The WIRED Guide to Cannabis

Humanity just can’t make up its mind about cannabis. For thousands of years, humans have used the stuff as medicine or to travel on spiritual quests. That, though, didn’t quite suit the British, who banned cannabis in colonial India. Then in the 20th century, the United States government declared war on marijuana, and most of the world followed suit.

But today, state after state is calling out the federal government on its absurd claim that weed should be a schedule I drug—an extreme danger with no medical benefits—and should fall in the same category as heroin. Even on the federal level, congressional reps like Elizabeth Warren are fighting to end the criminalization of cannabis use. The fact is, scientists have proven cannabis can treat a range of ills and that it’s actually much safer than alcohol. The twisty-turny journey of cannabis has landed us back at a central truth: It’s actually a powerful medicine that can help treat what ails the human body.

Yet as governments come around to the fact that the war on cannabis—which has had a massively disproportionate effect on black Americans—is both insane and unwinnable, the drug remains largely mysterious. The root of the problem: Unlike a relatively simple drug like alcohol, cannabis is made up of hundreds of compounds in addition to THC, all interacting in ways scientists are just beginning to understand.

But therein lies the beauty of it. Things are getting real nerdy with cannabis science. So let us guide you through the haze.

The History of Cannabis

The cannabis plant probably originated in Central Asia, and may have been one of the first plants cultivated by humans. In addition to its psychoactive charms, cannabis gave early growers nutritious seeds to eat and useful fibers for rope. (Today, the industry makes rope out of hemp, a variety of the plant with little to no THC, and therefore no psychoactivity. Hemp fibers are even making their way into construction materials.) And our ancestors were aware of some of the medicinal benefits of cannabis: The ancient Chinese deity Shennong, or “God Farmer,” recommended that cultivators grow “hemp elixir” to treat the sick. Cannabis has a particularly rich history in India, where it has been used for thousands of years as a spiritual aid.

Even as great societies of metal and stone formed, cannabis remained an indispensable crop. Ancient Rome, for instance, wouldn’t have been the sea power it was without super-strong hemp sails and ropes. The British and Spanish, too, powered their world-spanning empires with hemp riggings. George Washington grew the bejesus out of cannabis.

All the while, it wasn’t like humanity had forgotten that cannabis was also good for getting high. Mexico in particular emerged as a major cultivator of psychoactive strains in the early 1900s, and that cannabis wafted over the border into the United States. Then, in 1937, the US passed the Marijuana Tax Act, which effectively criminalized the drug. And in 1970 the Controlled Substances Act branded cannabis a schedule I drug, essentially equating it with the devil himself.

As with the prohibition of alcohol, banning the consumption of cannabis just drove the drug underground. Which brings us to the legend of Northern California, mecca of cannabis production. Over the last few decades, cultivators have hidden themselves in the wildlands, producing perhaps 75 percent of the domestically grown cannabis consumed in the US. Growers here have selected plant generation after plant generation for high THC content, to the point where you can now regularly find flower with 25, even 30 percent THC, whereas a few decades ago the average was around 5 percent.

While Northern California’s growers were proving themselves masters of cannabis cultivation, the plant remained—and to large degree still remains—mysterious. That’s because it’s extremely difficult for researchers to study a schedule I drug. Until 2016, for instance, the DEA claimed a monopoly on the official supply of research cannabis, licensing a single farm at the University of Mississippi that produced legendarily crappy weed that looks nothing like what’s out in the market. (Like, literally. It’s so bad it doesn’t even look or smell like weed as we consumers know it.)

That regulatory wall, though, is crumbling, and science is rejoicing.

The Future of Cannabis

Throughout history, humans have used cannabis as a medicine without the confirmation of methodical scientific studies. The Aka people of the Congo River basin, for example, use the drug to ward off intestinal worms. Anecdotally, cannabis is great for treating pain as well.

As more states legalize, researchers are getting better access to cannabis to prove out such claims. Scientists have already determined that the drug can treat ills ranging from glaucoma to inflammation. But because science hasn’t had a very good understanding of how the different components in cannabis interact in the body, medicine has sort of stumbled through this.

Take the case of Marinol, a synthetic form of THC used to treat nausea and lack of appetite. It does those things fine, mind you, but also produces nasty side effects like paranoia. Consider that another drug, Sativex, doesn’t tend to induce that kind of terror, probably because it’s THC paired with CBD, which seems to attenuate the psychoactivity. So deploying cannabis in medicine is about determining what compounds work to treat what, but also about what those compounds can do as a team.

Speaking of CBD. You may have heard it can treat every conceivable ailment that affects the human body. It’s in skin creams now, and it's touted as a cure for depression. But there’s almost zero research to back any of that up because, you guessed it, prohibition. Sure, a smattering of studies have shown that CBD might work to fight anxiety and inflammation, but the science is far from settled here. It’s hard to tell, for instance, how much CBD you might need to get an effect, and whether inhaling or taking it orally is best, or whether isolating it from other cannabinoids hobbles its effects. Draconian regulation has handcuffed science in its pursuit of answers to these big questions and in its attempt to learn how we can deploy cannabis for a wide range of medicinal uses. . The regulation borders on the comedic: the government-provided stuff is so crappy that researchers have been driving to cannabis users’ homes in a van to study the effects of the good weed they are actually buying.

More research is also shining light on the potential harms of cannabis. Like any drug, it has its downsides. Of foremost concern is cannabis use disorder, or CUD, a dependence on the drug. Studies have shown that perhaps 9 percent of users will develop CUD, and research suggests the prevalence of the disorder is on the rise, which may be due to higher potencies or simply more people seeking treatment as the stigma around cannabis crumbles. Figuring out who’s most at risk, and how we might mitigate that risk, and how we can best treat the afflicted, demands more research.

Now, a common distinction you’ll hear cannabis enthusiasts tossing around when talking about cannabis strains is indica (relaxing) versus sativa (uplifting). Getting even more granular, specific strains, like Purple Kush or Lamb’s Bread, are each supposed to produce unique effects. Not just different intensities of highs, but different complexities of highs—energizing or sedating, more of a mind high or a body high.

Except science says that dichotomy is mostly meaningless. In a 2018 study, researchers drove around to dispensaries and collected samples from 30 different cannabis strains, then compared their genetics. Almost every one of those strains had a genetic imposter—that is, its genotype didn’t match that of its supposed peers in the same strain. And the analysis found that the samples didn’t fit into the indica-sativa dichotomy, but instead into one of two novel genetic groups that don’t map to the indica-is-relaxing-and-sativa-is-uplifting distinction your local budtender insists is a thing.

The fact of the matter is that the chemical makeup of cannabis is way too complicated to neatly split into indica and sativa. We’re talking hundreds of compounds, and that’s just what scientists know about so far. We have cannabinoids like CBD, which seems to dampen the intoxicating effects of THC, as well as terpenes, which give cannabis that characteristic smell and may also play a part in forming the high that grips your brain.

It’s called the entourage, or ensemble, effect: THC doesn’t work alone to produce a high, but instead interacts with other compounds in the plant. It’s probably why smoking pure cannabis flower feels different than using a vape pen. With the distilled oil in the pen, you may be getting pretty much just THC, and lots of it. Add CBD, though, and the high might be less intense. (Edibles can be particularly intoxicating both because they usually contain THC without any CBD, and because when the body processes THC through the digestive system instead of the lungs, it metabolizes the compound into 11-hydroxy-THC, which is five times as potent.)

Why? It turns out that THC and CBD have a similar structure. When you ingest them, they bind to receptors in your endocannabinoid system called CB1. THC fits perfectly, activating the receptor. But CBD doesn’t activate it, and instead just sits in there, preventing THC from clicking into the receptor and producing a high.

In addition to science’s ever-better understanding of how cannabinoids interact in the human body, a new breed of indoor grower is taking cannabis experimentation to a new level of nerdiness. The genetics of a plant only determine so much—environmental factors come into play as well. In crazy-high-tech facilities, cultivators are learning how to tweak variables like light and nutrients and water to get genetically identical plants to produce different chemotypes. This allows them to manipulate how many terpenes or cannabinoids a particular crop produces. It’s the same deal as with any plant, really: The tomatoes in your backyard won’t grow big and strong without the right levels of water, sun, and nutrients.

At Portland State University, researchers are toying with the idea that the soil can lend unique characteristics to cannabis, like terroir for wine. They distributed genetically identical plants to farmers that shared a climate, yet grew on different soils. If the identical plants then provide flower with varying levels of cannabinoids and terpenes, that would suggest soil is playing a role, further complicating an already complicated plant. (Results from the study are forthcoming.)

This kind of nuanced research is fueling a transformation of the legal cannabis market. With recreational legalization comes the dreaded Big Cannabis—well-funded corporations that want to get in on the action. So we’re seeing a potential fracturing of the market: Big Cannabis sets up big indoor grow operations that churn out cheap meh weed, while small growers try to position their product as artisanal. In Northern California, for instance, the Mendocino Appellations Project is making the case that due to the unique terroir and weather of the region, they produce premium cannabis unlike any other in the world. That distinction is at the moment largely anecdotal, but the work at Portland State University and elsewhere is beginning to gather data to put behind those claims.

The good news is we only have more to learn about cannabis from here. Research is booming, as is the legal cannabis industry. And so one of the world’s most mysterious plants gives up its secrets.

Learn More

• Forget Growing Weed—Make Yeast Spit Out CBD and THC Instead
  As science continues to unravel the mysteries of cannabis, researchers in the lab have developed a workaround to the problem of procuring plant material: make yeast spit out cannabinoids instead. By splicing the plant’s genes into yeast, the researchers have turned the microbes into tiny CBD and THC factories.

• There's Still So Much We Need to Learn About Weed—and Fast
  The stigma and regulatory nonsense around cannabis are crumbling, which means more universities are jumping in to research the plant. Big universities, too, like UC Berkeley, which has opened an entire center dedicated to the environmental and social effects of cannabis. The verdict so far? Things are a right mess.

• What Should I Tell My Relative Who Wants to Try Cannabis?
  All this talk of weed might have you wondering: If my relatives ask me who much they should try for the first time, what do I tell them? It’s a tricky question with lots of perils that include having a very, very bad time if you overdo it. Here’s how to avoid the heartache.

• Weedmaps’ Grip on the High-flying California Pot Market
  You may have heard of Weedmaps, a service that helps you find dispensaries and delivery services. Convenient, right? Yes, but also way more drama-filled than you’d think.

• The Quest to Make California’s Weed the Champagne of Cannabis
  If you’ve used cannabis in the United States, chances are it was grown in Northern California, the weed capital of America. But now that Big Cannabis is moving into the market, small farmers are terrified they’ll be pushed out. So they’re on a quest to make their product the champagne of weed.

• Scientists Journey Into the Dark Side of Cannabis
  Yes, cannabis is far and away safer than alcohol. But like any drug, it comes with its own risks. One in particular has been on the rise of late: cannabis use disorder, a dependence that forms in an estimated 9 percent of users. Finding effective treatments is yet another reason to encourage the research, no prohibition, of cannabis.

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Last updated March 18, 2019.

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