Activation of Cannabinoid Receptors in the Brain Blocks the Addictive Potential of Cocaine

by Dr Sam Girgis on July 27, 2011

Over one century ago, cocaine became available on a large scale to many people in society.  Cocaine was touted as a wonder drug, and was thought to be a panacea.  Doctors and the lay public proclaimed cocaine as a cure for numerous maladies including morphine addiction, tuberculosis, and psychiatric illness.  Cocaine was sold in tonics, wines, powders, and famously in a soda drink that now bears its name.  The English author Sir Arthur Conan Doyle wrote about the drug in his depictions of a cocaine addicted detective named Sherlock Holmes.  The most famous of its early advocates was the Viennese neurologist Sigmund Freud.  Dr. Freud used cocaine to treat many of his patients with mental illness, as well as experimenting with the dangerous drug on himself.  Dr. Sigmund Freud is noted to have been addicted to cocaine.  Today, we understand that cocaine is a dangerously addictive and life destroying drug of abuse that had almost no beneficial properties or use in medicine.  Instead of using cocaine as a medication, science and medicine are now working on treating the addiction that results from its abuse.  Researchers lead by Dr. Zheng-Xiong Xi, from the National Institute on Drug Abuse, have found that several cannabinoid receptor agonist can block the addictive effects of cocaine in mice.  The results of their study were published online ahead of print in the journal Nature Neuroscience.  The researchers trained mice to self administer cocaine and then gave the mice a medication named JWH133, a selective CB2 cannabinoid receptor agonist.  JWH133 was shown to have a dose-dependent inhibitory effect on the self-administration of cocaine and an inhibitory effect on the cocaine enhanced locomotion of mice.  These effects were found to occur in the wild type and CB1 cannabinoid receptor knockout mice, but not to occur in the CB2 cannabinoid receptor knockout mice.  This result suggests that agonism of the CB2 cannabinoid receptor is needed to inhibit the addictive effects of cocaine.  The researchers obtained similar results using a second CB2 cannabinoid receptor agonist named GW405833.  The researchers were also able to show that extracellular dopamine levels in the accumbens were decreased with use of the CB2 cannabinoid receptor agonists.  These findings suggest that activation of the CB2 cannabinoid receptor with agonist medication may be a therapeutic option in the treatment of cocaine addiction and dependence.  The authors wrote, “our findings suggest for the first time, to the best of our knowledge, that activation of brain CB2 receptors inhibits cocaine’s rewarding and psychomotor-stimulating effects, which is congruent with a rapidly expanding corpus of published reports implicating brain CB2 receptors in modulating a variety of CNS functions, such as locomotion, pain, emesis, neurogen­esis and neuroprotection. This finding… suggests that brain CB2 receptors may be a target for the pharmacotherapy of drug abuse and addiction”.  There are several CB2 agonist medications that are currently in phase 1 clinical trial for the treatment of pain, but based on these results they may also have a role in the treatment of cocaine addiction.


Zheng-Xiong Xi et al. “Brain cannabinoid CB2 receptors modulate cocaine’s actions in miceNature Neuroscience published online July 24, 2011 doi:10.1038/nn.2874

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