A single dose of magic mushroom compound reduces anxiety and depression among cancer patients

In continuation of my update on psilocybin

Magic mushrooms are wild or cultivated mushrooms containing psilocybin, which is a naturally occurring hallucinogenic and psychoactive compound. A single dose of psilocybin provides long-term relief of anxiety and depression in cancer patients, a new study found.

A team of researchers at the New York University Grossman School of Medicine has found that a one-time, single dose of psilocybin, the compound found in psychedelic mushroom or magic mushroom, combined with psychotherapy, has been linked to a marked improvement in existential and emotional distress in patients with cancer. The drug’s effect has persisted for nearly five years after administration.

The study, published in the Journal of Psychopharmacology, highlights the efficacy of psilocybin in reducing anxiety levels and depression in cancer patients. Patients with cancer who received the compound reported reductions in anxiety, depression, demoralization, hopelessness, and death anxiety nearly five years after receiving a single dose of the drug and psychotherapy.

Psilocybin effects

Psilocybin is a known hallucinogenic substance commonly found in mushrooms growing in South America, Mexico, Europe, and the United States. A schedule-I controlled substance, the compound has a high potential for abuse. However, people use it as a recreational drug, and over the past years, studies have analyzed its potential for medical purposes.

The compound has both positive and negative effects. It has been studied to relieve symptoms of anxiety and depression but has been known to trigger psychotic episodes. The drug has long been used recreationally due to its hallucinogenic effects, which work by altering a person’s perception, thoughts, and feelings.

Promising results

In the current study, the researchers conducted a long-term within-subjects follow-up analysis of self-reported symptomatology among 15 participants, who agreed to participate at an average of 3.2 to 4.5 years, following the administration of psilocybin.

The researchers noted that among the participants, about 60 to 80 percent of them had met the criteria for clinically significant anxiolytic or antidepressant responses after 4.5 years after receiving the drug. Further, 71 to 100 percent attributed positive life changes, thanks to the combination of psilocybin and psychotherapy treatment, rating it among the most spiritually significant and personally-meaningful experiences in their lifetime.

“These findings suggest that psilocybin-assisted psychotherapy holds promise in promoting long-term relief from cancer-related psychiatric distress. Limited conclusions, however, can be drawn regarding the efficacy of this therapy due to the crossover design of the parent study,” the researchers wrote on the paper.

“Nonetheless, the present study adds 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,” they added.

The authors said psilocybin shows promise as an important tool for enhancing psychotherapy’s efficacy and eventually, providing relief for symptoms of anxiety and depression.  While the exact mechanism on how psilocybin works are not fully understood, the researchers believe the drug makes the brain more receptive to new thought patterns and ideas.

It is also believed that the compound targets a brain network, called the default mode network, which becomes activated when individuals perform mind wandering and self-reflection. These activities aid in making sense of oneself and a sense of coherent narrative identity.

In most people with anxiety and depression, the said network becomes excessively active and has been tied to feelings of worry, rigid thinking, and rumination. The compound appears to work to shift the activity in the network, allowing people to have a broader perspective of their lives and behaviors.

The team plans to further conduct additional studies with bigger trials in patients who belong to diverse ethnic and socioeconomic populations. Also, they hope to conduct more studies on patients with advanced cancer-related psychiatric and existential distress.

https://journals.sagepub.com/doi/abs/10.1177/0269881119897615?journalCode=jopa&

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.

Magic mushroom compound psilocybin could provide new avenue for antidepressant research

In continuation of my update on psilocybin

The small feasibility trial, which involved 12 people with treatment-resistant depression, found that psilocybin was safe and well-tolerated and that, when given alongside supportive therapy, helped reduce symptoms of depression in about half of the participants at 3 months post-treatment. The authors warn that strong conclusions cannot be made about the therapeutic benefits of psilocybin but the findings show that more research in this field is now needed.

"This is the first time that psilocybin has been investigated as a potential treatment for major depression," says lead author Dr Robin Carhart-Harris, Imperial College London, London, UK. "Treatment-resistant depression is common, disabling and extremely difficult to treat. New treatments are urgently needed, and our study shows that psilocybin is a promising area of future research. The results are encouraging and we now need larger trials to understand whether the effects we saw in this study translate into long-term benefits, and to study how psilocybin compares to other current treatments."

Depression is a major public health burden, affecting millions of people worldwide and costing the US alone over $200 billion per year. The most common treatments for depression are cognitive behaviour therapy (CBT) and antidepressants. However, 1 in 5 patients with depression do not respond to any intervention, and many relapse.

"Previous animal and human brain imaging studies have suggested that psilocybin may have effects similar to other antidepressant treatments," says Professor David Nutt, senior author from Imperial College London "Psilocybin targets the serotonin receptors in the brain, just as most antidepressants do, but it has a very different chemical structure to currently available antidepressants and acts faster than traditional antidepressants."

The trial involved 12 patients (6 women, 6 men) with moderate to severe depression (average length of illness was 17.8 years). The patients were classified as having treatment-resistant depression, having previously had two unsuccessful courses of antidepressants (lasting at least 6 weeks). Most (11) had also received some form of psychotherapy. Patients were not included if they had a current or previous psychotic disorder, an immediate family member with a psychotic disorder, history of suicide or mania or current drug or alcohol dependence.

Patients attended two treatment days -- a low (test) dose of psilocybin 10mg oral capsules, and a higher (therapeutic) dose of 25mg a week later. Patients took the capsules while lying down on a ward bed, in a special room with low lighting and music, and two psychiatrists sat either side of the bed. The psychiatrists were present to provide support and check in on patients throughout the process by asking how they were feeling. Patients had an MRI scan the day after the therapeutic dose. They were followed up one day after the first dose, and then at 1, 2, 3, and 5 weeks and 3 months after the second dose.

The psychedelic effects of psilocybin were detectable 30 to 60 minutes after taking the capsules. The psychedelic effect peaked at 2-3 hours, and patients were discharged 6 hours later. No serious side effects were reported, and expected side effects included transient anxiety before or as the psilocybin effects began (all patients), some experienced confusion (9), transient nausea (4) and transient headache (4). Two patients reported mild and transient paranoia.

At 1 week post-treatment, all patients showed some improvement in their symptoms of depression. 8 of the 12 patients (67%) achieved temporary remission. By 3 months, 7 patients (58%) continued to show an improvement in symptoms and 5 of these were still in remission. Five patients showed some degree of relapse.

The patients knew they were receiving psilocybin (an 'open-label' trial) and the effect of psilocybin was not compared with a placebo. The authors also stress that most of the study participants were self-referred meaning they actively sought treatment, and may have expected some effect (5 had previously tried psilocybin before). All patients had agreement from their GP to take part in the trial. They add that patients were carefully screened and given psychological support before, during and after the intervention, and that the study took place in a positive environment. Further research is now needed to tease out the relative influence of these factors on symptoms of depression, and look at how psilocybin compares to placebo and other current treatments.

Writing in a linked Comment, Professor Philip Cowen, MRC Clinical Scientist, University of Oxford, Oxford, UK, says: "The key observation that might eventually justify the use of a drug like psilocybin in treatment-resistant depression is demonstration of sustained benefit in patients who previously have experienced years of symptoms despite conventional treatments, which makes longer-term outcomes particularly important. The data at 3 month follow-up (a comparatively short time in patients with extensive illness duration) are promising but not completely compelling, with about half the group showing significant depressive symptoms. Further follow-ups using detailed qualitative interviews with patients and family could be very helpful in enriching the assessment."
Ref :http://dx.doi.org/10.1016/S2215-0366(15)00576-3

Single dose of psilocybin decreases anxiety, depression in cancer patients

In continuation of my update on Psilocybin

A single dose of psilocybin, the major hallucinogenic component in magic mushrooms, induces long-lasting decreases in anxiety and depression in patients diagnosed with life-threatening cancer according to a new study presented today at the annual meeting of the American College of Neuropsychopharmacology.

Patients who receive a cancer diagnosis often develop debilitating symptoms of anxiety and depression. Reports from the 1960s and 1970s suggest that hallucinogenic drugs such as LSD may alleviate such symptoms in cancer patients, but the clinical value of hallucinogenic drugs for the treatment of mood disturbances in cancer patients remains unclear. In this new study, Roland Griffiths and colleagues from the Johns Hopkins University School of Medicine investigated the effects of psilocybin on symptoms of anxiety and depression in individuals diagnosed with life-threatening cancer. Five weeks after receiving a dose of psilocybin sufficiently high to induce changes in perception and mystical-type experiences, patients reported significantly lower levels of anxiety and depression compared with patients that received a low dose of the drug. The positive effects on mood persisted in the patients at 6 month follow-up.

The authors suggest that a single dose of psilocybin may be sufficient to produce enduring decreases in negative mood in patients with a life-threatening cancer.

Single dose of psilocybin decreases anxiety, depression in cancer patients

Could 'Magic' Mushrooms Ease Depression?

Psychedelic mushrooms (see above picture) may point to new ways to treat depression, suggest two small brain imaging studies that seem to show how psilocybin (see right structure) the active ingredient in such mushrooms -affects the brain. 

One study included 30 healthy people who had psilocybin inserted into their blood while magnetic resonance imaging (MRI) scanners measured changes in their brain activity. The scans revealed that psilocybin caused decreased activity in what the researchers described as the brain's "hub" regions -- areas especially well-connected with other areas.

The second study included 10 healthy volunteers and found that psilocybin boosted their recall of personal memories and their emotional well-being for up to two weeks. The researchers said this suggests that psilocybin might prove useful as an adjunct to psychotherapy.

"Psychedelics are thought of as 'mind-expanding' drugs, so it has commonly been assumed that they work by increasing brain activity, but surprisingly, we found that psilocybin actually caused activity to decrease in areas that have the densest connections with other areas," Nutt said....

Researchers lead by Dr.David Nutt, add that result is consistent with earlier finding that psilocybin decreases mPFC activity, as many effective depression treatments do. The effects need to be investigated further and this study was only a small study, and  are interested in exploring psilocybin's potential as a therapeutic tool.....