We’ve covered psychedelics on the podcast before—first in 2019 with Ira Byock, where we explored their potential role in medicine, and then again in 2023 with Stacy Fischer, Brian Anderson, and Theora Cimino, focusing on the reasons to approach psychedelic use in patients with caution.

In today’s episode, we’re taking a closer look at the current state of the science around one specific psychedelic: psilocybin. We'll discuss three recent clinical trials involving patients with serious illness, joined by our guests James Downar, Ali John Zarrabi, and Margaret Ross.

We begin with a refresher on psilocybin—what it is, how it might work, what conditions it may help treat (including demoralization), and how it’s typically administered. What makes this episode especially compelling is our deep dive into the three studies, which highlight two different approaches to using psilocybin: daily microdosing, similar to traditional antidepressants, and a more intensive model known as psilocybin-assisted therapy. This latter approach involves three structured phases—preparation, the dosing session, and post-session integration with trained therapists.

Peter Selwyn, one of today’s guests, has been caring for people living with HIV for over 40 years. In that time, care of people with HIV has changed dramatically. Initially, there was no treatment, then treatments with marginal efficacy, complex schedules, and a tremendous burden of side effects and drug-drug interactions. The average age at death was in the 30s.

Now, more people in the US die with HIV rather than from HIV. Treatment regimens are simplified, and the anti-viral drugs are well tolerated. People are living with HIV into advanced ages. The average age at death is likely in the 60s. Nearly half of people living with HIV are over age 55. One in 10 people with newly diagnosed HIV is an older adult. Our second guest, Meredith Greene, is a geriatrician and researcher who focuses on care of older adults living with HIV, in the US and Africa.

On today’s podcast we discuss:

• Implications of aging with HIV for clinical care

• Loneliness and social isolation among older adults living with HIV

• Persistence of stigma

• Need to consider HIV in the differential diagnosis for older adults

• Screening for HIV

• Screening for osteoporosis in people living with HIV

• Dementia and cognitive impairment risk in people living with HIV

• When to stop anti-virals near the end of life

Toward the end we speak to the moment. More older adults live with HIV in SubSaharan Africa and the global South than anywhere else in the world. Funding for research and clinical care is at risk, as USAID and PEPFAR (which is under USAID), are shuttered. Millions of lives are at stake. Meredith wore a shirt that said Silence=death.

Eric gave me the hook during my live cover of One, by U2, a song released in 1992 whose proceeds went entirely to AIDS research. I couldn’t help it, forgive me dear listeners, I had to do a longer than usual cut at the start!

-Alex Smith

Useful links:

Peter's article on the evolution of HIV: https://link.springer.com/article/10.1007/s11524-011-9552-y

Peter’s book Surviving the Fall: Personal Journey of an AIDS Doctor

PEPFAR: Global Health Policy | KFF

Articles:

Geriatric Syndromes in Older HIV-Infected Adults - PMC

Loneliness in Older Adults Living with HIV

Management of Human Immunodeficiency Virus Infection in Advanced Age
https://pmc.ncbi.nlm.nih.gov/articles/PMC3684249/

About Act-up for those who might know the Silence=Death t-shirt reference:
https://www.npr.org/2021/06/16/1007361916/act-up-a-history-of-aids-hiv-activism

https://www.newyorker.com/magazine/2021/06/14/how-act-up-changed-america

More and more people are, “doing their own research.” Self-identified experts and influencers on podcasts (podcasts!) and social media endorse treatments that are potentially harmful and have little to no evidence of benefit, or have only been studied in animals. An increasing number of federal leaders have a track record of endorsing such products.

We and our guests have noticed that in our clinical practices, patients and caregivers seem to be asking for such treatments more frequently. Ivermectin to treat cancer. Stem cell treatments. Chelation therapy. Daneila Lamas wrote about this issue in the New York Times this week -after we recorded - in her story, a family requested an herbal infusion for their dying mother via feeding tube.

Our guests today, Adam Marks, Laura Taylor, & Jill Schneiderhan, have coined a term for such therapies, for Potentially Unsafe Low-evidence Treatments, or PULET. Rhymes with mullet (On the podcast we debate using the French pronunciation, though it sounds the same as the French word for chicken). We discuss an article they wrote about PULET for the American Journal of Hospice and Palliative Medicine, including:

• What makes a PULET a PULET? Key ingredients are both potentially unsafe and low evidence. If it’s low evidence but not unsafe, not generally an issue. Think vitamins. If it’s potentially unsafe, but has robust evidence, well that’s most of the treatments we offer seriously ill patients! Think chemo.

• What counts as potentially unsafe? They include what might be obvious, e.g. health risks, and less obvious, e.g. financial toxicity.

• What counts as low-evidence? Animal studies? Theoretical only?

• Does PULET account for avoiding known effective treatments?

• Do elements of care that are often administered to seriously ill patients count? Yes. Think chemotherapy to imminently dying patients, or CPR.

• How does integrative medicine fit in with this? Jill Schneiderhan, a family medicine and integrative medicine doc, helps us think through this.

• How ought clinicians respond? Hint: If you’re arguing over the scientific merits of a research study, you’re probably not doing it right. Instead, think VitalTalk, REMAP, and uncover and align with the emotion behind the request.

• Does the approach shift when it’s a caregiver requesting PULET for an older relative who lost capacity? How about parents advocating for a child?

For more, Laura suggests a book titled, How to Talk to a Science Denier.

And I am particularly happy that the idea for this podcast arose from my visit to Michigan to give Grand Rounds, and the conversations I had with Adam and Laura during the visit. We love it when listeners engage with us to suggest topics that practicing clinicians find challenging.

And I get to sing Bon Jovi’s Bad Medicine, which is such a fun song!

-Alex Smith