Trusted Content

Opiate Tolerance

Lori Minor MSN, MHSA, RN

Medically reviewed by

Lori Minor, MHSA, MSN, RN

February 4, 2019

Misusing or taking opiate medication for an extended period of time may lead to an increased tolerance and even addiction to the drug. Over time, the reduction of a drug, in a medically managed way, may help reduce an individuals tolerance.

When considering an opiate drug that has the potential to form a dependence and/or become addictive, we also consider that these situations include a person developing a tolerance. Tolerance occurs when a person uses such a frequency and quantity of a specific drug over a certain amount of time, that they find they require a greater amount of the drug to achieve the desired effects that the drug previously offered at lesser amounts. This phenomenon may occur with illicit opiate drug use, including that which is formed on diverted prescription opioid medications.

However, even opiates—also referred to as opioids—that are medically prescribed and used properly under a physician’s guidance and direction, may cause tolerance. This presents unique and pressing problems to both professionals within the medical community and the individual who faces the tolerance, in terms of addressing their medical needs for which the drug was prescribed in the first place.

What Is Opiate Tolerance?

An unfortunate number of prescription drugs, including painkillers, are diverted within the United States and used illicitly, largely fueling the growing opioid epidemic. Because of this, far too many people are experiencing destruction at the hand of a medication that was created for therapeutic and beneficial purposes. If a person is using a street drug, such as heroin or illicitly using prescription narcotic (opioid) painkillers in a manner of abuse, they may begin to develop a tolerance, as their use quickens into more compulsive patterns of addiction. Due to the highly addictive nature of the majority of opioid drugs, this may occur fast, with the tolerance rising quickly as well.

On the other hand, a person who is using their own prescribed prescription from a doctor may also engage in illicit drug use, as is far too commonplace in the world of narcotic painkillers. This may arise for two reasons—firstly, the individual may purposely seek the high or euphoria from misusing the drug, or secondly, a person may be experiencing such extreme symptoms of pain, that they decide on their own accord to alter the dose or how often they take the drug—either way, a tolerance, and even addiction may result.

It is important to understand that misusing your own prescription constitutes as abuse, and may lead to tolerance and addiction. In the case of the latter example, a person may commonly make this decision because they are in fact already experiencing a tolerance. Any time you feel that your medication is not working in the manner that it should be, or if it is not adequately addressing your symptoms, you should speak to your doctor and leave all medication changes and adjustments in their hands for your health and safety.

Lastly, even individuals with severe and/or chronic pain who take their medications exactly as prescribed may find themselves faced with the reality that their medicine is not sufficiently addressing their pain. This too may be because of tolerance and also a dependence.

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Understanding The Mechanisms Of Drug Tolerance

It is important to understand the difference between physical dependence and addiction when comparing the behaviors consistent with medically-manage prescribed use to those of illicit use. In the case of the former, a person may develop a physical dependence, which, according to the National Institute on Drug Abuse (NIDA), “occurs because of normal adaptations to chronic exposure to a drug,” as that which occurs during many instances of pain management. Physical dependence does not mean a person is necessarily addicted, however, in regard to illicit use, if this dependence is accompanied by compulsive drug seeking, chronic use, and a continuance of use despite the knowledge of the dangers, the person is then experiencing an addiction.

On a biophysical and chemical level, an opioid tolerance primarily occurs because of the ways the drug works towards impacting and changing your brain. Humans have opioid receptors naturally occurring within both their brain and body, due to the fact that we actually have naturally occurring opioids within our body, termed endogenous opioids. It is the activation of these receptors by the drugs, either illicit or prescribed, that causes the desired effects—either the high or euphoria or the pain-relieving qualities (analgesia) that a person seeks.

When a person uses these drugs on a regular or chronic basis, as in instances of prescribed use or addiction, respectively, their opioid receptors are constantly inundated with opiates, forcing their body to decrease the production of their own endogenous versions; as your body comes to rely on the external opiates, a physical dependency is borne. At this point, you find that your body now needs greater amounts of the drug to yield the previous effects. In the medical community, when a patient reaches this point within their pain management, it is commonly referred to as a “a dose ceiling,” or a tolerance. An opiate tolerance is cause for concern, whether you are an illicit user or one who responsibly uses prescribed medications.

Tolerance Within Prescribed Applications

The number of opioid pain medications that are prescribed annually within our country is growing at an astounding rate. With this increase comes the rising demands and concerns that are associated with greater and more frequent use within patient’s lives, one of the greatest perhaps being tolerance. When a patient experiences persistent, intermittent, and/or even overwhelming pain, a variety of opioid pain medications may be used as analgesics. Within these situations, it is the primary goal and focus of the medical provider to manage this pain.

Over time, however, this goal may become more difficult and obstructed as a person gains a tolerance. In these circumstances, many people may, through the course of their pain management, utilize more than one medication, at various points within their treatment, due to both the severity and nature of the pain and also this tolerance. However, as a person’s tolerance increases, the options and availability of well-functioning and applicable drugs drastically narrows.

Now the exact nature and extent of this change varies on several things, namely a person’s unique biology and physiology, the drug(s) in question, the length and intensity of use, and also how many times a person has encountered a pain regimen; these factors hold true for illicit abuse as well. This is called differential opioid tolerance, a situation presented by an article from the journal Anesthesiology.

It is at this point, that individuals—the patient and their family both—may begin to wonder if this tolerance will ever cease or go away? Perhaps a better way of considering this question is not if the tolerance goes away, but instead, how will it change?

Understanding How Drug Tolerance Changes

Foremost, as a person reduces their use, in a medically-managed and tapered way, in order to maintain the best measures of comfort and safety, their body begins to adapt to these chemical changes, creating over time a new threshold for the drug’s effects. Eventually, when a person is completely off the drugs, they will experience a different tolerance. This holds true for both illicit opioid and legitimate prescription drug use. Generally speaking, the physical tolerance lessons to a significant extent, however, this is not to say that the person is exactly returned to the state they were in prior to the drug use. Within this change, there are certain aspects that may influence the outcome that each individual experiences, these include:

  • Genetics — Tolerance may be due to genetics, termed innate tolerance; in this case then, we can infer that a certain measure of a person’s tolerance may never go away. Medscape elaborates, writing “In addition, genetic differences in how drugs are metabolized by the liver is increasingly recognized as a key factor in interindividual and ethnic differences in clinical response.” Certain people may need very small amounts of a drug to achieve a certain effect, whereas others may require more to obtain the same measure of relief or pleasure.
  • Psychological tolerance — For those that use illicitly, many report that even after prolonged periods of cessation, if they begin using again, they will not experience the high or euphoria as they once did. In this respect of pleasure and reward seeking, the full aspect of tolerance may never entirely go away or take a more prolonged period to do so—a person’s mind yet remembers and even craves the sense of satisfaction these drugs once offered. A person may, for a long while after quitting, yet associate feelings of pleasure or comfort with thoughts or behaviors of drug using.
  • Abstinence — Your tolerance will fall—after being abstinent, your physical tolerance for the drug declines, this is true with both illicit and prescribed use. Should you relapse to illicit drugs or return to a previous dosage of a prescription drug, at this time when your body isn’t as accustomed to the effects and dosage of drug you were previously accustomed to, your body, with its decreased tolerance may experience overdose.
  • Decreased instance of withdrawalWithdrawal occurs when a person has developed physical dependence accompanied by a tolerance. This situation presents the danger of a person relapsing in order to stave off the uncomfortable or painful symptoms that manifest at this time. As a person’s tolerance drops, due to reduced use or abstinence, the likelihood that they will encounter these intolerable feelings of withdrawal also decreases. Because of this, the possibility that they will again turn to using substances to create a perceived “normal” state also goes down.

What we do know in terms of drug abuse-related dangers, is that NIDA and others consider addiction to be a disease of the brain. With this diagnosis, even if a person becomes sober and lives a drug-free life, with a reduced tolerance, they may still have concerns of relapsing.

Managing The Concerns Within Medical Applications

Scientists are still working towards fully understanding the complete mechanism of opioid tolerance and pain management. As research progresses, new ways to manage this and treat the resultant pain emerge. It is dually important to better understand and conquer this fast-emerging issue, in order to better circumvent and protect patients from concerns of self-medication, diversion, and abuse, along with more successfully treating their pain. By effectively managing people’s pain concerns, and those of tolerance, the medical community may alleviate some concern of diversion and abuse of prescription drugs.

A Journal of Pain and Symptom Management article presents findings on using Ketamine, a NMDA receptor antagonist, to increase the potential for analgesia in those encountering high doses of opioids during cancer treatment. The paper’s authors suggest that the success may be due to the way it works towards a “reversal of opioid tolerance” that occurs while this drug is used adjacent to the analgesic.

Significantly older, yet still relevant research from 1980 posits that L-tryptophan, an essential amino acid notable largely for its role as a precursor to serotonin, may in fact have another powerful use—administered in 4 g/day as a dietary supplement, this molecule had exceptional impact on individuals who experienced opioid tolerance to morphine. Given to study participants in intervals ranging from two to nine weeks, individuals had “significant relief from pain…and were able to lead more active lives while reducing their daily opiate intake.”

It is thought this is due to the fact that chronic opioid administration hinders a person’s body’s ability to effectively dictate the serotonin turnover rate within the central nervous system. Hence, in supplementing a person’s diet with tryptophan, a better chemical equilibrium may have been created and subsequently a reduced tolerance and more effective process of pain management.

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If you’re concerned that you’re endangering your health or worried that your abuse may be accelerating towards an addiction, please contact today. We can help you learn more about the realities of how drug abuse shapes your life and health and help you find options for treatment.

Anesthesiology - Differential Opioid Tolerance and Opioid-induced Hyperalgesia: A Clinical Reality

Journal of Pain and Symptom Management - Burst Ketamine to Reverse Opioid Tolerance in Cancer Pain

University of Florida Health - Opioid Prescribing in “Naive” or “Tolerant” Patients

U.S. National Library of Medicine - Opioid Tolerance Development: A Pharmacokinetic/Pharmacodynamic Perspective

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