively, we can shape a world of healing possibilities and ignite a great revolution in the lives of those battling depression.

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