While researching into how cannabis interacts with other drugs in the brain, scientists inadvertently discovered why coffee and getting high go so well together. Caffeine reinforces the effects with THC, potentially making it more pleasurable.

To get a better grasp of how a substance affects the human brain, scientists sometimes look at the interaction between two drugs. To study THC, researchers gave squirrel monkeys (which have a long history of getting stoned in laboratories) the ability to get high with the pull of a lever, which triggered an intravenous release of THC from a small surgically implanted device.

After making the monkeys plenty familiar with the consequences of pulling the lever, they gave them doses of MSX-3, a water-soluble analog of caffeine. With 1 mg/kg (equivalent to less than half a cup of coffee for the average person), the squirrel monkeys pulled the lever less often than normal; and when they gave them 3 mg/kg (equivalent one or more cups of drip coffee), the monkeys pulled the lever even less. The caffeine-analog made it so they monkeys needed less THC to achieve the same effect.

After keeping the monkeys drug free as a rest period for the second part of the experiment, scientists gave them a shot of either THC or THC + MSX-3 (the caffeine analog), and then allowed them to pull the lever whenever they wanted to. After getting reintroduced to THC, all the monkeys started pulling the lever, but the ones who got an extra dose of MSX-3 pulled it more often.

Scientists conclude that A 2A antagonist drugs, like caffeine, “potentiated the effect of threshold doses” of THC and its natural counterpart anandamide, causing a “reinforcing effect.” In layman’s terms, this basically means caffeine allows you to smoke less while still achieving the same effect, but caffeine also makes it harder to quit one or the other if you consume both. On the other hand, very small doses of caffeine, less than half a cup of drip coffee, could theoretically help you stop smoking pot because of how it effects the dose-response curve.

Modern medicine has a good grasp on the mechanism behind addictive behavior in people consume alcohol, cocaine, opiates and amphetamine stimulants, but the jury is still out on cannabis. A significant amount of work gets put into designing drugs to help cure addictions, but finding one for cannabis has proved quite a challenge. While these studies may have stumbled upon an important clue in the cannabinoid-brain interaction puzzle, they do not imply any negative effects besides the mild short-term memory loss we all knew about.

THC targets cannabinoid receptors, which form part of a larger endocannabinoid system that regulate key functions in the body. Tylenol gets it pain-relieving effects by making your brain accumulate anandamide, a neurotransmitter produced by the brain that targets cannabinoid receptors as well.

Everyone knows coffee causes mild physical addiction, but could this research also explain why active, type-A personalities worship coffee so much? Exercise makes your body release anadamide, which also showed a similar response to THC in the squirrel monkey experiment. Caffeine would theoretically make you gain more pleasure from a lesser dose of anandamide, making a brisk walk feel just as exhilarating as long jog.

Now we know that two natural substances (caffeine and THC) people have consumed for millennia are not only perfectly safe, but even compliment each other. So stay active, sip some brew, get a little stoned and you’ll be sure to have a pleasant and productive day.