Psychedelic psilocybin-assisted therapy reduces depressive symptoms in adults with cancer and depression
Clinical trial results support further study of this psychedelic substance, administered with psychological support from trained therapists, in affected patients
Results from a phase II clinical trial indicate that psilocybin, a hallucinogenic chemical found in certain mushrooms of the genus Psiloybe, may benefit individuals with cancer and major depression. Trial participants treated with psilocybin not only experienced a lessening of depressive symptoms but also spoke highly of the therapy when interviewed at the end of the trial. The findings are published by Wiley in two articles appearing online in CANCER, a peer-reviewed journal of the American Cancer Society.
By binding to a specific subtype of serotonin receptor in the brain, psilocybin can cause alterations to mood, cognition, and perception. Psilocybin is currently classified as a Schedule I drug—defined as having no accepted medical use and a high potential for abuse—and is not approved by the US Food and Drug Administration for clinical use. However, multiple randomized controlled trials have demonstrated the safety and potential efficacy of psilocybin-assisted therapy—which combines psilocybin with psychological support from trained therapists—to treat major depressive disorder. Additionally, ongoing research is looking into the use of psilocybin-assisted therapy for various other mental health conditions, such as anxiety, addiction, and post-traumatic stress disorder.
In this latest phase II open-label trial involving adults with cancer and major depression, 30 participants at Sunstone Therapies in Rockville, Maryland received a single 25 mg dose of synthesized psilocybin plus a 1:1 session with a therapist and group therapy support.
“This study was differentiated by its group approach. Cohorts of 3-4 patients were simultaneously treated with 25 mg of psilocybin in adjacent rooms open at the same time, in a 1:1 therapist:patient ratio. The cohorts had preparation for the therapy as well as integration sessions following the psilocybin session as a group,” explained lead author Manish Agrawal, MD, of Sunstone Therapies.
Participants enrolled had moderate to severe depression scores at baseline. After eight weeks of treatment, Dr. Agrawal and his colleagues observed that patients’ depression severity scores dropped by an average of 19.1 points, a magnitude that would indicate the majority no longer experienced depression. Furthermore, 80% of participants experienced a sustained response to treatment, and 50% showed full remission of depressive symptoms after one week, which was sustained for eight weeks. Treatment-related side effects such as nausea and headache were generally mild.
“As an oncologist for many years, I experienced the frustration of not being able to provide cancer care that treats the whole person, not just the tumor,” said Dr. Agrawal. “This was a small, open-label study and more research needs to be done, but the potential is significant and could have implications for helping millions of patients with cancer who are also struggling with the severe psychological impact of the disease.”
Dr. Agrawal is also the senior author of a second study led by Yvan Beaussant, MD, MSc, of Dana-Farber Cancer Institute that gathered input from patients in the trial during exit interviews. Participants described generally positive experiences. In terms of safety, they noted that being a part of the group calmed their fears and increased their sense of preparedness to engage in therapy. Regarding therapeutic efficacy, they felt that being connected to the group deepened and enriched their experience, ultimately contributing to their experience of self-transcendence and compassion for one another. Also, the use of both individual and group sessions was found to support the therapy in different ways. For example, the implementation of individual and group sessions allowed the therapy to remain an intimate introspective process while adding a sense of “togetherness” to it.
“As a hematologist and palliative care physician and researcher, it was profoundly moving and encouraging to witness the magnitude of participants’ improvement and the depth of their healing journey following their participation in the trial. Participants overwhelmingly expressed positive sentiments about their experience of psilocybin-assisted therapy while emphasizing the importance of the supportive, structured setting in which it took place,” said Dr. Beaussant. “Many described an ongoing transformative impact on their lives and well-being more than two months after having received psilocybin, feeling better equipped to cope with cancer and, for some, end of life.”
Before this intervention is implemented into clinical practice, additional studies should include larger numbers of patients, along with a control arm to compare its effects with other treatments or placebo.
Additional information
NOTE: The information contained in this release is protected by copyright. Please include journal attribution in all coverage. A free abstract of this article will be available via the CANCER Newsroom upon online publication. For more information or to obtain a PDF of any study, please contact: Sara Henning-Stout, newsroom@wiley.com
Full Citations:
“Psilocybin-assisted Group Therapy in Patients with Cancer Diagnosed with a Major Depressive Disorder.” Manish Agrawal, William Richards, Yvan Beaussant, Sarah Shnayder, Rezvan Ameli, Kimberly Roddy, Norma Stevens, Brian Richards, Nick Schor, Heather Honstein, Betsy Jenkins, Mark Bates, and Paul Thambi. CANCER; Published Online: December 18, 2023 (DOI: 10.1002/cncr.35010).
URL Upon Publication: http://doi.wiley.com/10.1002/cncr.35010
“Acceptability of Psilocybin-assisted Group Therapy in Patients with Cancer and Major Depressive Disorder: Qualitative Analysis.” Yvan Beaussant, Elise Tarbi, Kabir Nigam, Skye Miner, Zachary Sager, Justin J Sanders, Michael Ljuslin, Benjamin Guérin, Paul Thambi, James A. Tulsky, and Manish Agrawal. CANCER; Published Online: December 18, 2023 (DOI: 10.1002/cncr.35024).
URL Upon Publication: http://doi.wiley.com/10.1002/cncr.35024
Contact for Dr. Agrawal: Tracy Cheung/Chris Gardner/Andrew Stern, at SunstoneTherapies@consilium-comms.com
Contact for Dr. Beaussant: Nicole Oliverio, Senior Media Relations Specialist, Department of External Communications, at nicole_oliverio@dfci.harvard.edu, or +1 617-257-0454
About the Journal
CANCER is a peer-reviewed publication of the American Cancer Society integrating scientific information from worldwide sources for all oncologic specialties. The objective of CANCER is to provide an interdisciplinary forum for the exchange of information among oncologic disciplines concerned with the etiology, course, and treatment of human cancer. CANCER is published on behalf of the American Cancer Society by Wiley and can be accessed online. Follow CANCER on Twitter @JournalCancer and Instagram @ACSJournalCancer, and stay up to date with the American Cancer Society Journals on LinkedIn.
About Wiley
Wiley is a knowledge company and a global leader in research, publishing, and knowledge solutions. Dedicated to the creation and application of knowledge, Wiley serves the world’s researchers, learners, innovators, and leaders, helping them achieve their goals and solve the world's most important challenges. For more than two centuries, Wiley has been delivering on its timeless mission to unlock human potential. Visit us at Wiley.com. Follow us on Facebook, Twitter, LinkedIn and Instagram.
JOURNAL
Cancer
ARTICLE TITLE
Psilocybin-assisted Group Therapy in Patients with Cancer Diagnosed with a Major Depressive Disorder
ARTICLE PUBLICATION DATE
18-Dec-2023
Trip or treat?
Scientists at the Medical College of Wisconsin make strides in designing non-hallucinogenic psychedelic treatments that may accelerate research on mental health benefits; research findings published in Nature Communications.
Peer-Reviewed PublicationIMAGE:
SCIENTISTS AT THE MEDICAL COLLEGE OF WISCONSIN MAKE STRIDES IN DESIGNING NON-HALLUCINOGENIC PSYCHEDELIC TREATMENTS THAT MAY ACCELERATE RESEARCH ON MENTAL HEALTH BENEFITS; RESEARCH FINDINGS PUBLISHED IN NATURE COMMUNICATIONS.
view moreCREDIT: MEDICAL COLLEGE OF WISCONSIN
NEWS RELEASE
FRI, DEC. 15
Trip or Treat?
Scientists at the Medical College of Wisconsin make strides in designing non-hallucinogenic psychedelic treatments that may accelerate research on mental health benefits; research findings published in Nature Communications.
Milwaukee, Wis. – Dec. 15, 2023 – There is nothing magic about the recent increase in interest around the study of psychedelic drugs as potential treatments for patients suffering from a myriad of mental health conditions.
“The excitement follows the science,” says John McCorvy, PhD, assistant professor of cell biology, neurobiology and anatomy at the Medical College of Wisconsin (MCW). “The number of landmark studies continues to grow, and the potential has caught the attention of academia and the pharmaceutical industry.”
The legal status of psychedelic compounds slowed research progress to a crawl for decades before some studies began to garner regulatory approval in the early 2000s. Even in approved clinical trials, the hallucinogenic properties of these drugs lead to additional hurdles. Research participants need to take the substances under strict supervision in a clinical setting. Trained therapists monitor participants for a long time as the length of a hallucinogenic experience ranges from about four to 12 hours depending on the drug and the individual. The treatment can cause confusion and anxiety for some patients who do not respond well to hallucinations, underscoring the need for vigilant healthcare personnel. For those who have tolerated the drugs and associated hallucinations, however, promising studies have indicated that participants have experienced a substantial and sustained improvement in symptoms after taking a single dose.
“We’ve seen double-blind, placebo-controlled trials with psilocybin where patients with major depressive disorder reported improved symptoms for months,” Dr. McCorvy says. “It is unheard of to get those kinds of results, especially without the patient having to take a pill every day.” Psilocybin is a naturally occurring psychedelic compound made by hundreds of types of fungi, often referred to as “magic” mushrooms.
As promising as these and other results may be, however, the legal and practical hurdles for scientists and would-be research participants continue to loom large. But what if you could remove the hallucinogenic properties of possible psychedelic treatments without reducing their therapeutic potential?
MCW scientists published results in Nature Communications in December 2023 from experiments investigating what causes a psychedelic compound to elicit hallucinogenic experiences and how this characteristic can be manipulated by drug designers to create new psychedelic treatments for depression.
“There was no clear answer as to why a drug is hallucinogenic just based on chemical structure,” Dr. McCorvy says.
To better understand the source of hallucinogenic potential in these compounds, the scientists began by investigating a serotonin receptor called 5-HT2A that is found on the surface of cells throughout the central nervous system. It appeared likely to be involved in hallucinogenic potential based on other research findings. The team knew that psilocybin and other well-known psychedelics would increase activity in this receptor, but it was unknown whether the compounds would favor one of two potential cellular signaling pathways. The scientists found that psychedelics did not completely favor either the Gq signaling pathway (the G protein responsible for typical cellular signaling) or the β-arrestin pathway (a protein that competes with Gq for the binding site to decrease signaling activity into the cell).
“We know that G protein signaling pathways are like the gas pedal for signaling and the β-arrestin pathway is like the brakes,” Dr. McCorvy says. “Our question was, which of these signaling pathways is responsible for the hallucinogenic effects?”
To find out, scientists at St. Joseph’s University, led by assistant professor Jason Wallach, PhD, synthesized hundreds of compounds and Dr. McCorvy’s lab profiled their ability to selectively activate one of the two pathways through the serotonin 5-HT2A receptor. Compounds that feature this type of pathway-selective activation are known as biased agonists. Ultimately, the team found the most effective option for discovering biased agonists is by adding additional molecular bulk to one of the compounds they had synthesized. This atomic manipulation reduced the Gq signaling while preserving the β-arrestin activity. Then, Adam Halberstadt, PhD, and his lab at the University of California San Diego began testing the compounds in mice using an automated head twitch measurement that predicts psychedelic potential in humans. They found that these modified psychedelic biased agonist compounds with reduced Gq signaling did not induce a number of head twitches that correlates to hallucinogenic experiences, suggesting Gq signaling from the 5-HT2A receptor is necessary for psychedelic effects.
“We took a psychedelic and made it non-psychedelic, and we did it in a structure-based fashion,” Dr. McCorvy says. “Hopefully in the future this will help increase study of these compounds if the hallucinogenic hurdles can be removed.”
Dr. McCorvy would like to see industry build on this research by developing and testing new potential psychedelic treatments without the hallucinogenic trip.
“My vision is to get some of these compounds properly vetted in trials and out to clinics in my lifetime,” Dr. McCorvy says. “I know too many people who have suffered from posttraumatic stress disorder and other mental health conditions without enough relief from current therapies. They need new treatment options as soon as it is prudent and possible.”
Reference: Jason Wallach, Andrew B. Cao, Maggie M. Calkins, Andrew J. Heim, Janelle K. Lanham, Emma M. Bonniwell, Joseph J. Hennessey, Hailey A. Bock, Emilie I. Anderson, Alexander M. Sherwood, Hamilton Morris, Robbin de Klein, Adam K. Klein, Bruna Cuccurazzu, James Gamrat, Tilka Fannana, Randy Zauhar, Adam L. Halberstadt, John D. McCorvy. Identification of 5-HT2A Receptor Signaling Pathways Associated with Psychedelic Potential. Nature Communications, 15 December 2023.
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About the Medical College of Wisconsin
With a history dating back to 1893, The Medical College of Wisconsin is dedicated to leadership and excellence in education, patient care, research, and community engagement. More than 1,400 students are enrolled in MCW’s medical school and graduate school programs in Milwaukee, Green Bay, and Central Wisconsin. MCW’s School of Pharmacy opened in 2017. A major national research center, MCW is the largest research institution in the Milwaukee metro area and second largest in Wisconsin. In the last 10 years, faculty received more than $1.5 billion in external support for research, teaching, training, and related purposes. This total includes highly competitive research and training awards from the National Institutes of Health (NIH). Annually, MCW faculty direct or collaborate on more than 3,100 research studies, including clinical trials. Additionally, more than 1,600 physicians provide care in virtually every specialty of medicine for more than 2.8 million patients annually.
JOURNAL
Nature Communications
METHOD OF RESEARCH
Experimental study
ARTICLE TITLE
Identification of 5-HT2A Receptor Signaling Pathways Associated with Psychedelic Potential
ARTICLE PUBLICATION DATE
15-Dec-2023
COI STATEMENT
JW, ALH, and JDM submitted a patent application for the novel compounds in this study entitled “Selective, partial, and arrestin-biased 5-HT2A agonists with utility in various disorders,” PCT WO2022241006A1. AKK is currently an employee of Gilgamesh Pharmaceuticals. All other authors declare no competing interests.
ALDOUS HUXLEY WORK ON PSYCHEDELICS
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