Threat Level: Drug Abuse

Parts Three and Four of this series on drug abuse cover how some of the characteristics of substance use disorder manifest themselves.  There are physical changes, cognitive changes, behavioral changes and emotional changes (often in combination) within the context of the individual and the drug(s) that are being abused.  Signs of increased drug tolerance and physical dependence are evidenced in these syndromes, but it is important to understand the distinction. 

We will focus on three primary concepts here: addiction, tolerance and physical dependence.  While all three can manifest themselves simultaneously, they can also occur exclusively. 

As we discussed in Part Two, addiction is a chronic disease that is an idiosyncratic reaction in biologically and psychosocially vulnerable people.  These individuals will continue to abuse drugs despite adverse consequences.  One can be a drug abuser without being a drug addict.  Likewise, one can develop a tolerance or physical dependence to certain drugs, but they should not automatically be categorized as being addicted to them.  This is especially the case where the drugs do not provide reward stimuli but are medically necessary.

The Icahn School of Medicine at Mount Sinai defines tolerance as the “reduced drug responsiveness with repeated exposure to a constant drug dose.”  When someone develops a tolerance to a drug they will need a larger dose of it to produce the same effect. It defines physical dependence as, “an altered physiological state that develops to compensate for persistent drug exposure.” There is a physical effect once the drug is removed. Tolerance is a phenomenon of addition, while dependence is a phenomenon of subtraction. The National Institute on Drug Abuse states, “the development of tolerance is not addiction, although many drugs that produce tolerance also have addictive potential.” The same can be said of physical dependence.

Tolerance can be caused by cellular responses to sustained exposure to receptors, or instances in which the receptors themselves are altered due to repeated exposure (pharmacodynamic).  It can also be metabolic (or pharmacokinetic), when it is caused by change in the rates of absorption, distribution, induction, and ultimately excretion of drugs in the bloodstream. 

Drugs taken orally (alcohol, for example) are susceptible to the development of metabolic tolerance, while drugs that are administered directly to the receptor sites (such as amphetamines) are more often susceptible to pharmacodynamic tolerance. This is a simplification of a very complex subject, of course, and there are other categories of drug tolerance, especially as it relates to pharmaceuticals. Sometimes increased drug tolerance is a desirable goal, such as through allergen immunotherapy. Finally, there is the entirely separate category of pathogens or cancers developing drug resistance, which should not be mistaken for drug tolerance. 

Drug tolerance can be reversable through a “drug holiday,” whereas physical dependence results in a reaction known as withdrawal when the drug is removed. This withdrawal can be a physical reaction or a psychological reaction, though it and is often a combination. Withdrawal must be managed carefully, depending on the drug, the dose, the frequency, and length of time the drug was taken.  Often withdrawal is so severe, an affected individual will continue taking the drug to avoid the withdrawal itself.

Some drugs, such as heroin, have a high dependence potential and drug abuse or drug addiction potential because of its rewarding stimuli.  Some drugs, such as beta-blockers, have a high dependence potential but a low drug abuse or drug addiction potential because of the absence of rewarding stimuli.

Drug addiction, tolerance, and dependence are associated concepts, but they are not interchangeable.  Unfortunately, they are often used interchangeably by the public and in the media.  During a time of increased drug abuse of pharmaceuticals and pain management opioids, it is even more important for clinical terms and lay terms to coincide.  As the American Society of Addiction Medicine (ASAM) put it in its consensus statement with American Academy of Pain Medicine and the American Pain Society, “disparities

contribute to a misunderstanding of the nature of addiction and the risk of addiction, especially in situations in which opioids are used, or are being considered for use, to manage pain.” 

I will discuss the Opioid Crisis in more detail in part seven of this series.  The next installment will touch on risk factors for drug abuse and substance use disorder.