Treatment with psilocybin, the active compound in hallucinogenic "magic mushrooms," results in fast and long-lasting relief from anxiety and depression among a majority of patients with cancer, including advanced disease, according to two similarly designed studies published online December 1 in the Journal of Psychopharmacology.
The reported efficacy is "unprecedented in psychiatry and psycho-oncology," said Roland Griffiths, PhD, a neuroscientist and the lead investigator of a 51-patient study at the Johns Hopkins University in Baltimore, Maryland.
When the study patients received a single high dose of synthetic psilocybin, the overall rate of clinical response at 6 months for the primary outcomes of depression and anxiety was 78% and 83%, respectively, and the overall rate of complete symptom remission was 65% and 57%.
"Psilocybin may represent a potential paradigm shift for treating patients suffering from cancer-related psychological distress," added Dr Griffiths, who spoke at a presscast for journalists.
Current drug treatments for cancer-related anxiety and depression "tend to not work any better than placebo" and have demonstrated a response rate of about 40% in meta-analyses, said Steven Ross, MD, a psychiatrist and lead investigator of the second study of 29 patients at New York University (NYU) in New York City.
Cancer-related distress is especially difficult to treat, he suggested, noting that standard drug therapies, such as fluoxetine (Prozac, Eli Lilly), have better efficacy for treating distress in patients with other serious conditions, including AIDS and stroke.
In the NYU study, at the 6.5-month follow-up, a single moderate dose of synthetic psilocybin was associated with "enduring" effects, as approximately 60% to 80% (depending on the measurement tool) of participants had ongoing, clinically significant reductions in depression or anxiety, reported Dr Ross and colleagues.
The findings may be a game changer for the field of psychiatry, as psilocybin has also recently been reported to be safely administered in patients with treatment-resistant depression and psychological distress associated with other life-threatening illness, as well as alcohol or tobacco dependency and obsessive-compulsive disorder, as reported today by Medscape Medical News
Patients participating in the two new studies, which are the largest randomized controlled trials of psilocybin for depression and anxiety in patients with cancer to date, also spoke at the press briefing.
Dinah Bazer, 69, from Brooklyn, New York, was diagnosed with ovarian cancer in 2010 and underwent successful surgery and chemotherapy, but had ongoing distress.
"I was absolutely totally consumed with anxiety and fear of recurrence," said Bazer, who participated in the NYU study. "During my psilocybin experience, I visualized my fear as a physical mass in my body. I become volcanically angry and I screamed at it 'Get the f--- out' and it was gone. I then went into a state, as an atheist it's hard to say…bathed in God's love. That continued for hours. When the experience was over, my fear and anxiety was still gone," she attested.
"This drug saved my life and changed my life," said Bazer.
"Psychedelic drugs" such as psilocybin have been studied in the past in the United States for a range of conditions, observes Craig Blinderman, MD, in an accompanying commentary. He is a palliative care specialist from the Columbia University Medical Center/New York-Presbyterian Hospital in New York City.
Such research halted when President Richard Nixon signed the Controlled Substance Act of 1970, placing so-called psychedelics into a Schedule I classification, which are "drugs with no currently accepted medical use and a high potential for abuse."
Dr Blinderman states that patients with cancer have a prevalence of anxiety and depression of 30% to 40%, which is much higher than the 7% to 10% in the general population.
Patients with cancer who experience anxiety or depression often have worse outcomes, including higher healthcare utilization, worse pain, decreased quality of life, and decreased survival, he writes, citing multiple studies.
The new studies are "groundbreaking" and report "extremely exciting" results, said Dr Blinderman, who also participated in the call with reporters.
One of the struggles in caring for patients with cancer, especially those with advanced disease, is "managing the existential distress," which is a syndrome characterized by hopelessness and helplessness due to a loss of purpose and meaning, according to Dr Blinderman.
The clinical challenge of addressing and treating existential distress is exacerbated by systemic problems, he continued. "Limitations in mental health coverage and available providers with expertise in psycho-oncology pose another barrier to cancer patients…in helping improve their well-being," he said.
What was "most interesting" to Dr Blinderman about the new studies was that both found a correlation between patients having a "mystical experience" and the extent to which anxiety and depression improved.
For example, in the NYU study, the authors reported that the intensity of the subjective mystical experience, which was rated with the self-reported Mystical Experience Questionnaire (MEQ 30), significantly "mediated" reduction in anxiety and depression symptoms in the medium term (eg, 6 weeks after dose 1).
"This is a profound outcome," said Dr Blinderman about the correlation between self-reported mystical experience and positive outcomes.
The findings also cast a new light on "the rise in interest in physician-assisted dying" in the United States, he said. The inability to relieve patients of their existential distress is the "main reason" patients choose physician aid in dying, said Dr Blinderman
We don't have any good treatments for existential distress," he observed. Before embracing such end-of-life measures, he commented, it seems appropriate to first attempt to explore such methods as treatment with psilocybin, which might alleviate the distress that is driving the desire for aided suicide.
Study Details
At Johns Hopkins, all 51 participants had a potentially life-threatening cancer diagnosis, with 65% having recurrent or metastatic disease. The cancer types included breast (n = 13), upper aerodigestive (7), gastrointestinal (4), genitourinary (18), hematologic (8), and other (1). All patients had been given a formal psychiatric diagnosis, including an anxiety or depressive disorder.
In terms of patient demographics, the average age was 56 years, half of patients were female, and most (92%) were white.
The study had a two-session (scheduled 5 weeks apart), double-blind, crossover design that compared the effects of a low vs high dose of psilocybin, given in capsule form. The low-dose effectively acted as a placebo because the dose was too low to produce effects.
In the alternate session, participants received a high-dose capsule.
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 the dose was not disclosed.
During each session, two monitors aided participants, who were encouraged to lie down, wear an eye mask, and listen to music through headphones in a "living-room-like" environment. Monitors were "nondirective and supportive," said the authors, and encouraged participants to "trust, let go and be open" to the experience.
The researchers assessed each participant's mood, attitude about life, behaviors, and spirituality with questionnaires and structured interviews before the first session, 7 hours after taking the psilocybin, 5 weeks after each session, and 6 months after the second session.
Measurement tools of the primary outcomes of depression and anxiety included the Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Beck Depression Inventory, and State-Trait Anxiety Inventory, assessed.
Psilocybin produced large and sustained effects on the two primary outcome measures, as well as most of the secondary measures assessed at baseline, 5 weeks after each session and at 6-month follow-up.
Of the 17 measures assessed, 16 showed significant effects (ie, a between-group difference at the post–session 1 assessment and/or a difference between post–session 1 and post–session 2 assessments in the low-dose-first group).
The authors summarized the highlights this way: "High-dose psilocybin produced large decreases in clinician- and self-rated measures of depressed mood and anxiety, along with increases in quality of life, life meaning, and optimism, and decreases in death anxiety."
Adverse events were minimal, and none were serious. About 15% of participants reported nausea or vomited, and 33% 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.
At NYU, the design was also a double-blind, placebo-controlled, crossover trial, but the placebo was niacin in one of the sessions. The primary outcomes were anxiety and depression assessed between groups before the crossover at 7 weeks.
Nearly two thirds of participants (62%) had advanced cancers (stages III or IV). The cancer types included breast or reproductive (59%), gastrointestinal (17%), hematologic (14%), and other (10%).
Most study participants were white (90%) and women (62%). The average age was 56.3 years.
All 29 participants had an anxiety-related diagnosis. Nearly two thirds (59%) had previously been treated with antidepressant or anxiolytic medication.
Clinical primary outcome measures (anxiety, depression) were assessed with measurement tools that included the Hospital Anxiety and Depression Scale, Beck Depression Inventory self-report depression measure, and Spielberger State-Trait Anxiety Inventory.
As with the Johns Hopkins study, secondary outcomes included cancer-related existential distress.
The NYU team reported that the psilocybin group (compared with the active control) demonstrated "immediate, substantial, and sustained" (up to 7 weeks postdosing) clinical benefits in terms of reduction of anxiety and depression symptoms.
They described the magnitude of differences between the psilocybin and control groups as "large" across the primary outcome measures, assessed at 1 day/2 weeks/6 weeks/7 weeks after dose 1.
There were no serious adverse events. The most common medical adverse events were non–clinically significant elevations in blood pressure and heart rate (76%), headaches/migraines (28%), and nausea (14%). The most common psychiatric adverse events were transient anxiety (17%) and transient psychotic-like symptoms (7%).
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