The Ins and Outs of Psilocybin-Assisted Therapy
What is Psilocybin?
Psilocybin is the psychoactive element that is in over 100 species of magic mushrooms. It is the chemical responsible for affecting people’s perception of reality, emotions, mood, concept of self, and ego.
While psilocybin can be ingested through eating magic mushrooms in their raw form, clinical professionals often use a chemically synthesized version of the same compound for therapeutic purposes. This is because natural mushrooms have very variant dosages – even two mushrooms that are the exact same size can have very different potencies. Chemical synthesis allows clinical facilities to control psilocybin potency with precisely dosed pill capsules.
How new is psilocybin research?
Before the ‘war on drugs’ shut down psychedelic research in the late 1960s, over 1000 scientific articles had been published about psychedelics, with hundreds focused specifically on psilocybin.
Now, we are in the midst of a resurgence in psychedelic research. While it might seem like psilocybin only started buzzing in the media a few years ago, this new wave dates back to the late 1990s. Since the ‘90s, researchers around the world – including teams at research institutions and private companies – have investigated psilocybin’s potential for therapeutic benefits.
In fact, more than 550 research grants for psychedelic research were approved between 2015 and 2020 alone. Excitingly, in this revamp of psilocybin research, recent advancements in neuroimaging have gifted current researchers with a far better understanding of the effects that psilocybin has on our brains.
How Many People Have Tried It?
A lot.
In a survey conducted in 2023, about 12% of Americans reported using psilocybin recreationally at some point in their lives, while 3.1% reported using it in the past year. That calculates out to about 8 million Americans using psilocybin recreationally in 2023 alone. With growing interest in mushrooms, internet searches about microdosing have risen by about 1,250% since 2015, suggesting that the number of people using psilocybin will only continue to grow.
8 million
An estimated
Americans used psilocybin in 2023
How Safe is It?
Psilocybin is considered to be the safest psychedelic drug and one of the safest central nervous system drugs. The Registry of Toxic Effects of Chemical Substances (RTECS) is a department within the CDC (Center for Disease Control) that tracks all reported toxic effects of substances. The RTECS gives psilocybin a better safety profile ranking than nicotine and even aspirin. Psilocybin has a very low risk for drug abuse, a very low risk of repeated use leading to toxic buildup, negligible public health effects, and negligible criminal effects. Taken together, psilocybin poses a very small risk of abuse and toxicity, and is a low risk to society on a large scale… but what about the individual effects of a one-time trip?
In a review of 24 psilocybin studies with over 600 participants, researchers examined the negative effects of single-dose psilocybin experiences and found...
The most common physical changes were increased blood pressure and heart rate, however, only a handful of participants required a low dose of medication to regulate their heart rate. Aside from that, the most common negative effects reported were mild to moderate headaches, nausea, and vomiting. There were no reported instances of serious physical harm or injury caused by psilocybin trips.
The most common psychological effect reported was anxiety, with ~16% of study participants reporting anxiety on the day of their trip. Most of those cases were mild to moderate levels of anxiety, although a few were severe, and 3 patients took anti-anxiety medication to relieve the effects. The studies only found short-term side effects and did not find the occurrence of any long-term effects, such as prolonged psychosis or mania.
A common and critical concern related to depression and psilocybin is the risk of suicidal ideation. The studies showed that there was no increase in suicidal ideation among psilocybin-trippers compared to participants who were in placebo control groups. And, of the 615 participants included in the review, there were no reported suicides related to psilocybin.
Taken together, prior psilocybin studies indicate that most commonly, people experience mild to moderate physical effects (increased heart rate, headaches, vomiting, nausea) and mild to moderate psychological effects (primarily, anxiety).
Taken together, prior studies indicate that most commonly, people only experience mild to moderate physical effects (increased heart rate, headaches, vomiting, nausea) and mild to moderate psychological effects (primarily, anxiety), both of which are short-term and terminate after the trip experience.
How Well Does It Work for Depression?
Psilocybin
Control
Psilocybin-assisted therapy works demonstrably well for depression and has even outperformed traditional antidepressants (such as SSRIs) during clinical trials.
One study reports that 57% of participants who took psilocybin reached remission, compared to a 28% remission rate in the control group that took a daily dose of a standard SSRI. Another study reports that 71% of participants who took psilocybin had a significant reduction in symptoms, with 54% of participants reaching remission within 4 weeks of their trip.
Similar rates of success are reported across various clinical trials, and a meta-review of 13 clincial trials, which included 686 participants, found an average remission rate of 45% in participants who took psilocybin, compared to a 22% remission rate in control group participants.
45%
22%
Average remission rates across 13 trials and 686 participants.
What Does It Do to Our Brains?
Neuroscientists primarily focus on three main effects of psilocybin: increased (1) neuroplasticity, (2) altered functional connectivity, and (3) interaction with serotonin receptors:
1. Neuroplasticity
Neuroplasticity can be thought of as our brain’s ability to be “flexible” and adapt to challenges. It allows us to learn new things, create new neural pathways, recover from injuries, and even form new brain cells when needed.
In depression, areas of the brain that regulate mood and emotions can become damaged. When neuroplasticity is lacking, depressed brains struggle to address this damage as they lack the flexibility to create new cells, adjust neural pathways, or complete other adaptive recovery processes.
Psilocybin stimulates genes that promote plasticity, while also allowing for better communication between brain cells. These effects allow depressed brains to become flexible and adaptable again – enabling them to recover from the damage caused by depression while restoring their access to the tools needed for tackling future challenges.
2. Functional Connectivity
Functional connectivity measures how connected different regions of the brain are. If two regions have high functional connectivity, it means that they activate at the same time or communicate with each other often – their functions are connected.
Because it is important for different regions of the brain to communicate, it can become an issue if one region very actively communicates within itself but fails to functionally connect to other brain networks.
In depression, this can happen when the default mode network (responsible for thoughts about ourselves and internal rumination) loses functional connectivity with the rest of the brain. This can cause lots of internal rumination and negative self thoughts, as the default mode network lacks access to the regions that interrupt harmful thought patterns.
Psilocybin is like a factory reset for functional connectivity in the brain. It jump-starts communication pathways and gets isolated regions (like the default mode network) back into the flow of information, reducing patterns of unproductive hyperfixation.
3. Serotonin receptors
Psilocybin is thought to be a serotonergic drug, meaning that it activates serotonin receptors. The psychedelic or 'trippy' effects of psilocybin are suggested to stem from its serotonergic activity, as a recent study demonstrated that during a psilocybin experience, serotonin levels in participants' brains correlated with the reported intensity of their trip.
After ingestion, our bodies convert psilocybin into a compound called psilocyin -- a near identical copy of serotonin.
People report seeing their lives in a completely new light, and experiencing embodied feelings of truths that felt out of reach for them before.
“Nobody could have told me that. Nobody could have come up to me and go, ‘You're so loved. You've got all these friends. You've got this great business.’...I'd be just, ‘Whatever.’ But it was a feeling I got during the hallucinogen's effect that made me feel that way.”
“The average person would say, ‘Okay, yeah, forgive yourself. That’s important for healing.’ But, until you actually feel it, you can say it to yourself, you can write it down, you can think about it, but when you deeply feel it, it’s very different. It’s such a real experience.”
“[I experienced] a reality that was clear, beautiful, bright and joyful… In short, this experience opened me up (gave me a tangible vision) of what I think is attainable every day.”
““It has definitely changed my trajectory of where I feel like I need to be moving towards. And I’ve been thinking that for a while. But this really just, it was almost like, it’s not like I had voices in my head, but it was like I was talking to myself and I was arguing with myself like, ’No, you need a career because you need the job.’ It’s like, ’No, you need to be happy. Cut the shit.’ So, I was arguing with myself over it. And the one voice, that one was the one that was been gnawing at me for a while. And that is, ’Do what makes you happy.”
Trippers often account feeling an increased sense of personal awareness and acceptance as they access deeper parts of themselves. Often, these introspective experiences do not seem to change people’s sense of identity, but rather provide them with an honest reckoning of their values.
“[Psychedelics] were part of the process of me becoming a truer version or a more authentic version of myself. And they certainly had a big impact in me rejecting more strongly certain practices and behaviors and people who I then saw as clearly not being aligned with what I value in my life. In that sense, they helped me to make these changes, and that's very transformative.”
”A lot of my values dealt with kindness and compassion, but I wasn’t really honoring those before, because I spend a lot of time not doing those things, towards myself, or maybe not always doing those things towards other people. But that’s really changed now, so I can honor my beliefs, and my values, a lot more now.
“I feel like a different person, which is weird. But yeah, I actually feel like I know myself more. Part of that is because I know my consciousness more, but I actually just feel more okay with myself, and I think that’s probably a big piece of it. So yeah, my identity has definitely changed”
This term is referenced a lot in conversations about psychedelics, but what exactly does it mean to lose your ego? Ego deaths are described as people losing the perception of themselves as a separate entity from everything around them. People often recount a feeling of becoming one with everyone and everything.
“Freedom from every conceivable thing including time, space, relationships, self, etc… It was as if the embodied “me” experienced ultimate transcendence – even of myself.”
“The feeling of no boundaries – where I didn’t know where I ended and my surroundings began. Somehow I was able to comprehend what oneness is.”
“The complete and utter loss of self… The sense of unity was awesome… I now truly do believe in God as an ultimate reality.”
““Every particle of existence felt like an extension of myself”
Trippers recount a deep sense of gratitude and forgiveness, both for themselves and people who have hurt them.
“I didn't realize how much resentment I had towards my mom. And so, during the ceremony, I felt this huge connection to my mom. I actually started feeling like I was going through labor... I had to keep changing my position. It wasn't so overwhelming pain though…But because of that pain, I felt so grounded, and connected to my mom. There was a point, where I was laying on my side, and I just was thinking, "I love you mom," … I didn't realize how much that resentment was getting in the way, of that relationship with her.”
“Not only did I feel forgiven for being just as I was, I saw that in reality there was nothing to forgive. This seemed to remove the obstacles to the experience of love and I felt an extension of love and forgiveness to all beings everywhere… My appreciation of life itself and of the simple tasks of everyday living was also profoundly enhanced. I found myself more open in my intimate relationships, and better able to give and receive love without fear. I also became aware of a desire to be of service in the world, to make some contribution to humanity through my work.”
Past trippers report a deeper commitment to their well-being, in addition to overall enhanced feelings of happiness and contentment.
“My wellbeing is on top of the list. It has always been, but I feel now I’m more assertive… I actually take the time to put myself at the same level of priority … so I feel I’m more assertive on my own wellbeing, my diet, my sleep as well. I don’t overcommit to social gatherings. I think my decision-making is—I have more clarity”
“At one point, I was a child again, a young child, and I played with my children as children and that was very happy. And I remember my mother too. It was a feeling of how connected I was with my children, with my own mother. It was beautiful.”
How do Previous Study Participants Describe the Experience?
Do the Antidepressant Effects Last?
Yes! One of the main draws to psilocybin is that after only a single-dose, people experience antidepressant effects lasting up to years.
A study with 27 participants diagnosed with major depressive disorder (MDD) included a 12-month follow-up, remeasuring all participant symptoms of depression.
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One Week After: 71% participants experienced a decrease in symptoms and 58% experience remission
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Twelve Months After: 75% participants experienced a decrease in symptoms and 58% experience remission
Another study, involving 19 patients with life-threatening cancer, included a 6-month follow-up and two long-term follow-ups
(~ 3.2 and 4.5 years after the psilocybin dose). At the 6-month mark, all 19 participants showed significant decreases in depression symptoms, with 57-79% demonstrating depression remission by the third follow-up.