Researchers have developed a novel molecule that binds and blocks a previously unknown opioid receptor in the brain, potentially revolutionizing pain, depression, and cancer treatment. 

According to the press release, opioid-related disorders such as severe pain are treated with drugs that act on the opioid system, which include oxycodone, fentanyl, and morphine. They work by targeting and activating opioid receptors, which prevents the natural “pain message,” according to the press release. Although these drugs are highly effective, they can be highly addictive. 

Researchers at the Department of Infection and Immunity of the Luxembourg Institute of Health developed a molecule known as LIH383. The molecule modulates the levels of opioid peptides produced in the central nervous system, which increases their natural painkilling and antidepressant properties. The findings, published in Nature Communications, stated that LIH383 specifically blocks ACKR3, which is an atypical chemokine receptor.

ACKR3 acts like a “scavenger,” trapping and secreting peptides to reduce the levels that can interact with opioid receptors, according to the press release. This causes them to act as a negative regulator of the opioid system. 

"Our findings essentially brought forward a new and previously unknown mechanism to fine-tune the opioid system and modulate the abundance of natural opioids by manipulating the fifth member of the opioid receptor family, ACKR3. We therefore set about developing a molecule that would be able to tightly bind to and block ACKR3, with the aim of potentiating the natural beneficial effects of opioids on pain and negative emotions. This is how LIH383 was conceived," co-first author of the publication Martyna Szpakowska, PhD, said in the press release. 

According to the press release, ACKR3 is abundantly expressed in tumors, such as the highly aggressive glioblastoma, and also appears in breast cancer. This means that not only can LIH383 be used to as a therapeutic answer to the opioid crisis, it may also be useful in the treatment of tumors, according to the study authors. 

Renewed hope for treatment of pain and depression (News Release); Luxembourg Institute of Health; June 19, 2020; Science Daily; accessed June 22, 2020