Clinical Trials

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.