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.