Beyond the opioids

The drug epidemic of early initiation, frequent use, and a polydrug reality


The national opioid epidemic is one of the most important public health challenges facing the United States today. This crisis has resulted in death, disability, and increased infectious and other comorbid diseases.

Pill bottles spill opioid tablets and capsules sdominick/iStock/Getty Images

Public attention has been focused on the medical management of pain, patterns of opioid prescriptions, and use of heroin and fentanyl. But the opioid crisis is, in fact, part of a far larger drug epidemic. The foundation on which the opioid epidemic is built is recreational pharmacology – the widespread use of aggressively marketed chemicals that seductively superstimulate brain-reward producing alterations in consciousness and pleasure, often mislabeled “self-medication.”

Drugs of abuse are unique chemicals that stimulate their own taking by producing an intense reinforcement in the human brain, which tells users that they have done something monumentally good. Instead of preserving the species, this chemical stimulation of brain reward begins the process of retraining the brain and reward system to respond quickly to drugs of abuse and drug-promoting cues. Drugs of abuse do not come from one class or chemical structure, but, rather, from disparate chemical classes that have in common the stimulation of brain reward. This bad learning is accelerated to addiction when drugs of abuse are smoked, snorted, vaped, or injected, as these routes of administration produce rapidly rising and falling blood levels.

Thanks to the science of animal models, we understand drug self-administration and abstinence. However, in animals, we cannot approximate addiction beyond the mechanical because of the cultural complexity of human behavior. Most animal models are good at predicting what treatments will work for drug addiction in animals. They are less predictive when it comes to humans. Animal models are good for understanding withdrawal reversal and identifying self-administration reductions and even changes in place preference. Animal models have consistently shown that drugs of abuse raise the brain’s reward threshold and cause epigenetic changes, and that many of these changes are persistent, if not permanent. In animal models, clonidine or opioid detoxification followed by naltrexone is a cure for opioid use disorder. Again, in animal models, this protocol is tied to no relapses – just a cure. We know that this is not the case for humans suffering from opioid addiction, where relapses define the disorder.

A closer look at opioid overdoses

Opioid overdose deaths are skyrocketing in the United States. The number of deaths tied to opioid overdoses quadrupled between 1999 and 2015 (in this 15-year period, that is more than 500,000 deaths). Then, between 2015 and 2016, they further increased dramatically to more than 60,000 and in 2017 topped 72,000. This increase was driven partly by a sevenfold increase in overdose deaths involving synthetic opioids (excluding methadone): from 3,105 in 2013 to about 20,000 in 2016.

Illicitly manufactured fentanyl, a synthetic opioid 50-100 times more potent than morphine, is primarily responsible for this rapid increase. In addition, fentanyl analogs such as acetyl fentanyl, furanyl fentanyl, and carfentanil are being detected increasingly in overdose deaths and the illicit opioid drug supply. Drug overdose is the leading cause of accidental death in the United States, with opioids implicated in more than half of these deaths. Moreover, drug overdose is now the leading cause of death of all Americans under age 50. As if these data were not bad enough, recent analyses suggest that the number of opioid overdose deaths might be significantly undercounted. Without intervention, we would expect 235,000 opioid-related deaths (85,000 from prescription opioids and 150,000 from heroin) from 2016 to 2020; and 510,000 opioid-related deaths (170,000 from prescription opioids and 340,000 from heroin) from 2016 to 2025.1 In these opioid overdose deaths, rarely is the opioid the only drug present. Data from the Florida Drug-Related Outcomes Surveillance & Tracking System show that, in that state, more than 90% of opioid overdose deaths in 2016 showed other drugs of abuse present at death, an average of 2 to 4 – but as many as 11.2

It is well-accepted that medicine – in particular the overprescribing of opioids for pain and downplaying the risks of prescription opioid use – has played a fundamental role in the exponential rise in addiction and overdose death. The prescribing of other controlled substances, especially stimulants and benzodiazepines, also is a factor in overdose deaths.

To say that the country has an opioid problem would be a simplistic understatement. It has been too easy to zero in on opioids while ignoring the ubiquity of polysubstance use by almost all individuals suffering from opioid and other substance use disorders and related drug problems, including overdose. Drug sellers are innovative, consistently adding new chemicals to the menu of available drugs. The user market keeps adding potential customers who already have trained their brains and dopamine systems to respond vigorously to drug-promoting cues and drugs. We are a nation of polydrug users without drug or brand loyalty, engaging in “recreational pharmacology.” Framing the national drug problem around opioids misses the bigger target. The future of the national drug problem is more drugs used by more drug users – not simply prescription misuse or even opioids but instead globally produced illegal synthetic drugs as is now common in Hong Kong and Southeast Asia. A focus exclusively on opioid use disorders might yield great progress in new treatment developments that are specific to opioids. But few people addicted to opioids do not also use many other drugs in other drug classes. The opioid treatments (for example, buprenorphine, methadone, naltrexone) are irrelevant to these other addictive and problem-generating drugs.

Finally, as a very recent report found, the national opioid epidemic has had profound second- and third-hand effects on those with opioid use disorders, their families, and communities, costing about $80 billion yearly in lost productivity, treatment (including emergency, medical, psychiatric, and addiction-specific care), and criminal justice involvement.1 Worse yet, missing from current discussion is the simple fact that drug users in the United States spend $100 billion on drugs each year. The entire annual cost of all treatment – both public and private – for alcohol and other substance use disorders is $34 billion a year. Drug users could pay for all of the treatment in the country with one-third of the money they now spend on drugs.

How much do drug users themselves spend on addiction treatment? Close to zero. The costs of both treatment and prevention are almost all carried by nondrug users. While many drug policy discussions call for “more treatment,” as important as that objective is, overlooked is the fact that 95% of people with substance use disorders do not think they have a drug problem and do not want treatment. What actions are needed now?


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