Clinical Trials

Clinical Trials

The results of clinical trials have provided a growing body of research that suggests psychedelics could be used for a range of therapeutic purposes. There is significant evidence that ketamine, psilocybin, and MDMA can work in combination with therapy to help alleviate a range of mental disorders, including PTSD, depression, substance-use disorders, and anxiety. The field is advancing rapidly, but the process for participating in psychedelic-assisted therapy as either a therapist or a patient can be complicated.

How Clinical Trials Work

Participating in a clinical trial is one of the few ways to experience psychedelics legally in the United States (aside from ketamine, which is not a classic psychedelic). Dozens of clinical trials are recruiting participants to test the safety and therapeutic potential of different psychedelics. 

Before initiating clinical trials with human participants, scientists have to complete a number of studies to demonstrate that the treatment under investigation appears to be acceptably safe when tested on laboratory animals and provides enough evidence to merit testing in humans. Once they’ve cleared that hurdle, scientists conduct clinical trials in three phases: first to test a treatment’s safety (phase I), then to determine its potential efficacy and side effects (phase II), and finally to examine its safety and efficacy for people with a particular disease or condition in a real-world health-care setting (phase III). 

Phase I

Scientists typically enroll twenty to one hundred healthy people to test whether the drug is acceptably safe to use relative to its potential benefits and begin cataloging side effects.

Phase II

Researchers enroll up to several hundred volunteers who are suffering from the condition they are hoping to treat. For example, in a phase II trial for MDMA-assisted treatment for PTSD, researchers enrolled people who had been diagnosed with chronic PTSD, including veterans and first responders. These trials test the effectiveness of the treatment and yield further data about its safety profile.

Phase III

Over the course of several years, scientists enroll a few hundred up to a few thousand participants who have the disease or condition being studied to provide regulators with sufficient high-quality data to determine whether the drug is safe and effective enough to gain approval for use in treatment. For example, during phase III trials for MDMA-assisted PTSD treatment, researchers established that, in combination with therapy, the drug was safe and effective enough to treat people with severe PTSD. 

Phase IV

Surprise! There’s actually a last phase of clinical trials that happens after regulators approves a treatment. These trials, also called Post-Market Drug Safety Monitoring, track the treatment after it has been allowed on the market to ensure that it remains safe for every population that uses it.

Clinical Trial Terms to Know

There are a few other terms that scientists and regulators frequently use in clinical trials.

Placebo-controlled

Placebo-controlled means that study volunteers are split into two groups. One group receives the drug that researchers are testing. The other group gets a placebo capsule that doesn’t contain the drug. In psychedelic studies, researchers often use an active placebo like niacin, which can cause perceptible effects like a flushed face but won’t induce a psychedelic experience. All the other study conditions for the two groups—where participants are, how they’re treated—remain the same as much as possible. That way, any difference in outcome can be more effectively associated with drug effects.

Double-blind

Double-blind means that neither the participants nor the researchers know who receives an active treatment or a placebo, helping to prevent bias. At the end of the trial, both participants and researchers are unblinded so they can see who got which treatment. In its 2006 psilocybin study, Johns Hopkins researchers used a double-blind method that included the scientists, the clinically trained session monitors, and the volunteers. Blinding in psychedelics research is challenging because study participants who receive a non-psychedelic (e.g., niacin, methylphenidate, or an inactive placebo) can often guess that it was not a psychedelic. Blinding is most effective with volunteers who have not previously had any experience with psychedelics.

Expanded access (in the United States)

The FDA sometimes allows patients to access a treatment outside of clinical trials before it’s been approved to go on the market. This expanded access, sometimes called “compassionate use,” is granted if the patient has a life-threatening disease with no other promising treatment, can’t enroll in a clinical trial for some reason, or has tried other therapies without success. The FDA has granted expanded access for MDMA-assisted therapy for people with serious or life-threatening PTSD, but not everyone is eligible, and the FDA only allows a limited number of patients to participate.

Participating in a Trial

People can legally consume psychedelic substances if they’re enrolled in a clinical trial, and there are many trials running in clinics across the country. For more information about specific trials in the United States, search for trials related to specific institutions, drugs, and conditions at clinicaltrials.gov

Psychedelic Alpha, a company that tracks news and investment in psychedelics, also maintains a list of ongoing trials.

Selected Sources

Therapy

The Past and Present of Psychedelics and Therapy

In the 1950s and 1960s, when psychoanalysis was the predominant form of therapy in the United States and Europe, some practitioners began to experiment with adding psychedelics to talk therapy.

Over the course of multiple sessions, patients would take small to moderate doses of psychedelics during a session, a practice labeled “psycholytic” therapy by British psychiatrist Ronald Sandison. (The term combines the Greek word word for soul—psycho—and “lytic,” derived from the Greek for loosening or breakdown.) This therapy understood psychedelics as tools that could give patients greater access to their subconscious. Other models that emerged during this era included the psychedelytic approach, incorporating multiple low dose sessions that eventually culminated in a high dose session, or an initial high dose administration along with intermittent low dose sessions with psychotherapy to integrate material.

Simultaneously, other therapists practicing psychedelic therapy experimented with allowing patients to experience a psychedelic without talk therapy, using subsequent sessions to discuss their experience and its meaning. These experiments almost completely stopped when the Controlled Substances Act and the United Nations Convention on Psychotropic Substances took effect in 1971.

Current research combining psychedelics and therapy can vary depending on what issues participants and providers want to address. Smoking cessation studies, for example, have tested psilocybin sessions in structured settings in combination with cognitive behavioral therapy (CBT).

Generally, most psychedelic-assisted therapy is divided into three stages.

The Three Stages of Psychedelic-Assisted Therapy

Preparation: Patients work with a therapist or a team of people to help explore why they’re taking the psychedelic, what issues they hope to address, and to build trust and rapport. Therapists will also brief the patient on the physical and psychological effects they might experience and give them tips for navigating the possible terrains.

Medication: This is when patients will take the psychedelic under the supervision of their therapist or team of providers. Usually, a course of treatment includes one to three medication sessions separated by some weeks, each of which last from six to eight hours. The psychedelic is administered in a comfortable environment. Patients lie on a bed or couch and may use eyemasks and/or use headphones to listen to music. How facilitators manage this part of therapy varies. Some may sit with, observe, and listen to patients while maintaining a neutral, non-judgmental stance. Others may encourage patients to confront or move through difficult issues that may come up during the experience.

Integration: In subsequent non-drug sessions, therapists work with patients to unpack what they experienced, interpret what happened, and use those insights to restructure a patient’s narrative or understanding of their inner self, relationships, and circumstances. Often these integration sessions happen during the “afterglow” phase when patients may have increased brain plasticity, making them more open to new ways of thinking and acting.

Reports of Abuse

Patients under the influence of a psychedelic can be uniquely vulnerable to abuse. In addition to the power imbalance between the therapist and the patient, taking substances like MDMA can heighten sexual openness, affect judgement, and create greater intimacy in an already close relationship. Feelings of openness and trust can also make patients more susceptible to sexual pressure from their therapist. The American Psychological Association’s Ethics Code states that psychologists should not have any sexually intimate relationships with their current clients and discourages relationships with any of their clients even after their therapy has ended. 

At least since the 1980s, research protocols have specified that psychedelic-assisted therapy should be conducted with two session monitors, traditionally one male and one female (although these gender norms are now being challenged), to prevent sexual abuse. Still, there are numerous reports of sexual abuse by therapists, shaman, guides, and other providers in Canada, Germany, Ecuador, the United States, and elsewhere.

The MAPS Code of Ethics for MDMA-assisted therapy specifies that practitioners shouldn’t “engage in sexual intercourse, sexual contact, or sexual intimacy with a participant, or a participant’s spouse or partner, or immediate family member, during the therapeutic relationship or after termination.” But many psychedelic guides are not licensed therapists, making it difficult for any licensing body or professional group to enforce these rules.

You can read more about abuse in the psychedelics field here. The Understanding Risk section has more information about how to navigate touch and the importance of trust in  psychedelic-assisted therapy. More specifics on consent, ethical codes, and finding the right therapist are below.

Set and Setting

While there is a growing body of evidence that psychedelic-assisted therapy can help alleviate depression, anxiety, substance-use disorders, and PTSD, people respond to psychedelics differently. Researchers are trying to better understand how and why people are affected in varying ways, and why people may react differently each time they take a psychedelic. Set and setting are two variables that can hugely affect a psychedelic experience. The “set” is internal: the mental state, or the thoughts, experiences, emotions, expectations, and life history that one brings into a psychedelic experience. The “setting” is external: the physical and social environment in which the experience takes place, such as in a forest, in a doctor’s office, or with a trusted friend at home. 

Click here to learn more about set and setting.

Best Practices and Consent

As with any therapy, in the case of a therapist working with psychedelics, it’s important for the client to feel safe and supported. The American Psychedelic Practitioners Association, or APPA, is a group of psychedelic therapists, guides, and researchers working to establish professional guidelines and accreditation standards for psychedelic therapists.

BCSP spoke with Megan Frost, a physician and chair of the APPA ethics committee, about best practices around communication and consent for psychedelic facilitation.


BCSP

“How can someone find the right psychedelic therapist and avoid the wrong one?

Megan Frost

“Just like with any type of health-care provider, meeting with them initially is an important step to evaluate your own level of comfort. That first conversation doesn’t commit you to working with them. You should feel comfortable with the provider and they should take adequate time to answer your questions, assess whether you would benefit from working with them, and then prepare you for the experience. You should not feel rushed or pressured. If you have any concerns about working with that provider, you should feel comfortable either discussing those concerns with them or finding another provider.”

“The use of touch is always voluntary and completely up to the client.”


BCSP

What questions should someone ask a potential therapist or guide about touch?

Megan Frost

Providers should have their own protocols regarding touch and be able to describe them to you. Regardless of their protocol, the use of touch is always voluntary and completely up to the client. There should never be any sexual touch between a provider and their client. There are types of somatic therapy where a provider is trained in specific kinds of therapeutic touch, and it’s reasonable to ask your provider whether they have training in these areas and what purpose the touch is meant to provide. Regardless of their training, the client should ultimately draw the line about their consent to touch.


BCSP

How should someone navigate consent with a guide about touch while on psychedelics?

Megan Frost

“Again, providers should have their own protocols regarding informed consent and touch, and they should cover it in detail while they’re preparing you for the experience. During the experience, if the client decides they no longer want touch that had previously been agreed upon, then the provider should cease all touch immediately. There are differing opinions on how providers should handle touch when it was initially declined in a preparation session and then asked for during a medicine session, so it’s reasonable to discuss this potential scenario with your provider during the preparation session and agree upon a comfortable solution for yourself.”

This interview was edited for length and clarity.

Finding Psychedelic Therapy Support

Due to current U.S. federal law, there is currently no easy way to find a qualified psychedelic therapist or guide who can be with you during a psychedelic experience. It may be easier to find therapists who can help you integrate a psychedelic experience afterward. For preparation, facilitated drug sessions, and integration, some people turn to underground guides. Others travel to countries like Brazil, Jamaica, or the Netherlands, where some psychedelics are legal. However, psychedelic tourism can harm Indigenous traditions, and there have been reports of misconduct in clinical trials, in the psychedelic underground, and at legal retreats abroad, although some legal retreats abroad have well-developed ethical standards.

The KRIYA Institute and Ketamine Psychotherapy Associates provide directories of therapists who offer ketamine treatment. There are also several online directories of practitioners who can help with integration more broadly, including MAPS and Psychedelic Support, but the providers have not been vetted. BCSP doesn’t endorse any specific providers.

Code of Conduct

In response to reports of misconduct and sexual assault during psychedelic sessions, research organizations have created several sets of professional guidelines for psychedelic practitioners and people participating in clinical trials.

A brief Code of Ethics for Spiritual Guides was first published in 1995 by the Council on Spiritual Practices, intended as a model for guidelines and standards of the profession. It has led to other codes, such as one from the MAPS, the Multidisciplinary Association for Psychedelic Studies. MAPS has also produced a treatment manual for conducting MDMA-assisted therapy to treat PTSD.

Therapist Training

There are a growing number of training programs for therapists, psychologists, and psychiatrists looking to integrate psychedelic treatment into their practice. 

Some for-profit companies advertise training programs, as do some organizations, including MAPS, the California Institute of Integral Studies, Fluence, COMPASS Pathways, Synthesis, and Naropa University. New York University, Yale University, and Johns Hopkins University are jointly developing a program as well. 

Beginning in September 2022, BCSP will launch its own Certificate Program in Psychedelic Facilitation, designed for advanced religious, spiritual-care, and health-care professionals working in areas such as chaplaincy, ministry, medicine, nursing, mental-health counseling, psychiatry, and social work. To learn more click here.

Oregon Psilocybin Services

In Oregon, voters approved a 2020 ballot measure that legalized guided psilocybin sessions in the state. (They remain illegal federally.) Oregon Psilocybin Services will regulate everything from the production of the psilocybe mushrooms to the training providers must have to legally practice in the state. Currently, Oregon is drafting a number of documents related to the ballot measure, including a code of conduct for providers and an approval process for training programs. The state will begin issuing licenses in 2023.

For more detailed and up-to-date information about how Oregon is navigating legalization, check out The Microdose.

Therapy

Today, there are few places in the United States where it is legal to access psychedelic-assisted therapy outside of clinical trials. But this is starting to change. Ketamine clinics are legal, and, in 2020, Oregon became the first state to legalize supervised psilocybin treatment. Oregon will start accepting applications for psilocybin treatment licenses in 2023, assuming the federal government doesn’t stop it. Several other states may soon follow Oregon’s lead. Regardless of whether psychedelic-assisted therapy is legalized, safety is still an important concern, and patients need to find the right space and therapist for them.

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