DMT and Psilocin Treatment Changes CD11b+ Activated Microglia Immunological Phenotype; Kozłowska et al. 2021

Friday Journal Club #3

PsyDAO

Mar 26, 2021

I’m really excited about this week’s article.
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I now present to you:

DMT and Psilocin Treatment Changes CD11b+ Activated Microglia Immunological Phenotype

Why they did it:

Inflammation is one way our body heals itself from wounds and infections. 🧑🏼‍⚕️
Brain inflammation causes cell death which leads to neurodegenerative disorders.
It is really difficult to treat inflammation in the brain, for a variety of reasons.
We know psychedelics have anti-inflammation properties, we know they can cross the blood-brain barrier, and we know they are relatively safe. 👌🏿

What they did:

They focused their study on microglia.
- Microglia are brain cells that monitor for infections, support the formation and reformation of neuronal connections, and clean up waste around the brain. 🧹
- Microglia build certain proteins to accomplish these tasks.
- Microglia can go rogue, produce too many proteins, and cause inflammation. 🤕
The researchers isolated microglia cells from mouse brains and grew the cells in petri dishes. 🐁 🧠 ➡️ 🧫
They put some microglia in dishes with standard media (i.e. nutritional gel) and some microglia in dishes with media mixed with LPS, a molecule from bacteria that tricks microglia into thinking there’s an infection. 🦠
They dosed each of these plates with either psilocin, DMT, or nothing.
After 12 hours, they measured the shape of the microglia and measured a variety of microglia proteins involved in inflammation pathways in the brain. 🧠
They measured these proteins by attaching a fluorescent tag to them, imaging the cells in a confocal microscope, and quantifying how much light is emitted from the fluorescent tags when excited at the proper wavelength. ⚡️🔬

Figure 3B & C: Microglial morphology under different treatments

What they found:

Psilocin and DMT both affect the immune properties of microglia
Psilocin has a stronger affect than DMT, and it also limits microglia’s ability to phagocytose (i.e. consume) neurons. 🤐
Specifically, psilocin upregulates a protein called TREM2.
- TREM2 helps rearrange synapses in the brain, and also helps microglia phagocytose dying neurons. These things are good for brains.
- When TREM2 doesn’t work, bad things happen to brains, and diseases such as Alzheimer’s and Parkinson’s can occur.
The researchers discuss the importance of the other molecules these psychedelics support, but you’ll have to read the paper for that. 📄
In sum, DMT and psilocin are similarly structured molecules that both seem to promote brain healing properties of microglia. However, the subtle differences in their structure grant psilocin a much stronger influence on these pathways. This study provides a mechanistic link between psychedelics and anti-inflammation in the brain. 👏👏👏

Figure 7: DMT-treated cells expressed **less** signal for TREM2 compared to control, while psilocin-treated cells expressed **more** TREM2 signal

My take:

This is an extremely exciting psychedelic paper. There is an overwhelming focus in psychedelic research on the action of psychedelics at neuronal receptors, most notably the serotonin 5HT2a receptor. It’s easy to assume the activation of these receptors contribute to the positive effects of psychedelics. However, about half of the brain is likely made up of glial cells, there are multiple types of glial cells, and glial cells are essential to brain function. This is the first paper I’ve seen (please send me more if you have them) that describes how psychedelics might promote cognitive health via a glial cell. I sincerely hope that more research funds go towards understanding psychedelic-glial cell interactions, because we are never going to get the whole picture of brain function, consciousness, and psychedelics if we only study half of the brain. 🤔

I should mention: This paper is currently published on BioRxiv, a database for pre-print papers. Pre-prints have not yet made it through the peer-review process that science depends on for ensuring that only quality science is published. Peer-review can take a awhile, so scientists post their research here so that they are available to the public and other scientists to read, discuss, and comment on. It helps science move faster. 🏃💨

I appreciate your feedback on how I did breaking down this science. Let me know in the comments:

📃 Here’s the paper:

Kozłowska U, Klimczak A, Wiatr K, Figiel M. The DMT and Psilocin Treatment Changes CD11b+ Activated Microglia Immunological Phenotype. bioRxiv. 2021;6.

Available here.

Weekend activities for you:

🐭💊 Ever heard of Mouse Party? It’s from an educational website clearly biased towards drug abstinence rather than harm reduction (meh) but putting schmacked and snozzled rodents into the big red chair is a dopamine rush in itself: