Chronic pain - defined as pain that persists for at least 12 weeks - is estimated to affect more than 76 million Americans, according to the National Institutes of Health.

Opioids are among the most commonly prescribed medications for chronic pain in the United States; in 2012, physicians wrote around 259 million prescriptions for the drugs - the equivalent to one bottle of pills for every adult in the country.

Though opioids might be effective for pain relief, their use has become a major public health concern. Opioids are addictive, and in 2014, the drugs were responsible for more than 28,000 deaths in the U.S. At least half of these deaths involved a prescription opioid.

Studies have also suggested that marijuana is an effective pain reliever, and a number of U.S. states have legalized its use for medicinal purposes. Still, marijuana use may pose a number of short- and long-term side effects, including altered sensory perceptions, hallucinations, delusions, impaired motor function, and memory loss.

The risks associated with the use of opioids and medical marijuana have fueled the search for safer, effective pain medications. Andrea Hohmann, of Indiana University in Bloomington, and team believe they may have moved one step closer to a potential candidate: a compound called CB1 PAM.

The researchers recently presented their findings at the Society for Neuroscience's 46th annual meeting, held in San Diego, CA.
CB1 PAM led to long-term pain relief in mice

For their study, the team administered a chemotherapy drug called paclitaxel to mice, which is known to cause nerve damage and pain in up to 40 percent of cancer patients.

The rodents showed hypersensitivity to cold and mechanical stimulation to the paws, the team reports, which is an indicator of increased pain.

Next, the researchers gave the mice a synthesized CB1 positive allosteric modulator (PAM) - a compound that binds to a cannabinoid receptor in the brain called CB1. This is the receptor that marijuana's primary psychoactive ingredient tetrahydrocannabinol (THC) targets to alleviate pain.

CB1 PAM was administered in combination with endocannabinoid breakdown inhibitors - drugs that increase endocannabinoid levels in the brain, which are natural pain-relieving compounds.

The researchers found that the rodents showed no pain in response to cold and mechanical stimulation after receiving CB1 PAM and behaved like normal mice.

Importantly, CB1 PAM did not trigger the "high" associated with marijuana use, and unlike the marijuana compound THC and endocannabinoid breakdown inhibitors, CB1 PAM showed long-term efficacy for preventing pain.

What is more, the team found CB1 PAM alone did not activate the brain's reward system, suggesting the compound is unlikely to lead to recreational abuse and addiction.

    "Our studies show that we can maintain or preserve therapeutic efficacy in ways that we haven't seen with some of the other classes of analgesics that are used in the clinic.

    The most exciting aspect of this research is the potential to produce the same therapeutic benefits as opioid-based pain relievers without side effects like addiction risk or increased tolerance over time."

    Andrea Hohmann

While further research is clearly required, the investigators say their results show it is possible to target cannabinoid receptors and reduce pain, while avoiding potentially severe side effects.