Addiction medicine is in the midst of a tectonic conceptual shift. The latest work of director Nora Volkov and the National Institute for Drug use (NIDA) colleagues crystallize the direction of change. What clinicians have historically listed as separate conditions—alcohol use disorders, opioid use disorders, cocaine use disorders—are now better understood as different expressions of a common vulnerability.
These NIDA experts reported nationally representative data from 92,000+ US adults who reported polysubstance use. ruler pattern among individuals with substance use disorders (SUDs). Almost three quarters (73%) stimulating– includes opioid-related overdose deaths.
Large population-level data make these facts difficult to ignore. Poly substance involvement is not a niche phenomenon limited to obscure cases. Instead, among those with opioid, stimulant, methamphetamine, or hallucinogen use disorders, the majority have at least one substance use disorder, if not several others
If we include nicotine and cannabis—as we should—the picture changes dramatically. Tobacco dependence is strongly linked to alcohol and other drugs, and cannabis use disorders increase the likelihood of involvement with other substances. When these substances are considered, the majority of individuals with substance use disorders use more than one substance. If the majority of patients do not have other substance-related disorders, the long-standing clinical instinct to identify the “primary” substance becomes impossible.
The second finding is this time effect of substance. Early onset, especially before age 18, is associated with a greater number and severity of future substance use disorders. On the contrary, individuals to delay onset before age 21 or later have significantly fewer and significantly fewer disorders lower moderate to severe addiction levels. Adolescence maturity in executive control, reward processing, stress regulation and decision making. Early exposure to psychoactive substances appears to activate a general liability for addiction that later appears across multiple substances.
Genetic studies show that addiction has significant overlap among alcohol, nicotine, cannabis, opioid, and stimulant use disorders. These are similar expressions of general vulnerability defined by reward sensitivity, impulsivity, stress response, and executive control.
Although different substances affect different receptors, they ultimately interact with a general reward system: mesolimbic dopamine signaling, stimulus salience, stress and antireward, and prefrontal regulatory networks. These shared pathways explain the clinical reality: patients do not use only one drug or stay in one substance category. They pass, merge and change. Polysubstance use is a predictable expression of system-level dysfunction.
These new data support a complete re-evaluation of the diagnosis and expectations. The designation of the “main” item remains because it is operationally useful. Instead of a DSM with multiple independent substance use disorders, it is more appropriate to conceptualize a single SUD in terms of polysubstance.
Current clinical practice is now organized around specific drugs, with substance-specific diagnostic systems, regulatory structures, and even insurance reimbursements. Pharmacotherapy is approved for specific disorders.
Therefore, when doctors identify an “underlying” substance, they are usually using pragmatics rather than identifying a unique disease. The first drug is often the drug that poses the greatest immediate risk—for example, opioids in the context of an overdose—and also the drug that is most effective for it. medicine can be placed. Or it’s what causes the most dangerous withdrawal syndrome. These are practical decisions. But it is conceptually unstable and outdated.
What is particularly remarkable is not only that the use of polygamy is common, but that it has become the default pattern. Four decades ago, people could be using one drug or at least one substance disorder at a time. Two decades ago, substance use disorders were often conceptualized as relatively discrete. Alcohol dependence, cocaine dependence, and opioid dependence were treated as parallel but separate trajectories. There was shared use, but it was often framed as such comorbidity rather than the original phenotype.
During the last 10-15 years, this difference disappeared. Prescribed opioids with benzodiazepines and alcohol have shown increased overlap. The subsequent transition to heroin and then fentanyl became even more obscure borders. In the mid-2010s, combinations such as opioids and stimulants became increasingly dangerous for overdose. In the fentanyl era, the actual drug supply has become polysubstance, with synthetic opioids frequently contaminating stimulants and other drugs, creating compulsive interactions.
Addiction is important to read
In earlier eras, only more “one substance” was found, because access to the drug was narrower, the illegal supply was less contaminated, and doctors did not have the control knowledge of today. However, in practice, residential treatment programs are treated alcoholismopiate or cocaine addiction, which are similar enough to the same models of mutual support, recovery frameworks, and residential interventions—clearly recognizing co-occurring disorders long before the neurobiology is fully understood.
The increasing prevalence of polysubstance use is not only a change in behavior, but also a manifestation of a unique vulnerability to addiction that has always existed but was previously recognized.
Over time, patterns of drug use have evolved to maximize euphoria or minimize side effects through functional combinations of drugs. Stimulants are used to counteract opioid sedation. Benzodiazepines are used to modify stimulants anxiety. The use of substances is strategic, determined by pharmacological effects, availability and cost.
What are the consequences?
First, prevention. If the initial exposure activates the general vulnerability to addiction, then prevention strategies should be greater than any other drug. A narrow focus on cocaine or fentanyl misses the developmental pathway. Delaying or preventing early use of alcohol, nicotine, and cannabis can have a greater impact on the risk of lifelong addiction, precisely because these substances are the most commonly introduced into the system.
Second, diagnosis. The field needs to move toward reflecting shared responsibility rather than discrete categories. Rather than asking which substance is the primary substance, it may be more clinically accurate to describe the severity, pattern, and current dangers of the drug. A formula such as “Severe SUD involving polysubstances, currently the highest risk from opioids” captures the unity of the disorder and the need for priority.
Third, treatment. The unified model supports person-centered care, rather than zero-sum systems organized around individual substances. It also focuses on treatments that target shared mechanisms—addiction, stress disorders, impaired executive control—rather than focusing on stopping or switching individual medications. Emerging pharmacological approaches, including those that regulate reward and metabolic signaling, make it possible to treat addiction at the level of the underlying drivers, rather than the individual expressions that currently use drugs.
Most importantly, this approach reframes clinical tasks rather than treating a patient’s opioid use or alcohol use in isolation. Instead, the whole person is evaluated and treated—the underlying disorder makes multiple substances compulsive, alternating, recurring, and persistent.
Many people with substance use disorders experience concurrent and sequential polysubstance involvement. A patient may concurrently use narcotics, stimulants, cannabis, or alcohol, or meet criteria for related disorders, while switching primary substances over a period of months or years, depending on availability, withdrawal status, mental symptoms, costs or changes in illicit drug supply. These developments are manifestations of the shared responsibility of addiction.
The convergence of epidemiological trends, developmental data, genetic findings, and neurobiological models is forcing psychiatry and addiction medicine to reexamine polysubstance disorders. manifestation shared neurobiological liability rather than independent diseases.
Today, the challenge goes beyond substance-specific silos to recognize addiction as a single disorder that is rarely limited to a single drug or a single psychiatric presentation. The specific substances may change over time and circumstances, but the vulnerability to addiction remains the same.
