Stopping marijuana mood-altering effects

Achieving pain-killing benefits from medical marijuana use without negative mood- and memory-altering side effects may now be possible...
10 July 2015


A way to achieve the pain-killing benefits of medical marijuana use without the negative mood- and memory-altering side effects has been uncovered by UK and Spanish researchers...

Marijuana is used, often without prescription, by patients suffering from a range of conditions.

Many report that it can help to dull pain, but it can also have profound impacts on mood and particularly memory and can also be dependence-forming.

Now, University of East Anglia scientist Peter McCormick, writing in PLoS Biology, has discovered a way to separate these outcomes, abolishing the psychoactive negative side effects while preserving the analgesic qualities of the agent.

Working with researchers based in Barcelona, the UEA team had initially found fhat mice lacking from their brains one of the chemical receptors for the nerve transmitter molecule serotonin, responded differently to the main psychoactive ingredient in marijuana, a chemical called THC - tetrahydrocannabinol.

Unlike normal mice, these animals did not show the same pattern of behavioural changes.

McCormick and his colleagues speculated that perhaps THC works in the brain by altering the serotonin signals, or the way brain cells respond to serotonin.

Using cultured cells in the dish, they were able to express the relevant chemical receptors for THC and serotonin in the cells, enabling them to study what happens when THC is administered.

In a surprising series of tests, they found that the THC receptor "teams up" with the serotonin receptor in the same cell.

The coming together of the two then produces the downstream signalling events that alter mood and affect memory.

Preventing the two receptors linking up like this, which the team achieved by designing a small protein molecule tailored to block the interaction, predictably blocked the mood-altering effects of THC.

Critically, however, all the while the analgesic effects of the THC were preserved throughout, mediated as they are through a different pathway.

"So, this shows that it's possible to dissociate the pain-killing effects of THC from the undesirable side effects, especially on memory," says McCormick. "But this is just the beginning. It's a proof of concept. Now we have to actually design a drug that can do this safely in humans..."


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