 Opioid drugs such as morphine are a mainstay of pain treatment, but they can also lead to sleepiness, decreased attention span, and reduced motor control, all of which deteriorate a patient's quality of life. Lowering the dose is one way to avoid such side effects, but this can lead to ineffective pain control. Now researchers have come up with a new way to counteract the sedating qualities of morphine without reducing its power as a painkiller in rats. To accomplish this, they've targeted the brain's arexan hypercretin system, which plays an important role in our ability to stay awake. Arexans are peptides produced by neurons in the hypothalamus. When these peptides interact with arexan type 2 receptors, they regulate sleep and wakefulness. Morphine inhibits arexan signalling, which is a likely source of the sedative effects of the drug. To negate these actions, the researchers used a novel compound named YNT185 to selectively boost the activity of arexan type 2 receptors, potentially enhancing feelings of alertness. The team gave the compound to rats along with morphine and then used electroencephalography to follow the animal's brain activity. They also used behavioral tests to monitor levels of pain relief, responsiveness, and movement. When the animals were given morphine alone, there were clear changes in their brain activity, as shown by the EEG data. They also showed decreased movement and were slower in responding to sudden noises compared to rats not given the drug. In contrast, when morphine and YNT185 were given at the same time, the compound balanced out the effects of morphine on brain activity, increased the rat's physical activity, and made the animals more responsive to sudden noise. Most importantly, the compound achieved these effects without reducing the pain relief gained from the morphine. Although further studies are needed before YNT185 will be ready for testing in humans, these findings suggest that new therapeutic options could one day allow opioid drugs to be used for pain management with fewer debilitating side effects.