Taking a Deep Look at Psilocybin for Depression Research

psilocybin for depression

Michelle Janikian

Psilocybin for depression is becoming a major avenue of clinical research. The Usona Institute out of Madison, Wisconsin is about to begin the largest psilocybin-depression study in the US. Part of the FDA’s drug approval protocol, this phase 2 clinical trial will test the magic mushroom compound in 80 individuals for safety and efficacy in treating major depressive disorder (MDD).

When Usona co-founder, Malynn Utzinger, MD presented at this year’s Horizons Conference, she explained that she and co-founder Bill Linton originally wanted to look at psilocybin for depression and anxiety in those with terminal cancer. But when they brought the idea to the FDA, the government organization basically said: Why limit yourselves to depression in cancer patients? And so they changed gears to research psilocybin for depression more generally.

“It is our duty to make sure a potentially effective medicine gets to the widest… group of medical need,” Utzinger said on stage. She went on to explain that depression affects 300 million people worldwide and is predicted to be the second-largest cause of medical morbidity by next year, to further show the need for this research.

Psilocybin Depression Studies

So could psilocybin help those millions of people? Usona is hopeful, especially among the large portion of people with depression for whom traditional treatment, like anti-depressant medication, does not work. They’ve recently secured 7 clinical trial sites that will conduct this research and give qualified participants psilocybin along with therapeutic support. The sites are located around the US and include Johns Hopkins University in Baltimore, the University of California San Francisco, Yale University in Connecticut, University of Wisconsin-Madison, private testing sites in Chicago and Miami, and NYU in Manhattan – which is also the first site to complete training of facilitators and begin recruiting participants.

People are very interested in trying this new depression treatment. In fact, Utzinger said in her talk that over 6,000 people have volunteered for the 80 available spots in their phase 2 trial. 

Although this is the biggest study in the US looking at psilocybin for depression, this isn’t exactly a new concept. Outside of clinical trials, folks have been reporting reduced depression symptoms from psychedelic experiences – and peak experiences in general – for a long time. In fact, a 2017 study that looked at lifetime psychedelic users in “naturalistic settings” (meaning outside of a trial, but whether it’s for fun or ceremony is unknown) found them to be less “psychologically distressed” and suicidal than users of other substances. 

Over at Imperial College London, their team of psychedelic scientists have been looking into this even further, trying to figure out how psilocybin works for depression, both on a psychological and neurological level. Clinical psychologist from the Imperial team, Rosalind Watts, PhD and her colleague Ashleigh Murphy-Beiner, spoke right after Utzinger at Horizons, and presented a paper Watts authored which gives practitioners a framework for facilitating psilocybin for depression therapy, called the “ACE (Accept, Connect, Embody) Model.” 

Watts developed this idea after facilitating participants’ psilocybin experiences during Imperial’s first psilocybin for treatment-resistant depression trial. During “psilodep 1” 20 people were given psilocybin-assisted therapy, and 19 had decreased depression symptoms at week 1 and nearly half at week 5. Plus, none of their participants began a new course of anti-depressants until after week 5

Now, she tells Psychedelics Today over the phone that Imperial is halfway through their second study on psilocybin for depression; they’ve seen 38 out of “65, possibly 70” participants in a trial that’s comparing psilocybin to an SSRI antidepressant for depression treatment efficacy.

Psilocybin for Depression: The ACE Model

The ACE Model (which should be published before the end of the year) highlights psilocybin’s ability to promote psychological flexibility as a key function in how this therapy works. Essentially folks move from a psychologically rigid place where they’re stuck ruminating on negative thoughts to a more flexible, open, and accepting place, post-psilocybin session. 

Watts describes it to me in terms of a ski slope. That our minds, or our “default mode network” is like a skier who follows the same path in the snow until they’ve become deeply ingrained grooves. Then a psilocybin-assisted therapy experience is like a snowplow that comes in and evens out the entire mountain. And so folks are suddenly freed from their ruminative ruts and now have the option to ski anywhere (or think about anything) they please. “They feel that they can think a different way. That they can have new thoughts and see themselves slightly differently,” Watts says. “They can have a sense of space and freedom, mental clarity, not stuck in those deep groves.”

It’s this same idea that her colleague at Imperial, Robin Carhart-Harris, PhD, made famous, that psychedelic experiences can “reset the brain” or “shake up the snow globe” allowing for new thoughts and perspectives. “It’s a disruption,” says Watts. “It’s actually that disruption that allows for a reset.” Yet, she explains that doesn’t happen so easily for everyone, and she doesn’t think it’s healthy for folks to go into these experiences with that expectation, because if they aren’t magically “reset”, they can be extremely disappointed.

“They’re often in very, very desperate states. Sometimes they haven’t been outside of their homes for years and their relationships have suffered and they’re feeling very isolated,” Watts says of the depression participants. “The amount of expectation and pressure that is on them for those experiences is huge.”

Therefore, in the ACE Model, they frame the whole experience in terms of a journey – rather than a reset – for participants, to try and lower the pressure and encourage the acceptance of all experiences as they come. That includes accepting challenging material that may arise as well as not making participants feel like a failure for “resisting” the medicine; in the ACE Model, it’s all part of the experience. And that’s where preparation and integration become critical to the whole healing process. 

“It needs to be a therapeutic intervention where that person’s unique set of fears and hopes can be gently sat with, processed and held so that the person that’s sitting with them has some sense of the complexity of the whole scenario,” Watts explains. “Because so often the healing isn’t actually just in the trip, it’s in the environment, it’s in the relationships that you have in the room. And actually, often it’s as much about the narrative, the story you co-construct [as the psilocybin].”

When all the pieces come together, when people feel fully supported and understood, then psilocybin can help folks out of depression by helping them see themselves and their lives more clearly. The process can also include planning actionable steps during integration that participants can take to improve happiness, like being less hard on themselves and spending more time with community or in nature. 

Watts described the psilocybin healing process in a 2017 paper as people “moving from disconnection to connection” or “from avoidance [of emotions] to acceptance” and that’s very much part of what they try to instill during the therapy sessions. The ACE Model also includes guided meditation, and during a preparatory session they have participants visualize a journey, often a diving expedition where they’re encouraged to go deep into the dark parts of their mind in search of pearls of wisdom. The therapists remind divers that pearls are often found in scary, prickly oyster shells, so it may not always be easy, but the value will be great and worth the struggle. 

This process of psilocybin-assisted therapy for depression is personal, and experts like Watts and Utzinger both point out its high rate of success is likely as much about the deep connections participants feel with their therapists as it is about the effects of psilocybin. Unlike taking anti-depressant medications for depression – which tend to numb people’s feelings – psilocybin and the therapy surrounding it encourage people to dig deep into their emotional worlds to try and heal themselves from the inside out.

The Future of Mushrooms for Depression

Even though psilocybin-assisted therapy is working for people in initial studies, it’s often not a permanent fix. Watts says many people from her trial have found that their depression symptoms come back after a few months. However, when I ask her about this, and about the potential future of legal mushrooms for depression therapy, she’s hopeful folks will have more options, including opportunities to do psilocybin sessions once every few months or so. She also adds that she thinks there’s lots of room to develop integration practices for more long-term depression relief, which could include integration groups that go out and do meaningful activities together, like planting trees.

Obviously this is just the beginning of scientific research looking into this treatment. And hopefully, as law and science catch up with nature, there will be more options for folks to access this therapy for depression in the near future. 

Michelle Janikian is a journalist focused on drug policy, trends, and education. She’s the author of, “Your Psilocybin Mushroom Companion: An Informative, Easy-to-Use Guide to Understanding Magic Mushrooms – From Tips and Trips to Microdosing and Psychedelic Therapy”, and her work has also been featured in Playboy, DoubleBlind Mag, High TimesRolling Stone and Teen Vogue. One of her core beliefs is ending the prohibition of drugs can greatly benefit society, as long as we have harm reduction education to accompany it. Find out more on her website: www.michellejanikian.com or on Instagram @michelle.janikian.

Jac Harrison – DMT Inspired Music: How DMT Mimics The Near-Death Experience

In this episode, Kyle sits down with Jac Harrison, a grammy nominated music producer. Kyle and Jac talk about music as therapy, how DMT mimics the near death experience, and how Jac produces music based on frequencies of mystical experiences.

3 Key Points:

  1. Jac shares his story about his near death experience, and how DMT has been a therapeutic option for him to cope with his crippling anxiety and PTSD.
  2. Jac is a music producer, who uses frequencies from mystical experiences to produce music. His music helps people with addiction, sleep issues, anxiety, and more.
  3. Music is not an FDA approved medicine, but if there is music that tricks your mind into thinking you have taken a medicine, then it should be an option for those suffering.

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Show Notes

About Jac

  • In 2008, Jac was newly married with a baby on the way
  • He needed a new job, and accepted one with Whole Foods Magazine
  • Around 2011, the owner of the company became ill, and gave his company to his daughter, who was awful
  • Jac said that he knew something had to change
  • He started his music career in 1993, went under a lot of stress, and went through a divorce
    • Everything started to go okay with his music career, money was pouring in
  • The first album Jac produced was the Musicians Collection Project
  • He had a ton of anxiety after the divorce, and had high blood pressure
    • He took some cold medicine, on top of his blood pressure medicine, totally forgot about it, then decided to have a glass of wine with a friend
    • The next thing he knew, he was in an ambulance getting his chest pounded on
    • They told him he was in and out all night, and practically died
  • After this near death experience, he felt amazing!
    • But the feeling of greatness only lasted about 3 weeks, and then his anxiety came back, and it was crippling

A Synchronistic Event

  • Jac says he doesn’t believe in magic or witchcraft or any woo woo
  • For his 39th birthday, he was working a trade show
  • He ran around his hotel in Las Vegas, screaming that he felt he was going to die
    • He didn’t know how, but he could feel it
    • Everyone thought he was crazy
  • Moments later, was the shooting right outside of his hotel
    • It was the Las Vegas shooting
  • He does believe in coincidence
    • He had this overwhelming feeling that something bad was going to happen, it was his intuition

Understanding the Experience

  • After trying to figure out what this all meant, he took a 2000mg bar of chocolate to blast off, trying to relive his near death experience
    • He said, there was a lot of frequency, and as a musician, he felt like he could mimic it
    • His first album, and first song on the album, Relief, was about his experience when he died
    • His music is found at MindToyBox
    • Each song he did after that, catalogs the DMT experience he had
  • “An old projector TV, I had one for a while, it was great. The light came on and told me I needed to change the bulb. I changed the bulb and saw in a new and clear way forever. That’s what DMT is like.” – Jac
  • Kyle says that when he attended COSM for the DMT Spirit Molecule release party, Rick Strassman was there and said that the idea that DMT comes out of the pineal gland is just a hypothesis, and people took it and ran with it as truth

Frequency for Healing

  • After he smoked DMT, he heard this humming, and so he started humming and recording it as a frequency for the album
  • He took opium, and then figured out the frequency that substance performs at
    • He wrote music, based on the mathematical equation on how opium works and releases
    • He says it has helped others detox off of opium
  • Jac cant take mushrooms because he is allergic, so he takes DMT
  • Jac worked with a man who had gone through a ton of trauma, he had gone through combat
    • He kept reliving his combat trauma when he would try to go asleep
    • He smoked DMT, and really relived the experience, and was able to let go of it after that
    • “Your mind is a bitch.” – Jac
    • “If you can lock onto a memory, and dissociate it with something, and re-associate it with something else, Every time you can go back to that memory,you can relive it in a way that it’s tolerable, and get over it.” – Jac
  • Jac says without this, he would not be able to function, and he would be institutionalized
  • Jac’s music is Alex Grey’s form of art creation
  • It is made to go with journeywork experiences
    • It is supposed to mimic taking a pill, so you don’t need to take the actual pill
    • It is supposed to guide people when taking different psychedelics
    • His tracks match the frequency of specific psychedelics

Malta Hypogeum

  • The Malta Hypogeum, the oracle chamber, is a cave with naturally occurring frequencies
  • Raymond Reif is an underestimated person in history
    • He beat cancer using frequencies in the 30’s and 40’s
  • “If we’re not going to someone to get drugs for something that we need drugs for, and solving our problems using plant based medicines, music therapy, and frequencies, we are much better off.” – Jac
  • Jac came across psychedelics when trying to treat crippling anxiety
    • Kyle is the first person he has told this NDE story to
  • Alzheimers is not a neurological problem, it’s a perception problem
    • Psychedelic medicine should be used for research to treat cognitive health problems, PTSD, alzheimers, etc
  • “If the earth gives us something for our body, we should be able to take that at the same time we are able to take modern medicine.” – Jac
  • Jac says that he started doing this type of work as more of an Atheist, and after the psychedelic experiences, he says he has become more spiritual


  • Jac says that his intuition and discernment came after his near death experience
    • Kyle says that this happens after mystical experiences, we become more in tune with what is going on around us
    • “I believe that we have something in us, that is triggered, when we have a fear of death.” – Jac

Final thoughts

  • Jac recommends Relief as the first track for listeners
  • He extends himself to people who are heavily anxious, have severe PTSD, or depressed, to come to him, and he will make music for them
  • He said that this is not medicine, but if there is music that tricks your mind into thinking you have taken a medicine, then it should be an option for those suffering



About Jac Harrison

Having spent most of his adolescent life medicated to treat ADD/ADHD, Jac developed a dependency on the medications and could not function without them. When he stopped using them, his anxiety was so bad that he was diagnosed with PTSD in 2009; so he took his love for music with his understanding of mathematics and developed music to help himself get off all the medication. Mind Toy Box is the result of his work.

Kyle Buller and Joe Moore – Exploring Psychedelic Integration and Coaching

In this episode, Kyle and Joe sit down to explore psychedelic integration. They cover different frameworks, resources and benefits of integration and coaching services.

3 Key Points:

  1. Integration is commonly confused as post-session only, but it includes pre-session, self care, and really begins at the point you decide to engage in self-work.
  2. It is important to remember the GPA framework when determining where you are at in the integration process, G – grounding, P – processing, A – action.
  3. Psychedelics Today offers many resources to assist with the integration process; Navigating Psychedelics Online Course (and Live Course), Coaching and Integration Calls, and books, Trip Journal and Integration Workbook.

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Navigating PsychedelicsTrip JournalIntegration Workbook

Show Notes


  • Kyle will be attending the ACISTE Conference this November
    • He is speaking and doing a breakout session with Michelle Hobart
    • Kyle is going to present on using technology for support with spiritual emergence
  • Kyle and Joe will not be offering any major workshops until spring.
  • They will be attending a conference in Exeter UK – Psychedelics and Philosophy

Psychedelic Integration

  • Kyle says his near death experience shows up in his life everyday
  • Integration is not only post session, it is also pre-session
  • Integration, at its root means bringing parts together into wholeness
  • Joe says you don’t need support to do integration, although it is helpful
  • Kyle’s analogy of a psychedelic experience as a big hallway with a lot of doors, and a ton of magical stuff, even scary monsters, are coming through the doors and wandering through the halls
    • The goal is to realize and say “this is a part of me” and learn to be okay with all of the stuff in the hall
  • Self care works until it doesn’t, and that is when integration comes in

Integration Framework

  • Kyle uses a framework and asks, what is your GPA?
    • G – grounding, post session, how are we getting re-connected to ourselves?
    • P – processing, once energy feels stable and centered, how can we process the material? It could mean journaling, therapy, body or somatic work, breathwork, yoga, etc.
    • A – action, moving it forward, breaking the leanings down into goals of things to work on
    • Kyle says that these things do not need to be done in order necessarily, but its a good framework to check in after an experience and see where you’re at
  • Joe reminds listeners of ‘pre-hab’, that preparation can make a world of a difference and weigh a lot more than post work in a lot of cases
  • “Life is integration, call your mom, pay your rent.” – Joe
  • Joe mentions the quote that “the opposite of addiction is connection”
  • Climate change can bring up a lot of existential dread, the connection piece, and other topics can be addressed with psychedelic integration


  • The Psychedelics Today, Navigating Psychedelics Course is a great way to learn more about integration
  • We offer two books, the Trip Journal and the Integration Workbook
  • We also offer Psychedelic Integration coaching calls and services
  • You don’t need an integration coach all the time, but for someone to just be there helps
  • If you have a retreat planned, integration and coaching can really help mitigate the risks
  • Integration within the psychedelic community is somewhat understood
    • Kyle says he gets tons of emails asking for medicine sessions
    • Psychedelic Integration and coaching services do not include medicine or guiding or providing of medicine, its simply pre and post session guidance
    • Psychedelics Today does not suggest underground or illegal psychedelic sessions/therapy and makes a significant effort to be ignorant of underground work, there are legal options to choose from


Psychedelics Today

Kyle Buller and Joe Moore

About Kyle

Kyle’s interest in exploring non-ordinary states of consciousness began when he was 16-years-old when he suffered a traumatic snowboarding accident. Waking up after having a near-death experience changed Kyle’s life. Since then, Kyle has earned his B.A. in Transpersonal Psychology, where he studied the healing potential of non-ordinary states of consciousness by exploring shamanism, plant medicine, Holotropic Breathwork, and the roots/benefits of psychedelic psychotherapy. Kyle has co-taught two college-level courses. One of the courses Kyle created as a capstone project, “Stanislav Grof’s Psychology of Extraordinary Experiences,” and the other one which he co-created, “The History of Psychedelics.”

Kyle completed his M.S. in clinical mental health counseling with an emphasis in somatic psychology. Kyle’s clinical background in mental health consists of working with at-risk teenagers in crisis and with individuals experiencing an early-episode of psychosis. Kyle also facilitates Transpersonal Breathwork workshops.

About Joe

Joe studied philosophy in New Hampshire, where he earned his B.A.. After stumbling upon the work of Stanislav Grof during his undergraduate years, Joe began participating in Holotropic Breathwork workshops in Vermont in 2003. Joe helped facilitate Holotropic and Transpersonal Breathwork workshops while he spent his time in New England. He is now working in the software industry as well as hosting a few podcasts. Joe now coordinates Dreamshadow Transpersonal Breathwork workshops, in Breckenridge, Colorado.