How Psilocybin Mushrooms Work

Whether you’re new to mushrooms or relatively experienced, you’ll likely agree the general public isn’t always fed good information about psychedelics. With decades of conflicting data, and a devastating drug war fueled by unjust drug laws that targeted minorities, it’s no surprise that if you don’t know much about mushrooms, you’re likely to perceive them as threatening, or even dangerous. 

The good news is, a great deal of studies have been done by groups of dedicated researchers and volunteers dating as far back as the 1950s, which have collectively disproven the false information and have successfully shown in controlled studies that mushrooms are one of the lowest, if not the very lowest, risk factor drugs out of any other – especially when compared to nicotine and alcohol. The tested low risk factors accounted for include: ingestion amount, LD-50 testing (50% of a lethal dose), physical risks, social risks, and psychological risks (all of which are mitigated by proper set and setting). The exception of course, depending on where you live, is the legal risk factor.

Legality aside, how exactly do mushrooms work to create the effects that they do, without being dangerous – even if you’re having a bad trip?

How psilocybin breaks down into psilocin and becomes psychoactive

When we think of what gets us high when we take mushrooms, we think psilocybin. And why wouldn’t we? It’s what everyone talks about when it comes to magic mushrooms – even experts. What isn’t talked about in detail as often is that psilocybin doesn’t get you high as it is. 

When you ingest psilocybin, it has to be processed by the body and metabolized into psilocin via a process called dephosphorylation, in order to become psychoactive. Once this conversion completes, then the blood carries active psilocin through the blood-brain barrier and into the serotonin 2A receptors in the cortex.

Overall, the amount of psilocin ingested will have the biggest impact on your experience of the drug. We’ll cover dosing in another post.

Interesting side note – broken down, non-psychoactive psilocin is what makes the blue bruises on magic mushrooms. Making how much blue you see is far from being an accurate marker of true psychoactive content.

How psilocin binds to the Cortex

No matter how horrid you might feel if a trip turns bad, there’s very little risk involved to you physically. The reason is that psychedelics aren’t able to bind to the brainstem, making major alterations in organ function highly unlikely. The reason for this lack of effect on the brainstem is because there are no serotonin receptors located there (or at least so little as to be of no consequence). All the interactivity of psilocin is confined to its ability to find, then bind to, a serotonin 2A receptor. Psilocin is able to bind to this receptor because it’s carboxyl structure is a nearly identical chemical clone to the serotonin hormone we produce in our guts and brains, meaning it can fit like a key (active psilocin) to a lock (the receptor).

Because of serotonin’s function in regulating cognition, sleep, hunger, perception, and sensory imputes, it’s no wonder why an interaction between an external compound and the brain can have such profound effects on how we experience reality and memory.

As signaling hormones change, so do the blood flow patterns in the brain. Different areas start to receive more blood than others as the default balances shift. One structure in particular seems to receive much less blood than baseline – the Default Mode Network (DMN).

Downregulation of the DMN lowers our hyper defensive patterns and allows the brain to process information in a much more flexible way – expanding awareness, dissolving your ego, enhancing consciousness, and producing sensory effects.

Common Sensory Effects During a Peak Moderate to High Dose Experience and How to Better Control It. 

No two experiences are the same when on magic mushrooms. Visual and auditory hallucinations, random thought patterns, physical disassociation, euphoria, elevated mood, low mood, and a vast other array of effects can vary on higher doses. 

With a general lack of control being a natural part of the experience, is there a way to help steer it all? 

There’s several key factors to consider that could be good predictors to setting yourself up for a good trip, or a bad one. These include: set and setting, thoughts entering the experience, mood, physical setting, intention, social surroundings, past drug experiences, substance interactions (alcohol and cannabis are the most common), and more.

If the majority of those factors are leaning to be more positive, then your chances of having a much more positive and happy experience go up dramatically.

Coming Down

Depending on dose (average 3-5g dried mushrooms) and bodyweight (average 65-75kg), the drug’s effects peak around 2-3.5hrs in, and begin to subside after about 5-6hrs. In that time, all sensory functions, ego, and blood flow all start to return to normal.

An interesting thing happens once mushrooms wear off called The Afterglow Effect. The duration of the effect varies widely depending on the person, but some reports suggest feelings of reduced anxiety and increased happiness and well-being have been reported several days to several months after the high dose. This of course again depends on the set and setting and the other factors, but used contextually with the goal of healing, the effect can be a significant discovery in modern medicine. 

There are little to no known reports of addiction, bodily damage from the drug, or lethality from magic mushrooms, but that doesn’t mean there aren’t risks associated. Always follow safe practices and ensure you have a grounded understanding of what a trip is, and that it can’t physically harm you. Knowledge will go a long way towards increasing the frequency of good trips, and helping better manage bad ones.

You can find many of the studies used in this post in the references below.


Prediction of psilocybin response in healthy volunteers – Studerus E, Gamma A, Kometer M, Vollenweider FX. Prediction of psilocybin response in healthy volunteers. PLoS One. 2012;7(2):e30800. doi: 10.1371/journal.pone.0030800. Epub 2012 Feb 17. PMID: 22363492; PMCID: PMC3281871.

Serotonergic hallucinogens and emerging targets for addiction pharmacotherapies – Ross S. Serotonergic hallucinogens and emerging targets for addiction pharmacotherapies. Psychiatr Clin North Am. 2012 Jun;35(2):357-74. doi: 10.1016/j.psc.2012.04.002. PMID: 22640760.

Functional connectivity measures after psilocybin inform a novel hypothesis of early psychosis – Carhart-Harris RL, Leech R, Erritzoe D, Williams TM, Stone JM, Evans J, Sharp DJ, Feilding A, Wise RG, Nutt DJ. Functional connectivity measures after psilocybin inform a novel hypothesis of early psychosis. Schizophr Bull. 2013 Nov;39(6):1343-51. doi: 10.1093/schbul/sbs117. Epub 2012 Oct 8. PMID: 23044373; PMCID: PMC3796071. – Carhart-Harris RL, Nutt DJ. Experienced drug users assess the relative harms and benefits of drugs: a web-based survey. J Psychoactive Drugs. 2013 Sep-Oct;45(4):322-8. doi: 10.1080/02791072.2013.825034. PMID: 24377171.

The Role of Serotonin (5-HT) in Impulsivity/Aggression, Anxiety/Stress and Cognition

Tomas Palenicek: Psilocybin´s Effect on Perception, Cognition and Brain Activity – Colloquium on Psychedelic Psychiatry, 2018. Organized by Nätverket

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