Genetic factors could be to blame for zombie drug Spice's worse side-effects

A team of scientists is on a quest to identify those most at risk of suffering from the worst side-effects of synthetic cannabinoids, commonly known as 'Spice' or 'k2'. The researchers want to understand how the body processes these man-made drugs and whether our genes play a role in their metabolism.

Synthetic cannabinoids are mind-altering chemicals related to those found in the marijuana plant and intended to mimic its psychoactive effects. However, they tend to act on the brain in a more potent, unpredictable and potentially life-threatening way.

Synthetic cannabinoids have been associated with a large number of debilitating side-effects including extreme agitation, hallucinations, tachycardia, syncope and seizures.

Recently, a new strand of Spice sold in the UK has turned the streets of Manchester into scenes reminiscent of The Walking Dead, as users stumbled through the city in an aimless, zombie-like state. This phenomenon had previously been seen in the US.

In both countries, synthetic cannabinoid abuse is a growing public health issue. The addictive potential of Spice is much higher than that of cannabis and anyone may become physically addicted in a matter of just a few weeks of regular use.

At the Experimental Biology 2017 meeting, a team led by Anna Radominska-Pandya, professor at the University of Arkansas for Medical Sciences, have presented the research they are conducting to understand the biological activity and toxicity of synthetic cannabinoids. They hope that their efforts will lead to the development of effective treatments and antidotes.

The role of our genes

Different types of synthetic cannabinoids are always getting banned, but new generations of structurally related compounds keep emerging. It's therefore difficult for scientists to study them all and to draw general conclusions.

Analysing the earliest version of Spice, the team reports that they have identified two enzymes that play an important role in the metabolism of synthetic cannabinoids by the body. These enzymes are known as cytochrome P450s and UDP glucuronosyltransferases.

The scientists hypothesise that genetic variation may affect the way these two enzymes metabolise synthetic cannabinoids. Genetic factors may leave individuals more at risk of metabolism defects. Less able to excrete synthetic cannabinoids, they may be more at risk of experiencing severe outcomes from the use of these drugs.

For the researchers, the next step is to continue their investigations of the pharmacological effects of new synthetic cannabinoids that keep appearing on the market, and to determine how metabolism may contribute to their toxicology.

"Our overall goal is to understand the molecular and behavioural pharmacology and metabolism of these compounds as a means to identify effective therapeutic strategies against their acute and chronic toxic effects in people," concluded Radominska-Pandya.