2-Minute Neuroscience: Psilocybin

Psilocybin is a substance found in a number of mushroom species that can be ingested to cause psychoactive effects. Although psilocybin itself is thought to have very little (if any) psychoactive effects, upon ingestion it is rapidly metabolized into a highly psychoactive substance called psilocin. In this video, I discuss our understanding of psilocin’s effects on the brain.

TRANSCRIPT:

Psilocybin is a substance found in a number of mushroom species that can be ingested to cause psychoactive effects. It is considered a psychedelic or hallucinogenic drug with some similarities to LSD in terms of effects.

Psilocybin itself is not thought to be very psychoactive, but soon after it is ingested it is metabolized into a substance called psilocin, which is highly psychoactive. Psilocybin is thus considered a prodrug, or a substance that is inactive until converted into an active drug after administration. Although we have some understanding of the activity of psilocin in the brain, it is not fully understood how this activity leads to the subjective experiences people have while taking psilocybin. Regardless, it is thought that psilocin’s activity at a subtype of serotonin receptor known as the 5-HT2A receptor is critical to the drug’s psychedelic effects. Psilocin is thought to act as a partial agonist at the 5-HT2A receptor, which means that it binds to the 5-HT2A receptor and causes a response that is a fraction of what the natural ligand, serotonin, does. Psilocin also interacts with other targets, like other serotonin receptor subtypes, some subtypes of dopamine, histamine, and adrenergic receptors, and the serotonin transporter. The role of these other targets in the effects of psilocybin, however, is not very clear.

Like many other psychedelic drugs, repeated administration of psilocybin over multiple days leads to rapid tolerance and substantially reduced effectiveness. This tolerance is thought to be associated with the down-regulation, or decrease in number, of 5-HT2A serotonin receptors. Psilocybin also exhibits cross-tolerance with LSD, meaning that if someone develops tolerance to one of these drugs, they may display tolerance to the other---regardless of their history with the other drug. Psilocybin, however, is not generally considered to be addictive and is thought to be safe in terms of its effects on the body.

References:

Geiger HA, Wurst MG, Daniels RN. DARK Classics in Chemical Neuroscience: Psilocybin. ACS Chem Neurosci. 2018 Oct 17;9(10):2438-2447. doi: 10.1021/acschemneuro.8b00186. Epub 2018 Jul 16.

Nichols DE.Psychedelics. Pharmacol Rev. 2016 Apr;68(2):264-355. doi: 10.1124/pr.115.011478.

[MrSchweppes]

“Psychedelics are illegal not because a loving government is concerned that you may jump out of a third story window. Psychedelics are illegal because they dissolve opinion structures and culturally laid down models of behaviour and information processing. They open you up to the possibility that everything you know is wrong.”
― Terence McKenna

[arsenik_beats]

Is it just me, or psychedelics are making a comeback in terms of research and public interest?

[alanbaker]

Psilocybin mushrooms healed me. I can't explain it but my experience has been spiritual and eye opening. I also started micro dosing. It really helped me get rid of depression and anxiety.

[johnmike]

One dose earlier this month took me out of my depression rut and has changed my daily life very positively.

[emmabeyza]

Psilocybin containing mushrooms saved my life. The drastically reduced my benzodiazepine withdrawal allowing me to quite illicit pill addiction after three years of heavy daily use before it would had became medically dangerous to quit. It has also helped me survive depression.

[naagars]

Eating mushrooms rn... wish me a good trip!

[teresavanhuyssteen]

Psilocybin helped me to wean and stop SSRI's with minimal withdrawal. As well as some other nasty substance addictions.

[Brainstorm]

There are (for the first time in decades) some really promising studies underway at both UCL and John Hopkins testing the efficacy of psilocybin on intractable depression. Very exciting times!

[jimmyfellows]

Break it down further. Psilocin and Psilocybin are 4 hydroxy dmt and serotonin is 3 meo dmt. Hence why it works it's a booster of your natural serotonin.

[Hayanomie]

Apparently it's stymied by interactions with anti depressants like Wellbutrin or effexor. In case someone experimenting tries psilocybin while on these, they may notice they have higher tolerance.

[etcetera]

For anyone not doing it for the first time.. I recommend doing nothing while you trip. Sit in your living room with the TV off, maybe a puzzle to stimulate you. Thank me later lol

[zahitism]

Hi there. What about the Neurogenesis effects of psilocybin?

[jopmens]

I really dont get why psilocybin is showed in binding diagrams with receptors (elsewhere).. Altho 5-HT2a is also present outside the brain i think, ofc that is not the interesting part.. Psilocybin cannot cross the BBB barrier so why do they show it binding?

[jacobheaton]

Was blessed with a QP. Gonna do it over a few months

[JessicaGilberts]

There’s a lot of potential in psychedelics, I can’t wait to try any of them mushrooms specifically but it’s just so hard to find a reliable source over here, I’ll be glad if anyone can be of help

[shitbag.]

Thanks so much for the videos and your time.

[dsnjzdx]

AKA you can't get addicted to what when it won't affect you anymore after the third day you would have to increase your dosage so much everyday just to feel anything

[Eric-yjxg]

why didnt you talk about neurogenesis?

[tpotturner]

It's very safe ... in controlled amounts. Other wise you're gonna ride a wave you don't want to surf. Unless you know.

[Rg-eskv]

ok il start these comments off reasonably, the whole world should take this and disassociate in order to better understand how we are controlled by our mammalian brains, and only through disassociation we the self can we achieve a truly harmonious world free of pain