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The Effects of Opioids on the Brain

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Opioids are a class of substances that reduce the perception of pain signals sent to the brain. By this mechanism, when used medically, they are beneficial in helping people to manage a number of pain-related conditions. The illegal drug heroin is an opioid, as are several prescription painkillers, including oxycodone, hydrocodone, morphine, codeine, fentanyl, and others. Opioids have been used to treat cough, diarrhea, acute pain, and more recently, chronic pain. Beyond their pain relieving and cough suppressant properties, opioids also activate reward areas in the brain and are associated with a dose-dependent euphoria. The rewarding effects of these drugs may reinforce the development of opioid abuse behaviors which may, in turn, progress to addiction over time. Addiction causes lasting effects on the brain, which can make it difficult to quit.

Why Do People Abuse Opioids?

Although the prescription opioids can be therapeutic, like heroin, they are also abused by many people who are merely seeking to get high and experience pleasurable effects. Some of these effects include:1,3

  • Pain reduction.
  • A sense of well-being.
  • Pleasure.

People who abuse the pill- or tablet-forms of some opioid medications may crush and snort these drugs, crush and dissolve them in liquid to then inject, or simply take them orally in larger or more frequent doses than prescribed. They may also combine opioids with other drugs to enhance their high. One particularly common pairing involves the combination of opioids with benzodiazepines, which have a calming or sedating effect, and are frequently prescribed to manage anxiety and panic.4 Some examples of benzodiazepines are Valium, Xanax, and Klonopin.4 It is very dangerous to combine substances in this manner, as both opioids and benzodiazepines are sedating, suppress breathing, and impair cognitive functioning.4

In addition to those who abuse opioids for the strict purpose of getting high, some people who are prescribed opioids for pain may begin to misuse their medication as tolerance to the drug effects begins to grow. Someone who builds a tolerance to an opioid requires higher or more frequent doses in order to experience the same effects as before. They may take the medication more often or in higher doses than directed by the doctor. This practice can speed up the development of physiological dependence, in which one’s body requires the drug to function optimally, and eventually addiction, which is characterized by compulsive use regardless of negative ramifications.

Statistics of Use

The abuse of opioids is a serious public health concern worldwide. It has been estimated that approximately 26.4 million to 36 million people abuse opioids across the globe.3 Additional revealing statistics regarding opioid abuse include:5,6,7

  • In 2015, 2 million Americans age 12 or older had a prescription opioid addiction and about 591,000 Americans had a heroin addiction.
  • In 2015, more than 32,000 people died due to opioid overdose.
  • About 23% of people who use heroin become addicted.
  • Approximately 80% of heroin users abused prescription opioids prior to using heroin.
  • Every day more than 1,000 prescription painkiller users are treated in emergency departments.
  • Nearly 50% of all drug overdose deaths in America involve a prescription painkiller.

Side Effects of Use

Again, there are some desirable effects of using opioids, such as pain reduction and a pleasant sense of euphoria.1 However, there are many negative and dangerous side effects associated with using opioids as well, including:1,8,12

  • Nausea and vomiting.
  • Constipation.
  • Impaired attention, memory, and judgment.
  • Dizziness.
  • Drowsiness.
  • Confusion.
  • Slurred speech.
  • Coma.
  • Respiratory depression.
  • Hormonal dysfunction.
  • Muscle rigidity.
  • Hyperalgesia (worsening of pain or increased sensitivity to pain).

How Do Opioids Affect the Brain?

When opioids travel through the bloodstream to the brain, they bind to and interact with opioid receptors located on the surface of certain brain cells.9 When opioids interact with a particular set of opioid receptors in regions near the base of the brain, the release of norepinephrine is suppressed, which can result in reduced blood pressure, respiratory depression, and drowsiness. These are all common signs of opioid intoxication, and the effects intensify as doses increase.9

Opioid use triggers activity within our brain’s reward system, which consists of vitral neuronal circuitry that normally underlies the feelings of pleasure associated with activities that promote survival, such as sex and eating. More specifically, the mesolimbic (midbrain) reward system is activated by opioids. Signals in the ventral tegmental area (VTA) result in the release of the neurotransmitter dopamine in the nucleus accumbens.9 The release of dopamine into this area is responsible for the euphoria users experience when they use opioids.9 Because of these pleasurable feelings, the brain creates a long-term memory associating these positive feelings with opioid use. In time, this conditioning can lead to opioid cravings when faced with triggers, such as old using locations or friends.9

Opioid use can also impact your ability to manage stress. People who struggle with opioid abuse may be more vulnerable to stress, which can lead to relapse and trigger opioid cravings. It’s hypothesized that opioid use increases levels of cortisol, a hormone involved in stress response. Increased cortisol levels may be involved with subsequent activation of the mesolimbic reward system, thereby potentially reinforcing the compulsion to continue use of these drugs. Opioid abuse can become a dangerous cycle, as stress may be a main factor that influenced opioid use in the first place, and it can prompt you to continue using by increasing cravings, making it more difficult to manage stress in healthy ways.9

In the early stages of abuse, the activation of the reward system encourages people to take opioids repeatedly. Long-term abuse of opioids can lead to neuroadaptations, or changes in the brain, that can negatively impact the user. Over time, opioid users will undoubtedly require higher doses of opioids in order to experience the desired effects; this results from a phenomenon known as tolerance. Some degree of tolerance is bound to develop, even in those who use these drugs according to their prescriptions. However, should significant tolerance develop, as it often does in those abusing these drugs, attempts to overcome it by increasing doses could result in a dangerously high risk of overdose. The concept of neuroadaptation is also instrumental in the development of opioid dependence, a process wherein the body comes to eventually require the presence of opioids to function optimally. When opioid dependence is significantly severe, the person will experience several unpleasant withdrawal symptoms when they stop or dramatically reduce use. Chronic use can lead to addiction, which is associated with additional, lasting brain changes. Some of these changes may result in a reduction in an opioid user’s response to natural rewards, such as eating. Even when someone who is addicted quits, the brain doesn’t immediately reverse the effects and return to normal functioning.13

To elaborate on this:

  • Tolerance occurs when the brain cells with opioid receptors on them become less responsive to opioid stimulation, meaning that more of the drug is needed to produce a pleasurable experience that is comparable to experiences of use in the past.9 More specifically, tolerance occurs when more opioids are needed to stimulate the VTA brain cells in the mesolimbic reward system to release the same, previous amount of dopamine in the nucleus accumbens.9
  • Dependence occurs when you need to continue using a substance to avoid the unpleasant symptoms of withdrawal. Symptoms of withdrawal may be created by neuroadaptations in the brain that result from opioid use. For example, when repeated exposure to opioids occurs, neurons in the locus ceruleus—which are associated with wakefulness, breathing, blood pressure, and general alertness—increase their activity.9 When opioids are consistently present within the system, they usually offset the increase in activity.9 However, when opioids are not present, such as when someone attempts to quit or cut back, they are not able to suppress this increased activity, so neurons in this region release excessive amounts of norepinephrine, which leads to symptoms of withdrawal, such as jitters, anxiety, muscle cramps, and diarrhea.9

The dual forces of tolerance and dependence, in part, can lead to compulsive drug seeking and using despite other negative consequences that result from use, such as financial problems, difficulties at school or work, issues within relationships, or legal problems—this is addiction.

Long-Lasting Effects

If you’re dependent on or addicted to opioids, acute withdrawal symptoms will emerge when you attempt to quit. Acute withdrawal symptoms may include:10

  • Excessive yawning.
  • Sweating.
  • Muscle aches.
  • Anxiety.
  • Agitation.
  • Insomnia.
  • Nausea and vomiting.
  • Diarrhea.
  • Goosebumps.

Furthermore, after these symptoms resolve, some long-term withdrawal symptoms may persist due to changes in brain chemistry. Some protracted, or long-term, withdrawal symptoms include: 11

  • Chronic anxiety.
  • Depression.
  • Sleep disturbances.
  • Fatigue.
  • Emotional numbness.
  • Irritability.
  • Decreased ability to focus on tasks.

The unpleasant symptoms of acute and protracted withdrawal may lead users to relapse in order to immediately alleviate these unwanted symptoms. Therefore, it is crucial that those who want to quit opioids seek professional detox and addiction treatment. These programs can provide you the support you need to avoid relapse and stay sober in the long run. Attending support groups and/or therapy sessions once your treatment program ends may be beneficial as well in order to build upon the skills you learned in rehab and receive help and encouragement from your peers.

Sources

  1. National Institute on Drug Abuse. (2016). Misuse of Prescription Drugs: Which Classes of Prescription Drugs Are Commonly Misused?
  2. National Institute on Drug Abuse. Opioids.
  3. National Institute on Drug Abuse. (2014). America’s Addiction to Opioids: Heroin and Prescription Drug Abuse.
  4. National Institute on Drug Abuse. (2017). Benzodiazepines and Opioids.
  5. American Society of Addiction Medicine. (2016). Opioid Addiction: 2016 Facts & Figures.
  6. National Institute on Drug Abuse. (2015). Prescription Opioids and Heroin: Prescription Opioid Use Is a Risk Factor for Heroin Use.
  7. Centers for Disease Control and Prevention. (2017). Prescription Opioid Overdose Data.
  8. Benyamin, R., Trescot, A.M., Datta, S., Buenaventura, R., Adlaka, R., Sehgal, N., … Vallejo, R. (2008). Opioid Complications and Side Effects. Pain Physician, 11(2), 105–120.
  9. Kosten, T.R. and George, T.P. (2002). The Neurobiology of Opioid Dependence: Implications for Treatment. Science & Practice Perspectives, 1(1), 13–20.
  10. MedlinePlus. (2017). Opiate and Opioid Withdrawal.
  11. U.S. Department of Health and Human Services: Substance Abuse and Mental Health Services Administration Center for Substance Abuse Treatment. (2010). Protracted Withdrawal. Substance Abuse Treatment Advisory: News for the Treatment Field, 9(1), 1–8. 
  12. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Publishing.
  13. University of Utah. (n.d.). Drug Use Changes the Brain Over Time.

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