A tolerance to a substance occurs when the body gets used to a substance (drugs, alcohol or medication) so that more of the same substance is needed to give the desired effect that was once received initially from smaller amounts.
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Depending on the substance, tolerance can develop acutely (quickly), in a manner of days, or chronically (slowly), over a number of weeks or months.
There are several mechanisms behind tolerance, including changes in the metabolism of a drug, cellular changes or behavioural/psychological effects. Tolerance is not always negative, and people may develop a tolerance to the side effects of a drug over time as well. We will look at these further down this article.
It’s important to understand that tolerance is not the same as dependence or addiction, but in the case of substances such as painkillers and alcohol, tolerance can predispose a person to these problems with continued use in ever increasing amounts.
What Is A Tolerance?
Tolerance is defined as “the diminishing effect of a medication or substance following repeated administration at a certain dose”. It is often a normal adaptive response to ingested drugs, as the body tries to maintain homeostasis (a natural, healthy balance).
The development of a tolerance toward a specific drug or substance can vary between different people (there is a genetic influence); with other drugs a person is taking; and with any underlying physical or mental health conditions that are present. Likewise, other things that can influence your susceptibility to increased tolerance can also include:
- Your weight.
- Your height.
- whether you’ve eaten.
- Whether you’ve drank alcohol.
- Whether any infections may be present in the body.
- And many others.
- Your genetic predisposition toward substance misuse & addiction.
Tolerance also develops at different rates for different effects of the drug. For example with opioids (heroin, morphine, codeine ect), people may develop more of a tolerance to the euphoria (high) caused by the drug than to the respiratory depression (slowed breathing) caused by the drug.
Acute Vs Chronic
A tolerance often develops chronically over many weeks or months, however it can still occur rapidly as well. “Tachyphylaxis” is the term used to describe the very rapid onset of tolerance, such as that seen after a single dose of cocaine or LSD. Tachyphylaxis can also occur with antidepressant medications and others.
Effects Vs Side Effects
As noted earlier, your tolerance may be a negative finding, such as when a drug loses effectiveness over time, but it can also be positive, such as when tolerance develops to the side effects of medication such as nausea or fatigue. In the case of allergy desensitisation programs for example, it’s the development of a tolerance that’s responsible for the effectiveness of the treatment.
In some cases, the opposite of tolerance occurs (sensitization), and a drug becomes more effective with repeated use.
Tolerance Vs Resistance
Resistance also differs from tolerance. With resistance (such as to antibiotics or cancer drugs), resistance develops because bacteria or cancer cells make substances that lead to the drug not working. However this most often isn’t the case when it comes to tolerances and developing an addiction.
Tolerance Vs Addiction Vs Dependence
The differences between tolerance, dependence and addiction are important. Many drugs that cause tolerance do have a potential to be addictive, but becoming tolerant does not mean a person is addicted to the drug. Similarly, dependence is defined as the occurrence of withdrawal symptoms when the drug is withheld and may occur in the absence of tolerance or addiction.
Mechanisms
There are several different ways in which a tolerance to a drug may develop. Some of these definitions can be a little confusing so bare with us! These include:
- Pharmacodynamic Resistance: In pharmacodynamic, dispositional, or functional tolerance, changes at the cellular level leads to resistance. For example, binding of a drug to a particular receptor on the surface of cells (such as opioid receptors) may fail to cause the signals to be transmitted as in the past, or the body may produce fewer receptors on the surface of cells for the drug to bind with.
- Metabolic Tolerance: With this mechanism of tolerance, a drug may be broken down and cleared from the body before it reaches its site of action. For example, alcohol can induce the activity of liver enzymes that metabolise the “drug.”
- Behavioural Or Learned Tolerance: In learned tolerance, people may become accustomed to the effect of a drug. For example, some people who are long-term drinkers can better “hold” their alcohol, even with the same blood concentration.
- Conditioned Tolerance: Environmental cues can also lead to tolerance. An example would be a person who routinely drinks at a bar having better eye-hand coordination at the bar than he or she would have at home (after the same number of drinks).
Examples Of Medication Tolerance
Drug tolerance (including medicines) are most often, but not always, related to drugs that affect your body’s brain and nervous system. A few examples include:
- Painkillers such as oxycodone, Co-codamol, morphine and others (most of which are opioid based).
- Benzodiazepines (aka tranquilisers) such as Valium (Diazepam) or Temazepam.
- Over-the-counter purchased sleep aids and products such as Benadryl (diphenhydramine).
Management & Treatment
How a tolerance is managed depends on the particular drug or drugs concerned, what are they being used for, and what alternatives are available. In some cases, increasing the dose may result in the drug working again (for a short time anyhow, though it may also amplify a tolerance at that dose as well). If a drug can be discontinued by becoming abstinent to that particular substance for some time, what’s known as a drug holiday, can often be restarted without a tolerance. However though a tolerance may again occur in time as it did initially.
In situations like these, it’s really important that you speak to your GP, Pharmacist or prescribing healthcare professional. Be honest and open with them about your development of a tolerance, after all, the more information they have, the better they can care for you. I may be that it would be better to swap you to an alternative medication that aren’t likely to cause a tolerance to develop, or they may stop the medication and start an alternative form of treatment.
There is always an answer to this problem if you address it at the earliest possible opportunity, are honest with your healthcare professional, and are able to recognise the warning signs as soon as you begin taking that particular substance or medication. With medicines, they contain an information leaflet. Take them out of the box and read them thoroughly before you begin taking the medication as the leaflet will tell you what to watch out for and what to do should something occur.
Tolerance & Cancer Treatment
In some settings, such as terminal cancer, apparent tolerance to opioid based medications are more often due to worsening cancer (tumour growth, new metastases or spread of cancer to other areas of the body) rather than a tolerance to the drugs. When an apparent tolerance does occur, it’s extremely important to rule out other potential causes of increased pain before automatically assuming that this is the case.
Even when a tolerance does occur however, issues of possible dependence and addiction are of a minor concern since the persons condition may be terminal and the development of an addiction is irrelevant to the outcome of the persons treatment plan.
While there is a cross-tolerance between different opioid based substances and medications, this is often not complete, and changing to another drug in this class may be helpful. Many of these drugs can also be given at very high doses (there doesn’t appear to be a ceiling or maximum dose), and, when increased gradually, there is less concern over problems such as respiratory depression, low blood pressure or cardiac arrest.
Tolerance & Substances Of Misuse “Chasing The Buzz”
When a person first consumes a potential substance of misuse, be it alcohol, prescribed opioids, illicit drugs or nicotine, the effects are more potent than they ever will be again. Most addicts are trying to “chase” and repeat the way that they felt the first time that they look the medication or substance in question.
This will never happen however and they will never experience the same level of pleasure that they felt the first time they took it. This effect of chasing the “buzz” then leads most addicts to use ever increasing amounts which then leads a person to need a larger and larger amount or dose of that particular substance or medication to feel any desired effects, thus setting themselves up for a vicious cycle of misuse, physical and psychological dependency and withdrawal.
The phenomenon of needing more and more drugs or medication to produce the desired effect is called tolerance.
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Cross-Over
When a person becomes tolerant of a certain central nervous system (CNS) depressant like alcohol, this person then usually becomes tolerant of other drugs of misuse like heroin. (Technically, opioids like heroin aren’t CNS depressants although they do have similar depressant properties.) This phenomenon is called cross-tolerance.
The Dangers Associated With Developing A Tolerance
Tolerance can be particularly dangerous for several reasons. When a tolerance develops to a different degree to different effects, the risk of overdose increase and can be significant. This is a tragic problem, with proof of this with the current opioid epidemic in the UK, USA and worldwide. As a tolerance develops more quickly to the euphoric properties of these drugs than to the respiratory depressive properties.
Switching between different medications in a category also raises the risk of complications. As noted, cross-over can vary, and people who switch between drugs such as heroin, codeine, morphine and others may end up taking a higher “dose” than they had planned to if there is less tolerance to the next drug they take.
Finally, many misused substances are combined with other drugs for which a physiological tolerance doesn’t develop. For example, opioids may be combined with Paracetamol (acetaminophen). While a tolerance may develop to higher doses of the narcotic so that respiratory depression does not occur, an excess of Paracetamol (even just a small excess) from products such as Vicodin (hydrocodone plus acetaminophen) or Co-codamol (codeine and paracetamol) could lead to liver failure.
Differences In Tolerance
Certain people exhibit a rapid tolerance or initial tolerance to a drug. These people may be at higher risk of drug dependence or substance misuse. This can happen for a number of reasons, some physical and some psychological. Look at the earlier sections called “what is a tolerance” and “mechanisms” for more information on this.
Stopping & Starting Substance Use
For those in recovery, tolerance can be dangerous in another way. Tolerance often decreases the longer the amount of time that you stay off of a drug. If a person who has been abstinent from the drug for an extended period of time (sometimes even as little as a week) resumes their previous level (dose) of use, a life-threatening overdose can occur, leading to many preventable and needless deaths worldwide annually.
Our Top 8 Tips To Help Avoid Developing A Tolerance To Medications Or Substances
Things you can do to help avoid developing a tolerance to a particular medication or substance:
- Try to use the smallest amount possible and as sparingly as you can.
- Try to use alternative coping strategies and techniques instead of always relying on a substance or medication to change the way you think or feel. You can find a wide variety of these throughout our blog and our website.
- Make sure that you follow the instructions you were given when you were prescribed your medication by the Pharmacist or Doctor.
- Learn to recognise the most common signs and symptoms of developing a tolerance to medications or substances.
- Ask other people around you if they have noticed a difference in your appearance, behaviour or medication/substance use.
- If you’re ever unsure, err on the side of caution and speak to your prescriber, GP or drug and alcohol service.
- Keep a diary of the amount of times in a day that you take a substance or dose of medication. Do you notice the amount of time you use go up or the dose/amount you take each time increase? How often are you needing a repeat prescription for the same medication? Is it getting more frequent?
- Are your symptoms getting worse or changing? Could this be due to you taking more and more of the same medication or substance than you needed to initially?
What To Do If You Are Concerned About Yourself Or Someone Else
If you feel that you or someone else may be experiencing or developing a tolerance to any prescribed, legal or illicit substance or medication, it’s extremely important to inform your GP or healthcare professional to get help straight away and without delay.
Substance misuse, drug dependence and addiction can have terrible and deadly consequences for you, your friends and loved ones and your society or community as a whole.
Please remember that there are trained and experienced health care professionals, therapists and support groups that specialise in drug treatment that are empathetic and understanding of your needs as many of them, especially those who would in drug and alcohol services, have been through the same or similar experiences themselves. Don’t delay reaching out as by doing so could have fatal consequences that are totally preventable and addictions or tolerances that are treatable.
You can find more information about effective treatments and therapies here. Likewise you can find a wide variety of groups, charities and organisations who can help you on our help and support page here. If you are still unsure, why not join our Facebook group where you can talk to others about their experiences with tolerance. After all, no one can help someone with an increased tolerance to drugs or medications than others who have been in that situation too! You can find our group by clicking here. You can also find other help resources, coping strategies and the latest research and treatments by following us on our social media pages. You can find links to all of these by clicking here.
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