Psilocybin and Depression

Psilocybin and Depression

Psilocybin works completely differently from conventional anti-depressants, so why does it appear to be such an effective treatment?

This past century has taught us a lot about the human mind, most especially we’ve learned enough to know that we have barely reached the tip of the iceberg in terms of our understanding of the human condition. Coincidentally, these past few decades have been inundated with both a demand and supply of antidepressants. 

The pharmaceutical industry has been poised to respond to a seemingly growing malaise in our societies. Big pharma has expanded its diagnostic dictionary to include a whole new list of diagnosable ailments. If it’s diagnosable then a pharmaceutical treatment is at hand, ready to be prescribed.

One of the most common and hard-to-treat ailments is depression.


What is depression?


Depression is when there is a flatness to our energy. A sense that everything has a heavy weight on it.  There is a sense of hopelessness and/or defeat that is palpable. Winston Churchill used to call it the Black Dog.

Depression can happen to people in different ways. For some, depression comes and goes like a cycle or a phase. For others, depression can be long-lasting and life-defining.

Cambridge University Press describes it like this: 

Major depressive disorder (MDD) is a common psychiatric disorder characterized by a variable mix of affective symptoms (such as sadness, feelings of guilt, low self-worth and suicidal ideation), reward-related symptoms (such as anticipatory, motivational and consummatory anhedonia), cognitive symptoms (such as an inability to concentrate) and vegetative disturbances (such as changes in weight, appetite, sleeping pattern, psychomotor activity, and energy levels).”

If we are not specifically prone to depression, chances are that we know someone who is.

Advice on how to deal with depression is plentiful. Everything from ‘Suck it up to ‘Go for a run’ is constantly repeated. 

Those that are not depressed have the best suggestions while often forgetting that those that are depressed have already made countless attempts to encourage themselves into a better state of mind.

Going for a run requires us to have the will to put on our running shoes in the first place. Many of us know that lacing up can sometimes feel harder than actually going for a run. This conundrum is one that Big Pharma thought they could answer.


Our serotonin receptors


According to an excellent medical article called Serotonin and brain function: a tale of two receptors, we have learned that there are 2 types of serotonin receptors in the brain: 5-HT1AR and 5-HT2AR. Conventional SSRI medication specifically targets the 5-HT1AR receptors. 

5-HT1AR-rich brains tend to experience less stress and are less prone to impulsivity, aggression, and anxiety. However, SSRIs can also blunt our emotions as a means of increasing our resilience, therefore reducing depression.  

Psilocybin works on the 5-HT2AR serotonin receptors enabling the individual to experience more optimism, open-mindedness, and sensitivity to current environments. Psilocybin allows for learning and unlearning to happen with greater ease and less effort.



The difference between these two serotonin receptors is significant. Rather than feeling numbed out, having access to a deeper sense of embodiment while simultaneously adopting healthier habits is a much more sustainable treatment protocol for a depression sufferer.

Those who microdose have been shown to have access to a more ‘plastic’ state of mind, a mind that is more adaptable to change, more environmentally sensitive, and with a higher capacity to learn.


Psilocybin on the brain


Psilocybin affects our brains in unique and beneficial ways. From reducing inflammation, increasing connectivity, and managing blood flow to our fight/flight system.

Cambridge University Press reported: 

The neurobiological correlates of psilocybin’s antidepressant effects have been explored using functional magnetic resonance imaging (fMRI). In 19 people with TRD, imaging before and 1 day after 25 mg of psilocybin showed a reduction in blood flow to the amygdala, which was correlated with a substantial antidepressant response (Carhart-Harris Reference Carhart-Harris, Roseman and Bolstridge 2017c).” 

What do these benefits feel like in actual day-to-day life? 

Reduced inflammation means less irritability, better sleep, and clearer thinking. Increased connectivity means creative solutions and open-mindedness. Managing blood flow to the amygdala means not experiencing road rage and/or symptoms of OCD.


Dosage matters

A little vs. a lot is an important consideration. Taking a larger dose requires guidance before, during and after. It is a more potent experience that definitely requires integration. When microdosing with psilocybin, the breaks between doses allow for a very smooth experience. Taking 48-72 hours break between microdoses means that we are taking in small sips and easy steps.

One single ‘hero’ dose can take months/years to integrate. Conversely, when we microdose the changes are small, subtle, but potent. Microdosing is about taking small manageable steps consistently, or as some call it: minimal effective dose.


Passive coping vs. active coping


This is a term used by the scientific community to define the different ways that psilocybin works on depression versus pharmaceutical medications.

Passive coping (tolerating a source of stress) is mediated by the 5-HT1AR receptors and characterized as stress management. Conversely, active coping (actively addressing a source of stress) is mediated by the 5HT2AR and is categorized as enhanced plasticity (heightened capacity for change)

Pubmed released a paper in 2017 called ‘A tale of two receptors’. This medical article suggests that the 5-HT1AR-mediated stress moderation may be the brain’s default response to adversity. Having said that, the improved ability to change one’s situation and/or relationship to it via 5-HT2AR-mediated plasticity may also be important, and will increase in importance as the level of advesity/stress increases. 


How does this impact my day-to-day?


Psilocybins’ ability to enhance our sense of presence, our open-mindedness, and our openheartedness also come with the added side effect of reducing the cravings for things that do not serve or benefit us.

Many studies have shown that microdosing helped people quit smoking once and for all. All the way back In 2014, Johns Hopkins carried out a study that reported: “15 study participants taking psilocybin achieved an 80 percent smoking abstinence rate over six months.”

Microdosers also tend to drink less over time, and spend more time in nature. Microdosers tend to appreciate music and carry a lighthearted playfulness.

These are all important metrics to observe and notice how this all points towards a positive, sustainable, and beneficial upward cycle. Rather than just passively coping, psilocybin allows for a sense of ease and a capacity to optimize daily habits. This is one of the few reasons why psilocybin is a game changer in the area of treatments for depression.

Non-toxic and non-addictive, psilocybin is potentially a powerful tool to treat a wide variety of mental illnesses including depression.


Hot off the press

Just last month Paul Stamets released a the largest clinical study on microdosing to date. This report concluded that “Psilocybin microdosers demonstrate greater observed improvements in mood and mental health at one month relative to non-microdosing controls”

The study is extensive, it covers Stamet’s ‘stacking’ protocols and discusses the findings regarding to age-related decline. It is a promising document encouraging the medical industry to continue it’s work. 

It reads: “Specifically, the clinical reconsideration and study of psychedelics presents an opportunity to reevaluate the extent to which expectancies and frank psychoactive effects might combine to influence subjective well-being in potentially meaningful ways”.


From: Psilocybin microdosers demonstrate greater observed improvements in mood and mental health at one month relative to non-microdosing controls


One more thing before I go

I have to share this amazing brain scan with you. The brain scan on the left is of a person using conventional SSRI and the scan on the right shows the effects of psilocybin on the brain. I’m no neurologist but a picture does speak 1,000 words.



All of that to say, psilocybin is powerful medicine, one that has shown very promising results so far. However, it is not for everyone and if you are currently taking any medication, please discuss your options with your doctor. 

If you decide to begin microdosing, be sure to journal and track your progress and your doses. Look out for benefits that may come from unexpected places. Perhaps you are jogging more often? Maybe you’ve been randomly smiling at strangers? Or your pet seems to like you recently?

The opposite of depression is agency. Having the personal agency and the will to engage with life on your terms is a path toward the upgraded version of yourself!


Shine bright. Do good. Flow strong.

Asha ✨



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Asha Sultana

Asha Sultana

I believe in the power of mushrooms and in the innate intelligence of our bodies. Fungi support human health like none other. Personally, I have used a wide variety of mushrooms to restore my health from heavy metal poisoning and its consequences. Currently living in Cape Town while raised in Canada and born in Romania. My travels have deepened my connection to natural medicines and my commitment to balanced living.

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