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Natural Medicine Journal

October 24, 2023

Research Update on Psilocybin

A discussion with integrative mental health expert Emily Whinkin, ND

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Natural Medicine Journal

This podcast is part of our February 2024 special issue. Download the full issue here.

Interest and research regarding psilocybin has grown considerably over the past several years. In this interview, Emily Whinkin, ND, discusses the latest research and provides clinical guidance on the use of psilocybin. Whinkin is a naturopathic physician with the Advanced Integrative Medical Science Institute in Seattle, where she also conducts research and explores altered states of consciousness.

Karolyn A. Gazella: Can you tell us a bit about what psilocybin is and how it works?

Emily Whinkin, ND: Psilocybin is a tryptamine that is a constituent of many species of fungal spores and fruiting bodies that are native to the Americas. Most psilocybin-containing species of mushrooms contain an average of about 1% of this tryptamine, but up to 2.25% of a dried, fruiting body of a mushroom could be the psilocybin constituent. The active constituent is actually its metabolite, psilocin, which is found itself in several fruiting bodies as well, but the human body can transform psilocybin into psilocin.

Psilocin is active at the 5-HT2A receptor, commonly known as the serotonin receptor. This receptor is found in the central nervous system, throughout the cardiovascular system, and in the gut tissue. We think that through agonism of this 5-HT2A receptor, psilocin impacts learning, mood, memory, and neurogenesis in the central nervous system. It also seems to reduce blood flow and therefore function of the default mode network, a kind of a neural network in the brain that is responsible for self-referential thinking and internal processing. The default mode network is also most active when we are retrieving memories about ourselves, as well as imagining our future and our place in it. So if this area of the brain or this network of the brain is getting less blood flow, if it's de-emphasized as our background way of thinking and being, there are novel ways to experience the world and ourselves and to imagine ourselves in the world. We think that this has to do with what's been shown to be powerful about psilocin and psilocybin in terms of treatment for mood disorders, including depression and anxiety. 

Gazella: You coauthored a paper about psilocybin and palliative care that was recently published in the journal Current Geriatrics Report. Tell us about that paper and its conclusions.

Whinkin: This was a 5-year review that looked at papers from 2017 to the point of publication (early 2023) to better understand if there was a role for psilocybin in palliative care specifically. Our definition of palliative care included total pain, which is not just physical pain, but includes psycho-spiritual pain, emotional pain, and the disconnection from community that patients can sometimes experience because of a condition that warrants palliative care medicine. We wanted to explore the role with psilocybin for each of these concerns independently—physical pain, existential distress that can come with a life-limiting illness, and cognitive issues. We found some compelling research to support each of these targets. 

Psilocin seems to support neuroplasticity that can promote novel modes of thinking and problem solving. It can help with rebuilding of neuronal tissue, so it can be helpful for people who have suffered traumatic brain injury or cognitive injury as well as readdressing someone's interpretation of their of their own pain. For pain that has become centralized in the nervous system, psilocin offers almost a rebranding of the person's interpretation of that and sometimes reduces the secondary impact of being seen as a palliative care patient.

Gazella: Interesting. How does psilocin help other conditions?

Whinkin: The way we think psychedelics work, including psilocybin-containing fungi, is they seem to have 2 central modes of action. One is more neurochemical. As I mentioned, the 5-HT2A receptor seems to be prominent in psilocybin effect. The other mode is more of a psycho-spiritual or psychological benefit. The ways that those 2 things are helpful are how they work together. When we think about where psilocybin and other psychedelics have been suggested to be particularly beneficial, we think about major depressive disorder, generalized anxiety disorder, obsessive compulsive disorder (OCD), and problematic substance use. These are all situations where there's extra rigidity in the mind. So we're thinking about the depth of neuronal grooves where people seem to suffer from thinking the same thoughts, feeling the same feelings, or pursuing the same behaviors over and over again, and there becomes this rigidity internally. Psychedelics open up an opportunity to have a different experience internally based on new thinking pathways, new opportunities to connect memories to emotions, novel ways of interpreting our somatic cues, and reflecting on our own experience. So overall, psychedelics seem to help in particular with rigid types of thinking and feeling states by facilitating more openness, more access to novel connections in the mind—and that reflects more hope or the ability to shift our own perspective about what could be possible for healing.

Gazella: It's fascinating. What does the research tell us about the safety of psilocybin?

Whinkin: We need more long-term data. Psilocybin is still a Schedule 1 drug in the United States, and under the Controlled Substances Act of 1970 is restricted in terms of how we can access and appropriately study some of the long-term effects. So whereas ketamine, for example, has been used and studied robustly since the 1970s and we have a lot of data about its safety, we don't have the benefit of 50 years of data for psilocybin. What we do know, based on its function at the 5-HT2A receptor is that it may have some cardiovascular adverse events or effects with longer term use. We know that when this receptor is targeted by other pharmaceuticals, there can be some damage to the endothelial cells along the vascular system and potentially some damage to heart valves. But contrary to other pharmaceuticals that target that receptor, research suggests that psilocybin doesn't need to be used even multiple times for durable effect. So we're measuring weeks of benefit after a single dose of psilocybin. That’s very different than other medications for similar concerns, like antidepressants or anxiolytics. There is probably a lesser risk of damage, but we just don't have the long-term data.

Gazella: The term “microdosing” comes up a lot with psilocybin. Can you tell us more about that?

Whinkin: I'll start with macrodosing as a comparison. We think that between 2 and 5 grams of whole fruiting body of a mushroom, which is the above-ground part of the fungus dried, appears to be a macrodose. Most of the single-dose studies isolate 25 mg of psilocybin to determine the outcomes that they're tracking. That equates at the 1% profile average that I mentioned earlier—maybe a 2.5 gram whole, dried mushroom equivalent. Microdosing is about a fifth of that, maybe 1 to 5 mg psilocybin. The reason we're using ranges is because there's a lot of variety in the extracts, the strains within the psilocybin-containing mushrooms, and the way the mushroom is prepared. Microdosing is more regular use, which tends to be a few days a week. Common protocols are 3 days on in a row and then 4 consecutive days off, for example, with the goal being a subperceptual effect. With microdosing, there's not a cognitive impairment so we are able to function, go about our day, and show up to our lives. But there may be some benefits, including feeling a little uplifted, feeling a little more clearheaded. Some people microdose for the creative benefits and the neuronal neurogenesis, promoting novel ways of thinking and problem-solving.

Gazella: Is there a way to standardize psilocybin extract?

Whinkin: I think that's coming. There are certainly ways to measure the amount of psilocybin and psilocin. And there are efforts to extract and standardize just those constituents. As a naturopathic doctor, I am curious about that because in other facets of herbalism, we know that using the whole herb has its own benefits. There are likely other constituents within these fungal fruiting bodies and these organisms that probably mediate the effects of psilocybin and psilocin and probably complicate the interaction with the human body in a way that I think should be studied. We don't necessarily know if that's harmful to us or if it facilitates some of the benefits of microdosing and macrodosing.

Gazella: Do you have concerns about the quality of the psilocybin products that are presently on the market or people who are doing their own thing with it?

Whinkin: I do have concerns. I practice from a harm reduction model with most of my patients who report to me that they're using what they believe to be psilocybin. I can't verify that’s what they're ingesting. Sometimes they don't know what strain they're using or how much they're taking. So it's a challenge to practice in a way that ethically respects that person's agency from a harm reduction model, while also trying to give them as much information as I can about how to use this in a safer way. I do hear stories where harm has occurred. Not medical harm, but people are underprepared for the experience of ingesting and being with a psilocybin-containing substance or a psychedelic in general, and there's not enough appropriate support afterward for what we call integrating the experience or making sense of a big shift in perception. Sometimes there are new insights or confrontation with pre-existing belief models that can occur during that experience. So it's more of a psychological risk that I'm hearing about and kind of concerned about. Of course, there's also a chance for a more physiological or medical concern to arise.

Gazella: It does seem like there are a lot of people using psilocybin, sometimes without proper guidance or any guidance. How do you advise people get the proper support when using psilocybin?

Whinkin: It's a great question. One part is making sure the medical community is well informed so they can field questions from their patients appropriately and without shame or judgment. From a harm reduction lens, we ask, “If this person, in their own agency, is going to use the substance, how can we work together to not just reduce the harm, but consider that there might be benefit for this person and try to optimize the benefits?” So one part is clinician education, and that includes psychotherapists and counselors, as well as other traditional healing routes like chaplains. The other piece is making sure that if we are not able to provide the support, then making an appropriate referral, just like we do for any other concern. I often refer people to a website called Psychedelic Passage, which connects people who are independently choosing to and sourcing psilocybin to trained guides for integration work or answering questions regarding these substances.

Gazella: For people without mental health concerns, are there any potential benefits to psilocybin?

Whinkin: There may be benefits to psilocybin-containing mushrooms in a way that's not contained within a medical model. That is to say that there are there are potential psychospiritual, psycho-emotional benefits of consulting these plant medicines. Taking an open stance towards what would happen, maybe what I confront, what is something that maybe I haven't even thought of, to ask myself or look at internally that that could facilitate some personal growth. I like that there is interest in that realm and it's not so contained within a clinical model where people have to meet criteria in order to access these medicines. They've been used traditionally for eons—originally, we think by the Mayan and Aztec people in what is now the Amazonian region. Were they thinking through the DSM-V and vetting people and diagnosing people before they could access these plant medicines and the insights therein? No. I think that should certainly be part of the conversation about how we move forward.

Gazella: As you mentioned, psilocybin is a Schedule 1 drug, so what is the exact legal status regarding its use for therapeutic purposes?

Whinkin: Federally, it’s still Schedule 1, which means there's basically no acknowledged therapeutic benefit out of out of federal level. But we do have some examples within the United States, specifically in Oregon and Colorado, where they're creating policy and pursuing the belief that this should be accessible to some extent and should be regulated so people can receive the potential benefits in an above-ground way. In Oregon, this is regulated by measure 109, which has a 3-pronged approach. First is that there's regulation of the growth and distribution of the psilocybin-containing mushroom itself. Second, there's regulation of the Certified Service Centers where a psilocybin experiential session could occur. That means there are sites and venues specifically certified, meaning it’s not legal to use psilocybin in somebody's house or out in the woods. Third is regulation of who can facilitate a psilocybin session, so they have accredited training programs and an exam to pass. 

Gazella: What would you like to see next when it comes to psilocybin?

Whinkin: I would love to see more science around the whole fungus. What can we learn about the other constituents? Can we assume there's an intelligence in the way that psilocybin has been used as a whole plant for thousands of years and also consult some people who are who are familiar with whole plant extracts within other mushrooms? There's a lot of good evidence and clinical herbalism with other mushroom species, so why not? I think this also reflects more of the real world, what people tend to be utilizing for microdosing, or when they source their own mushrooms. I'd love to see more research on the phenomenology of these altered states, including acknowledging what we know and what we don't. The results we get are only as thorough as the questions we're asking and what we're able to measure. So almost liberating ourselves from a strict medical monitor model and appreciating that there might be a lot of other planes of change that people are experiencing by utilizing these substances. 

For the percentage of folks who don't respond as expected, or maybe the duration of the benefit doesn't last, I want to know why that is. Are we not measuring the change that they do experience? Or is it different type of depression, for example, that would be better benefited from a different tool? Or are there things like single nucleotide polymorphisms or other changes in the enzyme that converts psilocybin to psilocin and that, for example, could explain why certain people benefit more in the ways we're able to measure? 

I think there are a lot of questions around who is really a good fit for this as a tool within the medical model, but also branching out and thinking a little bit more broadly about the benefits outside of a medical model.

This is an edited and condensed version of our interview. Listen to the full interview on the Natural Medicine Journal podcast.

Resources

Studies 

About the Expert

Emily Whinkin, ND (she/they), is an integrative mental health practitioner, researcher, and psychonaut currently practicing at the Advanced Integrative Medical Science Institute in Seattle. She holds Washington and Oregon licenses in naturopathic medicine and graduated with a master of science degree in integrative mental health from the National University of Natural Medicine in Portland, OR. Clinically, Whinkin works to provide person-centered, relationally informed care at the confluence of entheogenic spiritual medicine, mental health, and reproductive/generative health. As an undergraduate, she studied both biology and religious studies, formally launching her work to explore and affirm the interdependence of mind, body, and spirit with a focus on cycles, transitions, and environment. Community connection, belonging, and collective transformation are central to Whinkin's vision of being well in the world. She works to reflect this framework in caring for each patient’s foundational vitality, resilience, and health contexts as 'root cause' approaches to healing. She is certified in perinatal mental health (PMH-C) by Postpartum Support International and Holistic Pelvic Care™ with Tami Kent, and she often weaves mindful somatic therapy and botanical medicine within psycho-spiritual work with all genders across the lifespan.

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