U of G Researchers First to Unlock Access to Pain Relief Potential of Cannabis

Authored by news.uoguelph.ca and submitted by mvea
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University of Guelph researchers are the first to uncover how the cannabis plant creates important pain-relieving molecules that are 30 times more powerful at reducing inflammation than Aspirin.

The discovery unlocks the potential to create a naturally derived pain treatment that would offer potent relief without the risk of addiction of other painkillers.

“There’s clearly a need to develop alternatives for relief of acute and chronic pain that go beyond opioids,” said Prof. Tariq Akhtar, Department of Molecular and Cellular Biology, who worked on the study with MCB professor Steven Rothstein. “These molecules are non-psychoactive and they target the inflammation at the source, making them ideal painkillers.”

Using a combination of biochemistry and genomics, the researchers were able to determine how cannabis makes two important molecules called cannflavin A and cannflavin B.

Known as “flavonoids,” cannflavins A and B were first identified in 1985, when research verified they provide anti-inflammatory benefits that were nearly 30 times more effective gram-for-gram than acetylsalicylic acid (sold as Aspirin).

However, further investigation into the molecules stalled for decades in part because research on cannabis was highly regulated. With cannabis now legal in Canada and genomics research greatly advanced, Akhtar and Rothstein decided to analyze cannabis to understand how Cannabis sativa biosynthesizes cannflavins.

“Our objective was to better understand how these molecules are made, which is a relatively straightforward exercise these days,” said Akhtar. “There are many sequenced genomes that are publicly available, including the genome of Cannabis sativa, which can be mined for information. If you know what you’re looking for, one can bring genes to life, so to speak, and piece together how molecules like cannflavins A and B are assembled.”

With the genomic information at hand, they applied classical biochemistry techniques to verify which cannabis genes were required to create cannflavins A and B. Their full findings were recently published in the journal Phytochemistry. The Toronto Star also recently wrote about the research.

These findings provide the opportunity to create natural health products containing these important molecules.

“Being able to offer a new pain relief option is exciting, and we are proud that our work has the potential to become a new tool in the pain relief arsenal,” said Rothstein.

Currently, chronic pain sufferers often need to use opioids, which work by blocking the brain’s pain receptors but carry the risk of significant side effects and addiction. Cannflavins would target pain with a different approach, by reducing inflammation.

“The problem with these molecules is they are present in cannabis at such low levels, it’s not feasible to try to engineer the cannabis plant to create more of these substances,” said Rothstein. “We are now working to develop a biological system to create these molecules, which would give us the opportunity to engineer large quantities.”

The research team has partnered with a Toronto-based company, Anahit International Corp., which has licensed a patent from the University of Guelph to biosynthesize cannflavin A and B outside of the cannabis plant.

“Anahit looks forward to working closely with University of Guelph researchers to develop effective and safe anti-inflammatory medicines from cannabis phytochemicals that would provide an alternative to non-steroidal anti-inflammatory drugs,” said Anahit chief operating officer Darren Carrigan.

“Anahit will commercialize the application of cannflavin A and B to be accessible to consumers through a variety of medical and athletic products such as creams, pills, sports drinks, transdermal patches and other innovative options.”

WRCousCous on July 23rd, 2019 at 22:54 UTC »

Just for the record: both aspirin (Salix spp.) and opioids (Papaver spp.) are naturally derived. I’m all for drug discovery and alternative chemicals for reducing inflammation and pain, but why the nod towards the natural fallacy? Also...aspirin, cannabinoids, and opioids are completely different classes of chemicals with completely different (if tangentially related) treatment targets.

Why must every new drug (or molecule which might lead to a drug) discovery be touted as that which will replace opioids? Interesting research, terrible title.

feralpolarbear on July 23rd, 2019 at 21:47 UTC »

I work in drug discovery and just want people to understand what they actually did and not be misled by the sensationalized title.

In this paper the authors show the biosynthetic pathway for cannflavins A and B, which describes the enzymes with which the cannabis plant makes these compounds.

They do not discover anything new about the activity of these compounds in humans. The claim in the title that cannflavins are "30 times more powerful than aspirin" was actually from a paper in 1985 (Source: M.L. Barrett, D. Gordon, F.J. Evans. Isolation from Cannabis sativa L. of cannflavin--a novel inhibitor of prostaglandin production Biochem. Pharmacol., 34 (1985), pp. 2019-2024).

In this article, they used a single type of human cells (cultured synovial cells from the joint) and look at a single type of inflammatory marker (PGE2) and conclude that cannflavin works better than aspirin by a factor of 30, but also works worse than some other drugs that we have (indomethacin by 18x, dexamethasone by over 100x).

So, although the new research is very interesting in an academic sense, it's not really correct to make any kind of comment on how this compound can be a new or better anti-inflammatory based on such little preliminary data from 35 years ago. Of note, if we were to discover that the cannflavins had interesting drug-like properties in humans, we would not be using the pathway described in this paper to make it, but rather more efficient organic syntheses that we have at our disposal.

edit: thanks for the awards. I'm getting a lot of similar replies so I wanted to clarify a couple of things:

1) Regarding the experiment from 1985, I was just pointing out that when you compare 4 things in a study, the conclusion in the news article shouldn't be "look at how much better #3 was compared to #4" without mentioning #1 and 2. I'm not peddling indomethacin or dexamethasone; just highlighting that the experiment gives far too little data to say that any of these are better than the others for human use.

2) Cannflavins represent two out of potentially thousands of biologically active compounds in cannabis, if not more. For those of you who have had positive experiences with cannabis, there are many other molecules that can be studied to validate your experiences, even if this is not the one. Like many of you, I'm looking forward to future experiments in the field.

AdamCohn on July 23rd, 2019 at 21:02 UTC »

Wonder how long ago this would have been discovered if marijuana hadn’t been prohibited for so many years?