Depending on the dose, route of administration and extent of previous exposure, the effects of opioids begin within 15 to 30 minutes and can last several hours. [...] Opioids are widely distributed throughout the body, but their primary action is on the brain, not the site of the pain. [...] Outside of the brain, opioids have a direct effect on the intestines, causing intestinal tone to increase, slowing the movement of food, and dehydration. [...] Patterns of Use With repeated use, tolerance to opioids develops relatively quickly, which causes a reduction in the effectiveness of the drug and requires an increase in dose to maintain the desired effect. [...] Heroin is known to be used in combination with methamphetamine or cocaine (called a “speedball”) to increase the euphoric effects and lessen the negative effects associated with declining levels of heroin after the initial rush.