Topics: Psilocybin, cancer, existential distress, PTSD, near death experience, entropy

By now, many are aware of the seminal research recently published in the December issue of the Journal of Psychopharmacology since it has received wide-spread news coverage. Publication of this research and its "game changing" potential for Medicine and Psychiatry in particular was anticipated by me and others as we awaited its dissemination.

What follows is a review of this research with links to full-text articles plus three summaries.  The summaries are from MedicalXpress, Scientific American, and Medscape, a website by Physicians for Physicians and others (free registration).

Hallucinogenic drug psilocybin eases existential anxiety in people with life-threatening cancer

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 (Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial (PDF) - cited by), involving 51 adult patients, concurrently with researchers from New York University Langone Medical Center, who conducted a similarly designed study (Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial (PDF) - cited by) on 29 participants. Both studies are published in the December issue of the Journal of Psychopharmacology.

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.

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. MedicalXpress Dec 1, 2016

Psilocybin: A Journey beyond the Fear of Death?

A Scientific American interview with Johns Hopkins researcher Roland Giffiths.

What are the practical implications of this kind of neurological and therapeutic knowledge of psychedelics? 

Ultimately it is not really about psychedelics. Science is going to take it beyond psychedelics when we start understanding the brain mechanisms underlying this and begin harnessing these for the benefit of humankind

The core mystical experience is one of the interconnectedness of all people and things, the awareness that we are all in this together. It is precisely the lack of this sense of mutual caretaking that puts our species at risk right now, with climate change and the development of weaponry that can destroy life on the planet. So the answer is not that everybody needs to take psychedelics. It is to understand what mechanisms maximize these kinds of experiences, and to learn how to harness them so that we don’t end up annihilating ourselves.

Griffiths believes that psychedelics are not just tools for exploring the far reaches of the human mind. He says they show remarkable potential for treating conditions ranging from drug and alcohol dependence to depression and post-traumatic stress disorder. Scientific American 1 Dec 2016

Psilocybin May Be a Psychiatry Game Changer

Two similar randomized controlled trials in late-stage cancer patients suggest that a single, high dose of the psychedelic drug psilocybin has rapid, clinically significant and lasting effects on mood and anxiety. The findings may be a therapeutic game changer for psychiatry. 

The new findings have "the potential to transform the care of cancer patients with psychological and existential distress, but beyond that, it potentially provides a completely new model in psychiatry of a medication that works rapidly as both an antidepressant and anxiolytic and has sustained benefit for months," Stephen Ross, MD, director of Substance Abuse Services, Department of Psychiatry, New York University (NYU), Langone Medical Center, told Medscape Medical News.

"That is potentially earth shattering and a big paradigm shift within psychiatry," Dr Ross told Medscape Medical News. Ross also stated that what might be happening is a sort of “inverse PTSD”—a profoundly positive memory that affects participants for months, much like a severe trauma might in post-traumatic stress disorder. Medscape 1 Dec 2016

Many, perhaps most, people are afraid of death, a fear which is often heightened in those with a terminal diagnosis. Commonly prescribed medication for patients with terminal cancer such as antidepressants, anxiolytics, and narcotics do little to overcome this fear.

While the above studies demonstrate the controlled, therapeutic use of psilocybin to be highly effective in decreasing the fear of death, the existential distress of those with a potentially terminal illness, there is another group of individuals who have achieved the same release from this existential threat, those who have had a near death experience (NDE).  Taking the psilocybin route, however, appears to be the less drastic route.

Quotes from the psilocybin studies:

• “bathed in God’s love.” 
• “I felt an acceptance of the world as it is and myself as I am,” 
• “spectacularly gorgeous” and “beyond words.” 
• “I have a feeling that I tapped into something bigger than me,” Vincent said. “It did feel like it was connecting me to the universe.”
• “Whatever it was, it was a power that is in the universe,” 
• “Now I’ve experienced the death of the body, so I’m not so afraid.“
• “lost in space, lost in time“
• "opened me up to pursue meditation and spiritual searching," 
• “love was the most important thing,” 
• “one with everything in the universe. It was simply, perfection.”
• "I was floating on this immense expansive infinite sea of strength and beauty," 
• “I felt this connection with everything,” “a sense of connectedness that runs through all of us,” “I felt that I was bathed in love,” and “I was feeling pure love,” and later thoughts of gratitude “for everything for being alive, no matter whatever happens.”

Quotes from people experiencing a NDE:

• "There was no limit to the outpouring as I came to the rapturous awareness of the infinite nature of God's love. There was no place that God did not exist and I was within God. I am an inseparable part of the light. The truth of who I am, indeed, who we all are, is perfect love as a creation of God. All of God's creation is one creation and I am one with creation. God and I are one, Creator and created."
• "All the fear was gone. I just felt so incredible. And I felt as though I was enveloped in this feeling of just love. Unconditional love.”
• “I could see how we are all connected, part of each other, and part of God. I felt so much love. I felt such a joy that is indescribable. I really don't have the words to describe how completely joyful, perfect, whole, and part of everything I felt and knew.”
• “I had shed the sense of my body very quickly. I was simply nothing and everything all at once.”
• "I could have stayed there forever and I maybe did because time no longer existed."
• "we are loved and accepted unconditionally by a God even more grand and unfathomably glorious than the one I’d learned of as a child in Sunday school."
• "I was simply at One with Absolute Life and Consciousness."
• "I feel joy so deep that my whole self leaps with gratitude; I feel peace; I feel awe and belonging. I did not have a specific life review, but felt everything about me and my life was known, understood and not judged. I was profoundly loved."

There are obviously many common elements to a therapeutic psilocybin experience and a NDE although the NDE experience appears to be more profound.  An overriding theme appears to be a loss of self and a gaining of a oneness with all things.  Not a bad trade-off.

After a number of years pondering what is occurring in a physical sense, I've come to the conclusion that is has to do with the Second Law of Thermodynamics which states that the total entropy of an isolated system always increases over time.  According to this, the entire universe started at a relatively low entropy (ordered) state but is now winding down to a higher entropy (disordered) condition.

As we age, our entropy increases until we die which is perhaps total entropy for the body.  Regenerative medicine techniques such as stem cells for degenerative conditions attempts to decrease entropy. In an article ("The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs.") published in the journal Frontiers in Human Neuroscience (February 2014) researchers point to psilocybin resulting in a state of elevated entropy compared to that of normal waking consciousness. Could it be that the similarities between the quotes above somehow results from the experience of an increase in entropy?

If the universe is steady heading from a lower to a higher entropy state, perhaps that should be accepted as God's will, or the will of the Universe. To struggle against it may be the underlying principle to the Buddha's First Noble Truth that life is full of pain and suffering. Becoming more mindful is to accept the nature of things, to not constantly look forward or to the past but to live Now without judging what is right or what is wrong and not resisting entropy.

Just 'Let it Be'. (Who was Mother Mary?)

"Everything is good". 
Swami Satchidananda

It appears those quotes above by individuals with a therapeutic psilocybin experience and by those who experienced a NDE plus recent neurophysiological studies hint at this.

As less ethereal explanation for the similarities may come from one proposed by a prominent NDE researcher, Pim van Lommel MD, a Dutch Cardiologist who has numerous publication on the NDE, including one in The Lancet (2001).

Dr. van Lommel, in his book 'Consciousness Beyond Life: The Science of the Near-Death Experience' after considering various possible physiological causes of an NDE such as too little oxygen, too much carbon dioxide, brain electrical activity, and various neurochemicals, he found dimethyltryptamine (DMT - active ingredient of ayahuasca) to be an attractive candidate for coming closest to replicating the NDE plus DMT is found distributed throughout the body, especially in the pineal gland.  DMT is just one hydroxyl group (-OH) different from psilocin, the physiologic form of psilocybin.

Not surprisingly, there has been published research on this topic.  In the Journal of Near-Death Studies, Vol 31(1), 2012, 3-23 Dr. Michael Potts published the article titled 'Does N,N-dimethyltryptamine (DMT) adequately explain near-death experiences?'  From the abstract:

Some NDE researchers have suggested that because some users of psychedelic drugs have experiences purportedly similar to near-death experiences (NDEs), the neural receptors and neurotransmitters affected by a particular drug may underlie out-of-body experiences and NDEs. One of the most recent psychedelic candidates that allegedly causes NDE-like experiences is N,N-dimethyltryptamine (DMT), a natural substance that the body produces in small amounts. If DMT experiences are phenomenologically similar to NDEs, then it is possible that the human body in extremis may produce larger amounts of DMT that reach psychedelic experience-causing levels in the blood. In this paper, I explore the issue of whether DMT might play a causal role in the production of NDEs. The first section summarizes basic information about NDEs, focusing on their phenomenological aspects. The second section classifies theories of NDEs to place the DMT theory in the context of the history of the debate over the cause of NDEs. The following section discusses DMT's chemical composition, physical effects, and psychological effects. The final section explores whether NDE and DMT experiences have a sufficient degree of phenomenological similarity to justify a causal role for DMT in the production of NDEs and concludes that such similarity is lacking. 

For further comments on this article see Does DMT Explain the Near-Death Experience?