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Psilocybin & the TRIP program at Pacific Neuroscience Institute
June 14, 2021

Psilocybin and the TRIP Program at Pacific Neuroscience Institute

by Guest Author

A growing body of research now supports the potential use of mushrooms containing the chemical psilocybin for a range of cognitive, mental and behavior disorders.

Several research projects at Pacific Neuroscience Institute at Providence Saint John’s Health Center are aimed at determining the safety and efficacy for psilocybin-based therapies, says Keith Heinzerling, MD, an addiction medicine specialist and well-published clinical investigator.

Dr. Heinzerling is the director of the Pacific Treatment & Research in Psychedelics (TRIP) program at Pacific Neuroscience Institute. Psilocybin, which is found in a range of genus Psilocybe mushrooms, has been the subject of decades of research for treating such conditions as depression, anxiety, post-traumatic stress disorder (PTSD) and drug and alcohol use disorders.

PNI researchers are launching several clinical trials to investigate the life-changing possibilities of psilocybin. “My goal for the TRIP program is to provide very sound scientific methods, innovation and compassionate care,” says Dr. Heinzerling. TRIP researchers are currently conducting a clinical trial using psychotherapy combined with psilocybin for patients with alcohol use disorder. Other TRIP studies are in early stages, including one to help patients undergoing the complicated grief of losing a loved one to COVID-19 and another for terminal cancer patients experiencing psychological distress caused by their diagnosis.

TRIP pyschedelic assisted therapy at PNI

These studies all follow strict safety protocols and adhere to long-held concepts on the importance of set and setting. Consenting and eligible patients are first provided with psychotherapy sessions to prepare them to optimize their mindset. The actual psilocybin treatment or journey which lasts four to five hours takes place in a controlled setting in a comfortable room with eyeshades and music, under the supervision of two trained professional guides. In the days and weeks after the journey, patients receive talk therapy to help them integrate the experience.

How Does It Work?

A crucial factor in the psilocybin treatment’s effectiveness is whether the patient experiences a transcendent, often called “mystical,” experience during the session, Dr. Heinzerling says. “People will tell you that they saw the meaning of life, that they felt one with God or the universe, that their ego had dissolved,” he says. This experience can help patients have extraordinary insights into themselves and their behavior. “Traditional pharmaceuticals are useful in helping patients with depression or anxiety disorders feel better and those with substance abuse problems experience less cravings, but patients often relapse because underlying issues have not been addressed,” says Dr. Heinzerling. “And psychedelics like psilocybin can be a tool for a patient who wants to change and understand themselves better, even when it’s a hard process.”

According to Daniel F. Kelly, MD, a neurosurgeon and PNI director, psilocybin mimics serotonin, a brain neurotransmitter. By stimulating serotonin receptors called 5-HT2A receptors throughout the cerebral cortex, life-altering and behavior-altering insights can be achieved. “Based on several landmark studies from major research institutions—including Imperial College of London, Johns Hopkins and University of Zurich—the working theory is that psilocybin affects the brain’s default mode network which is a large-scale network located predominantly in the frontal and parietal lobes of the brain and can be considered a neural construct for one’s ego,” he says.

Global Neural Networks affected by Psilocybin
Source: Journal of the Royal Society Interface

The default mode network seems to be where people get stuck ruminating about the past, worrying about the future, focusing on addictions and generating negativity. Psilocybin seems to unlock or dampen down the default mode network allowing much greater connectivity between brain regions that don’t normally communicate. While the exact mechanism of this brain reset is still not clearly understood, the result for many patients is truly life-changing, he says.

“A remarkable aspect of psilocybin and similar compounds is that their impact is transdiagnostic, meaning they appear to be effective for not only depression and anxiety, but also possibly addiction and post-traumatic stress disorder,” Dr. Kelly says. A study published last year in the prestigious scientific journal Cell pointed to the effects of the substance on the 5-Hydroxytryptamine 2A (5-HT2A) receptor in the brain as a possible mechanism of action. Moreover, several landmark studies from major research institutions have brought research on psilocybin into the mainstream. Some of the studies include detailed brain imaging showing the physiological impact of the substance, he says.

Help with Addiction

One of the most needed areas of mental health distress is for addiction including alcohol, nicotine and opioids. Psilocybin-assisted therapy has shown promise in several early clinical trials for these disorders. A recent study conducted by the NYU Grossman School of Medicine and presented at the American Psychiatric Association 2019 annual meeting found that one or two psilocybin sessions significantly reduced alcohol cravings.

psilocybin mushrooms

The TRIP program’s clinical trial for alcohol use disorder is investigating whether the number of subjects who have this epiphany-like experience, which is key to its success, can increase by changing the session’s setting. According to Dr. Heinzerling, patients in the TRIP alcohol use disorder study will be given 25 milligrams of a pharmaceutical, synthetic version of psilocybin that is identical to that in the genus Psilocybe mushroom. At the beginning of the session, half the patients have the standard setting, which is putting on eye shades and listening to music, which helps them focus internally. The other half will view a 40-minute nature-themed film with music created by award-winning filmmaker Louie Schwartzberg who produced the 2019 film Fantastic Fungi.

“Researchers at the Imperial College in London have noted that reconnecting with nature can be therapeutic for people who have depression, anxiety or alcohol use disorder,” says Dr. Heinzerling. “We wanted to see if by including Schwartzberg’s Visual Healing films, we can increase that connection to nature to help people cut back or stop their alcohol use.” Interest is also growing regarding psilocybin for helping with nicotine addiction. One small study from Johns Hopkins University found 70% of study participants who smoked had stopped smoking six months after a single psilocybin-assisted therapy session with preparation and integration sessions on either side of the psilocybin journey.

Emotional Healing and Long-term Relief

Caregivers left behind

Dr. Kelly says that TRIP is hoping to launch another psilocybin clinical trial for people with “complicated grief,” to be conducted in collaboration with Françoise Bourzat, a somatic psychologist and experienced guide, and Dr. Chris Adrian, a palliative care expert. “That trial looks to enroll 40 patients who lost a loved one during the COVID-19 pandemic and are suffering from prolonged grief of six months or more,” says Dr. Kelly. The need for more effective therapies to help people consumed by prolonged grief is all too apparent in the COVID-19 pandemic, when funerals and memorial services have been long postponed, says Dr. Heinzerling. “So many people who have lost loved ones to COVID-19 are suffering because they had to put their grief on hold.”

TRIP is also planning research on the use of psilocybin to help terminally ill cancer patients who are experiencing anxiety, depression and other forms of spiritual distress, says Shanthi Gowrinathan, MD, director of psycho-oncology and cancer support services at the Saint John’s Cancer Institute and director of psycho-oncology at PNI. Research conducted at the NYU Grossman School of Medicine and published in the Journal of Psychopharmacology showed that one dose of psilocybin in combination with psychotherapy can provide cancer patients with long-term relief of emotional distress. “Psilocybin is markedly tailored for cancer patients because it’s relatively medically benign,” Dr. Gowrinathan says. “It’s fairly well tolerated and doesn’t have the side effects and issues that may make it hard to use for someone with cancer. ”

Philanthropy helps support the meticulous biological and early clinical research that will help answer key questions about genus Psilocybe mushrooms, Dr. Heinzerling says. “We are grateful for the seed money we’ve received from the Annenberg Foundation and other private donors,” he says. Such research has the potential to pave the way toward much-needed, larger clinical trials. Therapies based on genus Psilocybe mushrooms may fill a void in psychiatry, says Dr. Gowrinathan, noting that one of her cancer patients who died recently had suffered severe emotional distress in her final months. “I wasn’t able to help her using traditional psychotropic medications,” Dr. Gowrinathan says. “I would have loved to have something else to offer her. I can’t put enough value on the ability to give someone peace of mind at the end of life. Nothing would be more rewarding than that.”

Adapted from Saint John’s Magazine Spring 2021 issue

About Dr. Keith Heinzerling

Keith Heinzerling, MD

Dr. Keith Heinzerling practices internal medicine and is an addiction medicine specialist at the Pacific Brain Health Center, Pacific Neuroscience Institute. His clinical and research focuses are on the treatment of alcohol, drug and substance use problems, with anti-addiction medications. As director of the TRIP program, he is involved in the development of psychedelic-assisted therapies for those suffering with addiction, depression, anxiety, and PTSD. 


About Dr. Daniel Kelly

Daniel F. Kelly, MD

Dr. Daniel Kelly, a board-certified neurosurgeon, is the Director and one of the founders of the Pacific Neuroscience Institute, Director of the Pacific Brain Tumor Center and Pacific Pituitary Disorders Center, and is Professor of Neurosurgery at Saint John’s Cancer Institute at Providence Saint John’s Health Center. Considered to be one of the top neurosurgeons in the US, he is a multiple recipient of the Patients’ Choice Award, and has been awarded the Southern California SuperDoctors distinction 15 years in a row. 

About Dr. Shanthi Gowrinathan

Shanthi Gowrinathan MD

Dr. Shanthi Gowrinathan, is an accomplished inpatient and outpatient psychiatrist, specializing in both Women’s Psychiatry and Psycho-oncology (Cancer Psychiatry) who works collaboratively in the care of her patients. She integrates her recommendations with the patient’s medical teams to ensure a whole person, interdisciplinary and cohesive treatment approach. Gifted with the strong ability to empathetically connect with her patients quickly, Dr. Gowrinathan is proficient at diagnosing and treating psychiatric disease in the context of complex medical issues such as cancer diagnosis.

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Last updated: August 6th, 2021