Will psychedelic-assisted therapy gain acceptance as a legitimate treatment option?
Psychedelic-assisted therapy, once a fringe area of study, is now emerging as a promising and potentially viable option for mental health treatment. With mental health disorders continuing to rise, the search for effective, innovative treatments has never been more important. The 2022 World Health Organisation World Mental Health Report found that a staggering one billion people (more than one in eight adults and adolescents) worldwide have a mental disorder (1). Depression (280 million people) and anxiety (301 million) are the largest groups, but developmental disorders, attention-deficit hyperactivity disorder, schizophrenia, bipolar and conduct disorders also affect millions of people worldwide.
Traditional therapies often fall short for patients with severe or treatment-resistant conditions. This has led to a renewed interest in psychedelics - substances that were, for decades, stigmatised and pushed to the margins of clinical research.
The resurgence of psychedelic research has sparked debate. Could these controversial substances hold the key to treating some of the most complex mental health conditions? Or is the path to regulatory approval too challenging to allow for their widespread use?
As research progresses, the question remains: will psychedelic-assisted therapy gain mainstream acceptance as a legitimate treatment option?
The evolution and promise of psychedelic-assisted therapy
To understand the potential of psychedelic-assisted therapy (PAP), it's essential to understand what psychotherapy means when applied to psychedelics. PAP is a therapeutic approach that combines the use of psychedelic substances with traditional psychotherapy techniques. This approach aims to enhance the therapeutic process by leveraging the unique psychological effects of psychedelics. Key aspects of PAP include the substances used, the therapeutic setting, and the structured process known as "set and setting."
Common psychedelics in PAP include psilocybin (found in magic mushrooms), MDMA (commonly known as ecstasy), LSD (lysergic acid diethylamide), and ayahuasca. These substances are administered in controlled, clinical settings designed to support the patient's psychological exploration and healing. The process typically involves three phases: preparation, the psychedelic session, and integration.
The exploration of psychedelics in a therapeutic context has a rich, and tumultuous, history. Psychedelics such as LSD and psilocybin were first studied in the 1950s and 1960s, with early research suggesting they could be effective tools in psychotherapy. However, concerns about recreational misuse and the cultural backlash against the counterculture movement led to a regulatory crackdown in the late 1960s. Research was halted, and these substances were classified as Schedule 1 drugs, deemed to have no accepted medical use and a high potential for abuse.
In recent years, there has been a resurgence of interest in psychedelics driven by new scientific studies and changing public attitudes. For example, in February 2024, the UK’s independent Parliamentary Office of Science and Technology issued a rapid response on psychedelic-assisted therapy for anxiety disorders (2). The rapid response covered psychedelics for anxiety, including treatment options for anxiety disorders, lifestyle factors and psychological treatments.
Alongside this, leading research institutions such as Johns Hopkins University and Imperial College London have conducted thorough clinical trials, demonstrating the potential of psychedelics to treat a range of mental health disorders. Psilocybin, for instance, has shown promise in treating major depressive disorder and anxiety associated with terminal illness, and MDMA has been studied for its potential to treat post-traumatic stress disorder (PTSD).
In 2023, Australia's medicines regulator (TGA) announced that psychiatrists in Australia would now be able to prescribe MDMA and psilocybin for controlled clinical use in the treatment of PTSD and depression (3). Studies have also displayed promising results treating various forms of addiction, such as alcoholism and smoking.
The therapeutic benefits of psychedelics are thought to stem from their ability to promote neuroplasticity and temporarily reduce the influence of the default mode network (DMN), which is associated with ego and self-referential thinking. This can help patients break free from rigid patterns of thought and behaviour.
Unlike traditional antidepressants, which often require long-term use, psychedelics might offer lasting benefits after just a few sessions. Some patients experience rapid relief from symptoms after just one or a few sessions, with benefits sometimes lasting for up to 12 months after treatment. This makes PAP a potentially transformative approach, particularly for those suffering from treatment-resistant conditions.
However, the road to mainstream acceptance looks to be long and challenging. The stigma surrounding psychedelics persists and concerns about safety, ethical considerations, and regulatory hurdles remain significant. As promising as the research is, the question of how soon psychedelic-assisted therapy will be fully integrated into clinical practice remains unclear.
Navigating the regulatory maze, ethical considerations and public perception
The regulatory landscape for psychedelic research presents one of the most significant challenges in the field. The classification of psychedelics as Schedule 1 substances under the United Nations Convention on Psychotropic Substances and similar national laws means that they are considered to have no accepted medical use and a high potential for abuse. This classification imposes stringent regulations on their study, making it exceptionally difficult for researchers to obtain the necessary approvals and funding to conduct clinical trials.
And the design and execution of clinical trials for psychedelics present unique challenges. Placebo controls, a cornerstone of clinical research, are particularly difficult to implement in psychedelic studies due to the profound and unmistakable effects these substances have on participants. Blinding, where neither the participant nor the researcher knows whether a placebo or the active drug is being administered, becomes nearly impossible when the effects of the drug are so evident. This complicates the process of generating reliable data that can withstand the scrutiny of regulatory bodies.
Ethical considerations also play a crucial role in the regulatory challenges of psychedelic research. The intense and often unpredictable nature of psychedelic experiences raises concerns about participant safety. Researchers must ensure that participants are fully informed of the potential risks, including the possibility of challenging or distressing experiences. There is a risk of adverse psychological reactions, such as anxiety, paranoia, or even psychosis, especially in individuals with a history of mental health disorders. These difficult experiences require careful management and thoughtful integration during and after the therapy sessions to mitigate potential harm and ensure the safety and well-being of the participants. The long-term effects of psychedelic use, particularly in therapeutic contexts, are not yet fully understood, raising some ethical questions about the widespread adoption of these treatments.
When comparing psychedelic research to other therapeutic areas, such as gene therapy or immunotherapy, it becomes clear that psychedelics face a unique set of obstacles. While other innovative treatments also contend with regulatory and ethical challenges, the cultural and historical baggage associated with psychedelics adds an additional layer of complexity. For these reasons, gaining approval for psychedelic therapies involves navigating not only the typical regulatory pathways but also overcoming deeply entrenched societal and institutional biases.
One of the major areas of concern, and perhaps the biggest hurdle for researchers, is the position of regulators like the FDA, EMA, and MHRA on PAP when it comes to marketing authorisation or approval. These agencies are designed to approve drugs, not psychotherapies or the combination of drugs with psychotherapeutic interventions. While evidence suggests that integrating psychotherapy with drug therapy enhances treatment outcomes, this approach falls outside the traditional frameworks these regulators are accustomed to. As a result, the concept of approving a treatment that combines both elements may be difficult for regulators to fully embrace or adapt to.
Many were stunned when the FDA advisory panel voted against MDMA therapy for PTSD on a new drug application for MDMA-assisted psychotherapy earlier this summer (4). However, this outcome wasn't entirely surprising when considering the factors stacked against approval:
The combination of drug and psychotherapy is an innovative approach that was ill-suited for FDA review, but it might be a path to optimal care. The proposed effectiveness of MDMA was specifically linked to psychotherapy, defined as a total of nine sessions divided across preparation, drug administration, and integration of the drug experience. Regulators are not accustomed to this novel idea of linking a medication to psychotherapy, but there is data demonstrating that a combination of medication and psychological treatment is better than intervention alone, as seen in treatments for anxiety and mood disorders.
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Although the FDA didn't outright reject the application, their request for an additional Phase III trial due to insufficient data highlights a key issue: the regulatory system is not optimised for mental health care.
Despite ample data showing the value of standardised psychological interventions, no agency reviews the effectiveness and safety of specific psychological interventions. Psychotherapy is seen as a procedure, like surgery, that falls outside the FDA’s scope. However, unlike surgery, psychotherapy is often delivered in outpatient settings or online therapy platforms.
From a regulatory perspective, psychedelic-assisted therapy is challenging to assess but innovative in its combination of medication and psychotherapy as a joint application. Regulators must develop new processes that view psychological treatments as key facilitators rather than confounders of behavioural change.
The FDA’s decision on the MDMA-assisted psychotherapy for PTSD application has been appealed, and spectators wait anxiously for the result. If approved, it would be the first new FDA-approved treatment for PTSD in over two decades. While the FDA's request for an additional phase III trial is a setback, the decision was reached specifically for the approach taken in this case, and it cannot be generalised to all MDMA therapies or even psychedelic therapies as a whole.
Dr Shoona Vincent on the future of psychedelic research
Dr Shoona Vincent, Vice President of Clinical Science at MAC Clinical Research, has spent his career at the forefront of clinical research. With a wealth of experience in managing complex clinical trials, Dr Vincent offers a unique perspective on the potential of psychedelic-assisted therapy:
“Psychedelic-assisted therapy holds significant promise for treating various psychological conditions, offering unique benefits that traditional therapies often cannot match. However, it also presents considerable risks and challenges that must be meticulously managed. In my view, one of the most pressing concerns—and perhaps the biggest hurdle for developers of psychedelics—is the stance of regulatory bodies like the FDA, EMA, and MHRA regarding the marketing authorisation and approval of these treatments. These regulators are accustomed to approving drugs, not psychotherapies or the combination of drugs and psychotherapy. The future of psychedelics in therapeutic practices will heavily depend on continued research, the evolution of legal frameworks, and the expansion of public and professional education.”
MAC’s role in advancing psychedelic research
MAC Clinical Research has been working on the design and execution of functional psychiatry studies for over 30 years. In that time, we have developed a strong and safe clinical offering to overcome the challenges encountered in these studies.
Our infrastructure is tailored to deliver seamless, full-service drug programs for complex central nervous system (CNS) trials. From early-stage development—provided by our MHRA accredited early phase neuroscience centre of excellence—through to late-phase research study protocols delivered across our network of fully equipped, dedicated and experienced late-phase research centres.
Over the past five years, MAC has conducted 14 psychedelic studies and established itself as a pioneer in psychedelic research. We are the first clinical research company in the UK to not only administer high doses of psychedelics in a clinical setting but also the first to dose Ibogaine, 50 mg of Psilocybin, and Deuterated DMT (IV/IM). We also have extensive experience with a wide range of other compounds, such as IV Psilocin, LSD, R-MDMA, and more.
MAC’s commitment to psychedelic research is reflected in our state-of-the-art facilities, which are designed to provide a secure, safe, and relaxing environment for participants. Our dedicated suites and private rooms are specifically aligned with the requirements of psychedelic and hallucinogenic research to minimise distress and ensure the well-being of our patients.
Our team of highly trained professionals - including psychiatrists with expertise in psychedelics, in-house psychologists, and experienced facilitators - is fully equipped to oversee psychedelic treatments and closely monitor patients throughout their experiences. With extensive experience in a variety of psychedelic and dissociative drugs, we are well-prepared to handle studies with complex designs and outcomes.
Looking Ahead: the future of psychedelic-assisted therapy
Psychedelic-assisted therapy stands at the crossroads between possibility and uncertainty. While the potential benefits of these treatments are significant, the challenges to their acceptance as mainstream therapeutic options are equally daunting. The resurgence of research into psychedelics has brought hope for new solutions to some of the most difficult-to-treat mental health conditions, but the path to widespread acceptance is complicated by regulatory hurdles, ethical concerns, and the need for thorough clinical evidence.
As research continues and societal attitudes evolve, the future of psychedelic-assisted therapy remains uncertain but promising. Continued research will be crucial in determining whether these therapies can transition from experimental treatments to accepted standards of care. With continued commitment to high-quality research and a cautious approach to development, there is a real possibility that psychedelic-assisted therapy could one day become a mainstream option for treating mental health disorders.
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