Scientists have figured out how to separate the pain relieving qualities of medical marijuana from its psychological side-effects in an effort to offer people a new high-free option. 

The research focussed on the main psychoactive ingredient in cannabis, known as THC (tetrahydrocannabinol), which is not only responsible for the high associated with the drug - plus hallucinations, delusions, memory loss, and feelings of anxiety or calm - it's also been shown to slow tumour growth in mice. And now, scientists have figured out that the mechanisms by which the drug delivers its desired medical effects and negative psychological effects work independently from one another - which means that one can be switched off while the other one works its magic.

"There has been a great deal of medical interest in understanding the molecular mechanisms at work in THC, so that the beneficial effects can be harnessed without the side-effects," one of the team, Peter McCormick from the University of East Anglia in the UK said in press release. "THC acts through a family of cell receptors called cannabinoid receptors. Our previous research revealed which of these receptors are responsible for the anti-tumour effects of THC. This new research demonstrates how some of the drug's beneficial effects can be separated from its unwanted side effects."

When investigating how THC is able to shrink tumours, the researchers figured out that negative psychological side-effects of the drug, such as memory defects, mood swings, anxiety, and paranoia, were triggered by a single pathway in the brain that was separate from the pathway that triggers the drug's cancer-killing properties. In an effort to better understand the drug's ability to cause these negative effects, the team isolated this particular pathway and experimented on it in mice.

They noticed that two types of cell receptors were present in this pathway - the cannabinoid receptor and the serotonin receptor - and these happened to be positioned very close together, which suggested that the drug was acting on both at the same time. 

To figure out what effect this was having, the team blocked the activity of a specific type of serotonin receptor -  called 5HT2AR - in the brains of mice, and gave them a dose of pure THC. The mice were then put through memory, behaviour, pain, and motor skills tests. "These animals, lacking the serotonin receptor, showed differences only in the memory and mood tests - not in the pain tests," McCormick told Liat Clark at Wired. "There were no side effects in memory, and that's exactly what we were looking for."

Reporting the results in PLOS Biologythe team says with 5HT2AR turned off in mice, the THC was still able to reduce pain as well as tumour growth, but without the negative psychological effects. 

What they want to do now is figure out if the same mechanisms are in play in human brains, and then see if they can mimic the same serotonin receptor-blocking effect they achieved in the mice. McCormick calls this effect a "Chinese wall" that sits between the serotonin and cannabinoid receptors, and thinks it could be the key to medical marijuana without the negative side effects.

"For me, the ideal drug would be in one of two scenarios: a drug that does not recognise the THC cannabinoid receptor when near serotonin, or alternatively a drug you could add with THC that would provide that Chinese wall between the two," he told Wired.