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Tackling Depression With Psychedelic-Assisted Therapies

Andrew D. Penn.
Andrew D. Penn, MS, PMHNP.

Psychedelics are currently a popular topic of discussion within the field of mental healthcare, with many speculating that they may completely transform psychiatric practice.

On Monday, September 19, at the 3rd Annual Psych Congress in New Orleans, Andrew D. Penn, MS, PMHNP, associate clinical professor, psychiatric clinical nurse specialist, University of California, San Francisco, presented his session entitled, “Psychedelic-assisted Psychotherapy: How is it Different From What We Already Do?” before an audience of mental healthcare professionals, including doctors, nurse practitioners, care advocates, and non-profit representatives.

Ahead of his presentation, Penn spoke with Psych Congress Network about why psychedelic-assisted psychotherapy is a great treatment option for depression and the role of trust in the patient-clinician relationship.

Missed Part 1 of this exciting expert Q&A? Read it here. For more insights direct from the session rooms, check out the Psych Congress newsroom here.


Brionna Mendoza, Associate Digital Editor, Psych Congress Network (PCN): You mention in your session that psychedelics are well-suited to treat depression—why is that? What makes them different from other therapies?

Andrew Penn, MS, PMHNP: Depression can be thought of as a low-entropy state. That’s a fancy way of saying that it’s resistant to change. We see this phenotypically, often in the behavior of the person who is struggling with depression and wants to change, but seemingly cannot. We also see it in functional network connectivity in fMRI scans of the brains of people with depression. In this state, the default mode network (DMN) is over-dominant, reflecting a kind of “pathological introspection” or rumination, common in depression. When the DMN is running the show, other networks, the ones that we need to make decisions and get things done each day, like the task-positive network, can’t get out from under the DMN.

Psilocybin appears to disrupt this system so that when the drug wears off, that some of these networks have “reset” to a more normal function. Additionally, in the psychedelic state, patients have the opportunity, with help from a therapist, to examine patterns and beliefs that aren’t working for them. This may help to contribute to the therapeutic benefit of psychedelic-assisted therapies (PAT).

Mendoza, PCN: Can you explain the role that trust in the clinician-patient relationship plays in psychedelic-assisted psychotherapy, and why that trust is so important? 

Penn: A person in a psychedelic state is often quite vulnerable, as their ability to think and perceive normally will be altered. Additionally, they may need help with basic tasks like getting to the bathroom. In addition to this protection of the body, they need to be able to trust the therapist with their inner thoughts and feelings. That’s why we spend considerable time before the drug is even administered in non-drug, preparatory psychotherapy. During this time, the patient gets to know the therapists while the therapists get to know what is most important for the patient and what psychological issues may emerge during the drug session. The therapist(s) and patient co-create a safe container for healing. That can only happen in an environment of trust. 

Mendoza, PCN: What else should healthcare professionals know about psychedelic-assisted psychotherapy that we haven’t yet touched upon? 

Penn: We’re living in heady times. There are a lot of effervescent claims about the benefits of psychedelics and there’s more hope than I’ve seen in a while in psychiatry, which is wonderful. That said, we also need to learn how to deploy PAT with nuance. There will be some people who may need different types of treatments from what were done in clinical trials. We’re going to have to figure out those variances. There will be some people who need additional support then has been provided in current trials. And there will be some people for whom psychedelics don’t work or could be harmful. We need to figure that out, too. It’s very much a work in progress. 


Andrew Penn, MS, PMHNP, 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. He has completed extensive training in Psychedelic Assisted Psychotherapy at the California Institute for Integral Studies and has published in the American Journal of Nursing, Bipolar Disorders, and Frontiers in Psychiatry. He was a study therapist on the MAPS-sponsored Phase 3 study of MDMA assisted psychotherapy for PTSD and is currently a co-investigator on the Usona-sponsored phase 2 study of psilocybin facilitated therapy or major depression.

Currently, he serves as an Associate Clinical Professor at the University of California-San Francisco School of Nursing where he teaches psychopharmacology and is an Attending Nurse Practitioner at the San Francisco Veterans Administration with the joint UCSF/SFVA NP residency program. He has expertise in psychopharmacological treatment for adult patients and specializes in the treatment of affective disorders and PTSD. He has published on the risks and benefits of cannabinoids in psychiatric treatment.

As a steering committee member for Psych Congress, he has been invited to present internationally on improving medication adherence, cannabis pharmacology, psychedelic assisted psychotherapy, grief psychotherapy, treatment-resistant depression, diagnosis and treatment of bipolar disorder, and the art and science of psychopharmacologic practice. In 2021, he was awarded the Distinction in Teaching Award by the UCSF Academic Senate.