The Link Between Psilocybin and Depression
Recent clinical trials have shown the enormous potential of psilocybin for depression and many people don’t want to wait until it’s legal to start using it.
Psilocybin is a psychedelic compound that has been shown to decrease symptoms of depression in as few as one to two sessions. For the 13% of Americans taking antidepressants on a daily basis, typically for years at a time, this alternative option sounds enticing. There are a few potential reasons psilocybin could be having such a major impact on depressive symptoms.
Studies have shown that people with depression have higher levels of inflammation. Fortunately, psilocybin has anti-inflammatory effects, which may explain the mechanism behind psilocybin’s benefits because anti-inflammatory treatment has antidepressant effects.
Psilocybin has also been shown to increase neuroplasticity by actually changing the structure and function of neurons in the cortex. This is especially important for depressed patients because depression is associated with the atrophy of cortical neurons and the loss of dendritic spines. Along with the physical changes in the brain, psychedelics may facilitate learning, adaptability, and flexible thinking.
As psilocybin has been shown to have an impact on depression, a recent study compared how effective it was to a commonly prescribed SSRI, escitalopram. Both compounds decreased depression scores comparably, but psilocybin generally performed better in the secondary measures (alternative measures for depression, anxiety, experiential avoidance, work, social life, etc.).
Another study looked at the connections in the brain using functional magnetic resonance imaging (fMRI). They found that functional networks became more interconnected and flexible a day after psilocybin treatment, whereas no such changes or connectivity was seen in the escitalopram group.
Access to Psilocybin
Psilocybin isn’t legal in most parts of the world so the only options people have for access right now are to apply to be a participant in a clinical trial or to go to a psilocybin retreat center in another country.
The issue for people on antidepressants is that some clinical trials and retreat centers are asking people to discontinue any medications before attending. MycoMeditations wants to maximize psilocybin’s benefit while Synthesis says, “it’s hard to anticipate how SSRIs might interact with psilocybin.” There are a couple of reasons for their concern.
Combining Psilocybin and Antidepressants
Serotonin syndrome (SS), also known as Serotonin Toxicity, is a potentially life-threatening condition resulting from the combination of drugs that increase serotonin levels in the 5-HT2A synapse receptors. Both SSRIs and psilocybin fall into this category so it seems that the combination of the two could potentially lead to SS. Kelan Thomas, Associate Professor at Touro University California College of Pharmacy, studies the adverse effects of drug-drug interactions. He explains that “psilocybin, being a psychedelic partial agonist at the serotonin 5-HT2A receptor, seems to have the lowest risk of any type for serotonin syndrome.” He says there’s “shaky” evidence when you look at case reports.
Dr. Erica Zelfand, Licensed Family Doctor and Psychedelic Facilitator hosted a recent webinar on antidepressants and psilocybin with almost 400 participants. She has been working with patients taking psilocybin while on antidepressants and suggests that there is not enough scientific backing to warrant the request of asking patients to get off their antidepressants, noting that “severe cases of serotonin toxicity with psilocybin are rare.” Dr. Zelfand emphasizes the difficulty of coming off medications.
For people on SSRIs over a long period of time, the nervous system adapts to the blocking of the reuptake channel and the increased serotonin in the synapse. Eventually, serotonin receptors are downregulated, which means that a lesser amount of receptors become available while the ones that are present become less sensitive over time.
This mechanism also helps to explain the reason for withdrawal symptoms when SSRIs are discontinued.
Withdrawal symptoms, or Antidepressant Discontinuation Syndrome (AWS), are common, with about 20% of patients experiencing symptoms after abruptly discontinuing their medication. When describing their experience one patient said, “When I went off them, I felt I had electric shocks
going off in my brain.”
The Benefits of Slow Tapering
To prevent AWS from occurring, slow tapering is recommended if patients would like to discontinue their medications.
Dr. Zelfand notes that the most common mistake made by those interested in using psilocybin to alleviate depressive symptoms will often taper too quickly. She mentions that she’s frequently asked by her patients if they can taper in a shorter amount of time or even stop cold turkey because of a retreat opportunity that arises quickly.
She strongly recommends that they don’t attend a retreat before their bodies and minds have been able to rebalance after a slow taper. Studies recommend tapering over a minimum of 2-4 months at a 10% reduction in dosage every few weeks for the safest and most effective chance at success.
Studies Show It May Not Be Necessary to Discontinue Antidepressants
Interestingly, patients may not need to discontinue SSRIs if they would like to work with psilocybin.
A recent study has shown that SSRIs combined with psilocybin are safe.
https://ascpt.onlinelibrary.wiley.com/doi/pdf/10.1002/cpt.2487
In the study, 27 participants either took the SSRI, escitalopram, or placebo daily for two weeks before a mushroom journey. The patients were then crossed over so that the placebo group then started taking escitalopram for two weeks and vice versa before another mushroom journey. The results showed that the group on the SSRIs still experienced positive mood effects from the psilocybin. The group on SSRIs experienced significantly lower negative drug effects such as anxiety, nausea, headache, and fatigue so SSRIs may have a protective effect.
The study concluded: “Stopping escitalopram treatment before psilocybin administration may not be warranted.”
Even before this study, people had been experimenting with psilocybin while on SSRIs and many people reported a common effect. Many anecdotes online say that they noticed a significant decrease in the effects of psilocybin.
Recall that in an unmedicated brain, mushrooms stimulate the 5HT2A receptor which causes the psychedelic effects, while a brain on SSRIs may have fewer receptors available so that there is less stimulation.
However, the Principal Investigator of the escitalopram study, Dr. Matthias Liechti, didn’t see an impact of psilocybin’s effects in the group taking the SSRI though it should be noted it was a small study. He said, “These results indicate that psilocybin may be dosed during escitalopram treatment without apparent impact on the effect of psilocybin.
The Effects Can Vary By Patient
Dr. Zelfand, however, has worked with patients who do experience lesser psychedelic effects while on SSRIs.
“In my own anecdotal evidence, what I have found is that ppl who have been using SSRIs long-term, need higher doses of psilocybin. They need to eat more mushrooms, by about 30 to 50% more, in terms of their dosage.”
As an example, if an unmedicated user would take 3g for a moderate trip, an SSRI user would need to take between 4 to 5 grams. Which can be considered a strong trip for an unmedicated user. Fortunately, there’s no known lethal dose of psilocybin.
Dr. Zelfand concluded her presentation with a case report of one of her patients named Judy. Judy was 53 years old and had chronic depression, negative self-talk, and challenges with her parents, and she had been on Citalopram for a few years. She chose to stay on her prescription and to maintain weekly therapy sessions before, during, and after her psilocybin journeys.
Her first dose of psilocybin was 8 grams and six months later, she had 10 grams along with cannabis. Judy’s results were healthier boundaries with her family, the ability to enjoy time with her mother, and the ability to stand up for herself. She is now on a lower dose of the SSRI.
It is important to note that psilocybin isn’t the only way to increase neuroplasticity or decrease inflammation in patients with depression. In Dr. Zelfand’s webinar, she emphasizes the importance of holistic health and that whether someone tries psilocybin or not, there are many other ways to increase neuroplasticity.
Research-backed methods include exercise and getting quality sleep, intermittent fasting, learning new skills, and memory games like crossword puzzles and Sudoku. To alleviate symptoms of depression, patients are encouraged to use any tools available to them.
Depression is challenging to treat, so it’s promising to see new research investigating psilocybin as an alternative to standard antidepressant treatments. Although it’s too early to say whether patients should taper off antidepressants or combine them with psilocybin treatment, both practitioners and patients must share their stories and help contribute to the research.
