The brain and marijuana: Chinese and US researchers uncover ‘perfect fit’ behind the buzz

How does the active ingredient known as THC bind with cells? According to a collaborative study, specific receptors are tailor-shaped to the marijuana molecule

PUBLISHED : Friday, 28 October, 2016, 8:02am
UPDATED : Monday, 12 June, 2017, 12:53pm

Chinese and American scientists studying the precise mechanism of how marijuana gets people high have discovered within our brain cells “a pickpocket with three arms”.

The active compound in marijuana, or Cannabis sativa, was discovered in the 1960s, but the exact process of how it produces its narcotics effects on the brain remained largely a mystery.

The study, in this month’s issue of the journal Cell, sheds new light by unveiling, for the first time, the physical structure of human cannabinoid receptor 1 (CB1), a protein in our brain cell membranes that introduces the narcotic chemicals in marijuana to our brain cells.

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The discovery, the researchers say, could lead to new pharmaceuticals with fewer side effects.

The CB1 receptors, which are naturally occurring proteins in human brain cell membranes, bind with tetrahydrocannabinol (THC) to produce “feel good” signal in neurons. Researchers have spent more than a decade trying to unravel the biochemical pathways underlying the process.

The new study, led by researchers at ShanghaiTech University and the Chinese Academy of Sciences, found that CB1 has a unique structure consisting of many “pockets” tailored to bind with specific chemical signals from the outside environment.

The researchers found that within CB1’s pockets were numerous spiral bands of proteins, guarded by a V-shape loop of protein, like a plug, to keep out unwanted chemicals.

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THC has a structure with three arms. When the THC molecule passes a receptor, its short arm makes a fast grip on a helix. Its long arm then reaches down like an anchor into the bottom of the pocket. The remaining arm, strong and bulky, pushes on the helices, causing them bend outward. It is these mechanical movements that generate the narcotic signals to the neuron.

The researchers said the discovery could help the development of synthetic drugs that mimic the effects of the plant with fewer side effects, so they could be used legally in most countries.

“We found that the CB1 receptor consists of multiple sub-pockets and channels,” said Dr Alexandros Makriyannis, director of the Centre for Drug Discovery at Northeastern University in Boston, and a co-author on the paper.

“This complex structure will allow chemists to design diverse compounds that specifically target portions of the receptor to produce desired effects.”

Researchers have spent decades studying how marijuana works on our brain. In the 1960s, THC was isolated and identified as the plant’s most important effective component. In the 1990s, researchers confirmed the existence of CB1 and its role in cannabis signalling, but its molecular structure remained unknown.

As a kid we ate marijuana seeds as snacks. Some species are definitely not evil
Yin Jiantao, botanist, Xishuangbanna Tropical Botanical Garden

Lai Ren, a molecular biology researcher at the Kunming Institute of Zoology, said carrying out cannabis-related research in China was difficult due to strict controls on access to the plant and its derivatives.

Yin Jiantao, a botanist at the Xishuangbanna Tropical Botanical Garden, said the knowledge gleaned from the Chinese-US research might ease restrictions on cannabis cultivation and use in China and the rest of the world.

Marijuana, which is indigenous to Central Asia and the Indian subcontinent, is illegal for recreational use in China, which also imposes tight controls on its medical use.

But in the southwest province of Yunnan, which borders Vietnam, Laos and Myanmar, residents had eaten marijuana seeds and chewed its leaves for centuries, Yin said.

“As a kid we ate marijuana seeds as snacks. Some species are definitely not evil,” he said.