Your Body Learns What You’re About to do Next

In 2016, over 64,000 overdose deaths occurred in the United States alone. A majority are from opioids, with 116 people in the US dying daily – enough for it to be termed an epidemic. This number has been increasing and has actually driven US life expectancy down over the past two years.

Sometimes drug overdoses seem intentional. Given the August 5th anniversary of her death in 1962 I’ve been seeing more stories recently about Marilyn Monroe, who overdosed on barbiturates after reportedly taking over 40 pills. When someone consumes such a large quantity the death is often ruled a suicide. However, factors leading up to an overdose are unique and unfortunately often unclear. Despite this, there is no question that many are unintentional. The drug is being used recreationally for desired positive effects but – depending on the drug – the dose consumed can sometimes overwhelm the body and cause respiratory distress in mere minutes.

It might seem a bit odd that overdoses can happen to people who are frequent users. Shouldn’t they be familiar with how to use the drug, or know what dose to take to get the desired effect? However, our bodies have fascinating adaptability and ability to predict what we’re about to do next. This ability often serves us well, but in the case of drug use sometimes things can go awry. A scientific understanding of how we learn can provide a clearer appreciation as to the conditions under which overdoses are likely to occur… and it’s not always intuitive.

I’ve previously discussed how difficult drug withdrawal can be here, but I want to instead delve more into how our bodies react when we use substances first casually… and then sometimes habitually. In the next blog post I’ll describe how this relates to drug withdrawal and tolerance, but first you need a basic understanding of classical conditioning. Even if you’re not very fluent in Pavlovian conditioning, it’s not super challenging to understand how it impacts our body’s reaction to drugs or other nondrug stimuli. To provide a few examples easing into the basics:

Some things in the world elicit an automatic response from our bodies (without our implicit knowledge, intention, or awareness). To use the classic example from Pavlov’s research – food is something that automatically elicits saliva production when it’s in our mouth. Because it does this biologically, food is an “unconditioned stimulus” (US) – the production of saliva is not something we can control, not something dependent on a conditioning history. It’s literally unconditioned. In this example, saliva is the unconditioned response (UR) for the same reasoning. It is a bodily response that occurs naturally when a specific stimulus is presented. So – those are the first two components – a simple reflex between a stimulus and a response (food leads to salivation).

While reflexes are interesting in their own right, the plot thickens with what comes next. Based on our interactions and experiences in this world, other items associated with the US can tag along for the ride so to speak and start to elicit a response of their own! You can test this out with yourself right now. Imagine a sour candy wrapper – sour skittles, sour patch kids, warheads perhaps. If you’re really trying to picture this candy wrapper, you might notice you’re starting to salivate. But – why? You haven’t even put the candy in your mouth! This is classical conditioning. A candy wrapper is an initially neutral stimulus that can acquire the ability to make you produce saliva on its own (henceforth becoming a conditioned stimulus) because, in the past, when you have seen that wrapper you have been likely to put the sour candy in your mouth. Your body has learned this association and in essence is predicting your next move. It’s producing an increase in saliva to begin to combat and break down the tart sour candy that’s expected based on your past history of seeing the candy wrapper right before eating. Pretty amazing, right?

Extending this to drugs is fairly straight-forward with one notable difference – the conditioned response that your body produces is not always the same as the unconditioned response. With the prior example of food, the UR and CR are indeed qualitatively similar– both food AND the candy wrapper produce increased saliva production (with the candy wrapper perhaps producing a quantitatively lower magnitude response). However, with other stimulus/response combos the CR could be completely opposite of the UR.

Before you deem this all too confusing – hear me out. A good way to think of it is this: your body is doing its best to predict what’s coming next and prepare for it. Sometimes this preparation requires the same CR. When you see a sour candy wrapper, often times in the past you were about to consume the candy – so producing increased saliva as a CR and a UR makes sense. Candy wrapper OR candy in the mouth = increased salivation to assist in digestion. But, with other unconditioned stimuli sometimes the opposite response makes sense.

Let’s consider a drug example.

Drugs are unconditioned stimuli in that when they’re administered they produce automatic changes in our bodies. It’s as simple as saying that drugs produce drug effects (US –> UR). That part is pretty obvious. Next comes the plot thickening part. Particularly for drugs with salient drug effects, we naturally (without “intention” or overt awareness) learn what environmental stimuli best predict drug taking. Those stimuli – previously neutral, can become conditioned. The specific ones that become conditioned will differ for every user, but anything in our environment that’s reliably predictive of drug use is fair game. The sight of a needle, a lighter, your friend’s living room, your car, even the time of day.

Research has demonstrated that those conditioned stimuli can evoke responses that are at odds with the unconditioned drug effects. As just one example – drugs such as alcohol produce a lowered body temperature. The conditioned response that can be produced by associated environmental stimuli is hyperthermia – an increased temperature (e.g., Crowell et al. 1981).

I’ll continue in my next post with more examples about how conditioned responses can be opposite to the natural drug effects, and how this relates to tolerance and withdrawal. This understanding provides some key information about WHY unintentional drug overdoses occur. And interestingly, it gives us some clues about drug treatment and how best to help addicts recover. Given this ever-widening societal issue – this epidemic – the more we can understand drug use and treatment the better.