Global Ganja Report

For a generation now, science has known of two cannabinoid receptors—specialized protein molecules that interact with the active compounds in the cannabis plant for the human body. These are CB1 and CB2, both discovered in the early '90s. Now there is growing awareness of a third such receptor that was identified in 2007. This receptor, GPR55, may be key to understanding a wide spectrum of therapeutic applications for cannabinoids—and especially the non-psychoactive cannabidiol, or CBD.

A scientific study published last year was the latest to focus the research community on the criticality of the GPR55 receptor, which is now known to be the third identified receptor in the human endocannabinoid system. It found a role for the receptor in the use of CBD to treat Dravet syndrome, a rare and severe form of epilepsy.

The research team from the University of Washington at Seattle also saw potential to "extend the scope of CBD treatment to autistic-like behaviors, and provide initial mechanistic insights into CBD’s therapeutic actions," according to the abstract in the Proceedings of the National Academy of Sciences (PNAS).

It was a 2007 study published by the National Center for Biotechnology Information (NCBI) that first identified what was until then the "orphan receptor" GPR55 (meaning one whose function had not yet been determined) as a "novel cannabinoid receptor." In the years since then, evidence has been mounting that the GPR55 receptor could explain the actual biological mechanisms for many of the benefits reported by cannabis users.

A 2009 study published by PNAS found a role for the GPR55 receptor in regulating osteoclast function—that is to say, bone formation and healing. A 2016 study published by the NCBI found a similar role in controlling inflammation. Most impressive was a 2015 overview published by Frontiers in Pharmacology finding that two orphan receptors as well as the "deorphanized" GPR55 "may be promising therapeutic targets, with diverse physiological roles," ranging from gastrointestinal to bone disorders.

Robert Sindelar is chief science officer and head of product development at BAS Research, a Berkeley-based licensed manufacturer of "white-label" cannabis products—that is, products marketed by other firms. "We take plant material and convert it into enriched oils on behalf of other companies, to produce topicals, sprays, mists, edibles, and vape products," he explains to Cannabis Now.

Asked about the significance of the new GPR55 research, Sindelar starts by cautioning: "The endocannabinoid system as been a black box for many years, partially due to federal restrictions on research. Everyone seems to be aware of the CB1 and CD2 receptors, and the THC and CBD interaction with these recpetors. But CBD seems to have a much more complex interaction with the body than THC. I don't want to put THC is a box, because one thing science tells you is there is always more to be discovered. But the GPR55 receptor may explain a lot about how CBD works."

The GPR55 receptor—the 55th in the series of G-protein-coupled receptors that also include CB1 and CB2—is found in the brain and gastrointestinal tract. The G stands for guanine, which is a nucleotide base—one of the so-called "building blocks" of DNA. Guanine is associated with the g-proteins through which these receptors interact with cells. As Sindelar describes it, the receptor "receives the chemical and sends messages to cells such as neurons."

"Basically, we're starting to find out—how does this stuff do this?" Sindelar tells Cannabis Now. "People with seizures are being affected by CBD. How does this actually happen? With the new work on GPR55, scientific research is catching up with what traditional knowledge and anecdotal evidence have documented for hundreds of years."

As an example, he points to Dravet syndrome. "It's a rare disease that was basically thought to be untreatable. Many sufferers have found their only relief in taking a steady regimen of CBD. Now they've found the mechanism or mode of action by which CBD sends a message to something in the brain that tells a child suffering from Dravet syndrome to either have a seizure or not."

Sindelar sees "a growing body of evidence that allows the academic community to rally around that this. The GPR55 receptor can be a potential target for epilepsy treatment, especially in terms of how it interacts with CBD. This provides validation for what everyone involved in cannabis treatments has already been seeing in their friends and loved ones."

And Sindelar sees these studies as ultimately having political ripples. "Research is eliminating the scientific mystery about what people see in practice, or anecdotally. This could provide the body of evidence we need to deschedule these chemicals. In many ways, I feel it's inevitably leading to a change in the way cannabinoids are federally classified to allow further investigation into these things. That opens it up to federal funding."

Sindelar says of BAS Research, "We are currently operating under state sanction—the emergency regulations instated by the California Bureau of Cannabis Control." These are the interim regs now in place while California authorities frame a permanent oversight regime.

But Sindelar holds out hope for change at the federal level. "Sooner or later we will have to deschedule or at a minimum reschedule cannabis, so we as a society can benefit from its potential therapeutic uses. At a certain point we will reach a critical mass, where everyone on you know and everyone in the federal government will have one degree of separation from someone who has benefited from the therapeutic effects of cannabis. And when we reach that critical mass, we'll see the walls come tumbling down."

Cross-post to Cannabis Now

Image of THC molecule via Schaffer Library of Drug Policy

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