Psilocybin Benefits in Cancer Sustained Nearly 5 Years Later

Nancy A. Melville

January 28, 2020

Cancer patients who were treated with a one-time, single dose of the psychedelic drug psilocybin, combined with psychotherapy, showed significant benefits on measures of emotional and existential distress nearly 5 years after receiving the therapy, new research indicates.

In addition to reporting improved well-being or life satisfaction, some patients rated the treatment as being "among the most personally meaningful and spiritually significant experiences of their lives," the authors note.

The study, the longest-spanning evaluation to date of the effects of psilocybin in the treatment of cancer-related psychiatric distress, was published online January 9 in the Journal of Psychopharmacology.

It follows up on patients who took part in a randomized placebo-controlled trial published in 2016, which was reported by Medscape Medical News at the time.

The new findings of long-term benefit add "to the emerging literature base suggesting that psilocybin-facilitated therapy may enhance the psychological, emotional, and spiritual well-being of patients with life-threatening cancer," the authors comment.

"This approach has the potential to produce a paradigm shift in the psychological and existential care of patients with cancer, especially those with terminal illness," added lead investigator Stephen Ross, MD, associate professor of psychiatry in the Department of Psychiatry at NYU Langone Health, New York City, in a press statement.

"These findings have meaningful implications for the clinical management of cancer-related existential distress," the authors write.

Psilocybin-assisted psychotherapy could represent the first empirically driven pharmacotherapy intervention to treat such patients.

Within Western medicine, existential distress is underrecognized and undertreated in cancer patients, the authors note. Depression and hopelessness associated with a diagnosis of cancer can be severe stressors and are well-known risk factors for suicide.

"The potential rapidity and long-term durability of psilocybin-assisted psychotherapy's effects represents a promising protective strategy against suicides," the authors write.

Uniquely Effective for Depression in Cancer Patients?

Psilocybin, the active component in "magic mushrooms," has been studied as a treatment for various types of depression, but the drug appears uniquely effective for depression associated with cancer, said Matthew W. Johnson, PhD, from Johns Hopkins University School of Medicine, in Baltimore, Maryland.

An associate professor in the Behavioral Pharmacology Research Unit, he was not involved in this study, but he has conducted his own research into the use of psilocybin among cancer patients.

"This treatment has a way of getting at the existential issues that are central to the psychological suffering that can come with cancer," Johnson told Medscape Medical News.

"That said, we and others are finding positive findings for depression outside of cancer," he continued.

"We don't have the research needed to confidently compare the populations, but my impression is that the effect size of depression reduction is going to be larger for cancer patients than those without cancer."

Johnson commented that the new findings reflect what he has observed among his patients. "My lab has been contacted informally by many of our 51 patients who were in our psilocybin cancer study, some who were treated well over 5 years ago, with claims that they were still seeing lasting reductions in depression and anxiety," he said.

"So it is valuable to have a formal evaluation such as this new publication."

An important caveat with respect to his own research as well as the current study is that the studies were only double-blind until about a month before the crossover, Johnson noted.

"So while the new long-term descriptive results are valuable and suggestive, we cannot exclude the possibility that placebo and other expectancy effects are not at least partially driving results," he cautioned.

Although the results of the long-term study were not surprising to Johnson, he said they likely will be to many researchers.

"And it should be," he said. "Such results are a game changer for psychiatry, in my opinion."

Longest Follow-Up of Psilocybin-Treated Cancer Patients

The original study included 29 patients who were experiencing cancer-related psychiatric and existential distress. They received either a single dose of psilocybin (0.3 mg/kg) or a single dose of niacin (250 mg) in conjunction with nine psychotherapy sessions. The groups switched treatments after 7 weeks in the double-blind study.

The results showed that the patients who received psilocybin-assisted psychotherapy experienced improvements in psychiatric and existential distress, quality of life, and spiritual well-being.

At a follow-up visit held 6.5 months after the treatment, 60% to 80% of the patients continued to meet criteria for clinically significant antidepressant or anxiolytic responses.

There were no serious adverse effects related to the psilocybin-assisted therapy, and there were no reports of abuse or addiction to the drug.

The new study reports long-term benefits regarding 16 patients (of the original 29) who agreed to participate in two additional follow-up assessments at an average of 3.2 years and 4.5 years following the psilocybin treatment. One patient died from cancer-related causes after the first of the two long-term follow-up evaluations.

The mean age of the participants was 53 years at the first long-term follow-up; 60% were women.

The study showed sustained reductions (in comparison to baseline) in anxiety, depression, hopelessness, demoralization, and death anxiety at both long-term follow-ups, with large within-group effect sizes at both time points.

Specifically, at the second long-term follow-up of 4.5 years, more than half (57%) of the participants showed clinically significant responses on the Hospital Anxiety and Depression Scale (HADS) for anxiety, and 71% reported significant reduction in global psychological distress on the HADS total score, which measures anxiety and depression.

In addition, clinical responses for depression on the HADS and the Beck Depression Inventory ranged from 57% to 79%.

Remission rates for symptoms of depression ranged from 50% to 79% at the 4.5-year follow-up.

Cancer Remission Status

Patients in this study had a variety of cancers, including gynecologic cancers (33%), breast cancers (20%), and lymphomas (20%). At the endpoint of the original study, 60% were diagnosed with early-stage (I–II) disease, and 53% were diagnosed later-stage (III–IV) disease.

Notably, at the second long-term follow-up, 71% of patients reported that their cancer had entered partial or complete remission.

"This is an important variable. However, we controlled for this and found that cancer remission status did not significantly interact with any of the changes in outcomes, [such as] anxiety, depression, existential distress, and so on," lead investigator Gabrielle Agin-Liebes, a PhD candidate at Palo Alto University, in California, told Medscape Medical News.

In addition, approximately half (53%) of participants reported that they had previously used a hallucinogen on one or more occasions, which Agin-Liebes said is higher than the national sample, in which the rate is only about 20%.

"What this means is unclear," she said. "Our sample may have been somewhat biased towards people who had tried a psychedelic before and may be a reflection that this type of person may be more open to trying this type of therapy," she explained.

"The key would be to recruit enough people who had never done a psychedelic in a bigger sample to more closely look at this issue, as a moderator of therapeutic outcomes," she commented.

Psilocybin May Induce a "Flexible Brain State"

Psilocybin is a serotonergic hallucinogen that acts as a 5-hydroxytryptamine 2A receptor agonist. Although the mechanisms behind its long-term effects in cancer-related depression are not well understood, a key theory involves an alteration in how the brain processes information and forms perceptions, Agin-Liebes noted.

"The most compelling and scientifically grounded theory relates to psilocybin's potential for inducing a flexible brain state, particularly people who experience more rigid brain states," she said.

"Psychedelics appear to relax the brain's biased patterns of information processing and beliefs and allow for more 'bottom-up' information to enter into one's consciousness," Agin-Liebes said, citing research that describes the theory.

The current study received funding from the Source Research Foundation. The parent study was supported by grants from the Heffter Research Institute, the RiverStyx Foundation, and the New York University–Health and Hospitals Corporation Clinical and Translational Science Institute. Funding for the trial was also provided by William Linton, Carey and Claudia Turnbull, and Efrem Nulman. The authors have disclosed no relevant financial relationships. Johnson has consulting relationships regarding the potential development of psychedelic medicines, including relationshps with Beckley Psychedelics Ltd, Entheogen Biomedical, and Otsuka Pharmaceutical Development and Commercialization.

J Psychopharmacol. Published online January 9, 2020. Abstract

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