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A psychedelic renaissance is underway in psychiatric medicine, with a growing number of studies showing the potential of psychedelic-assisted therapy to treat several conditions, including depression, posttraumatic stress disorder (PTSD), obsessive compulsive disorder, and various addiction disorders.

The US Food and Drug Administration has designated psilocybin and 3,4-methylenedioxymethamphetamine (MDMA) breakthrough therapies for treatment-resistant depression and PTSD, respectively — a designation that reflects their potential superiority over existing therapies.

Two phase 3 trials of psilocybin for treatment-resistant depression are underway, and one phase 3 trial of MDMA for PTSD has wrapped up. These therapies could be approved in the United States within a few years.

PharmaTher's racemic ketamine product Ketarx for use in Parkinson's disease, Rett syndrome, and mental illness could be the first to market. Other psychedelics in development include ibogaine and lysergide d-tartrate–based medicines.

As drugmakers continue to invest in these agents and regulatory agencies consider loosening restrictions to approve these novel treatments, experts believe it won't be long before psychedelic compounds move from the research setting to clinical practice.

Yet, there is growing concern that obtaining meaningful informed consent for psychedelic treatment will be a challenge, given the unique effects of psychedelic drugs, including what's often described as the ineffable elements of the psychedelic experience.

There is currently an unmet need for informed consent processes tailored to the challenges of administering psychedelics in settings, said experts who authored a special communication published online on April 10 in JAMA Psychiatry.

"We reviewed publicly available informed consent documents for existing psychedelic trials and found that they often underemphasized or overlooked certain risks of psychedelic medicines," first author Mason Marks, MD, JD, with the Project on Psychedelics Law and Regulation (POPLAR), The Petrie-Flom Center for Health Law Policy, Biotechnology, and Bioethics at Harvard Law School, Cambridge, Massachusetts, and law professor, Florida State University in Tallahassee, Florida, told Medscape Medical News.

To help fill those gaps and improve informed consent processes as psychedelics start moving from trials to clinical practice, Marks and his coauthors have developed seven "essential" elements of informed consent for psychedelic therapy. Here's a snapshot of each:

1. Possibility of Short- and Long-Term Perceptual Disturbances

In addition to standard disclosures regarding adverse effects, treatment alternatives, and patient rights, the range of possible effects, including the "high" likelihood of acute perceptual changes should be discussed with the patient, while acknowledging the challenges of predicting which effects may occur, their intensity, and how patients might respond, the authors noted.

Patients should be informed that some clinical trial participants have reported new or worsening symptoms, and there is a "seemingly low but poorly understood" risk for hallucinogen persisting perception disorder.

Patients should be told that psychedelic-induced effects may be tough to interrupt for hours, and they may need to remain on site until they pass.

2. The Potential for Personality Changes and Altered Beliefs

Patients should be informed that after psychedelic therapy, some people have experienced lasting personality changes and altered metaphysical beliefs. These changes may be desirable, such as changed attitudes toward addictive substances, allowing patients to decrease use, or undesirable, such as altered beliefs and personality or even a sense of fatalism, which is the belief that events are predetermined and inevitable, the authors suggested.

Because psychedelics may temporarily alter patient values, making patients more empathetic and possibly susceptible to persuasion, clinicians should advise patients not to make major life decisions or put themselves in compromising positions in the weeks or months following psychedelic therapy.

3. The Limited Role of Reassuring Physical Touch

The authors noted that physical touch has historically been avoided in psychoanalytic and dynamic therapy models and is "controversial" in psychedelic therapy. Clinicians who administer psychedelics may use limited forms of reassuring touch, including holding the patient's hands or lightly touching their shoulders.

However, because psychedelics alter one's mental state, the capacity to understand and consent to physical touch may be impaired. Clinicians must have clear procedures for obtaining consent for limited physical touch before psychedelic administration. Clinicians should not exceed the agreed-upon parameters unless touch is necessary to prevent injury, they cautioned.

Clinicians could adopt a color-coding system, such as brightly colored badges or bracelets worn by the patient to reflect the types of touch to which they have consented. Green would mean the patient has consented to all forms of limited appropriate physical touch, while red would mean the patient has not consented to any forms of touch.

Yellow would mean the patient has consented to some forms of limited touch such as hand-holding but has not consented to other forms. Blue would mean the patient has consented to some forms of touch but has an injury, condition, or medical device that requires an individualized approach.

4. Increased Susceptibility to Patient Exploitation and Abuse

Psychedelics can induce vulnerable states, and patients may be easily influenced during and after their treatment. The authors acknowledged that it can be challenging for clinicians to discuss the potential for exploitation or abuse, especially because it could imply that patients should be wary of the very person who is engaging in the informed consent process, which sends a mixed message. Nonetheless, clinicians should tell patients of these risks and the measures in place to mitigate them. This can promote transparency and trust, they pointed out.

5. The Role and Risks of Data Collection

Because psychedelics induce vulnerable states, information collected during psychedelic sessions may be particularly sensitive and could expose people to social, legal, and professional risks. Due to the sensitivity of information collected during psychedelic sessions, additional elements regarding data should be built into informed consent processes. Marks and colleagues said clinicians should discuss the risks and benefits of data collection and research in sufficient detail to enable patients to decide whether to contribute information.

6. Relevant Practitioner Disclosures

Clinicians with diverse backgrounds and experience may administer psychedelics and monitor their effects, including physicians, clinical psychologists, social workers, nurses, and other professionals. Clinicians should disclose their credentials and appropriate scope of practice and inform patients of actual and potential conflicts of interest, such as relationships with psychedelic pharmaceutical companies and their funders.

7. Interactive Patient Education and Comprehension Assessment

Making the consent process interactive may enhance patient education and understanding. Eventually, clinicians might use virtual reality and augmented reality to simulate perceptual psychedelic effects. Until then, role play and computer-based simulations can help, and quizzes can be used to assess patient comprehension, the authors said.

Marks emphasized that these elements are not comprehensive.

"There are aspects of informed consent to receive psychedelics that are not unique or that pose little difficulty for clinicians and patients, such as describing potential drug interactions or common and easily understood side effects such as transient anxiety or headache," Marks said. "We chose to emphasize elements of informed consent that are more challenging or unique to psychedelic medicines."

Manage Expectations, Emphasize the Unknowns

In an accompanying editorial, Paul S. Appelbaum, MD, professor of psychiatry, medicine, and law, Columbia University in New York City, noted that the content of consent process is likely to change as additional knowledge about psychedelic treatment becomes available.

"Equally important is the recognition that our current knowledge of the outcomes of psychedelic treatment is incomplete, which means that it is premature to reify the contents of consent disclosures," Applebaum wrote.

"With regard to the benefits of treatment, the optimal number of psychedelic episodes and the duration of response to psychedelic therapy are unknown, as is the likelihood of response to repeat administration in the event of a relapse. At present, all that can — and should — be shared with patients is the profession's uncertainty about these important issues," Applebaum advised.

He believes allowing patients contemplating psychedelic therapy to talk to others who have undergone treatment could be particularly valuable.

"Since patients' experiences will vary, a video compilation of prior patients recounting their narratives might be a particularly effective way of conveying the variety of outcomes that are possible," Applebaum wrote.

It will also be important to manage patients' expectations, given the "exuberant" media coverage of psychedelic therapy.

"Unreasonable beliefs about the nature of the psychedelic experience and its likely effects should be identified and addressed," he added.

"The extent to which psychedelic treatment will play a role in the future of psychiatry remains to be determined. However, it is not too early for clinicians to begin to plan for the introduction of psychedelics into clinical treatment, including how we will discuss psychedelic therapies with patients and obtain their informed consent," Appelbaum concluded.

This work was supported by the POPLAR at The Petrie-Flom Center for Health Law Policy, Biotechnology, and Bioethics at Harvard Law School and by the Gracias Family Psychedelics Research Initiative and Bootcamp in Ethics Regulation Fund at Harvard Law School. Marks reported receiving nominal fees for journalism on psychedelics and served as a volunteer member of the Oregon Psilocybin Advisory Board. Applebaum had no relevant disclosures.