A number of drug companies are trying to develop strong painkillers that don’t make people high, according to The Wall Street Journal. Such drugs would be less likely to be abused.

Companies seeking new painkillers include biotech startups, as well as large drug manufacturers such as Pfizer and Biogen. Experts say a safer painkiller could achieve annual sales in the billions of dollars.

Some companies are testing drugs that trigger different opioid receptors in the brain than the ones triggered by traditional opioids, which can cause euphoric effects. The companies hope these different receptors will have similar painkilling properties, without triggering euphoria.

Pfizer and Biogen are studying drugs that do not involve opioid receptors. Their new drugs aim to blunt the functioning of a protein that helps nerve cells send pain signals. These drugs are much less likely to trigger euphoria, according to the companies.

A lab in Salt Lake City, PRA Health Sciences, conducts dozens of studies annually to assess whether experimental drugs are likely to be abused. The lab uses volunteers who are recreational drug users, but who are not addicted. Under a deal with the Food and Drug Administration, volunteers are protected against any law enforcement action.

The lab conducted one study of an experimental drug made by Cara Therapeutics. The study, which included 40 drug-using volunteers, compared two doses of the drug against an older opioid painkiller called pentazocine. The volunteers said both doses of the experimental drug were less desirable, and gave them a lower “feeling high” score, than pentazocine. The drug, CR845, got the same “liking” score as a placebo, but a somewhat higher score for “feeling high.” Cara plans to test the drug in a much larger clinical trial.