Understanding Psychedelic Therapy in Clinical Trials

Exploring the Science, Process, and Potential of Psychedelic Therapy

With a focus on well-being and emotional integration, psychedelic-assisted therapy can be a transformative treatment that may help address complex mental health challenges. With proper screening, preparation, guidance, and support, psychedelic therapy shows remarkable promise as a treatment in current clinical trials.

Preliminary evidence suggests psychedelic medicines have the potential to dissolve the concepts of self and ego temporarily. This ego-dissolving effect may enable people to reframe entrenched narratives about themselves, unlocking insights and emotional breakthroughs that traditional therapies sometimes struggle to reach.

While psychedelic therapy is producing promising results, it comes with challenges and risks that require specialized training and continued scientific study. This is an introduction to psychedelic-assisted therapy: its medical indications, potential benefits, risks, and more.

What Is Psychedelic-Assisted Therapy?

Psychedelic-assisted therapy is an emerging therapeutic approach combining the controlled use of psychedelic medicines, such as psilocybin, MDMA, and LSD, with professional psychological support. Psychedelic therapy aims to facilitate profound and transformative experiences to address mental health issues like depression, anxiety, PTSD, and addiction. Psychedelic medicines can produce shifts in thought, emotion, and perception that may open new pathways for psychological insight. When administered in a safe, structured, and medically supervised environment, psychedelic-assisted therapy has shown promising results in early clinical research.

To see our patients struggle with something so deep and so devastating, and find healing on the other side, is very powerful.

Manish Agrawal, MD CEO & Co-Founder

The Neurobiology of Psychedelic Medicines

Classical psychedelic medicines work by interacting with the brain’s serotonin receptors, particularly the 5-HT2A receptor. When substances like psilocybin, LSD, or DMT bind to these receptors, they can induce alterations in thought processes, mood, and perception.

Non-classical psychedelics like ketamine and MDMA have other mechanisms of action involving the modulation of additional receptors. The psychedelic response produced by this action can result in a range of effects, including changes in consciousness, hallucinations, and altered sensory perceptions.

While the precise mechanisms of action are complex and not fully understood, researchers believe they involve alterations in neural connectivity, plasticity, and communication patterns within the brain. A psychedelic experience will vary from person to person, influenced by factors like dose, set and setting, and personal psychology.

Psychedelics in a Therapeutic Setting

Within a structured therapeutic framework, psychedelics may support deep introspection and emotional processing. When administered by trained professionals in a controlled setting, these compounds can help individuals gain new perspectives, enhance self-awareness, and explore personal experiences in meaningful ways.

Psychedelics such as psilocybin and LSD can intensify thoughts and emotions, making them more accessible for reflection and therapeutic processing. This heightened state may allow individuals to engage with familiar memories, patterns, or challenges from new perspectives. When past traumas or repressed emotions surface in a safe and therapeutic setting, it may present an opportunity for recognition, reflection, and emotional processing.

What Makes Psychedelics So Powerful for Healing?

Psychedelic medicines can induce profound changes in consciousness and have the potential to engender meaningful self-reflection. These compounds tap into parts of the mind that are often inaccessible, allowing patients to face and settle repressed emotions, traumatic memories, and unresolved inner conflicts.

Psychedelic medicines may enhance neural plasticity, facilitating the rewiring of neural pathways to promote healthier thought patterns and behaviors.

In psychedelic-assisted therapy, these medicines are administered by professional therapists who provide a sense of safety and guidance throughout the process as the patient prepares for, undergoes, and integrates their psychedelic experience.

Key Psychedelic Compounds, Side Effects, and Therapy Use

Psychedelic Medicine	Onset and Duration of Action	Effects	Therapeutic Uses & Indications	Contraindications & Risks
Ketamine A rapidly-acting non-classical psychedelic medicine classified as a dissociative anesthetic.	Rapid onset with an average duration of action of 40–70 minutes	• Potential physical side effects include nausea, vomiting, dizziness, double vision & drowsiness. • Potential psychological side effects include dysphoria & confusion.	Ketamine is being studied as a treatment for MDD, TRD & PTSD.	• Ketamine has the potential for abuse.
MDMA An empathogen and synthetic methamphetamine derivative that bears chemical similarities to both stimulants and hallucinogens.	Dose-dependent effects can last around 6 hours, with peak effects 1.25–2 hours after the initial dose.	• MDMA can induce an altered state of consciousness. • This state can be characterized by increased compassion & openness, enhanced communication, introspection & prosocial effects, and anxiety reduction. • Potential acute physical side effects include mild muscle tightness, nausea, decreased appetite, increased sweating, palpitations, or tachycardia.	MDMA is being studied as a treatment for PTSD and AD.	• There is a risk of intense emotional responses or psychological distress, including the potential for suicidal ideation. • Symptoms may worsen after the experience. • MDMA has a moderate abuse potential.
Psilocybin A classical psychedelic compound that occurs naturally in mushrooms of the genus Psilocybe. This compound may also be chemically synthesized.	Dose-dependent effects can last 3–6 hours.	• Psilocybin can induce an altered state of consciousness characterized by changes in mood, thinking patterns, & perceptual experience, including changes in affect, vision & time. • Potential physical side effects include headache, nausea, fatigue & insomnia.	Psilocybin is being studied to treat MDD in people with cancer.	• Psilocybin should not be combined with SSRIs and MAOIs. • For people with a history of complex trauma, unprocessed emotions may arise. • These include fear or despair, which may require psychological processing. • There is also a risk that psychological & emotional symptoms may worsen following the experience.
LSD A powerful hallucinogenic drug that is chemically synthesized from ergot, a naturally occurring fungus.	Depending on dosage, effects can last 6–12 hours, with peak effects 1–5 hours after initial administration.	• The effects of LSD include an altered state of consciousness characterized by an enhanced capacity for introspection, altered psychological functioning & perceptual changes.	LSD is being studied to treat GAD, depression, and cluster headaches.	• Because LSD may increase access to traumatic memories, there is a risk of traumatic flashbacks & reactivations. • There is also a possibility that LSD can trigger schizophrenia in people with a predisposition.
5-MeO-DMT A fast-acting, psychedelic tryptamine.	Immediate onset with an average duration of a psychedelic experience of 15 to 20 minutes.	• The effects of 5-MeO-DMT can include transient anxiety, confusion, paranoia, loss of body perception & flashbacks.	5-MeO-DMT is being studied as a treatment for depression (including TRD).	• Potential psychological side effects, though transient, can be overwhelming. • There is a risk of traumatic flashbacks & reactivations. • Combining 5-MeO-DMT with MAOIs can be dangerous.

The Psychedelic-Assisted Therapy Process

Psychedelic-assisted therapy is an emerging treatment approach and is considered an experimental treatment. While early results are promising, much remains to be learned about how to deliver these therapies safely and effectively. Given the complexity and intensity of psychedelic experiences, therapists must receive specialized training to support participants appropriately. Clinical trials typically follow a structured model that includes preparation, dosing, and integration.

Western medicine is fragemented into specialties to treat this or that. Sunstone provides care that begins with the psyche and is designed to support each individual’s broader wellbeing.

Chris Baer Co-Founder

What to Expect

Preparation

In preparing for psychedelic-assisted therapy, therapists build trust with patients to form a robust therapeutic relationship. This can be accomplished in various ways, including exploring intentions, honing practical skills, emphasizing safety measures, and sharing personal histories. Thorough preparation provides a sense of safety that empowers patients to navigate altered states of consciousness with curiosity and openness, creating conditions that support the most beneficial outcomes.

Dosing

On the day of the psychedelic therapy session, the medicine is carefully administered in controlled doses by trained professionals. Therapists accompany patients through the journey with expert emotional guidance while ensuring patients’ physical, emotional, and psychological well-being at all times. To offer the most comprehensive support, therapists must be knowledgeable about the effects of psychedelic medicines on the mind and body, as well as the potential risks and benefits of using them in a therapeutic setting.

Integration

Following dosing, the focus shifts to the exploration and incorporation of the psychedelic experience. This phase aims to help patients integrate insights into their daily lives, enabling them to achieve meaningful growth and appropriate processing. Skilled therapists help patients integrate the experience into their ongoing therapeutic work.

The Structure, Setting, and Science of Psychedelic Therapy at Sunstone Therapies

During a psychedelic-assisted therapy session, a therapist administers a controlled dose of psychedelic medicine in a safe and supportive environment. At Sunstone, a trained psychedelic therapist guides the patient as they process the range of thoughts, feelings, and insights that may arise. The psychedelic experience can be intense, producing profound changes in perception, mood, and cognition. When used in a therapeutic context, the aim is to enable patients to gain new perspectives on their thoughts, feelings, and behaviors, with the ultimate goal of facilitating lasting healing and improvement.

Two things stand out to me in my work with cancer patients and group therapy. The profound difference psychedelic-assisted therapy can make in people’s lives and the sense of meaning that develops from connection.

Betsy Jenkins, LCSW Sunstone Therapist

Set & Setting

“Set” and “setting” are critical to facilitating positive outcomes in psychedelic-assisted therapy.
Set refers to the mindset or mental and emotional state of the person using psychedelic medicine, while setting describes the physical and social environment in which the experience takes place.

Mindset and setting create the foundation for a safe, productive, and potentially transformative experience. Together, they set the stage for patients to explore their inner world, process emotions, and gain valuable insights for personal growth and healing.

Set (Mindset)

The patient’s mindset can significantly influence their experience. Factors such as expectations, beliefs, and intentions play critical roles.

Setting (Environment)

Setting also significantly impacts the psychedelic experience. This includes physical environment, lighting, sound, and the presence of others.

A safe, comfortable, and supportive environment can help foster relaxation, security, and openness, while an uncomfortable, unfamiliar, or chaotic environment can lead to a more challenging and unsettling experience.

The aspects of setting that may contribute to positive patient outcomes include:

Physical Safety

A physically safe and comfortable environment is essential during psychedelic sessions. Every element of the space is designed to support patient well-being.

Psychological Safety

Designed for participants to feel supported, respected, and emotionally secure throughout the process.

Therapeutic Atmosphere

The physical environment plays a supportive role in the therapeutic process. Purposeful design choices—such as soft lighting, natural materials, and calming spaces—are intended to help patients feel safe, comfortable, and at ease during their participation.

The Benefits of Psychedelics

Psychedelic-assisted therapy is being explored as a potential treatment for a range of complex mental health conditions. Early research suggests that these compounds may support emotional processing, new psychological insights, and long-term symptom relief in some patients.

Psychedelic-assisted therapy is being evaluated as a potential treatment for multiple indications, including:

Adjustment Disorder (AD)
Alcohol Use Disorder
Eating Disorders
Emotional Distress* in Patients with Cancer
End-of-Life Care
Fibromyalgia Pain Management
Generalized Anxiety Disorder (GAD)
Major Depressive Disorder (MDD)
Obsessive Compulsive Disorder (OCD)
Posttraumatic Stress Disorder (PTSD)
Treatment-Resistant Depression (TRD)

To explore other clinical studies, visit the National Institute of Health Clinical Trials website.

Understanding the Risks of Psychedelic Therapy

While psychedelic-assisted therapy has shown promising results in early studies, it also carries risks and contraindications (specific situations or conditions in which psychedelic therapy should not be used because it could be harmful).

Like any medical intervention, it may lead to both harm and benefit. Potential adverse effects may become more apparent as psychedelic use increases and further research is conducted. Sunstone Therapies is helping to shape protocols that minimize risk and support safety, drawing on extensive clinical experience to inform emerging standards of care.

These are some of the most common risks associated with the use of psychedelic medicines (click each dropdown to learn more):

Trauma

People with a history of severe trauma may be at risk of worsening symptoms during a psychedelic session. Psychedelics can unearth buried traumatic memories, which can be distressing and challenging to process. The guidance of an experienced therapist enables patients to navigate difficult experiences safely and constructively.

Psychological Vulnerability

People with a history of specific mental health conditions, like schizophrenia and bipolar disorder, may be at higher risk of a psychotic or manic episode. In comparison, those with severe personality disorders may be at higher risk for emotional instability.

Further research is needed in these populations to determine the safety and potential benefits. For this reason, patients with these conditions or family histories have traditionally been excluded from participating in psychedelic clinical research.

Medical Conditions

Some medications can interact negatively with psychedelics. Combining certain antidepressants like SSRIs and MAOIs with psychedelics can cause a potentially fatal condition called serotonin syndrome.

Substance Abuse

Though psychedelics show promise in treating Alcohol Use Disorder (AUD), people with a history of substance abuse may be at risk of using psychedelics in an unhealthy manner or experiencing cravings or relapse after a psychedelic experience. This risk is higher with certain non-classical psychedelic medicines like ketamine.

If you are considering psychedelic therapy, a thorough screening and assessment process is essential to determine your safety and suitability for the treatment.

Sunstone’s thorough assessment considers your medical history, mental health, current medications, and potential situations or conditions in which psychedelic therapy should not be used because it could cause harm. From screening to integration, the therapeutic process is conducted by trained professionals in a controlled and supportive environment, minimizing risks and ensuring the best possible outcomes.

Find answers to common patient questions

Each trial has its own set of eligibility criteria that participants must meet, such as age, medical history, and previous experiences with psychedelics. Our team will assess your eligibility during the screening process.

The primary goal of our trials is to explore the safety, effectiveness, and therapeutic potential of psychedelic medicines in a safe and supportive environment. We aim to provide participants with a healing experience while contributing to the advancement of psychedelic science.

To apply for a clinical trial, click here. We will guide you through the application and screening process.

Frequently Asked Questions

A Research-Driven Path When
Other Treatments Haven’t Been Enough

Sunstone Therapies offers a safe, structured environment for patients exploring psychedelic-assisted therapy. Designed for those navigating complex mental health conditions, our clinical approach combines evidence-based protocols with thoughtful support. Every journey is different. We’re here for yours.

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