New Research Reveals the Therapeutic Potential of Psilocybin

The term psychedelic is derived from the Greek word meaning "mind-manifesting." It is believed that psychedelics such as psilocybin have the potential to uncover aspects of the mind that may be hidden. This mind-revealing process can result in long-term changes in behaviors, values, and experiences. But what does the research reveal about the therapeutic use of psilocybin?

Mechanisms of Action

Psilocybin is a hallucinogenic compound found in certain mushrooms. In the human body, psilocybin is converted to psilocin, which is the active compound. Psilocin is a 5-HT2A receptor antagonist and interacts with other 5-HT and non-5HT receptors. 5-HT receptors are commonly known as serotonin receptors, and they are found throughout the central nervous system, with an abundance in the brain, as well as in the cardiovascular system and gut tissue.

Research also demonstrates that psychedelics, including psilocybin, interact with the Default Mode Network (DMN), the area of the brain that influences self-referencing, mind wandering, and autobiographical memories. The DMN is implicated in neuropsychiatric conditions such as depression, anxiety, post-traumatic stress disorder, attention-deficit-hyperactivity disorder, obsessive-compulsive disorder, and others. A psychedelic experience seems to change the connectivity and function of the DMN, perhaps explaining the relief it provides to people living with these conditions.

“Psychedelics, including psilocybin, appear to have two central modes of action,” explained physician, mental health expert, and researcher Emily Whinkin, ND, MS. “One is more biochemical—for example, activity at the 5-HT2A receptor by psilocybin or NMDA receptor antagonism by ketamine, or promotion of a brain-derived neurotrophic factor (BDNF), which is involved in learning—and the other mode is more psychological and psychospiritual.”

Whinkin, who is with the Advanced Integrative Medical Science (AIMS) Institute, believes the dual chemical and psychospiritual effects of psilocybin help explain, in part, the many benefits seen in the scientific literature.

In addition, Whinkin explains that psilocybin appears to reduce mental rigidity, a key characteristic of major depressive disorder, generalized anxiety disorder, obsessive-compulsive disorder, and some cases of substance use disorders.

"When we look at conditions that psilocybin can treat, we think of the depth of the neuronal grooves where people suffer from continually thinking the same thoughts, which leads to that internal rigidity,” said Whinkin in a recent Natural Medicine Journal Podcast. “Psychedelics open up an opportunity to have a different internal experience by creating novel ways to interpret somatic cues and reflect on one's experiences, which can facilitate healing.”

Recent Palliative Care Study

Whinkin was the lead author of a paper recently published in the journal Current Geriatrics Report that evaluated research associated with psilocybin use in palliative care. Whinkin and her colleagues looked at total pain, which was not just physical pain but also psychosocial pain, emotional pain, community disconnection, cognitive function, and existential distress.

“We found that there is compelling research that has taken place over the past five years that indicates psilocybin can benefit each of these areas within the palliative medical community,” she said. “We also found that there is a rebranding of a person’s interpretation of pain, and we believe that is because psilocybin can help rebuild neuronal tissue as evidenced in cases of traumatic brain injury.”

Whinkin and her colleagues conclude that there are major legal, ethical, and financial barriers to access, especially for geriatric and palliative care patients.

Other Recent Studies

As more research is published, perhaps the barriers to this therapy will be lessened. 

A 2022 complex study published in Frontiers in Pharmacology set out to investigate the positive effects of psilocybin on self-reported “mystical” experiences of 28 healthy female volunteers 18 years and older. The researchers concluded that feelings of love, beauty, and connection to the Universe may be important factors that influence the lasting positive effects of psilocybin therapy.

More clinically concrete studies are also being published. For example, a 2023 review of four studies published in Frontiers in Psychiatry found that psilocybin was beneficial in alleviating substance use disorder symptoms.

A 2023 paper published in the Journal of Psychopharmacology found that psilocybin positively influenced cognition and creativity. 

Some of the most recent research is focusing on major depressive disorder. For example, a 2022 paper published in The Lancet found that one dose of psilocybin resulted in a significant reduction in major depressive disorder symptoms, which was maintained 14 days later. No serious adverse events were reported in that study. 

A 2022 prospective 12-month follow-up study published in the Journal of Psychopharmacology found that patients with major depressive disorder who received two acute doses of psilocybin continued to have fewer symptoms one year later, with 58 percent of the participants considered to be in remission. Again, no adverse events were reported in that study.

A 2023 randomized trial for the treatment of major depressive disorder published in JAMA showed that a single 25 milligram (mg) dose of psilocybin was associated with a clinically significant and sustained reduction in symptoms and functional disability without serious adverse events. 

Research demonstrates that of all the psychedelic compounds available, psilocybin has the most favorable safety profile with a low potential for addiction.

Future Research and Potential Clinical Applications

Legal issues aside, clinical trials are ongoing. Presently, the University of California San Francisco has six clinical trials in progress, with three of those open to eligible people. Johns Hopkins has a robust psychedelic and psilocybin research effort as well. The Healthy Mind Lab with Washington University School of Medicine in St. Louis is also taking on psychedelic research, including psilocybin. The Center for Psychedelic Medicine with New York University, as well as many other prestigious organizations, are getting involved in this growing area of research.

A recent news post by the American Society of Clinical Oncology (ASCO) outlines a long list of conditions that may benefit from psilocybin. In oncology, there is research demonstrating reductions in suicidal ideation, depression, anxiety, and end-of-life care. Many other future conditions have been identified, including treatment-resistant depression, tobacco and alcohol use disorders, cluster headaches, and migraines. ASCO concludes that continued research will help clarify clinical practice guidelines to help ensure its appropriate use. Presently, psilocybin has been decriminalized and legalized in Oregon, Colorado, and California.