by Manisha Kashyap, PhD
In recent years, there has been a resurgence of interest in the therapeutic potential of psychedelics, marking a significant shift in mental health treatment paradigms. A new open-access narrative review, published July 2, 2025 in npj Mental Health Research, delves into the clinical evolution of psychedelic treatments, shedding light on both historical and contemporary research practices. The review, titled “A Rapid Narrative Review of the Clinical Evolution of Psychedelic Treatment in Clinical Trials,” authored by Ronit Kishon, Nadav Liam Modlin, Yael M. Cycowicz, Hania Mourtada, Tayler Wilson, Victoria Williamson, Anthony Cleare, and James Rucker, explores the development and application of psychedelics in treating various psychiatric disorders.
Historical Context and Pre-Prohibition Era
The initial exploration of psychedelics, such as mescaline and LSD, began in the late 19th and early 20th centuries. Early studies provided valuable insights into the potential benefits of psychedelics for psychiatric patients. Sandoz Pharmaceuticals played a pivotal role by distributing LSD to researchers worldwide, promoting its use as an adjunct to psychotherapy.
During this pre-prohibition era, clinicians experimented with psychedelics to treat a range of psychiatric conditions, including schizophrenia, depression, and personality disorders. These studies highlighted the importance of the treatment context and the clinician’s role in positive patient outcomes. Despite the limitations of early research methods, these studies laid the groundwork for contemporary investigations.
The Revival of Psychedelic Research:
The resurgence of psychedelic research since 2006 has focused on the safety and efficacy of these substances in randomized controlled trials. Modern studies have demonstrated potential benefits in treating severe psychiatric conditions such as treatment-resistant depression, anxiety disorders, and substance use disorders. This renewed interest has led to the development of rigorous clinical protocols and frameworks.
Contemporary psychedelic treatment protocols often include three phases: preparation, psychedelic treatment sessions, and integration. These phases are designed to enhance the therapeutic experience and ensure patient safety. Researchers have found that the set (patient’s mindset) and setting (environmental context) are critical factors influencing treatment outcomes.
Non-Pharmacological Factors and Clinician Roles
One of the key findings of both historical and modern studies is the significance of non-pharmacological factors in psychedelic treatment. The patient’s psychological state, the therapeutic environment, and the clinician’s interpersonal skills all play crucial roles in the success of the treatment. Clinicians are required to create a safe and supportive environment, guiding patients through their experiences without directing them toward specific insights.
The enhanced sensitivity of patients to the therapeutic context and clinician interactions underscores the need for specialized training for those conducting psychedelic-assisted therapy. The review highlights the importance of these elements, emphasizing the need for clinicians to support patients in reflecting on their experiences to achieve therapeutic benefits.
Future Directions
The review suggests that future research should continue to explore the complex interplay between pharmacological and non-pharmacological factors in psychedelic treatment. Understanding these interactions will be crucial in developing best practice guidelines and optimizing treatment protocols. Additionally, further studies are needed to investigate the long-term effects and potential risks associated with psychedelic therapies.
As the field of psychedelic research progresses, it holds the promise of transforming mental health treatment, offering new hope for patients with challenging psychiatric conditions. This rapid narrative review provides a comprehensive overview of the clinical evolution of psychedelic treatment, offering valuable insights for researchers, clinicians, and policymakers alike.
[npj Mental Health Research article]
About the Writer:
Dr. Manisha Kashyap (Dr.MK)
BDS (Hons), MSc, PhD (Healthcare)
Manisha Kashyap earned a BS in Dentistry (Gold Medalist) and an MS in Clinical Research, and she is a driven PhD scholar in Health Policy and Management.
With a rich background as a Drug Safety Analyst for top-tier bio pharmaceutical companies, she blends clinical expertise with a passion for advancing healthcare accessibility and innovation through her writing career for the love of science and technology via MedKnow Research Writing Solutions linkedin.com/in/medknowresearchwritingsolutionsbydrmk.
Dr. Kashyap’s PhD thesis is on “Artificial Intelligence (AI) and Public Health: Harnessing the Power of AI for Enhanced Public Health Policy and Management.”