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How we get high: Unlocking the secrets of the endocannabinoid system

The endocannabinoid system that helps cannabis get us high is also vital to many other aspects of our health. Now we’re finally starting to understand why – and what that means for devising new treatments

By David Robson

29 September 2023

W3TAKD Marijuana effects on the brain and cannabis mood altering chemicals or psychology and drugs concept in a 3D illustration style.

The endocannabinoid system was first identified decades ago, but we’re still just beginning to understand its complexity

Brain Light / Alamy

The discovery of cannabis’s principal active ingredient is the stuff of scientific legend. In the early 1960s, a scientist in Israel named Raphael Mechoulam obtained some high-quality hashish from the police, who had confiscated the stash from smugglers. He isolated the components and then tested their effects, one by one, on monkeys in his lab. Mechoulam, who died in March of this year, knew he had found his target as soon as he administered tetrahydrocannabinol, commonly known as THC. “It made them act like they were all at Woodstock,” says Peter Grinspoon, a physician at Massachusetts General Hospital and author of Seeing Through the Smoke: A cannabis specialist untangles the truth about marijuana.

Mechoulam was hopeful that his discovery would accelerate scientific research into THC’s mechanisms. But it was another two decades before scientists began to come to grips with the ways that THC works its magic.

This research in turn led to the discovery of the “endocannabinoid system” (ECS) – an ancient cell signalling network that helps maintain an organism’s homeostasis. “It keeps the body in balance,” says Grinspoon. The vital role of this system quickly became clear, but the legal and logistical challenges of studying cannabis meant research progress has been slow there, too.

That is finally starting to change, in large part thanks to shifting views and laws about cannabis. Research is now starting to unravel long-standing mysteries of the ECS – as well as the…

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