it is also true that the vast majority of these individuals first used other drugs before or with their first use of opioids.13 Further, transition from pain medicine use of opioids to heroin is unusual although not rare; only about 4% of people who use prescription opioids nonmedically initiate heroin within five years of first prescription opioid use.14


Finally, and


equally importantly, the current narrative which focuses on prescribed opioids does not recognize the increasing sophistication and effectiveness of the illegal global drug market to supply heroin, the newer synthetic opioids and many more illegal and addicting drugs.


Contrasting Medical Opioid Use for Pain and Opioid Use Disorders Let’s start with opioids as a first-line treatment for pain and how it relates to opioid addiction before we turn to the subject of overdose deaths. Te majority of outpatient pain patients treated with opioids without a prior history of substance use disorders take the opioids only orally and only in doses as directed by the prescribing physician. Most prescription opioid users do not recreationally use these medicines with alcohol and other drugs—and thus are at litle risk of addiction. However, a large minority of pain patients uses prescribed opioids in ways not intended by the prescribing physicians, including use by non-oral routes of administration and use of prescribed opioids in conjunction with other drugs of abuse such as alcohol and benzodiazepines, like Xanax. Tis notable minority of medical patients that uses their prescribed opioids nonmedically is at grave risk of addiction and overdose death. Additionally, a subset of medical patients sells or gives away their prescribed opioids adding to the risk of overdose death and addiction in the community. At least 50% of people who misuse opioids—unintended populations—access them free from friends and family, implying that unused/unneeded


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opioids are supplying a significant population of misusers.15 Although the majority of pain patients do not misuse their prescribed opioids and are at litle risk of addiction, those patients who take significant amounts of prescribed opioids over longer duration (e.g., more than a week or so) become physically dependent on them.16


Tis means that


the non-addicted, compliant medical pain patients are likely to experience agonizing withdrawal symptoms if they abruptly discontinue their opioid use. For the majority of medical patients using long acting and/or high doses of opioids chronically as prescribed to treat pain and who are physically dependent on, but not addicted to, these drugs, there are two pressing health concerns that are separate from the risks of addiction and overdose death. Te first is the growing recognition that the opioids are oſten unsatisfactory in suppressing pain and improving lifestyles when used for years.17


For example, among 4,493 individuals


treated for opioid addiction whose first exposure to opioids was through a prescription from their physician, notably 94.6% reported prior or coincident use of other psychoactive drugs.18


Alcohol was


used by 92.9%, nicotine by 89.5% and marijuana by 87.4%, and excluding these top substances, fully 70.1% reported other prior or coincident drug use. For many opioid-addicted individuals,


drug use began in early adolescence with the use of alcohol, marijuana and other drugs. Early polydrug use oſten sets the stage for later transition from medical to addictive use of opioids that are prescribed for pain. Like addiction to other drugs, a central


Second, it is difficult


for patients who have been using opioids continuously for many years to stop using them entirely by gradually reducing their daily doses, especially when they get down to lower doses. Contrasting the physical dependence


that occurs with non-addicted opioid patients with addictive use of these same medicines shows that these two groups of users of medically-prescribed opioids use the medicines in very different ways. Individuals addicted to opioids prescribed for pain commonly use these medicines at higher doses than prescribed and by routes of administration other than oral, such as snorting, smoking, shooting, vaping and chewing or otherwise overcoming the intended slow release of the prescribed opioid to get a far larger and faster drug delivery. Tese addicted patients commonly use their prescribed opioids with alcohol and other drugs, oſten using several other addicting drugs at the same time.


feature of opioid use disorders that distinguishes them from mere physical dependence is continued drug use despite serious problems caused by their drug use. Moreover, individuals suffering from opioid use disorders oſten hide or lie about their drug use—to their families, physicians and other people in their lives—because they want to keep using drugs addictively when others want them to stop their drug use. Why are the paterns of opioid use so


different between medical patients who are physically dependent and medical patients who are opioid-addicted? A significant part of the difference is determined by genes related to pleasure centers in the brain. Individuals with opioid use disorders seek out brain reward, a specific and powerful reaction of the brain to certain chemicals and experiences that are reinforcing, more than individuals who are less prone to addiction. Medicines that can produce brain reward are labeled “controlled substances” because they are dangerous when taken by those especially prone to addiction, amounting to about 10–15% of the population. For this reason, prescribed opioids are tightly controlled and for this reason physicians must take precautions to help their patients who are prescribed opioids and other controlled


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