This Psychedelic Is Fighting The Good Fight Against Treatment-Resistant Depression

Where traditional treatments are missing the mark, this synthetic psychedelic is making waves against chronic depression.

By Mark Travers, Ph.D. | July 15, 2024

Treatment-resistant depression, or TRD, is a severe condition that can profoundly affect even the most resilient individuals, often leaving them feeling overwhelmed and without hope. With roughly 30% of those experiencing depression not responding to traditional treatments, it's high time we explore beyond conventional solutions.

Take Emma's case, for example. She has tried several antidepressants, various therapy methods and even explored alternatives like acupuncture and meditation—all with little to no relief. Each failed attempt adds layers of frustration and despair, making her feel increasingly trapped in her own mind.

Individuals like Emma, battling TRD, face significant challenges due to the limited understanding of their condition by science. This makes effective psychological intervention crucial yet difficult.

Today, one of the most promising treatments for TRD is electroconvulsive therapy, or ECT. Despite its potential, ECT is often a last resort, underutilized due to lingering stigma and some valid concerns about memory-related side effects. Although there is recognition that ECT should be more accessible to those in need, relying solely on traditional medicine and psychological care to fully embrace and enhance such treatments is not viable when millions are suffering daily.

This Is Why Psychedelic Treatment Research Is Seeing A Renaissance

From the early to mid-20th century, psychedelics have been explored for their potential in treating various mental health issues, especially depression. Psilocybin, a compound naturally found in psychedelic mushrooms and isolated in 1958, was extensively studied until such research was largely halted by regulators in the 1970s.

Today, as the scientific and medical communities revisit psychedelics like psilocybin, a synthetic version of the compound has been developed for clinical settings, promising a new era of effective treatments for those like Emma.

"Investigational COMP360 psilocybin treatment is a synthetic form of psilocybin, manufactured to FDA-mandated good manufacturing practice standards that ensure safety and consistency," explains Steve Levine, SVP, Patient Access and Medical Affairs at biotechnology pioneer Compass Pathways.

We've heard about psychedelic experiences helping people beat various mental health issues ranging from substance use disorder to PTSD. But this is largely anecdotal and also risky, given the unpredictable and uncontrollable nature of such experiences. Dosages may vary, and negative experiences or "bad trips" can remain with people long after the effects of the substance fades away.

However, there is real data to suggest that controlled use of well-regulated synthetic psilocybin can have a positive impact in the treatment process for those who are unable to respond to traditional treatment.

In a study published in November, 2022 involving 233 individuals with TRD, COMP360 demonstrated promising results. The trial, which was the largest of its kind and conducted across 22 sites in 10 countries, showed that after just a single 25 mg dose, about 30% of patients were in remission by week three. What's more, twice as many patients sustained their response at week 12 compared to those who received a minimal dose—1 mg—indicating clinically valid, rapid and durable effects.

How Safe Is This Treatment?

Given that the synthetic psilocybin is manufactured per FDA regulations, the substance itself is safe. However, to understand the safety of the treatment process, understanding the psychological and biological effects of this form of psilocybin is important.

"COMP360 psilocybin is known to interact with a specific serotonin receptor in the brain, an interaction that can alter how people feel and how they perceive themselves and their surroundings. It is thought to help create new connections in the brain, a process known as neuroplasticity," Levine says.

While depression is a complex mental health issue with several causes, one of the most promising approaches to treating it involves enhancing neuroplasticity—the brain's ability to reorganize itself by forming new neural connections.

By activating this ability, COMP360 psilocybin could potentially help "rewire" the brain's pathways that are negatively impacted by depression. This process not only improves symptoms but could also offer a long-term solution by fundamentally changing the brain's response to stress and emotional challenges.

While this sounds very promising, researchers are mindful that special care needs to be taken when individuals actually undergo treatment.

The 2022 study is currently undergoing a follow-up. The protocol for this phase of the trial reflects what actual treatment under the COMP360 treatment might look like in practice. The treatment framework includes comprehensive training for therapists, involving online learning modules, role-play-based workshops and clinical observations.

To maintain quality and consistency, therapists participate in monthly meetings with specially trained mentors. In addition, both the therapists and mentors have access to recordings of the sessions between therapists and trial participants, allowing for detailed feedback and self-assessment.

Moreover, in the current phase, an added layer of oversight is introduced where a third-party vendor monitors these recordings and independent fidelity raters review a sample of the sessions. These raters are tasked with identifying any potential misconduct, ensuring that the therapeutic process adheres strictly to protocol and ethical standards.

Can Our Current Mental Healthcare Infrastructure Support These Innovative Ideas?

Psychedelic treatment is slowly but surely beginning to win favor within the status quo. Compass Pathways has successfully advocated for the creation of a new CPT III code with the American Medical Association. This code covers in-person monitoring and intervention services during the administration of psychedelic treatments, a crucial step toward securing reimbursement from U.S. healthcare payers. This is essential for facilitating broad and equitable access to such treatments, ensuring that patients across diverse demographics can benefit from these innovative therapies.

Compass is also building a comprehensive and diverse network of research collaborations to inform how COMP360 may be delivered to patients with treatment-resistant depression across the US, if approved.

Journey Clinical is one of the recently announced collaborations. Levine says, "With a network of more than 2,000 therapists and a training and education program, Journey Clinical has the infrastructure to support broad access to new psychedelic treatments for mental health conditions. We will work with them to better understand the patient care experience, treatment pathways for patients living with depression and care reimbursement processes."

A similar version of this article can also be found on Forbes.com, here.