An alternative to medical marijuana for pain?

Medical marijuana is proliferating across the country due to the ability of cannabis ingestion to treat important clinical problems such as chronic pain. However, negative side effects and the development of tolerance limit the widespread therapeutic use of Δ9-tetrahydrocannabinol (Δ9-THC), the major psychoactive ingredient in cannabis.

THC's side effects are produced via its actions at cannabinoid CB1 receptors in the brain. Thus, scientists theorized that an agent with similar mechanistic actions, but that activate CB2 receptors instead, may eliminate the unwanted side effects while maintaining an equivalent level of efficacy.

Dr. Andrea Hohmann and her colleagues at Indiana University tested this strategy and found that, unlike Δ9-THC, repeated dosing with the cannabinoid CB2 agonist AM1710 suppresses chemotherapy-induced pain in mice without producing tolerance, physical withdrawal, motor dysfunction, or hypothermia. Moreover, the therapeutic effects of AM1710 were preserved in mice lacking CB1 receptors but absent in mice lacking CB2 receptors.

Their findings are reported in the current issue of Biological Psychiatry.

"Our study is important because it demonstrates beyond doubt that activation of cannabinoid CB2 receptors suppresses neuropathic pain without producing signs of physical dependence (i.e., a withdrawal syndrome) or other unwanted side effects associated with activation of CB1 receptors in the brain," said Hohmann.

Their studies used animals that were treated with a chemotherapeutic agent (paclitaxel) to produce pain. When animals were given AM1710, a CB2 agonist, its pain-suppressive effects were fully preserved and its therapeutic effects were maintained even after repeated dosing.

The marijuana plant contains several chemicals that may prove useful for treating a range of illnesses or symptoms, leading many people to argue that it should be made legally available for medical purposes. In fact, a growing number of states (20 as of March 2014) have legalized marijuana’s use for certain medical conditions.

The term “medical marijuana” is generally used to refer to the whole unprocessed marijuana plant or its crude extracts, which are not recognized or approved as medicine by the U.S. Food and Drug Administration (FDA). But scientific study of the active chemicals in marijuana, called cannabinoids, has led to the development of two FDA-approved medications already, and is leading to the development of new pharmaceuticals that harness the therapeutic benefits of cannabinoids while minimizing or eliminating the harmful side effects (including the “high”) produced by eating or smoking marijuana leaves.

Alternatively, and as expected, when animals were given Δ9-THC, they developed complete tolerance to the pain-suppressing effects of THC and with repeated dosing, THC was no longer effective in suppressing neuropathic pain.