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Depression as Disconnection: New Lessons From Psychedelic Psychotherapy Studies

November 02, 2017

By Andrew Penn, RN, MS, NP, CNS, APRN-BC
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The opinions expressed by Psychiatry & Behavioral Health Learning Network bloggers and those providing comments are theirs alone and are not meant to reflect the opinions of the publication.

Recent studies, reviewed in a paper by Kelan Thomas and colleagues1, have shown significant effects of psilocybin-assisted psychotherapy in the treatment of depression. These studies not only showed effect sizes larger than what is typically found with conventional treatments such as antidepressants, but these benefits often endured for weeks, if not months, following the treatment—long after the psychoactive effects had subsided. These findings offered tantalizing hope that this ancient fungi, long used as healing medicine in indigenous cultures and currently demonized as a drug of abuse in our culture, may become a powerful tool in our psychiatric armamentarium.

But the question remained: how could a few sessions with a therapist, under the influence of psilocybin, bookended by preparatory and integrative psychotherapy sessions, have such a powerful and lasting effect?

Recent qualitative studies by Rosalind Watts and colleagues in the United Kingdom2 and Alexander Belser and colleagues in the United States3, on subjects treated with psilocybin, may begin to help us understand the subjective experience caused by the drug that may lead to its antidepressant effects.

MORE: Psilocybin Studies: A New Ray of Hope for Psychiatry?

The findings, distilled to their essence: Depression disconnects us from the world around us and leaves us resistant to change. Imprisoned by depression, we are unable to enjoy our senses, unable to avail ourselves of meaningful emotional attachment to other people. Despite the suffering that this creates, the depressed person struggles to make the changes that would reverse this experience, and because of the depression, is often unable to take corrective action. This vicious cycle serves to worsen the experience of depression and the feelings of alienation. Psilocybin–assisted therapy provides a corrective experience that enables the person with depression to feel connected with others and the world around them, and to feel a willingness and agency for change. This is different than current antidepressant treatments, which may provide temporary relief of depression, but often at the cost of emotional numbness. Additionally, while an antidepressant may push away symptoms of depression, the depression often waits in the wings and returns upon the cessation of the drug.

Most of the subjects in the psilocybin studies described their experience of depression as one of feeling trapped in their own minds, disconnected from themselves, from others, the world at large, and their sensory experiences of pleasure and joy. They described the experience of rumination, which psilocybin may change through shifts in functional network connectivity in the default mode network4, as one that not only impairs executive function, but adds to the experience of isolation in depression, as one’s thoughts become increasingly inward focused and recriminative.

Additionally, work by Katherine MacLean and colleaguesfound a relationship between the degree of mysticism experienced by normal (healthy) subjects under psilocybin and changes in the personality trait of openness as measured on the NEO Personality Inventory. Other measured traits—neuroticism, extroversion, agreeableness, and  conscientiousness—did not change as a result of the psilocybin experience. These changes in openness persisted at the 16-month follow-up. Similar findings were reported by Mark Wagner and colleagues6 this year in an analysis of subjects with post-traumatic stress disorder (PTSD) treated with MDMA-assisted psychotherapy. They found post-test reductions in neuroticism and increases in openness in patients who had responded to the treatment with reductions in PTSD symptoms, as measured by the Clinician-Administered PTSD Scale (CAPS). These changes towards a more open, less neurotic personality persisted at long-term follow-up, on average 45 months after the initial treatment.

MORE: The Role of Psychedelics in the Future of Psychiatry

These findings raise an important and provocative question in a field that has often looked at our psychopharmacologic interventions as providing a lytic treatment against depression in the same way that our colleagues in infectious disease have used antimicrobials. They ask: “Could psychedelic-assisted psychotherapy treat depression by fundamentally changing the experience of suffering caused by the illness? Might some of the suffering generated by depression be the experience of relational disconnection from others, from the world, from our sense, and from ourselves? Can these experiences leave us more open and less neurotic, therefore paving a path to greater mental health?” If the answers prove to be “yes,” we are looking at a fundamentally different approach to treating depression—one that is more akin to psychotherapy than biologic psychiatry, one that seeks to change the subjective relationship our patients have with their illness and in doing so, integrate the pain associated with the illness, rather than trying to eradicate the illness outright. Put more simply, the pain of depression may not be optional, but we may have some say in the degree of suffering we experience. This change in perspective brought about by psychedelic-assisted psychotherapy may be at the heart of the healing.


  1. Thomas K, Malcolm B, Lastra D. Psilocybin-assisted therapy: a review of a novel treatment for psychiatric disorders. Journal of Psychoactive Drugs. 2017 May 8;[Epub ahead of print].
  2. Watts R, Day C, Krzanowski J, Nutt D, Carhart-Harris R. Patients’ accounts of increased “connectedness” and “acceptance” after psilocybin for treatment-resistant depression. Journal of Humanistic Psychology. 2017;57(5):520-564.
  3. Belser AB, Agin-Liebes G, Swift TC, et al. Patient experiences of psilocybin-assisted psychotherapy: an interpretative phenomenological analysis. Journal of Humanistic Psychology. 2017:57(4):354-388.
  4. Carhart-Harris RL, Leech R, Hellyer PJ, et al. The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs, Frontiers in Human Neuroscience. 2014 February 3.
  5. MacLean KA, Johnson MW, Griffiths RR. Mystical experiences occasioned by the hallucinogen psilocybin lead to increases in the personality domain of openness. Journal of Psychopharmacology. 2011;25(11):1453–1461.
  6. Wagner MT, Mithoefer MC, Mithoefer AT, et al. Therapeutic effect of increased openness: investigating mechanism of action in MDMA-assisted psychotherapy. Journal of Psychopharmacology. 2017;31(8):967-974.

Andrew Penn was trained as an adult nurse practitioner and psychiatric clinical nurse specialist at the University of California, San Francisco. He is board certified as an adult nurse practitioner and psychiatric nurse practitioner by the American Nurses Credentialing Center. Currently, he serves as an Associate Clinical Professor at the University of California-San Francisco School of Nursing. Mr. Penn is a psychiatric nurse practitioner with Kaiser Permanente in Redwood City, California, where he provides psychopharmacological treatment for adult patients and specializes in the treatment of affective disorders and PTSD. He is a former board member of the American Psychiatric Nurses Association, California Chapter, and has presented nationally on improving medication adherence, emerging drugs of abuse, treatment-resistant depression, diagnosis and treatment of bipolar disorder, and the art and science of psychopharmacologic practice. 

The views expressed on this blog are solely those of the blog post author and do not necessarily reflect the views of Psych Congress Network or other Psych Congress Network authors. Blog entries are not medical advice.

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