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How Hemp Is Putting The 'Pharm' In Pharmacy

A purported panacea awaiting regulation, hemp products line retail shelves beckoning the adventurous consumer. Humans cultivated the cannabis plant for over 5,000 years before we made it illegal and more potent.

With nationwide legalization, physicians, pharmacists and researchers are starting to embrace cannabinoids in the modern age.

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Seré Williams / KUNC
Researchers have been hesitant to study hemp because of its affiliation with marijuana. Fewer than 6,000 research papers containing the word “cannabis” were published before 2000. But with gradual legalization, scientists have increased efforts threefold in the last 20 years.

Some people who use hemp products tout medical benefits apart from the psychoactive affects the cannabis plant is known for. So, what are these cannabinoids doing in us?

The endocannabinoid system

Just like the immune system or endocrine system, it turns out we have another system: the endocannabinoid system (‘endo’ is Greek for ‘internal’). And, we discovered it by using the cannabis plant.

“It’s a little confusing ‘cause we’ve got this internal cannabinoid system, but it’s named after plants. So, it’s like we went outside in,” said Dr. Sharon Montés, a physician in Loveland.

She said our bodies naturally make chemicals — internally produced endocannabinoids — that function in this system: AEA and 2-AG. Like a lock and key, these chemicals bind to specific receptors on the cell surface and signal a change in the cell. We know of at least two cannabinoid receptors — CB1 and CB2 — but there are thought to be more.

In 2016, a patient with chronic neuropathy came to Montés with a “prescription” from a dispensary — and it worked.

Healthy Choices Unlimited Education, Ltd.
The nonprofit organization, Cannabis Clinicians Colorado (www.coscc.org), is helping educate doctors about the medicinal properties and uses for cannabis.

Montés recalled, “I said, ‘okay fine. My resistance is done. I understand plant medicine. I will integrate this into my clinical practice.’” She understood plant medicine, but she needed to learn about cannabis.

Physicians are not routinely taught about the endocannabinoid system in medical school.

“I ended up talking in conversations with 14 different doctors. Of those 14 different doctors, not one knew about cannabis,” said Montés. “We’ve got cannabis, we’ve got clinicians, and we’ve got consumers; there’s a gap. And frequently, the consumers know a whole lot more about how to use this plant than the clinicians do.”

“But what I did is I spent six months volunteering on a medicinal hemp farm,” she resolved.

And it turns out, cannabis is not just THC and CBD.

“We’ve got over 500 cannabinoids, terpenes, flavonoids — this is plant medicine,” said Montés. Terpenes give plants their smell. Flavonoids are antioxidants that can give plants their color.

Seré Williams / KUNC
A bottle of terpenes extracted from hemp at Green Cherry Organics in Fort Collins, Colorado. The scent is similar to that of a pine tree or grapefruit, since pines and citrus also produce terpenes.

Montés now incorporates cannabis into her clinical practice when it makes sense and when her patients are open to it. She said people are used to interacting with plants this way.

“Coffee, chocolate, tea,” she said, “every food we eat. So whole plants have chemicals that affect our function. So, whether it’s fiber to decrease colon cancer; willow bark, salicylic acid…”

Salicylic acid is a plant hormone. It’s also the activated ingredient that comes from aspirin.

Over-the-counter analgesics – like aspirin and ibuprofen – are typically synthesized by chemical manufacturers and play a huge role in how we manage pain. Research suggests cannabinoids are effective for managing long-term chronic pain as well as effectively treating other conditions, but we need clear instructions and dosing.

If cannabis is going to be medicine, we need to know what we’re taking and how much of it.

Measuring plant chemistry

To understand how a compound works, we have to isolate it — while keeping all other variables constant – to identify its direct affect. This is how plant medicine becomes a pharmaceutical.

Chemists have isolated cannabinoid compounds and determined their structures.

Seré Williams / KUNC
Stop sign-like stick figures link up to form rings or sometimes trail off making jagged tails. These lines represent the bond between atoms in these three common cannabinoids: CBG, CBD and THC.

Greg Matthews is an analytical chemist at High Grade Hemp in Longmont. “You want to see the poster? I have a poster right over here,” said Matthews over a Zoom call, as he pointed his computer camera towards the only adornment in an otherwise sterile-seeming room: a poster of the chemical structures of different cannabinoids.

“A big thing is like the closure of the ring,” Matthews explained. “Like with CBGA — this one right here — you pretty much only have one ring. Then you go over to CBD. It’s got two rings. THC, three rings almost, this one has the oxygen in it.”

Chemists can tell the difference between one, two or three rings — and our bodies can too.

Chemists use chromatography — like smeared ink on wet paper — to separate out the cannabinoids by size, shape and charge. Sharp peaks appear on what’s called a “chromatogram,” like rock towers lining the landscape in Monument Valley, Utah. Each rock tower represents a different compound from the “ink smudge” or plant sample.

There are important distinctions between each chemical structure.

“To clarify,” Matthews said, “in the plant itself, it’s really only making acidic cannabinoids.” Like in THCA or CBDA, the “A” stands for acidic.

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Seré Williams / KUNC
THCA is converted to THC with heat. Our endocannabinoid receptors are more responsive to non-acidic cannabinoids (like THC), which is why the plant material is heated before use.

A chromatogram will separate THCA and THC into two different peaks – because chemically, they are a little different. But he says it takes only a minor amount of heat to convert an acidic cannabinoid into a regular one.

Federal regulation strictly requires hemp to contain less than 0.3% THC. If a lab only measures THC and not THCA, they could be missing THC that forms after the material is heated. Colorado regulatory agencies specify that the combined total THC and THCA must be below 0.3%, but this varies on a state-by-state basis.

And, there are other nuances — like the difference between delta-9-THC and delta-8-THC — which has to do with the orientation of the molecules to one another (like turning your hand palm-side-down or palm-side-up). Previously, only delta-9-THC was on the radar, but as of Aug. 21 the Drug Enforcement Agency issued an interim final ruling concerning delta-8-THC that will change how hemp extract has to be processed.

Comments on the interim final ruling are accepted until Oct. 20, 2020.

The informed consumer

As state and federal regulatory agencies sort this out, consumers still need to know what’s in the product they’re consuming.

Results from the chromatography test are returned in a “certificate of analysis.” This simple piece of paper signals the success or failure of a hemp farmer’s crop.

“I’m looking at one right now,” said Chuck Winters, owner of the online hemp retailer, OrganaHempUSA.com, based in Northern Colorado. He paused to scan the certificate and then said, “There’s 15 different compounds…”

It looks like a nutrition information label. But instead of grams of fat, protein and sugar, it lists amounts of cannabinoids, pesticides, microbes and heavy metals found in the plant.

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Seré Williams
This Certificate of Analysis shows that each gummy contains 10.7mg of CBD and does not contain any THC, signs of microbes, or heavy metals.

The certificate of analysis is for the farmer and the regulatory agencies. There is no standardized way to inform consumers exactly what’s in a hemp product. Some companies provide a QR code and a lot number that links to the certificate of analysis (as shown above), but most don’t.

Standardized testing

But the problem of testing goes even deeper — currently, standards don’t exist to verify that the various types of chromatography methods are equal. It doesn’t mean the testing methods are faulty, it just means that the instruments aren’t calibrated properly.

The National Institute of Standards and Technology (NIST) is developing the Cannabis Quality Assurance Program (CannaQAP).

“Now part of the issue in the industry though is, you probably heard, is they can send it to three or four labs and get three or four different values,” said Brent Wilson, who is heading up CannaQAP.

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Brent Wilson, NIST
Three different instruments produce three different chromatograms from a cannabis sample. NIST is working to make sure the various instruments that different labs use all produce consistent results.

Seré Williams / KUNC
This fungus growing on a barley head produces a toxin that can make you vomit. Barley elevators test for the toxin before purchasing a truckload of barley, and the standards for this test are made by NIST.

NIST is the governmental organization behind making sure low-nicotine tobacco is what it says it is. Or, that beer doesn’t make us vomit from the fungal-produced “vomitoxin” that can grow on barley.

“We have a material for mycotoxins in corn. We’ve been doing pesticides in other types of food matrices,” said Wilson, but there are not standards for cannabis yet.

To provide reliable standards to labs across the country, NIST needs material, and they especially need bad material that contains heavy metals or pesticides. In complete innocence and irony, this governmental agency — that just wants to make sure measurements are accurate — is asking hemp farmers to send them their “bad” material.

NIST is assuring all contributors that they are not involved in regulation; regulation is up to the Food and Drug Administration, the U.S. Department of Agriculture and the Drug Enforcement Agency.

Unfortunately, NIST cannot use isolates, like purified CBD, because the plant material — what they call the “matrix” — affects how an instrument measures the compounds.

Plant medicine

It seems that our bodies respond to whole-plant compounds differently from isolates, too.

“People have interacted with this plant for thousands of years and gotten health benefits,” said Dr. Sharon Montés in Loveland. We can assume they weren’t interacting with isolates.

As a physician, Montés has found that her patients respond best to the combination of cannabinoids, terpenes and flavonoids found in the plant matrix — what people in the hemp industry call “whole-“ or “full-spectrum.”

“The message is over 500 active, medicinal, healing chemicals. So, it’s like calling someone ‘nose.’ You know? It’s like one piece of a whole,” she said.

But in the 1970s, the same decade that THC from cannabis was listed as a Schedule 1 drug, the FDA approved the pharmaceutical use of Marinol (also known as Syndros). The drug contained synthetically derived THC — the chemical mirror-image of the plant-derived THC — prescribed to stimulate appetite and prevent sleep apnea.

Ideally, a product would be tested at a NIST-certified lab, the contents would be listed on the container, and an informed consumer would decide how they wish to interact with a cannabis product.

Seré Williams / KUNC
Omega-3 oils from fish are available from a local grocery store.

In the future, we may use cannabis products as simply as we use Tylenol today. The difference will be if we get it from a chemist or a plant.

As Matthews (the analytical chemist from High Grade Hemp) noted, other nutraceuticals, like omega-3 oils, already work this way; you can get omega-3s from a pharmacy or a fish.

“There’s a pharmaceutical drug approved by the FDA called Lovaza which is basically omega-3s in a pill. Your doctor can prescribe that and you can go to a pharmacy and get it,” he said. “Also, you can go to the supermarket and you can just buy salmon — which has omega-3 in it — and eat it.”

Editor's note: A previous version of this story misstated the full name of NIST as the National Institute of Standards and Testing. It has been corrected to the National Institute of Standards and Technology.

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