Basic research studies at Indiana University are investigating whether a synthetic non-psychoactive cannabinoid that shows promise for relieving certain types of pain may also be effective for reducing risks associated with prescription opioid use, including addiction and fatal overdose.
Through the Responding to the Addictions Crisis Grand Challenge, Andrea Hohmann, Gill Chair and professor of psychological and brain sciences in the IU Bloomington College of Arts and Sciences, and her team are working to see if this compound could offer both an alternative, non-addictive remedy for managing some types of pain and a means of helping opioid users avoid addiction, withdrawal, and overdose.
The compound is a cannabinoid that acts on specific types of receptors known as CB2 receptors in the body’s own cannabis-like system. The CB2 receptor is different from the CB1 receptor that is abundant in the brain and also linked to the characteristic "high" associated with cannabis. Unlike opioid receptors, cannabinoid receptors are not found at high concentrations in brain regions associated with breathing functions, which is why cannabis does not stop breathing with the same toxicity associated with an opioid overdose.
Hohmann’s lab is testing whether this compound may actually block the rewarding effects of opioids in rodents. This compound was tested by the pharmaceutical industry in people for a different indication, knee pain from arthritis. Although it was not successful for that purpose, it was shown to be safe for humans. Hohmann hopes that, if her hypotheses are supported, the compound could be repurposed to fast-track solutions to the current opioid epidemic.
Hohmann and her team conducted earlier research with mice that indicated the compound may be effective in treating neuropathic pain, which results from damage to the nervous system and is often caused by chemotherapy treatment for cancer. These studies also indicated that when the drug was used in combination with the opioid morphine, the mice did not develop a tolerance to morphine; the opioid remained effective in reducing pain at the initial (safe) dosage.
Moreover, the compound appeared to reduce opioid withdrawal symptoms. Hohmann’s research, in collaboration with Amey Dhopeshwarkar and Ken Mackie, also confirmed that human receptors for the drug use the same mechanisms to initiate a biological response as rodents’ receptors, suggesting that humans would have similar responses to the drug.
For her project, Hohmann’s team is studying the behavior and physiological responses of rats to see how the drug affects opioid reward and motivation to self-administer opioids as well as the reduced breathing function from opioid overdose. Collaborators include Jonathon Crystal, George Rebec, and Xiaoyan Lin, a postdoctoral fellow in the Hohmann lab. Lin and Hohmann previously showed that this compound suppressed neuropathic pain, and, strikingly, that neuropathic mice treated with this compound showed lower levels of opioid withdrawal symptoms and did not develop tolerance to opioids.
Preliminary findings from the Grand Challenges research are very promising, Hohmann said. If the drug is advanced to clinical trials, she said it could be a major step forward in reducing opioid-related death, preventing addiction, and treating pain without opioids’ unwanted side effects.
