Tolerance is a contributing factor to overdose. It works like this: The more of a drug that is put into a person’s system, the more her body will get used to it. Once the body acclimates to the original dose, it will require more of the drug to achieve the original results.

A person who is addicted to a drug is going to seek the same high and therefore will likely begin using more of the drug, or a more potent version of it. Of course, increasing the amount and intensity of a drug increases the drug’s tax on the body, and over time as the amount increases, the chance of an overdose becomes more likely.

Tolerance and addiction often happen without the person even realizing it, subtly progressing from that first try to regular use to out of control. Young people seem to move more quickly through these stages than adults, according to the U.S. National Library of Medicine.[i] The common stages of addiction development are:

The Science of How Tolerance DevelopsHow Continued Drug Use Leads to an Overdose

Addiction affects multiple brain circuits, including those involved in reward and motivation, learning and memory, and inhibitory control over behavior.[ii] Drugs actually change the brain, which is why addiction is considered a brain disease. Prolonged drug use alters the brain’s chemistry, doing damage that can take weeks, months, even years to reverse.[iii]

“Tolerance to drugs can be produced by several different mechanisms,” the National Institute of Drug Abuse (NIDA) reports,[iv] “but in the case of morphine or heroin, tolerance develops at the level of the cellular targets.”

When morphine binds to opiate receptors in the brain, it triggers the inhibition of an enzyme “that orchestrates several chemicals in the cell to maintain the firing of impulses. After repeated activation of the opiate receptor by morphine, the enzyme adapts so that the morphine can no longer cause changes in cell firing,” NIDA explains. This means that the brain cells have adapted to the new norm of getting the drug, which reduces the effect of the same amount of the drug. In turn, this causes the person so seek more of it.

Tolerance Is Tricky

How fast a person will or will not develop a tolerance to a drug depends on heredity, the dose of the drug, the size of the person, and the frequency of drug administration. Tolerance usually occurs with depressants, which include alcohol, opiates, synthetic narcotics, barbiturates, some minor tranquilizers, and volatile substances such as ether and glue. Tolerance to amphetamines when used in large doses have also been found.[v]

If a person develops a tolerance to one drug in a certain classification, such as depressants, he is more likely to develop tolerance with another drug in that classification. This is called cross-tolerance. As an example, people who are dependent on alcohol show an increased tolerance to barbiturates, synthetic and natural opiate narcotics, and anesthetics.[vi]

So just switching from one drug to another may mean that more of the new drug will also be needed to reach a high. This could also lead to an overdose because the person may start using the second drug at a higher rate and frequency.

Who Can Become Addicted?

Anyone can become addicted to a drug, but there are certain factors that may increase the likelihood and speed of developing an addiction, according to the Mayo Clinic:[vii]

Is It Really a Big Deal?

Substance use disorders impact the lives of millions of Americans. According to the Substance Abuse and Mental Health Administration (SAMHSA), there were almost 17,000 prescription drug overdose deaths in 2010, which was almost double the number of similar deaths in 2001.[viii]

So yes, it is a big deal. With overdose deaths on the rise, it is important to understand how continued drug use can lead to an overdose. If you have questions or concerns about your own situation or that of a friend or family member, call our admissions coordinators anytime — we’re available 24 hours a day, seven days a week.


[i] “Substance Use Disorder,” U.S. National Library or Medicine, last updated Jan. 13, 2016,

[ii] “Principles of Drug Addiction Treatment: A Research-Based Guide (Third Edition),” National Institute on Drug Abuse, last updated December 2012,

[iii] “Why Didn’t Drug Rehab Work? 5 Wrongs that Don’t Make a Right,” by Dr. David Sack,, updated June 9, 2015,

[iv]  “The Neurobiology of Drug Addiction: The Definition of Tolerance,” National Institute on Drug Abuse,

[v] “Information About Drugs,” Indiana University, Bloomington,

[vi] Id.

[vii] “Drug Addiction/ Risk Factors,” Dec. 5, 2014, The Mayo Clinic,

[viii] Opioid Overdose Prevention Toolkit, Substance Abuse and Mental Health Administration, updated 2014,