March 2023 – Countlesssheep

or the Magic Mushrooms Keychain

“Magic mushrooms” are fungi that contain Psylocibin.

When we ingest Psylocibin, it gets degraded by the acid juices of our stomachs and loses its phosphate group (P), giving rise to a compound called Psilocin.

Psilocybin de-phosphorylation to Psilocin @countlesssheep.com — Psilocybin de-phosphorylation to Psilocin

What is interesting is that Psilocin (organic name: 4-hydroxy-N,N-dimetiltryptamine) is very similar to Serotonin – a very important neurotransmitter involved in our mood, learning and a plethora of other fundamental physiological processes.

Psilocin & Serotonin: similarities and differences @countlesssheeo.com — Psilocin & Serotonin: similarities and differences

As such, when Psilocin reaches our prefrontal cortex, it can easily bind to our serotonin receptors, because they look so similar – it’s like two old keys that look almost alike and can open the same door at our grandmother’s house.

But Psilocin and Serotonin are indeed different.

As such, Psilocin is able to do certain things in our brains when it binds to the similar Serotonin “door lock”, causing hallucinations and emotional changes that seem to alter the perception of space and time. Psilocin is like that funny cousin that can create chaos when it comes to visit during summer vacations… And, not all trips seem to be good trips, because as all things in life, a lot depends on the surrounding environment and the dosage. So, if a person comes through that door in a poor state of mind, it will just go down the “dark-hole” even further – so they say…

In fact a couple of years back, psychopharmacologists Robin Carhart-Harris and David Nutt from the Imperial College London did a fMRI study (functional magnetic resonance imaging) to evaluate the effects of Psilocybin in the brain², and decided to give it IV (intravenously) to quicken the trip-effect because they were scared the “voyage” inside of the tight-noisy fMRI machine could be scary for the 30 individuals high on Psilocybin³. The results were quite interesting and showed that the effects of this psychedelic drug could be caused by a decreased activity and connectivity in the brain’s key connector hubs, like enabling a state of unconstrained cognition³. It seems Psilocybin reduced the blood flow and neural activity in the posterior cingulate cortex and medial prefrontal cortex – almost like making a “software reset” of the brain.

As such, Psilocin has been considered a serotonergic psychedelic compound; and it has been banned since the 70’s because people at the time thought it had no therapeutic value.

But Psilocin seems to have an effect in the treatment of Major Depressive Disorder (MDD), a leading cause of disability worldwide. Robin von Rotz and team at the Neurophenomenology of Conscious Lab from the University of Zürich, Switzerland, have just released the results of a randomized double-blind clinical trial ¹. This clinical study showed that a single, moderate dose of Psilocybin (0.215 mg/Kg) significantly reduced depressive symptoms compared to a placebo, the “sugar-pill” that they give to the control group.

Even though the results were only evaluated for a period of two weeks after ingestion, the depression severity scores significantly improved in the treated patients in comparison with controls. So, this is one of the first clinical studies to actually demonstrate improvements directly attributed to Psilocybin/Psilocin itself. If we think that the state of deep depression is actually a neural circuitry disfunction, then Psilocin with its similar key structure to Serotonin might be able to open and clean the faulty neuronal-wires that contribute to the brain disfunction seen in MDD.

Several larger clinical studies are currently under way that could eventually pave the way to full regulatory approval, and the removal of Psilocybin from the banned WHO list of pure psychedelic drugs. The U.S. Food and Drug Administration already gave psilocybin the “breakthrough therapy” designation for MDD and Treatment-Resistant Disorder; and, in Australia some psychiatrist can have permission to use it under certain conditions for Post-Traumatic Stress Disorder. The European Medicines Agency (EMA) is following suit, and its Chief Medical Officer has just released a statement that it is actively engaged with developers of psychedelic therapies and academic researchers to help them identify what it takes to move forward and fully bring psychedelics as medical therapies to our pharmacies (and not street dealers)⁴.

We will be on the lookout for those results…

References:

1 von Rotz, R. et al. Single-dose psilocybin-assisted therapy in major depressive disorder: a placebo-controlled, double-blind, randomised clinical trial. eClinicalMedicine 56 (2023). https://doi.org:10.1016/j.eclinm.2022.101809

2 Carhart-Harris, R. L. et al. The administration of psilocybin to healthy, hallucinogen-experienced volunteers in a mock-functional magnetic resonance imaging environment: a preliminary investigation of tolerability. J Psychopharmacol 25, 1562-1567 (2011). https://doi.org:10.1177/0269881110367445

3 Miller, G. Mapping the psychadelic brain. Science Brain & Behaviour (2012). https://doi.org:10.1126/article.27824

4 https://www.linkedin.com/pulse/second-chance-psychedelics-european-medicines-agency

It is well known that a growing global population drives an increased meat consumption. As such in response, there has been a huge movement to find other protein sources besides animal meat. By now, insects, plants or fungus-based substitutes combined with soy, wheat gluten or pea protein have become staples at our local supermarket.

This drive has also led to the development of “cultivated meat” as an alternative source of protein. This “cultivated meat” is produced in the laboratory by a process that is commonly used in medical tissue engineering, to regenerate skin patches for example to treat burn wound victims.

As such, the first patty grown from cells sourced directly from an animal happened in 2013; and the first commercial sale of cell-culture meat derived from chicken cells happened in a Singapore restaurant in December 2020. There’s currently a lot of hype from start-ups and regulatory agencies to get this process rolling in a more efficient and standard way.

So, the objective of this regenerative procedure is to recreate the complex structure of an animal muscle using only a small number of cells. A biopsy is taken from the muscle of a live animal, and this piece of tissue is cut into small pieces to release the stem cells, which then have the ability to multiply and transform themselves into different kinds of cells depending on the medium that they are grown. As such, once these cells are cultured in a specific liquid medium, which usually contains Fetal Bovine Serum (FBS) – a serum made from the blood of a dead calf, which contains all the nutrients needed – these cells will start to grow and proliferate. Rumour goes that start-ups are already working on finding plant ingredients that can be as efficient and nutritious growing cells as FBS – which is quite expensive, and of course not animal-friendly.

Trillion of cells can be grown this way, and the marvel with nature is that these cells can naturally merge to form muscle tubes (myotubes), which can then grow to form small pieces of muscle tissue – and eventually make up a patty. To scale this process, bioreactors are used, which work similarly to the way different pharmaceutical drugs are currently produced.

Unfortunately, the resulting patty is still far away from real muscle, which is made up of organized fibers, blood vessels, nerves, connective tissue and fat cells; as such, producing a thick piece of meat like a real steak is only a vision. “Cultivated meat” lacks the natural process of reperfusion, which is the bubbling of oxygen perfusion of blood vessels inside the meat necessary to mimic real-time nutrient diffusion. Furthermore, the richness of flavors is still significantly lower than traditional meats; with umami, bitterness and sourness still lacking due to a diminished amount of different aminoacids – the building blocks that form a protein. It’s like, such in vitro patties are only made of blue and yellow Lego^TM, missing all the other colors that will make us feel fulfilled.

The problem remains that this food cannot be called vegan, because it comes originally from animal cells – whether from a chicken, or a cow, or even a frog…. And, growing meat in the lab is also not cheap at all. High amounts of liquid serum are needed to grow a couple plates of cells, not to mention grow a couple of patties to feed a family of four. Furthermore, there is a need to warm the cultured cells to mimic body temperature, so that energy needs to come from somewhere, probably coupled with CO₂ emissions if fossil fuels are used. Additionally, fast growing cells are a known trigger to develop cancer – so, there needs to be a strong safety and quality assessment to make sure that cancerous cells have not developed in those in vitro meats. And another major issue is contamination: without the use of antibiotics or some other pharmaceutical means of pathogenic control, there is a high likelihood of a fully diverse & inclusive germs-party happening in those cell plates.

But truth be told, the current pressure on our food system and the increasing demands for food security, make a strong argument to find solutions for all environmental and health concerns that might arise from the field of “cultivated meat”.

It might take some years, but it will be coming to our tables…

Would you try it?

References:

Fountain, H. Building a $325,000 Burger. The New York Times https://www.nytimes.com/2013/05/14/science/engineering-the-325000-in-vitro-burger.html, 1 (2013).

Chriki S, Hocquette JF. The Myth of Cultured Meat: A Review. Front Nutr. 2020 Feb 7;7:7. doi: 10.3389/fnut.2020.00007. PMID: 32118026; PMCID: PMC7020248.

Joo ST, Choi JS, Hur SJ, Kim GD, Kim CJ, Lee EY, Bakhsh A, Hwang YH. A Comparative Study on the Taste Characteristics of Satellite Cell Cultured Meat Derived from Chicken and Cattle Muscles. Food Sci Anim Resour. 2022 Jan;42(1):175-185. doi: 10.5851/kosfa.2021.e72. Epub 2022 Jan 1. PMID: 35028582; PMCID: PMC8728501.

Month: March 2023

Psilocybin & Psilocin: Serotonin’s funny cousins

Cultivated meat, anyone?!