This Story begins with Cancer and Ends with Psilocybe cubensis.

It is a very timely topic given the lockdown induced suicide, anxiety and depression.

In fact, Psilocybin has been awarded FDA breakthrough status for these very things. https://www.medscape.com/viewarticle/921789

Johns Hopkins has looked into this in Terminal Cancer Depression.
http://archpsyc.jamanetwork.com/article.aspx?articleid=210962
https://www.thelancet.com/pb/assets/raw/Lancet/pdfs/S2215036616300657.pdf

It is time to take a deep dive
but first the Cancer story

In 2016, I became a green thumb on a mission. My father had stage4 bone mets with BRAF:K601E mutations

While cannabinoids were unmatched by western medicine for cancer related cachexia, pain and nausea, there was an added hopeful kicker; Cannabinoid were non-toxic potent AKT1 inhibitors. Just what the Foundation medicine report called for ...except they had to stick to FDA drugs.

The Drugs for AKT1 inhibitors were all in phase 2 and 3 small trials with different tumor types. Not much promise there.

But the pathway was obvious.
I grew my 1st type II cannabis plants, learned hydro, made extracts, and PCR and HPLC QC’d them. He was immunocompromised. Microbial contamination was our main concern. Cross state trustworthy supply was limited to CBD, CBDA, and CBG by law.

This is where people think we're nuts.
More links to assure you we are not.

The pathway has many in vitro models. The drugs are non-toxic and are the only thing that allowed him to Eat. But our supply for THCA needed to be local due to federal and state law conflict.

I knew too much about the microbial contam occurring in the state of Mass as they largely adopted culture based microbial regulations which are all voodoo. Most pathogenic microbes dont culture. Particularly the ones effecting Immunocompromised patients.
https://pubmed.ncbi.nlm.nih.gov/26100839/ 

I had to grow it myself for THCA and THC.
This turned into the Jamaican Lion genome project, recently honored as one of the most significant advances in the cannabis industry in 2020.
https://thecannabisscientist.com/business-profession/the-innovation-awards-2020

It was legal to do this Mass but there was always the federal risk which complicated every trip to the hospital and to their home in NH. Drug dogs visited their home in NH. Imagine dying of cancer and frisks. The police kindly turned a blind eye once they saw the circumstances.

This in and of itself is a wild and amazing story and I encourage anyone interested to read this tribute to his amazing life and our journey through this process here:
https://www.medicinalgenomics.com/tribute-to-richard-t-mckernan/

When you perform a deep dive on cannabinoids and cancer, it’s hard not to run into the JHUs work on terminal cancer depression and psilocybin and while my Father never needed this, it never left my radar as sometimes family members are equally effected but such trying times.

Another medicinal genome that was left un-sequenced due to prohibition and it was a small target. I could do it in a weekend and assemble it on my laptop.

So I did.

But I was afraid to publish it. I was my father’s caretaker. A raid would end his cannabinoid supply and while a remote fear, it would have devastating consequences. This was the time frame when Ross Ulbricht @Free_Ross was being persecuted for allegedly hosting the Silk Road.

Double life sentence + 40 years for hosting a website where users traded mostly cannabis and mushrooms.

How does one publish a genome anonymously in 2016?

This is where I began to see the ugly choke hold of journals on the dissemination of scientific information.

I discovered this is not easy. Any website would have ties back to a user acct. Blockchains came to mind but the systems for blockchain file storage was nascent. IPFS was exciting but hard to index and search. The genome remained difficult to find on esoteric corners of the web.

Another group (Fricke et al) published a beautiful genome and pathway characterization in 2017. We sequenced a different one in 2016 and have aligned that to Fricke et al and placed it public for everyone to surf.

SNPs in the key genes involved in synthesis of Psilocybin, Psilocin, Baeocystin,NorBaeocystin, Aeruginascin may provide a deeper understanding of the entourage effects in Cubensis.

With Oregons’ legalization and the FDA declaring Psilocybin a Break-Through therapy, it is time to blow the dust off this genome.

Here it is. Open source. send it around.
https://genomevolution.org/coge/GenomeInfo.pl?gid=59605

There are 120K-280K SNPs between the two genomes (depending on the SNP caller). About a SNP every 160 bases. Notice the High impact variants in PsiK, the gene responsible for Phosphorylating the molecule from Psilocin into Psilocybin.

Variants in the Methyltransferase are equaling interesting as they may govern the synthesis of Baeocystin, norBaeocystin and Aeruginascin.

Why genomics? These are very difficult molecules to synthesize in the lab and as a result a genomics based approach is likely to lead to the most productive dissection of the pathways and variants related to the chemotype diversity in P.Cubensis. Fricke has done much of this work

We need to end the drug war and free the prisoners like @FreeRoss that are caged up over this for 2X life. This is a war on science and on people. It is impacting very powerful compounds that can address many of the comorbidities seen in C19 and the depressing reaction to it.

If you want to learn more about cannabinoids and cancer, come to CannMed 2021. @CannMedEvents

The Videos from the last 4 years of the conference are open source and online.
https://cannmedevents.com/2019-videos/ 

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