When is it meaningful to speak of the pharmacology of a drug causing a person's behavior? I think that this concept has been overdone, particularly with respect to the "opioid epidemic" narrative.
Start with the easy cases, where we can definitely attribute the response to a drug to its pharmacology. Some drugs clearly reduce a person's capacity, mental and physical. Alcohol slows your reaction time and can even make you fall asleep at the wheel. Opioids can likewise make someone drowsy or unresponsive. Obviously they are used as general anesthetics for surgery. A dose much lower than that used in surgery can have a milder but still noticeable effect. Someone in such a state of diminished capacity might be prone to accidents, but I don't want to call this a "behavior." A drunk driver and a sober driver are both trying to get to their destination safely, it's just that the drunk is much worse at it. The ability of certain drugs to incapacitate their users is "pure pharmacology". That's not what I want to discuss here. I'm trying to get to behaviors, deliberate actions, that are in some sense caused by drugs.
Sometimes people who drink alcohol are more likely to get into fights or behave violently toward family members. The same is true of people who use certain stimulants. Someone in a very excitable state may be on a hair-trigger and might throw a punch in a situation that their sober self would handle more calmly. I think it makes sense to label this kind of thing "pharmacologically induced violence." It's not mere diminished capacity as described in the above paragraph. It's not that the drunk was reaching for his beer, stumbled, and plowed his knuckles into someone's cheek. Starting a fight is different from stumbling on the sidewalk or crashing your car. It's a behavior. There is an underlying intent. It's a choice, and the drunk is simply worse at making choices than his sober self.
There are certain drugs that can drive people into extremely excitable states. Synthetic cannabis (sometimes called Spice or K2) can sometimes make users extremely irrational. A paramedic friend of mine once described to me an episode in which he had to handle such a person, who was clearly out of his mind. This kid smoked too much Spice and was kicking and flailing at the first responders who were trying to help him. Some psychoactive substances, which are sold in head shops as "bath salts", have a similar reputation for driving people insane. PCP has a mostly unearned reputation for causing similar outbursts; Jacob Sullum corrects the record on PCP in his book Saying Yes. Some of these stories are overblown or apocryphal. The man who famously ate someone's face off was not high on bath salts, even though it was initially reported that he was. (Why is it that the initial report is always 100 times louder than the retraction?) People occasionally do shocking, crazy things, and for whatever reason "He must have been on drugs" always seems like a plausible explanation. Sometimes first responders or medical personnel make incautious statements to the media before actually double-checking the likely causes of someone's outburst, and media outlets dutifully repeat the message to a receptive public. The public loves a good drug-panic story, whether it happens to be true or not. Exaggerated or not, there are certainly cases where drug-induced psychosis is the best explanation for someone's shocking behavior. It makes sense to talk about the pharmacology of the drugs causing someone to have an irrational outburst (shouting obscenities are random passers-by, starting a fight, etc.). The drug can legitimately be considered the cause of the behavior in a but-for sense.
What about opioid addiction and overdose? More to the point, what about legitimate medical prescriptions leading to an opioid addiction? Here I think it's an incorrect framing to posit the drugs as the cause of the behavior. It is true that if someone is on opioids for an extended period of time, they will probably develop a physical dependence on opioids. They will have developed some degree of tolerance, and they will experience withdrawal symptoms when they stop taking them. The physical symptoms can be quite unpleasant. But physical dependence is quite distinct from addiction. Physical dependence is not a behavior. It will not by itself cause a person to seek opioids on the black market. Someone who takes a long-term course of opioids and is then tapered off by his doctor will not be driven to addiction if he follows the doctor's directions. Addiction is what happens when someone deliberately and repeatedly deviates from "use as directed." It makes little sense to speak of prescriptions "turning patients into addicts". Even if we posit that some people get a mildly pleasant buzz from taking their pills regularly, it's just not the case that this pleasure causes them to escalate their dose or to continue to seek opioids after their prescription runs out. There is nothing inherent to the pharmacology of the opioids that causes these behaviors. Indeed, the vast majority of opioids users don't have any kind of problem going off them when their course ends. Some sloppy writers and commentators have tried to cast this as a cosmic game of dice or Russian Roulette in which patients are subjected to a random risk, as if every ten thousandth pill contained the "addiction virus." It's much more useful to think of addiction as a series of deliberate behaviors that eventually become hard to control.
(I once heard Doctor Jeff Singer, someone who I correspond with occasionally, describe a patient's hesitation about opioids. The patient's concern went something like, "I want to be careful about this, because last time I was prescribed opioids I got addicted and experienced nasty withdrawal symptoms." Jeff explained that the patient was emphatically not an addict. He had experienced physical dependence, but not addiction. In fact the patient was quite deliberately avoiding these substances because he'd had such an adverse reaction to the withdrawal. Addiction, by contrast, is the compulsive, continued use of a substance despite the harm its causing you. I thought this was a nice illustration of the difference between addiction and physical dependence.)
Let's grant that physical dependence can be so extreme and the withdrawal symptoms so severe in some opioid patients that continued use is irresistible. Such a person continues to use after their prescription is gone, purchasing pills or even heroin on the black market. It's a stretch to say that the pharmacology of opioids led to their addiction. As difficult as withdrawal is, continued use is a very deliberately chosen path. But forget that for a moment. Let's grant for the sake of argument that this is an instance of pharmacologically induced behavior. It might make sense to blame their use of black market pills or even heroin on the body's physiological response to an opioid prescription. Certainly the continued use of opioids leads to nasty withdrawal symptoms, and opioids purchased on the black market relieve those symptoms. But take a closer look at what's actually killing these people. "Drug overdose" is a misnomer, a short-hand term that misstates the true cause of death. The CDC actually refers to these deaths as "drug poisonings." The term "overdose" seems to imply that the decedent took too large a dose of a single substance, but that's the exception rather than the rule. Most drug-related deaths are multi-drug poisonings. See where I've written about this previously, here and here and here for example. Let's dispel this notion of a hapless addict popping pill after pill until he just keels over. This just doesn't match the reality. It isn't the case that it's just "so good" that the addict needs another and another until he's taken too much. A much more likely scenario is that someone is taking opioids with benzodiazepines (~1/3 of prescription opioid related deaths involve this combination) or alcohol (~14%) or cocaine (~12%). Maybe some of the benzo plus opioid poisonings are accidental mixtures of medications, but it appears that many opioid users take benzos because it potentiates the high. Presumably many or most of them know it's dangerous but they do it anyway. Even granting the premise that the pharmacology of prescription opioids causes continued opioid use, it's far from clear that it should cause the patient to mix medications or start using cocaine. It just makes a lot more sense to model this behavior as deliberate thrill-seeking than as "I lost a game of pharmacological roulette and it turned me into an addict."
I think it's worth taking a serious look at the risks of prescribing opioids for pain, acute or chronic. Some people are fast or slow metabolizers, depending on whether they have zero, one, or two copies of a certain gene. Some of these people really are effectively playing a game of pharmacological roulette, as in they might have a fatal reaction to a dose that's benign for an average person. And we certainly want to warn people about withdrawal symptoms so they can make an informed decision. Even granting all that, any talk about the "risk of addiction" is badly missing the mark.
By the way, if there is a "risk of addiction" that roughly corresponds to the ratio of addicts to opioid prescriptions, apparently that risk has been coming down on a per-prescription or per-patient basis. Rates of opioid misuse and addiction have been basically flat or even falling over a time period when prescriptions were skyrocketing. This makes little sense if you think that there is some disembodied probability, the "risk of addiction", faced by all opioid patients. But it makes perfect sense if we think there's a more or less fixed population of extreme risk-takers, and they happen to be using whatever drugs are most available. In this light, I find it just atrocious that state governments are going after Purdue and other opioid manufacturers. We need to purge this notion that addiction is something that is done to you, that passively happens to you as you dutifully take your meds. People don't simply sleep-walk into addiction when taking their medication as directed, and there is nothing inherent in the drugs pharmacology that makes them deviate from "use as directed." We need to debunk this absurd idea that smooth, sophisticated pharmaceutical firms just had their way with us, even getting past the doctors who stood as gate-keepers.
I hope it's clear that this isn't mere hair splitting about what to name something. There are some very important implications, political, moral, and legal. If the pharmaceutical companies aren't culpable (as I think they are not), then they shouldn't be sued for selling opioids. They should be able to continue selling to their very willing buyers, some of whom commit suicide when they are involuntarily tapered. If the addicts are deliberately engaging in risky behaviors, we should not be restricting opioid prescriptions for their sake. Restrictions make it harder for desperate pain patients to acquire opioids. It seems to me that the moral weight of a single pain sufferer who is involuntarily cut off from opioids ought to outweigh the voluntarily undertaken self-harm of many dozens or even hundreds of addicts. Tens of millions of Americans suffer from chronic pain at any given moment (I've seen estimates as high as 1 in 3 that will eventually suffer from it), compared to less than one percent of the population being addicted to pain pills (having a "use disorder within the past year" anyway). It would be hard to make this calculus work out in favor of restricting access. Even supposing some utilitarian calculation gave the nod to further restricting opioid prescriptions, most of us are not amoral utilitarians. People rightly apply a fairness standard to public policy. "You can't have opioids, because, while I'm quite sure you won't have any problems, there is some small chance that Jonny over there will steal them from you and abuse them." This seems terribly unfair. It makes sense to worry about who is harmed or helped and to give consideration to whether that harm is self-imposed or not.
If this narrative of pharmaceutical companies involuntarily converting normal patients into addicts is wrong (and I insist it is), then basically all the policy responses and "public service announcements" by our institutions of public health have been deeply misguided. Sure, some individuals have impulse control problems. But we're not zombies. We're not programmable robots who can simply be re-programmed to serve big corporations' earnings goals. Habit-forming drugs don't sink "chemical hooks" into our brains and control us against our will. There is an element of free choice in all of this that is quite separate from the drugs' pharmacological effects.
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Something I haven't touched on in this post is the fact that most opioid addicts don't even get their start with a prescription, an observation that should relieve opioid manufacturers of any culpability. The idea that I'm arguing against in this post, the notion that drugs take over people's minds and make them do things they don't want to do, is sometimes called "voodoo pharmacology." There is apparently some powerful voodoo going on here. Apparently the pharmaceutical companies are hijacking the brains not of their legitimate patients, but of other people in society who acquire opioids illicitly. Manufacturers, distributors, and patients are by and large acting responsibly, but highly motivated addicts are stealing left-over pills from unfinished prescriptions (a peculiar phenomenon, by the way, for a drug that is supposedly so irresistible). It might make some sense to hold the patient culpable for inadequately securing their leftover pills, but to follow this back up to the manufacturers? This is an absurd concept of legal liability, one which I don't believe anyone has even tried to defend.
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