Vape Carts Health Crisis Megathread

[Deleted Member 1643]

Can you imagine THC produced in the same manner as insulin (making bacteria our bitch LOL)? Amazon prime a barrel or two

Yeast, not bacteria:
Complete biosynthesis of cannabinoids and their unnatural analogues in yeast
Nature volume 567, pages123–126 (2019)

Cannabis sativa L. has been cultivated and used around the globe for its medicinal properties for millennia1. Some cannabinoids, the hallmark constituents of Cannabis, and their analogues have been investigated extensively for their potential medical applications2. Certain cannabinoid formulations have been approved as prescription drugs in several countries for the treatment of a range of human ailments3. However, the study and medicinal use of cannabinoids has been hampered by the legal scheduling of Cannabis, the low in planta abundances of nearly all of the dozens of known cannabinoids4, and their structural complexity, which limits bulk chemical synthesis. Here we report the complete biosynthesis of the major cannabinoids cannabigerolic acid, Δ9-tetrahydrocannabinolic acid, cannabidiolic acid, Δ9-tetrahydrocannabivarinic acid and cannabidivarinic acid in Saccharomyces cerevisiae, from the simple sugar galactose. To accomplish this, we engineered the native mevalonate pathway to provide a high flux of geranyl pyrophosphate and introduced a heterologous, multi-organism-derived hexanoyl-CoA biosynthetic pathway5. We also introduced the Cannabis genes that encode the enzymes involved in the biosynthesis of olivetolic acid6, as well as the gene for a previously undiscovered enzyme with geranylpyrophosphatelivetolate geranyltransferase activity and the genes for corresponding cannabinoid synthases7,8. Furthermore, we established a biosynthetic approach that harnessed the promiscuity of several pathway genes to produce cannabinoid analogues. Feeding different fatty acids to our engineered strains yielded cannabinoid analogues with modifications in the part of the molecule that is known to alter receptor binding affinity and potency9. We also demonstrated that our biological system could be complemented by simple synthetic chemistry to further expand the accessible chemical space. Our work presents a platform for the production of natural and unnatural cannabinoids that will allow for more rigorous study of these compounds and could be used in the development of treatments for a variety of human health problems.

 

[mephisto]

Thanks @Accept, that is possibly the coolest thing I have ever read (and actually comprehended).
Who thinks of this stuff?

 

[Deleted Member 1643]

No problem. Actually did some molecular biology in its stone age. At the time, cloning entire biosynthetic pathways was out of reach, but thought about cannabis. Imagined expressing them in another plant (which might also be possible) rather than yeast.

 

[Tranquility]

Yeast, not bacteria:
Complete biosynthesis of cannabinoids and their unnatural analogues in yeast
Nature volume 567, pages123–126 (2019)

At what point is it still "yeast" when the trick in the study was inserting genes into the sequence? They say we share 50% of our genes with a banana and 98-99% with a chimp. Maybe we can go with Planet of the Apes nomenclature and call it "Yeast plus".

https://planetoftheapes.fandom.com/wiki/Grape_Juice_Plus

 

[olivianewtonjohn]

@Accept I actually wondered if I should have said yeast before posting because I read that study in February (and it blew my mind ). I was mostly referring to how insulin is made (via bacteria) but I should have been more clear. Thank you for bringing it up, its really mind blowing stuff. Here is the science daily article on it (in case someone wants a more digestible read or doesn't have access to the journal):

https://www.sciencedaily.com/releases/2019/02/190227131838.htm

@OldNewbie Gene expression. Gene regulation. And gene regulation of the gene regulation LOL. From googling it seems a lot of what we share with bananas is regulation of cell cycling and DNA replication. We arent really "97%+ chimpanzee" for example because theres another layer (or two) to genetics and thats gene expression (why most of us arent as hairy as chimps). I learned about Genomics for a semester (aka barely scratched the surface), it's a very new and interesting field, on the forefront of whats understood in genetics (kinda like the quantum mechanics of biology, or at least thats how I thought of it). Its crazy that human genome was sequenced just 16 years ago and here we are today talking about the importance of "junk DNA" and how in the future we could have personalized medicine based on an individuals genetics .

 

[Deleted Member 1643]

I was mostly referring to how insulin is made (via bacteria) but I should have been more clear.

Insulin is a peptide, a gene product, so it's much more straightforward. With something that's synthesized by enzymes, you need to clone in the genes for all of the required enzymes in the pathway and get them working together.

 

[Tranquility]

https://cannabislifenetwork.com/tree-of-life-genetic-framework-sequenced-cannabis-included/
Tree of life: Genetic framework sequenced, cannabis included
Andres Markwart and The Canadian PressOctober 23, 2019

In other news, scientists have sequenced the vegetative transcriptomes of 1,124 species that span the broad diversity of plants, including green plants (Viridiplantae), glaucophytes (Glaucophyta), and red algae (Rhodophyta), providing a robust phylogenomic framework for examining the evolution of green plants.

What does this mean? In essence, we now have a genetic framework for the proverbial Tree of Life.

Researchers from around the world, including several Canadian universities, through nine years of work, have analyzed the genetics of plant species ranging from algae to elm trees. That work, released Wednesday in the scientific journal Nature, has allowed them to pinpoint a billion years of evolutionary relationships between plants as different as orchids and oaks, cannabis and cucumbers.

Cannabis is usually phylogenetically organizing through the clade Rosids, a monophyletic grouping of flowering plants, containing about 70,000 species, broken up into 16-20 orders. Within the specific order Rosales, it’s join by members such as strawberries, apples, pears, and roses. But is itself further organize into the family Cannabaceae, a grouping it shares with the beer ingredient, hops (genus Humulus).

“Everything interrelates,” said the University of Alberta‘s Gane Wong, one of the papers dozens of co-authors.

Scientists have long known that even species with significant dichotomous differences can be related through a common evolutionary ancestor. In plants, those relationships have been studied mostly through how they look or behave. Are they trees? Do they have trunks? Are they herbaceous? Do they have flowers? How their seeds formed?

Wong and his fellow colleagues, nearly 200 of them that together author the paper, instead chose to explore how the links are highlight through genetics.

Isolating and sequencing genetic RNA material from over a thousand different plant species. They took care to cast a wide net, selecting a broad variety of plant types, not solely focusing on species, such as cereal crops, that are important to humans.

“We wanted to look at how plants evolved,” said Wong. “This is going all the way back to algae.”

“One of the things biologists constantly argue over is which came before what. How did this species evolve?”

New species are create when a mutation begins splitting one species into two. Eventually, the two themselves mutate, which leads to another two, and so on, until there’s a vast branching tree of life with a half-million different plant species in it.

Wong and his colleagues wonder if the record of those ancient mutations would be preserved in the RNA.

“Can we, from the RNA sequence, draw this tree of life for all 1,000 species?” asked Wong. “For 95 percent or so, the answer is, yes, we can do it quite well and probably better than you could do by just looking.”

The computing power needed to resolve that much information was significant. Data to be analyzing was measure in terabytes, where one terabyte equals a million bytes.

Even then, the team couldn’t resolve everything. They couldn’t find branches in the tree for about five percent of species. Either because there wasn’t enough data or because it has dated from so long ago it couldn’t be read accurately.

“We’re talking about events that happened a billion years ago.”

But the work is already yielding concrete benefits.

Proteins taken from an obscure algae species studied by the researchers were found to turn certain brain neurons on and off. Those proteins now being used in clinical trials to treat blindness.

This is proof of the value of basic research said, Wong and also proof of the value of nature. Which has been solving problems and getting things done for a long, long time?

“It’s all based on exploring the diversity of life because evolution or nature has solved a lot of important problems,” Wong said.

“Sequencing is a way to learn about it. It’s trying to learn to use all the lessons that have been learned by nature over billions of years.”​

 

[C No Ego]

Again I did not say THC made in the lab would be the same to vaporizing a plant (that has thousands of compounds) because that wouldnt make any sense. If you're saying there would be a difference between the THC refined from the plant and THC made in the lab, then I would love to see some references for that claim. If you're pointing out the differences in cost then I agree with you (and mentioned it in an earlier post).

@OldNewbie Yes exactly, economics play a big factor. Im sure organic chemists can make THC in the lab and separate the reagents the question is how much would it cost and is there a cheaper alternative.

Can you imagine THC produced in the same manner as insulin (making bacteria our bitch LOL)? Amazon prime a barrel or two

Each THC molecule will be different , not the entire spectrum making one molecule different via entourage though that works too... but the plant created THC molecule will be different than a lab made THC molecule because of the subtle enzymes... I found the info from the sacred plant series ( lots of vids) and do not remember exactly which one... I think it was Allen Frankel https://duckduckgo.com/?q=Allen+Frankel+sacred+plant+series&t=ffcm&atb=v165-1&ia=web

biosynthetic cannabinoids and yeast https://duckduckgo.com/?q=biosynthetic+cannabinoids+and+yeast&t=ffcm&atb=v165-1&ia=web

 

[Tranquility]

but the plant created THC molecule will be different than a lab made THC molecule because of the subtle enzymes...

This is the basic claim that some of us dispute. While it might be harder and more expensive in some instances, a lab created molecule can be exactly the same as a plant-created one.

Exactly the same.

 

[C No Ego]

This is the basic claim that some of us dispute. While it might be harder and more expensive in some instances, a lab created molecule can be exactly the same as a plant-created one.

Exactly the same.

I'm sure pharma would like you to believe... there is Zero chance we can replicate an exact form./.. r you talking 3-d printed cannabinoids?

 

[olivianewtonjohn]

I'm sure pharma would like you to believe... there is Zero chance we can replicate an exact form./.. r you talking 3-d printed cannabinoids?

The two links you listed do not say what you claim. Appealing to conspiracy theories is lazy.

 

[Tranquility]

The two links you listed do not say what you claim. Appealing to conspiracy theories is lazy.

Just what someone in the conspiracy would say.

 

[Deleted Member 1643]

Some e-cig regulation news: Reynolds submitted a premarket application for its VUSE products two weeks ago. The press release gives is an idea of just how difficult it's likely to be for e-cigs to gain FDA approval.

FDA has issued guidance explaining criteria for PMTA submissions, which make clear that manufacturers must provide not only information on the composition, design and manufacturing process associated with the product, but also chemistry, toxicological and behavioral studies that demonstrate the product − when used − is appropriate for the protection of the public health. To support the applications and meet this guidance, Reynolds' submission to FDA includes more than 150,000 pages of documentation.

"Today's application marks the culmination of years of hard work across multiple teams, involving more than 100 individuals, including dozens of Ph.D. team members collaborating every day, with a substantial financial investment," noted Dr. James Figlar, Executive Vice President of Scientific and Regulatory Affairs at Reynolds. "This is an important first step in a long process for the millions of adult cigarette smokers who may want a legal alternative to combustible cigarettes, thus we look forward to working with the agency as the process moves forward."

One possible difference between natural and synthetic THC would be if they're isomers of each other - they have the same chemical formula but the atoms are arranged in the molecule differently. For example, some molecules exist as two mirror images of each other. Living organisms typically produce one or the other, but chemical synthesis can produce a mixture of both. In many cases, only one isomer is biologically active. If it's a drug, the active isomer can sometimes be isolated. If there are few adverse effects, prescribing twice the dose of the mixture might also be appropriate.

With macromolecules, like proteins, there can be many differences depending on how they're made, because living organisms modify these large molecules in very specific ways.

 

[olivianewtonjohn]

One possible difference between natural and synthetic THC would be if they're isomers of each other - they have the same chemical formula but the atoms are arranged in the molecule differently. For example, some molecules exist as two mirror images of each other. Living organisms typically produce one or the other, but chemical synthesis can produce a mixture of both. In many cases, only one isomer is biologically active. If it's a drug, the active isomer can sometimes be isolated. If there are few adverse effects, prescribing twice the dose of the mixture might also be appropriate.

With macromolecules, like proteins, there can be many differences depending on how they're made, because living organisms modify these large molecules in very specific ways.

That's not in anyway, shape or form related to what I said. Again it's just atoms, if you want to be accurate about the comparison it would be ~99% extracted THC vs THC made in lab; other than economics if both are the same compound with the same chirality (if THC has chirality, I don't care to check) then they will be the same.

It's the foundation of pharmacology and broadly speaking chemistry and physics.

Yes, thats a large reason why chirality is covered in most (if not all) Organic Chemistry 1 courses and also why I was specific when the topic first came up.

Not every reaction is going to give a racemic mixture (50/50 R/S enantiormers), stereo selective reactions exist which will give high amounts of one or the other desired enantiomer (enantioselective synthesis). In cases where you want an enantiomer, chromatography (chiral resolution) can be used after enantioselective synthesis. Id imagine it would be expensive but thats an economic/practical debate not a natural vs synthetic debate.

composition, design and manufacturing process associated with the product, but also chemistry, toxicological and behavioral studies that demonstrate the product − when used − is appropriate for the protection of the public health.

Im all for FDA reducing harm and that criteria makes sense to me. But yeah if 150,000 page documents are necessary that seems excessive/potentially counter productive.

 

[Deleted Member 1643]

Yes, thats a large reason why chirality is covered in most (if not all) Organic Chemistry 1 courses and also why I was specific when the topic first came up.

Oops, missed that post - you covered your bases!

Im all for FDA reducing harm and that criteria makes sense to me. But yeah if 150,000 page documents are necessary that seems excessive/potentially counter productive.

It's what's needed, at a minimum, for inherently risky products like e-cigarettes. Those 150,000 pages will include full study data for most if not all of the studies conducted with the product. FDA will spend months reviewing it. Very curious to see how it turns out. If it's not approved, and there's a good chance it won't be, it's difficult to imagine how small e-cig companies could ever succeed.

 

[Planck]

if 150,000 page documents are necessary that seems excessive/potentially counter productive.

It's far worse than you imagine. Certainly excessive but counterproductive, perhaps not at all when the goal is to hand the nic vape market to our old friends big tobacco.

it's difficult to imagine how small e-cig companies could ever succeed.

That is the whole point.

 

[C No Ego]

The two links you listed do not say what you claim. Appealing to conspiracy theories is lazy.

O)k, you seem much more intelligent for that response. do you have a personal issue with me? are you seriously claiming we can do a thing better than millions years plant life doing it? or that our version isthe Exact same? What in the Fuck?
plus you asked.. there's the Fucking hours of Video for you... Days... week days

and to not seem like to much of an asshole and reference the other link I linked out - bio-synthetic cannabinoids made from yeast and e-coli will mimic and match the real living plant cannabinoids better than current tech to do it... when we get there

 

[olivianewtonjohn]

O)k, you seem much more intelligent for that response.

Thank you I appreciate the compliment.

do you have a personal issue with me?

No, what gave you that impression? I do have an issue with baseless non-scientific arguments and poor epistemology, but theres nothing personal in that.

are you seriously claiming we can do a thing better than millions years plant life doing it? or that our version isthe Exact same? What in the Fuck?
plus you asked..

You would have to be a lot more precise for me to answer the first question. If you're asking if its possible to make a physically identical molecule in lab as nature, then the answer is yes (and hence my first reply). Can you explain why that is such a controversial idea for you?

Again here is the initial post you replied to:

Lets clear this up!

Likewise, if a compound has the same atoms and 3D arrangement it is identical to another compound with the same properties, whether it is found in nature in that arrangement or its made in a lab, they are the same compound. This isnt debatable, this is very basic science. As far as what you said about a plant being different than a narrow set of compounds? I mean isnt that obvious? You're arguing with a different point that I did not make.

there's the Fucking hours of Video for you... Days... week days

So in response to someone asking you for evidence, you link them to "fucking hours of video"? Do you not see where someone might think you're being extremely unreasonable? Instead you're saying here watch "fucking hours of video....days...." of videos? Why cant you give any evidence that delta 9 - THC will have magical proprieties when made in nature vs in the lab? I literally clicked the first link you gave, wasted my time watching the video which said nothing about identical molecules having different properties. I "learned" that CBD can help with sleeping, so I guess....Thanks? LOL

and to not seem like to much of an asshole and reference the other link I linked out - bio-synthetic cannabinoids made from yeast and e-coli will mimic and match the real living plant cannabinoids better than current tech to do it... when we get there

So this search term is going to tell me that I was wrong when I said this?

Likewise, if a compound has the same atoms and 3D arrangement it is identical to another compound with the same properties, whether it is found in nature in that arrangement or its made in a lab, they are the same compound. This isnt debatable, this is very basic science.

I am skeptical you understand my initial post let alone the idea that this search is going to tell me physics, chemistry, and biology are all wrong.

 

[TommyDee]

Its a cooking problem. You can't simply throw all the ingredients in a pan and expect cake to come out the oven. Intermediate processes must take place for the full treatment. Now eating the mess that comes out of the oven if you did just throw it together may or may not function properly in us as an organism. We'd hope the salmonella wasn't too concentrated in the egg to survive, for instance. Part of the 'process' is to minimize the variation of exposure or maximize contact with another ingredient for an action to take place as a incremental process. It seems the whole argument above is just semantics of getting to making a 'proper' cake. Identifying -every-single-stinking-interaction down to a molecular level or even further is today impossible but we're a whole lot closer than even 5 years ago. This is where we learn how to activate genes in DNA remotely.

 

[chris 71]

Regardless even if , we , them us . Guys and girls in lab coats growing canabiniods in yeast whatever .

Even if we , can ,.could or would or will some day learn how to make every canabiniod . And even if they are exactly the same . And then mixed and matched with also seperatly created , terpinoinds and flaviniods and what ever eles .

Then all patched back together in a pill or some kinda liquid to be taken or smoked or what ever woren as a patch maybe .

This will not be cannabis it cant , its fake , its Frankenstein lol no matter what the tiny human does he is millions of years from being nature.

I want cannabis by nature .
Maybe future races or cyborgs will be into frankenbionds not me though thanks anywy

 

[Deleted Member 1643]

We have two different but related questions. The answers to both seem uncontroversial. Maybe the issue is separating them.

1: Can the complex and variable mixtures of substances present in natural cannabis preparations be duplicated?

Probably not, but it depends on the preparation. A quick search finds >99.9% purity THCA isolated from cannabis. If true, it's essentially pharmaceutical grade. There are probably FCers who have experience with high-purity crystal preparations. Curious how the effects differ from more familiar broad spectrum preps.

2: Is (−)-trans-Δ⁹-tetrahydrocannabinol produced in the lab identical to (−)-trans-Δ⁹-tetrahydrocannabinol produced in cannabis plants?

Yes, the (−)-trans-Δ⁹-tetrahydrocannabinol is the same, because it's defined by the nomenclature at the molecular level. Isomerization isn't even an issue, because the superscript "9" after delta specifies one, unique isomer. If the substances are different, then one of them isn't (−)-trans-Δ⁹-tetrahydrocannabinol.

Edit: Thinking back to organic chemistry, it's conceivable that there are features of the molecules that aren't captured in the nomenclature. Loved O-chem, but it was a long time ago, and it was O-chem for biologists. Not sure that's what @C No Ego is saying.

 

[chris 71]

Ya i mentioned in another post somewere saying i personally have no interest in isolates for the exact same reason

Just my personal prefference though im sure lots of people will be buying the vape pens with the yeast grown canabiniods .

That maybe coming soon actully

alot of them might think differenlty if they knew how they were made .

Maybe not though , but me na

 

[invertedisdead]

There are probably FCers who have experience with high-purity crystal preparations. Curious how the effects differ from more familiar broad spectrum preps.

IMO compared to other preparations, isolated THCA makes for a pretty unimpressive vaporizing experience.

 

[Kilo Crusher]

Finally...My lab is testing for Vit E acetate..I only drop samples off every 2 months or so , and last month they were aware of the problem but did not have the equipment to test for it..they do now..if the issue is cut carts..this will only solve a small portion of the problem...I figure most of the cutting would be post testing..most not all..

I have to outsource bulk supplies at times..I have to admit..not one time has the COA matched my 3rd party testing and I'm not talking 5 or 10%...this whole procedure..of processing bulk...TESTING of bulk...manufacturing of products with COAs that are given with the bulk....to dispensary...to consumer....is a sham...unless the peps after the test CARE...
I test my CBD to the max..although I'm not required to test it at all..actually harder to find clean supplies than you might expect...scary..
Random spot testing in distribution areas or directly off the dispensary shelf is the only answer to the legal market. MAKE PEOPLE ACCOUNTABLE...shit always runs down hill ask a plumber.

or Aways know your sourse and your good.

 

[hafalump]

the plot (cutting agent) thickens. https://news.google.com/articles/CA...AowjJ0RMKC-AjD5m7AF?hl=en-US&gl=US&ceid=US:en