Not all users want to get high (Image: Aaron McCoy/Getty)

An ingenious set of experiments has teased apart the mind-altering and pain-relieving effects of the main component of cannabis. This could open the way to cannabis-like drugs that provide pain relief without causing unwanted highs.

Cannabis is taken as a painkiller – to dull pain in cancer for example – but it can produce unpleasant side effects such as hallucinations and impaired mobility.

Now, a team led by Li Zhang of the US National Institute on Alcohol Abuse and Alcoholism in Bethesda, Maryland, has shown that tetrahydrocannabinol (THC) – the active component in cannabis that makes people high but that is also thought to dull pain – binds to different molecular targets on cells to produce these two effects.


It has long been known that THC gives people a high by binding to a molecular anchor on cells called the cannabinoid type-1 (CB1) receptor. Zhang and his team discovered that THC relieves pain by binding instead to receptors for the brain-signalling compound glycine and increasing their activity.

Through experiments on mice, they then confirmed that if the glycine receptor is absent or if its activity is blocked by another drug, the animals experienced pain in a standard “tail-flick” test even when given THC, confirming that the drug’s pain-relief and psychotropic effects can be decoupled.

Target receptor

“We found that this glycine receptor could be a primary target for developing non-psychoactive forms of cannabis,” says Lhang.

“This is an important breakthrough in the long-sought separation of intoxicant effects of THC from its desired medical effects,” says Les Iversen at the University of Oxford in the UK, who studies the effects of marijuana.

However, Stephen Wright, director of research and development for GW Pharmaceuticals in Porton Down, UK, thinks that there are other ways that cannabis-based medicines may be able to provide pain relief without the side effects. Last year the firm launched a cannabis-based medicine in Europe called Sativex to dampen painful muscle spasms in patients with multiple sclerosis.

Wright says that no persistent psychotic effects have been seen with the product, partly because it is released into the body 20 to 40 times more slowly than THC is released when cannabis is smoked. As well as THC, GW’s preparation contains cannabidiol, a component of marijuana thought to dampen psychotic reactions to THC.

No psychotic effects been seen in the US, where Sativex is being trialled to combat pain in cancer patients.

Journal reference: Nature Chemical Biology, DOI: 10.1038/nchembio.552