Around 4 percent of adults worldwide smoked cannabis at least once in the last year according to a United Nations study. That makes it the most used illegal drug in the world. But it may not remain that way. It’s not that people will use it less, but that cannabis may become legal in more places. Already, two US states and Uruguay have legalized its use.

Changing laws reflect change in the public perception of the drug. In elementary school, I was taught to just say no to cannabis. Now, it is widely held that it’s safer than alcohol. While perception may be in flux, one thing hasn’t changed: cannabis’ effects. With those effects cropping up in conversation more frequently as cannabis laws make headlines, it’s high time I found out what cannabis does to the brain.

We’ve long known how cannabis—the scientific name of the plant often called marijuana or pot—makes us feel. By 100 CE, the Chinese, the first culture to have a historical record of cannabis use, were giving it as an anesthetic before surgeries. Even then, they knew it numbed pain.     

More recently, William Breathes, a pot critic for Denver’s Westword newspaper, described the effects, saying he smokes, “for mellowing out and easing anxiety after a stressful day.” One strain is “definitely great for appetite and all-around mood enhancement” he says, while another, is “naptime ganja…slamming you down, face-first, into a pillow.” But to cause those effects, cannabis must be altering brain function.

By the 1970s, neuroscientists had isolated molecules in cannabis to test which affect nerve cells. They determined that, of the many molecules contained in cannabis, delta-9 tetrahydrocannabinol, or THC, was the chief one that changed nerve cell function. When they squirted a drop of THC on a nerve cell, the cell’s charge decreased, making it less likely to fire a message its neighbors. For THC to lower charge, cells need a receptor that responds to THC—a cannabinoid receptor—yet no one had ever identified one. At that point, cannabinoid receptors were like gravity: we were pretty sure it was there, but we had never seen it.

One of the problems with finding a cannabinoid receptor is that THC is lipophilic, meaning it is attracted to fat molecules. This is great if you want to make pot brownies, since fats—like butter and oil—soak up the THC in cannabis leaves and taste good when baked with chocolate. But for a scientist trying to determine how THC affects nerve cells, it’s a problem. A cell’s surface is made almost entirely of fat molecules, so THC seems to interact everywhere. But all that mingling that makes it hard to find the spot where THC exerts its effects. We needed a new tool to help uncover a cannabinoid receptor.

THC structure

In 1974, some chemists at Pfizer developed a tool that might help. They created a molecule that had a similar structure to THC, but preferred water to fat. The fat molecules on a cell’s surface repulsed this water-loving molecule, called CP-55,940. That meant it could only approach a cell in places with a receptor that attracted it, since receptors are proteins, not fats. In 1988, William Devane and Allyn Howlett, pharmacologists at St Louis University, showed that CP-55,940 bound to a receptor on a nerve cell that had never been described. When CP-55,990 did bind to that receptor, it caused the same effects on a cell as THC. Light it up and smoke it, the cannabinoid receptor was found.

After identifying the cannabinoid receptor, the next step was figuring out how it caused a high.

Come back for part 2 of this topic to find out about 7 short term effects marijuana has on the brain. Part 3 discusses long term effects of marijuana.

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