They have custom made a new drug molecule that thus far in mice exhibits the same pain dulling capabilities of opioids without the more common side-effects (interference with breathing, constipation). And interestingly, it also bypasses the dopamine-driven addiction circuitry in the brain. http://www.valuewalk.com/2016/08/new-painkiller-morphine/ Whole thing sounds fascinating as it was this big collaborative effort to go from the ground-up. Instead of taking morphine and tweaking its structure to try and reduce side-effects, which is the usual approach, a professor at UC San Francisco used recently discovered and known atomic structure of the mu-opioid receptor (which was discovered in 2012) to start designing brand new molecules that would bind to the receptors. Over a two week period they performed four trillion virtual experiment computations of different molecules hitting the receptor at different angles looking for candidates most likely to fit into the receptor and activate it, avoiding molecules that also stimulate beta-arrestin2 which is part of the biological pathway that leads to respiratory suppression and constipation among other side-effects. Once the computational squad found a number of candidates, they passed it onto a pharmacology team at UNC to make the drugs and test which are the most potent. Once that team found the most potent candidate, they enlisted the aid of a guy at Friedrich-Alexander University Erlangen-Nürnberg in Germany to optimize the compound's chemical efficacy. The result is PZM21. The UNC team then replicated the theoretical effects in lab mice numerous times, finding that the opioid dulled pain without respiratory suppression or constipation. In fact, they found that it would only bind to opioid circuits in the brain and would leave the spine unaffected. The opioid receptors in the spinal cord mediate pain reflexes and so affecting them wouldn't necessarily be desirable. They've not seen any opioid do this, affect the brain only and not the spine. They did some more behavioral tests on the mice and found that there was no drug-seeking behavior modification. Usually what happens is the mice exhibit behavior where they prefer to hang out in the chambers where they have received the opioid in the past, and this correlates with addiction behavior in humans. The mice were ambivalent toward hanging out in the drug releasing chambers. The drug also did not produce hyperactivity in the mice, which is usually triggered by activating the brain's dopamine systems. They'll go into human trials and that'll be the real test obviously because there are typically a lot of issues going from mice to men. But it sounds promising.