Understanding Tolerance, Dependence, and Addiction

Table of Contents

It is important to understand the meaning of the terms tolerance, dependence, and addiction when discussing substance abuse and the use of prescription medications such as opioid painkillers. Unfortunately, both professionals and lay people often misuse these terms, leading to the mistaken belief that tolerance, dependence, and addiction are just different names for the same thing. However, knowing the distinction between these terms can lead to a better understanding of the dangers of drug abuse.

The most important distinction between these concepts is that tolerance and dependence refer to the physical consequences of drug use. In contrast, addiction is a descriptive term that refers to a need to engage in harmful behavior such as drug use.

Drugs that result in the development of tolerance and physical dependence often have the potential to cause addiction, but not always.

What Is Tolerance?

Tolerance is defined as a person’s diminished response to a drug that is the result of repeated use 1. People can develop tolerance to both illicit drugs and prescription medications. As stated above, tolerance is a physical effect of repeated use of a drug, not necessarily a sign of addiction. For example, patients with chronic pain frequently develop tolerance to some effects of prescription pain medications without developing an addiction to them.

There are 3 main types of tolerance:

  • Acute, or short-term, tolerance is caused by repeated exposure to a drug over a relatively short period of time. Cocaine abuse often results in acute tolerance. Experiments have shown that after a first dose of cocaine, test subjects experience a euphoric high and an increase in heart rate and blood pressure. However, despite nearly doubling the levels of drug in the blood, a second dose of cocaine 40 minutes later does not result in a dose-dependent increase in the “positive” effects of the drug, including a further increase in heart rate or blood pressure 2.
  • Chronic, or long-term, tolerance develops when an individual’s body adapts to constant exposure to a drug over weeks or months. People who regularly abuse prescription opioids build up chronic tolerance to the euphoric effects of these medications, leading many of them to increase the dosage taken or switch to more potent ways of taking these drugs, such as snorting or injecting
  • Learned tolerance may result from frequent exposure to certain drugs. For example, people who abuse alcohol for months or years often do not appear intoxicated to others. Experimental studies have shown that drinkers can compensate for the effects of alcohol on their coordination when they practice a task repeatedly while under the influence 3. However, this tolerance disappears if the task is altered.

Finally, most drugs have more than one effect, and tolerance does not necessarily develop equally to all effects. Abusers of illicit and prescription opioids, such as heroin or oxycodone (OxyContin), quickly develop tolerance to the euphoric high these drugs produce but not to the dangerous side effect of respiratory depression (slowed breathing rate). Opioid abusers who take large doses of these drugs to overcome tolerance and get high are frequently hospitalized—or even die—because they stop breathing.

What Is Dependence?

The words dependence and addiction are often used interchangeably, but there are important differences between the two. In medical terms, dependence specifically refers to a physical condition in which the body has adapted to the presence of a drug. If an individual with drug dependence stops taking that drug suddenly, that person will experience predictable and measurable symptoms, known as a withdrawal syndrome.

Although dependence is often a part of addiction, non-addictive drugs can also produce dependence in patients. A prime example is prednisone, a synthetic form of the steroid hormone cortisol that is used to treat asthma, allergic reactions, Crohn’s disease, and many other inflammatory conditions. Prednisone is not known to produce addiction. However, if a patient has taken prednisone for several weeks and then stops suddenly, they are likely to suffer from withdrawal symptoms such as fatigue, weakness, body aches, and joint pain 4.

Dependence is caused by changes in the body as a result of constant exposure to a drug. In the case of prednisone, the body adapts to repeated doses of the drug by decreasing its own cortisol production, which can leave the body without a baseline level of cortisol “support” when prednisone use is stopped—resulting in steroid withdrawal symptoms until the normal balance is re-established.

Drug dependence is a medically treatable condition. The goal is to separate the patient from the drug slowly, instead of suddenly, to allow the body to readjust to normal functioning. For patients who have developed dependence as a side effect of taking a needed medication (e.g., an opioid painkiller), a doctor can use the tapering method (slowly decreasing the dose of the drug over time) to minimize withdrawal.

For individuals who are dependent on illicit or prescription drugs due to abuse rather than medical need, detoxification (detox) facilities may also use a controlled taper and/or medications to prevent serious withdrawal symptoms. They may also substitute dangerous drugs with similar—but safer—drugs to manage dependence. For example, people detoxing from heroin are often given a longer-acting opioid like methadone or buprenorphine to alleviate withdrawal symptoms and cravings.

Detox is a relatively short-term process lasting several days to several weeks that helps drug abusers safely stop taking drugs while avoiding dangerous withdrawal symptoms. While the detox process is a necessary step towards recovery, detox does little itself to treat addiction in the long term. Research has shown that individuals who do not participate in drug treatment programs after undergoing detox are likely to relapse and end up needing detox again in the future 5.

Just as some drugs that cause dependence are not addictive, there are also highly addictive drugs that do not produce physical withdrawal symptoms. Even after long periods of abuse, psychostimulant drugs, including cocaine and methamphetamine, do not produce pronounced physical withdrawal symptoms like vomiting and shaking, although there can be psychological symptoms such as depression, anxiety, and drug cravings 6. Despite a lack of visible, measurable physical signs, chronic psychostimulant abusers may indeed be addicted.

What Is Addiction?

According to the National Institute on Drug Abuse (NIDA), addiction is a “chronic, relapsing brain disease that is characterized by compulsive drug seeking and use, despite harmful consequences” 7. In other words, addiction is an uncontrollable or overwhelming need to use a drug, and this compulsion is long-lasting and can return unexpectedly after a period of improvement.

Addiction is a psychological condition that describes a compulsion to take a drug or engage in other harmful behaviors. Individuals can develop addictions to illicit street drugs, prescription medications, and even activities such as gambling. Addictions are persistent, and addicted individuals can relapse into drug use after years of abstaining.

Although addiction used to be thought of as a sign of moral weakness, it is now understood by the majority of those in the substance abuse and addiction treatment sphere to be a condition that arises in association with changes in the brain caused by the use of addictive substances. This is because nearly all addictive drugs either directly or indirectly activate an area of the brain, the nucleus accumbens, that is normally stimulated by naturally rewarding activities important for survival like eating, having sex, or spending time with friends.

To the addicted brain, obtaining and taking drugs can literally feel like a matter of life and death.

Addictive drugs stimulate pleasure and motivation pathways in the brain much more strongly than natural rewards. Therefore, repeated exposure to these drugs can fool the brain into prioritizing drug-taking over normal, healthy activities.

The effect of addictive drugs on the brain’s reward pathways helps explain two important features of addiction:

  1. The inability to limit or cease substance use.
  2. The irresistible urge to continue seeking and taking the drug despite serious negative consequences.

People with an addiction to alcohol, for example, may intend to stop for a quick beer on the way home and yet find themselves still sitting on the barstool hours later at closing time. Likewise, addicted drinkers will not be deterred from drinking even if they are advised by a doctor to stop for health reasons, receive a DUI, or are dismissed from a job.

This irrational persistence is what sets addiction apart from mere physical dependence. Many people in our society are dependent on caffeine and experience withdrawal symptoms such as headache, fatigue, and difficulty concentrating if they miss their morning cup of coffee 8. But no matter how unpleasant going without caffeine may be to people who are dependent on it, it is unlikely many of them would commit a crime in order to get an espresso or refuse to give up coffee entirely if told by their doctor that it might kill them. Learn about drug detox helplines

Addiction results from a complex interplay of a number of social, biological and psychological factors, including 7

  • Genetic makeup.
  • Socioeconomic status.
  • Family environment.
  • Drug accessibility.

The treatment of addiction is likewise complex and requires medical attention, behavioral counseling, and long-term support to prevent relapse.

Drug addiction is a dangerous and often fatal condition, and it can be virtually impossible for an addicted individual to break the cycle of compulsive drug use without assistance. Fortunately, there are many effective professional treatment programs that can help. If you or a loved one is struggling with drug addiction, call 1-888-744-0069 today to learn about the options available and how you can start the journey to recovery.


  1. Hussar, D. A. Tolerance and Resistance to Drugs. Merck Manuals Consumer Version.
  2. Foltin, R. W., & Haney, M. (2004). Intranasal cocaine in humans: acute tolerance, cardiovascular and subjective effects. Pharmacol Biochem Behav, 78(1), 93-101. doi:10.1016/j.pbb.2004.02.018
  3. Vogel-Sprott, M. (1997). Is behavioral tolerance learned? Alcohol Health Res World, 21(2), 161-168.
  4. Mayo Clinic. (August 5, 2014). Prednisone withdrawal: Why taper down slowly?
  5. Mark, T. L., Vandivort-Warren, R., & Montejano, L. B. (2006). Factors affecting detoxification readmission: analysis of public sector data from three states. J Subst Abuse Treat, 31(4), 439-445. doi:10.1016/j.jsat.2006.05.019
  6. MedlinePlus. (April 13, 2015). Cocaine withdrawal.
  7. National Institute on Drug Abuse. (2003). Preventing Drug Use among Children and Adolescents: A Research-Based Guide for Parents, Educators, and Community Leaders.
  8. Johns Hopkins Medicine. Behavioral Pharmacology Research Unit (BPRU) Fact Sheet: Caffeine Dependence.
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Dr. MacLaren, PhD, earned his doctorate in Pharmacology from the University of Colorado Health Sciences Center in 2005 for his research work on the genetics of alcoholism.

He has conducted laboratory research in cellular and molecular neuroscience at the Sanger Institute in the United Kingdom, the Ottawa Hospital Research Institute in Canada, and the University of Colorado Boulder. Dr. MacLaren has worked as a freelance medical writer since 2013 in the fields of drug abuse, oncology, and diabetes.

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