Analyzing therapeutic psychedelics: Opportunities, challenges

What are therapeutic psychedelics?

Therapeutic psychedelics are psychedelic drugs that are used to treat or manage a disease or condition alongside other treatment protocols. This process can also be called psychedelic-assisted therapy (PAT). According to the Association for Behavioral and Cognitive Therapies, PAT combines psychotherapy and psychedelics for mental health treatment.

Although the process and treatment have been around since the 1950s, new and ongoing research has led to renewed interest in therapeutic psychedelics over the past few years.

Despite being distinct drug categories, psychedelic drugs and therapeutic drugs are often lumped together when discussing therapeutic psychedelics. Psychedelic drugs include psilocybin, lysergic acid diethylamide (LSD), dimethyltryptamine (DMT) and mescaline. In addition, there is another class of psychedelics beyond the classic types called entactogens, which includes 3,4-methylenedioxymethamphetamine (MDMA), commonly called ecstasy. Meanwhile, dissociative drugs include ketamine and phenylcyclohexyl piperidine (PCP).

Ongoing therapeutic psychedelic research

Anxiety and depression are two of the most common use cases of therapeutic psychedelics. While these conditions can often be managed with a combination of psychotherapy and traditional antidepressants or anxiolytics, some patients do not have favorable outcomes with this treatment method and need to escalate treatment.

That is where psychedelic drugs come in. For example, LSD-assisted therapy has been effective in managing anxiety associated with terminal illness. Additionally, psilocybin has been effective in managing end-of-life anxiety.

Besides anxiety, researchers have also seen psilocybin's efficacy in managing treatment-resistant depression (TRD) and major depressive disorder (MDD).

Studies have also been exploring ketamine treatment for TRD and MDD. A 2023 study in the New England Journal of Medicine even compared the efficacy of ketamine therapy to electroconvulsive therapy, noting similar outcomes for managing TRD.

Challenges and opportunities of PAT

There is a constant tug-of-war in the therapeutic psychedelics landscape between the potential for innovation or improved treatment outcomes and the barriers that limit the expansion of these treatment methods.

Panelists and moderators at the WMIF discussed the different challenges and opportunities in this field.

Complicated patient history, comorbidities

One of the greatest challenges in this landscape is managing patients with complicated health histories and comorbidities. On the one hand, there is a tremendous opportunity for therapeutic psychedelics to benefit patients with a history of failed treatments; however, complicated medical histories mean providers have to be careful and attentive when treating.

"The patients we see in an academic ketamine clinic are very different from the patients seen at a private ketamine clinic because our patients tend to have many more comorbidities -- both psychiatric comorbidities and medical comorbidities," explained Cristina Cusin, M.D., director at the Massachusetts General Hospital Ketamine Clinic and psychiatrist at the Depression Clinical and Research Program. "They [have a] far more complicated long history of treatment resistance and failing many medications prior to coming."

For example, in Cusin's clinic, about one-third of patients have failed in other therapies, including treatments as drastic as electroconvulsive therapies and transcranial magnetic stimulation, meaning many of these patients are out of treatment options.

"A lot of patients need this kind of intervention because the medications and standard treatments they've been getting just don't work. That is a critical medical issue that shortens lifespan, produces disability, disrupts work, and all of that. One of the things that these drugs do is transform the idea of what's acceptable treatment. We don't have to settle for [treating] symptoms without trying more definitive kinds of interventions. And that's just so hopeful for so many people," explained John Krystal, M.D., department of psychiatry chair at Yale School of Medicine.

In addition to being out of options, many patients also have comorbidities that must be acknowledged during the treatment process. Although esketamine is only approved for treating major depressive disorder, over 65% of patients who have MDD also have a comorbid psychiatric disorder, such as PTSD, GAD or ADHD. For patients with multiple comorbidities, their conditions must be managed in conjunction with their ketamine treatment.

Although there is a notion across the industry that suggests ketamine might be beneficial beyond depression for conditions such as GAD and PTSD, Cusin notes that it's not always the case. On one hand, patients with multiple comorbidities might see all or multiple of their conditions improving; however, some patients will see their depression symptoms resolve while the symptoms of their other comorbidities become more apparent.

Beyond complicated medical and psychiatric conditions, many of these patients also encounter external challenges, including financial and transportation issues.

"The situations are usually fairly complicated, and they require a multipronged, multidisciplinary approach, not simply the treatment. The administration of the treatment is the easy part, but the coordination, the transportation, the support coordination with the team and multiple specialists involved in their care is the difficult part that requires an incredible amount of time that is not reimbursed anywhere," Cusin added.

Demand vs. availability

In addition to challenges on the individual patient level, the experts also pointed out challenges associated with access and availability. There is a lot of opportunity for growth in this industry, as many mental health patients need new alternative treatment methods.

However, developing facilities that can meet patient demand will remain a challenge.

Krystal explains that it took a long time before ketamine clinics could be up and running. It started in academic medical centers that conducted early-phase clinical trials, and as clinical trials progressed, more centers became experts in the treatment process.

He added, "The demand continues to outstrip the availability of these treatments by a large degree. I would expect the rollout to be something that emerges over time as more and more clinics become experts in delivering the treatments."

Growth vs. cost

Another battle includes the opportunities for growth, expansion and innovation in this field and the cost-related challenges that will inevitably arise.

"It sounds like everybody feels like if the science continues to show [promise], eventually we're going to get there. It might be this year, it might be next year or a couple of years, but eventually MDMA, psilocybin and likely some of these others are going to receive FDA approval," said Kerry Ressler, M.D., Ph.D., chief scientific officer at McLean Hospital and professor of psychiatry at Harvard Medical School.

Despite that optimism, there are nuanced challenges in the cost and reimbursement space that must be addressed before these drugs will ever "take off."

"It's a complicated answer because esketamine, for example, was approved in 2019. We couldn't get approval from an insurance company or coverage for 2 1/2 years. There was no path; there was no way to get any insurer to pay for it. So there was a gap of 2 1/2 years where we had a drug potentially available and the way to build infrastructure, but no one paying for it," Cusin explained. "I would imagine at the beginning, it would be available only for patients who can pay out of pocket for the entire treatment sessions and eight hours of psychotherapy. If there are two therapists plus the drug and infrastructure [it] is going to be a serious price tag that not many patients are going to be able to afford."

Addressing the challenges posed by this field will be critical for continued innovation and growth across the therapeutic psychedelic landscape.

Veronica Salib has covered news related to the pharmaceutical and life sciences industry since 2022.