Discovery may render cocaine less palatable

A cannabinoid receptor has been discovered in the brain that, when stimulated by drugs, can counteract the behavioural and addictive effects of cocaine. Greg Dash reports.

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EDINBURGH: A cannabinoid receptor has been discovered in the brain that when stimulated by drugs, can counteract the behavioural and addictive effects of cocaine.

For the first time, a study has identified that brain cannabinoid receptors (CB2) play a vital role in controlling the reward mechanism responsible for drug addiction. This finding, due to be published in Nature Neuroscience, could lead to new drugs that target the receptor, helping sufferers overcome drug abuse.

“This finding not only challenges recent views that CB2 receptors are absent from the brain, but also suggests that brain CB2 receptors may be a novel pharmacological target for the development of new medications for the treatment of drug abuse and addiction”, said lead researcher Zheng-Xiong Xi, of the National Institute on Drug Abuse, Baltimore.

A new target

Special proteins in the brain, known as cannabinoid receptors, have been known to be responsible for the behavioural and psychoactive effects of some drugs, including cocaine and heroin. These receptors control signalling in brain circuits involved in emotion, motivation, attention and memory.

The two major types of these receptors are known as CB1 and CB2. Until now it was generally believed that CB1 receptors were responsible for these effects, but new research has now identified that CB2 receptors play a vital role in modulating the rewarding and stimulating effects of cocaine in mice, probably through a mechanism involving dopamine.

Xi and colleagues used drugs to target and activate the CB1 and CB2 receptors in the brains of mice. When CB2 was activated, the mice showed a reduction in self-administration of cocaine – an effect not seen when CB1 was activated. The drugs were also found to reduce uptake of dopamine, a neurotransmitter that plays a major role in addiction.

Potential for the future

This finding suggests that future drugs could potentially be developed that to switch off addiction by activating this receptor, but first more research is needed to discover if this mechanism is also present in humans.

“We already know that there are significant species differences in CB2 receptor gene, receptor expression and function between humans and rodents. If the present findings can be replicated in other species such as primates and humans, CB2 receptor agonists may constitute a novel target in medication development for treatment of substitute addiction as well as other neuropsychiatric diseases,” said Xi.

David Nutt from the Imperial College London, who was not involved in the study, said: “This finding is not implausible – there is growing evidence of a cannabis receptor link to addiction in general – the CB2 receptor has not really been considered before because it has been largely seen as related to immune function, but there are [CB2] receptors in the brain, so maybe they do have a role in addiction.”

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