American Scientist

George Weiblen is a plant biologist at the University of Minnesota who studies Cannabis sativa, the plant species that includes two notorious cultivars, hemp and marijuana. When he began studying the plant in 2001, he was one of the first biologists with permission to research and grow the plant. Legal marijuana is the fastest-growing industry in the United States—in 2016 sales grew by 30 percent, to $6.7 billion. Hemp, which does not have the psychoactive properties associated with marijuana, is used in a range of products, constituting annual sales of about $580 million and including food, fiber, cosmetics, and herbal supplements. Most hemp sold in the United States is imported from other countries, because it is illegal to transport hemp plants and seeds across state lines. In the United States, industrial hemp has been legalized in at least 16 states—in some only for pilot or research purposes, and in others for commercial use—and marijuana has been legalized in 8 states (plus the District of Columbia), with an additional 20 states allowing medical marijuana. In light of these developments, along with increased interest in developing a domestic hemp industry, Weiblen’s research has become especially relevant. Digital features editor Katie L. Burke spoke with Weiblen as one of Sigma Xi’s Distinguished Lecturers in December. (A video of the full interview is available here.)

What is the purpose of your research on hemp and marijuana?

In the bigger picture, [my research] is bringing some clarity and objectivity to an economically important plant that is widely misunderstood. People have strongly held opinions about it, good or bad, but they lack evidence to support their positions. Hemp products are not going to have the kind of psychoactivity that is a risk to health and safety. Medical marijuana is not as safe as many people think it is. There’s just a lot of confusion out there on the issue.

Broadly speaking, what is the difference between hemp and marijuana?

They differ in the qualities that people find of economic interest. Hemp is primarily associated with the fiber and the seed production, and marijuana with drug production.

How did you get into this controversial area of study?

For my PhD research, I had studied a related group of plants: fig trees. The ancestry that figs and cannabis share wouldn’t be obvious, but in fact, hemp, hops, figs, mulberries, and stinging nettles are all plants that are part of a big lineage that I’ve been studying now since my graduate days.

When I was hired as an assistant professor at the University of Minnesota back in 2001, we had a populist governor named Jesse Ventura, a professional wrestler, who called for looking into the problems associated with industrial hemp. [People wanted to know:] Why can’t we grow industrial hemp in Minnesota, even though we did back in World War II, and now our neighbors to the north in Manitoba and Saskatchewan are growing it and we’re buying it from them? So there was a call to take up this research. At the time, I got nothing but ridicule from many quarters about being “the professor of pot.”

A lot has changed since then. Now there are hundreds of researchers who are interested in cannabis. By some miracle or, perhaps, just a lot of patience and persistence, I went through the formal process of getting a research registration from the U.S. Drug Enforcement Agency (DEA) to study a Schedule I controlled substance, which is the most restrictive class of controlled substances you can study. We had to develop tight protocols to prevent any kind of diversion of material out of the lab or out of the growth facility and to make sure we destroyed everything at the end of these experiments.

What do biologists know about the evolution and history of cannabis?

Cannabis is one of the oldest cultivated plants. We have archaeological records going back 13,000 years that show that humans were using this plant in a variety of ways early on in agriculture. Pretty much every major ancient civilization except for those in the Americas used hemp, which originated in the Old World and was brought to the New World by European colonists. In fact, the Founding Fathers in the United States were hemp farmers.

Particularly where I’m from in the upper Midwest, hemp was widely cultivated. Probably the most recent hemp agriculture we had was during World War II, when the Army built hemp mills and distributed hemp seed to Minnesota farmers, who grew it as a source of fiber for the war effort, making canvas and cordage. Recently, we’ve started to try to understand what’s happened to the plant genetically since it escaped from cultivation and became a ditch weed.

As an annual plant, this escaped hemp has been through many generations of natural selection, adapting to the environment. We discovered that, although industrial hemp’s seed usually germinates readily, here in Minnesota we have a difficult time germinating the seed of this escaped cannabis, because it requires cold. It’s adapted to survive our harsh winters.

A number of folks are working on trying to unravel the history of domestication. It’s complicated. We’re tackling this question using the new high-throughput DNA sequencing that can deliver a genome at lightning speed.

The big difference between marijuana and industrial hemp is the drug content. What are the genetics underlying levels of tetrahydrocannabinol, or THC, the psychoactive compound in marijuana that is used in many state policies to distinguish marijuana from hemp?

[We published a paper in the New Phytologist in 2015 reporting] an experiment in which we crossed hemp with marijuana [over a couple of generations], a lot like what Gregor Mendel did, crossing his peas to discover the simple laws of inheritance.

The second most abundant cannabinoid in cannabis plants [after THC] is cannabidiol, or CBD. In our experiment, we found that there are three basic chemical classes: high THC plants, high CBD plants, and intermediate plants that have an intermediate ratio of THC and CBD. In our population, they fell into a neat ratio of 1:2:1. For every one high THC plant and every one high CBD plant, there are on average two intermediate plants, and that suggests a single gene with two different variants. 

But when we looked at the THC gene, which we thought would be the candidate for that [trait], it turned out that all the plants shared the same copy of the gene, and so it couldn’t [cause the variation we saw]. It turns out that [THC and CBD] share the same building-block precursor molecule.

Our study showed that it’s not the gene for THC that makes a marijuana plant have more THC than a hemp plant, but, in fact, it’s a mutation in the gene for the CBD enzyme. This mutation knocks out this competing enzyme so that the marijuana plants make only THC, whereas in the hemp plants we’ve looked at, the enzyme for CBD is a superior competitor. The winner of this race succeeds because the competitor gets knocked out before reaching the finish line. That’s how we end up with plants that have a lot of THC.

Although many states have passed legislation to make it easier to grow hemp domestically, it still is challenging to do so. How is the policy evolving?

The Controlled Substances Act of 1970 is written in such a way as to exclude the cultivation of cannabis in the United States. The challenge is that the same species that can produce what is a Schedule I controlled substance under federal law also includes other forms of the plant that are not a threat to health or safety. 

There’s a provision in the 2014 farm bill that opens up the door to doing research on industrial hemp and cultivating industrial hemp in states that have laws that define hemp on the basis of THC content and a low THC level. Since that 2014 law passed, things have opened up quite a bit. It’s still not legal to transport hemp plants or viable seed across state lines. That’s a real problem for a young industry.

[Our lab offers] genetic testing now. If there’s a question about whether a plant is likely to produce THC in a quantity that exceeds the legal thresholds, we can test for that.

CBD oil has recently become a trendy topic because of potential health benefits. How did this topic develop?

One recent development that has complicated my life telling the story of hemp is that a few years ago, some marijuana breeders in Colorado introduced a new type of cannabis that contains a lot of the CBD molecule and not so much THC. These high CBD strains of cannabis have attracted a lot of attention because for some individuals, high doses of CBD appear to have some health benefits. It got the most attention in the case of a rare seizure disorder called Dravet syndrome. Young children with this disorder suffer hundreds of seizures a day and don’t live long. A couple of parents seeking an alternative therapy stumbled upon these high CBD strains and found that symptoms miraculously dissipated. Right now, I guess you’d call CBD oil one of these nutraceuticals. It’s not approved or regulated by the U.S. Federal Drug Administration. It’s in this gray area.

The way that each of these cannabinoids interacts with our nervous systems is dramatically different. It takes very little THC to produce dramatic effects. For CBD, because of the way it interacts with the body, it takes a lot of CBD to see effects. That has driven up the demand for this particular cannabinoid, because on a quantity basis, people are taking thousands of times more CBD than they would take in the form of THC to achieve some effect.

How does CBD oil compare with hemp oil, and what might that mean for the policy definition of hemp?

Some people market this high CBD oil by calling it “hemp oil,” when we also have hemp seed oil, which doesn’t have cannabinoids in it. It’s all fatty acids. People are moving around [this CBD oil] as though it’s hemp. That muddles definitions even more, because now we have CBD being used as medicine and sold as hemp when we’ve been saying hemp is not a drug for so long. 

CBD oil can be extracted from hemp plants, but honestly, most of what is being sold as CBD oil is probably derived from these hemp–marijuana hybrids that have been selected to produce lots of the cannabinoids. If you measure the cannabinoid content in your typical commercial hemp strain, it’ll be 1 to 2 percent of the dry weight of the plant. These drug types now, thanks to breeding, have a cannabinoid content of 20 to 30 percent dry weight. Depending on which genes the plants have, you can produce mostly THC, mostly CBD, or an intermediate quantity of each. 

It gets tricky when we talk about hemp and marijuana. I don’t think the plants that produce 20 to 30 percent CBD can fairly be called hemp plants. They’re something else, and I don’t think we have a name for them yet.

In 2015, your home state of Minnesota passed the Industrial Hemp Act, making it legal to grow hemp there. How has that policy changed your research?

Prior to the [change in] state law, we were working only within the protocols that we were able to get approval for through DEA, which limits the sources of material to what we can import from abroad or acquire from other registered cannabis labs. When I first started studying the subject, there were few registered cannabis labs from which I could get material. We had to import from abroad. That was extremely difficult, because you have to get permits from both countries.  

We’re going to use the wild populations that we’ve sampled to try to confirm the results we published previously. Ultimately, the hope is that we develop some useful hemp genetics from these old populations that descended from the American hemp that was distributed during the war effort and was probably originally bred in Kentucky.

There is no seed bank for that original material because of cannabis being regarded as a drug. Seed collections were purged. Material was destroyed. We don’t have a lot of material to go back to from American hemp—only what exists in a few repositories around the world. So we’re hoping we can learn something useful from these wild populations.

The direction we’re taking next is to continue studying the crossed population to further understand how hemp and drug-type cannabis are different. We’re also gearing up for an agronomic field trial. In collaboration with the Minnesota Department of Agriculture, we’re planning to plant out about 12 different commercial varieties of hemp and see how they perform at sites in Minnesota. This is similar to work that’s going on in North Dakota, Kentucky, Colorado, and other states.

There’s great interest in developing certified seed that Minnesota farmers could produce to supply a market should we reach a point when domestic hemp production and demand are matched up. I think we are probably growing closer to that day, certainly a lot faster than I ever expected. When I started doing this project 15 years ago, I never could’ve imagined what we’d be talking about in 2016. It’s a dramatic evolution and turn of events.