Psilocybin to target persistent concussion symptoms in Australia's first clinical trial

In continuation of my update on psychedelic

Monash University researchers have launched Australia's first clinical trial to test whether the psychedelic drug psilocybin is an effective treatment for persistent post-concussion symptoms.

There are few effective therapies for the debilitating long-term effects of mild traumatic brain injury, more commonly known as concussion.

But researchers now think psilocybin, a psychedelic compound found in some mushrooms, could be the answer.

A recent preclinical study from Monash University indicates that a single macrodose can reduce the symptoms that often appear after brain injury. The research is published in the journal Cell Reports Medicine.

The project will leverage leading-edge capability and a track record in neuroimaging and biomarkers of psychedelics within the Monash Trauma Group, and clinical implementation and assessment within the Clinical Psychedelic Lab.

Why researchers are hopeful

Lead researcher on the trial, Professor Terence O'Brien, head of Monash University's School of Translational Medicine, program director Alfred Brain, and deputy director of research at Bayside Health Alfred, said the clinical trial is a huge step forward and will provide hope for many patients.

"Given the lack of effective treatment options for persistent and debilitating concussion symptoms, we are excited to be studying a promising new approach," O'Brien said.

"In addition to alleviating symptoms, research suggests it can also target the biological effects concussion has on the brain."

Up to 50% of people who sustain a concussion will experience persistent post-concussion symptoms.

These commonly include cognitive and emotional issues, plus other debilitating symptoms such as headache, dizziness, irritability and sleep disturbances.

How the trial will work

The Monash-led trial will take place in Melbourne over three years, beginning in 2026.

It is Australia's first randomized, double-blind, active placebo-controlled clinical trial investigating the efficacy of psilocybin-assisted therapy for persistent post-concussion symptoms in humans.

It will study the effect of the drug on people who have had persistent post-concussion symptoms for at least six months, regardless of the cause of the original concussion.

Professor Sandy Shultz, from the Monash Trauma Group in the School of Translational Medicine, said researchers expect psilocybin will reduce neuroinflammation and enhance the brain's ability to form new neural connections.

"We will also be looking at blood and neuroimaging biomarkers in the brain so we can understand exactly what the drug is doing in the body and how it is helping reduce symptoms," Shultz said.

"These benefits could last for at least six months post-treatment, which would be a game changer, and we will test this in the trial."

Support and broader collaboration

Dr. Josh Allen, a research fellow in the Clinical Psychedelic Lab at Monash's School of Clinical Sciences, said while many think this kind of trial isn't for them, it's worth reaching out if you suffer from persistent post-concussion symptoms.

"Participants are supported every step of the way," he said.

"This includes preparation sessions before, guided care during the psychedelic experience, and integration therapy afterward.

"Our approach will promote safety and maximize benefits for all trial participants."

Dr. Paul Liknaitzky, head of the Clinical Psychedelic Lab, said the research will address a major unmet need for people with persistent post-concussion symptoms.

"We're testing a combined treatment approach that targets both the neurological and psychological drivers of patients' symptoms and functionality," Liknaitzky said.

The project is a collaboration between the university's Department of Neuroscience and Department of Psychiatry. Also part of the research team are Dr. Georgia Symons, Dr. Jennifer Makovec Knight, Dr. Zhibin Chen and Dr. Andrew Gibbons, all from Monash University, as well as Professor Karen Caeyenberghs from Deakin University, Professor Joshua Byrnes from the University of Queensland, Professor Karen Barlow from the University of Queensland, and Naomi Fuller from Connectivity Traumatic Brain Injury Australia.

Ref: https://en.wikipedia.org/wiki/Psilocybin

Psilocybin to target persistent concussion symptoms in Australia's first clinical trial

Psilocybin linked to reduction in depression

In continuation of my update on Psilocybin  

A study of 19 patients with treatment-resistant depression treated with psilocybin in Switzerland found psilocybin was associated with a significant reduction in depression symptoms. The study is published in The Lancet Regional Health—Europe.

Psilocybin—a naturally occurring psychedelic compound found in some species of mushrooms—has demonstrated promising antidepressant effects in depression and treatment-resistant depression in controlled clinical trials. However, its effectiveness and safety in real-world treatment settings remain largely unknown.

This study analyzed the medical records of 19 patients who received one to four clinical dosing sessions of psilocybin at the Psychiatric University Hospital Zurich as treatment for treatment-resistant mild to severe depression.

On average, the clinician-reported depression rating scores decreased from approximately 31/60 before psilocybin treatment to 20/60 within 42 days after the final dosing session. The patient-reported depression scores decreased from an average of 32/63 to 23/63. Side effects were reported in 30/40 psilocybin dosing sessions, with the most common being fatigue, headache, and tearfulness, but no serious or sustained side effects were documented.

The authors say their findings suggest that results from clinical trials may translate into routine clinical practice, although outcomes appear smaller in scale. They highlight that the small sample size of this study limits generalizability and, as there was no longer-term follow-up, it is not known if the improvements in depression symptoms were maintained. They call for larger real-world studies.

https://en.wikipedia.org/wiki/Psilocybin

Hallucinogenic drug offers relief for people with cancer-related anxiety or depression

In continuation of my update on psilocybin

In a small double-blind study, Johns Hopkins researchers report that a substantial majority of people suffering cancer-related anxiety or depression found considerable relief for up to six months from a single large dose of psilocybin -- the active compound in hallucinogenic "magic mushrooms."

The researchers cautioned that the drug was given in tightly controlled conditions in the presence of two clinically trained monitors and said they do not recommend use of the compound outside of such a research or patient care setting.

The Johns Hopkins team released its study results, involving 51 adult patients, concurrently with researchers from New York University Langone Medical Center, who conducted a similarly designed study on 29 participants. Both studies are published in the Journal of Psychopharmacology on Dec. 1.

The Johns Hopkins group reported that psilocybin decreased clinician- and patient-rated depressed mood, anxiety and death anxiety, and increased quality of life, life meaning and optimism. Six months after the final session of treatment, about 80 percent of participants continued to show clinically significant decreases in depressed mood and anxiety, with about 60 percent showing symptom remission into the normal range. Eighty-three percent reported increases in well-being or life satisfaction. Some 67 percent of participants reported the experience as one of the top five meaningful experiences in their lives, and about 70 percent reported the experience as one of the top five spiritually significant lifetime events.

"The most interesting and remarkable finding is that a single dose of psilocybin, which lasts four to six hours, produced enduring decreases in depression and anxiety symptoms, and this may represent a fascinating new model for treating some psychiatric conditions," says Roland Griffiths, Ph.D., professor of behavioral biology in the Departments of Psychiatry and Behavioral Sciences and of Neuroscience at the Johns Hopkins University School of Medicine. He notes that traditional psychotherapy offered to people with cancer, including behavioral therapy and antidepressants, can take weeks or even months, isn't always effective, and in the case of some drugs, such as benzodiazepines, may have addictive and other troubling side effects.

Griffiths says his team's new study grew out of a decade of research at Johns Hopkins on the effects of psilocybin in healthy volunteers, which found that psilocybin can consistently produce positive changes in mood, behavior and spirituality when administered to carefully screened and prepared participants. The study was designed to see if psilocybin could produce similar results in psychologically distressed cancer patients.

"A life-threatening cancer diagnosis can be psychologically challenging, with anxiety and depression as very common symptoms," says Griffiths. "People with this kind of existential anxiety often feel hopeless and are worried about the meaning of life and what happens upon death."

For the study, the investigators recruited 51 participants diagnosed with life-threatening cancers, most of which were recurrent or metastatic. They were chosen from a total of 566 individuals reached through flyers, web advertisements and physician referrals. Most participants had breast, upper digestive, GI, genitourinary or blood cancer, and each had been given a formal psychiatric diagnosis, including an anxiety or depressive disorder.

Half of the participants were female with an average age of 56. Ninety-two percent were white, 4 percent were African-American and 2 percent were Asian.

Each participant had two treatment sessions scheduled five weeks apart, one with a very low psilocybin dose (1 or3 milligrams per 70 kilograms) taken in a capsule and meant to act as a "control" placebo because the dose was too low to produce effects. In the other session, participants received a capsule with what is considered a moderate or high dose (22 or 30 milligrams per 70 kilograms).

To minimize expectancy effects, the participants and the staff members supervising the sessions were told that the participants would receive psilocybin on both sessions, but they did not know that all participants would receive one high and one low dose. Blood pressure and mood were monitored throughout the sessions. Two monitors aided participants during each session, encouraging them to lie down, wear an eye mask, listen to music through headphones and direct their attention on their inner experience. If anxiety or confusion arose, the monitors provided reassurance to the participants.

In addition to experiencing changes in visual perception, emotions and thinking, most participants reported experiences of psychological insight and often profound, deeply meaningful experiences of the interconnectedness of all people.

The researchers assessed each participant's mood, attitude about life, behaviors and spirituality with questionnaires and structured interviews before the first session, seven hours after taking the psilocybin, five weeks after each session and six months after the second session. Immediately after the sessions, participants completed questionnaires assessing changes in visual, auditory and body perceptions; feelings of transcendence; changes in mood; and more.

Structured clinical interviews, such as the Hamilton Depression Rating Scale and the Hamilton Anxiety Rating Scale, and patient questionnaires, like the Beck Depression Inventory and the State-Trait Anxiety Inventory, assessed depression and anxiety. Other questionnaires assessed quality of life, death acceptance, meaningful existence, optimism and spirituality -- generally defined as a search for the meaning of life and a connection to something bigger than one's self. To measure the changes in attitudes, moods and behavior over time, the researchers administered a questionnaire that assessed negative or positive changes in attitudes about life, mood and behavior.

With regard to adverse effects, Griffiths says 15 percent of participants were nauseated or vomited, and one-third of participants experienced some psychological discomfort, such as anxiety or paranoia, after taking the higher dose. One-third of the participants had transient increases in blood pressure. A few participants reported headaches following the session.

"Before beginning the study, it wasn't clear to me that this treatment would be helpful, since cancer patients may experience profound hopelessness in response to their diagnosis, which is often followed by multiple surgeries and prolonged chemotherapy," says Griffiths. "I could imagine that cancer patients would receive psilocybin, look into the existential void and come out even more fearful. However, the positive changes in attitudes, moods and behavior that we documented in healthy volunteers were replicated in cancer patients."

Up to 40 percent of people with cancer suffer from a mood disorder, according to the National Comprehensive Cancer Network.

Anticipating wide interest in the psilocybin research from scientists, clinicians and the public, the journal solicited 11 commentaries to be co-published with the study results written by luminaries in psychiatry, palliative care and drug regulation, including two past presidents of the American Psychiatric Association, a past president of the European College of Neuropsychopharmacology, the former deputy director of the U.S. Office of National Drug Control Policy, and the former head of the U.K. Medicines and Healthcare Products Regulatory Authority. In general, the commentaries were supportive of the research and of using these drugs in a clinical setting as tools for psychiatry.