We are in the midst of an opioid epidemic. More than 27 million people use opioids and their derivatives for acute and chronic pain treatment or as recreational drug abuse. Headline news occur daily regarding the addictive damage and growing prevalence. However, what is often not reported are the adverse health effects of opioid use regardless of properly prescribed or addictive use. These adverse effects on the body must be understood by those who must use the drugs or are considering them as a part of their treatment. These powerful drugs do help many with severe, disabling pain, but there is price that the body pays with long-term use.

Common opioids include morphine, heroin, codeine, Oxycontin, Vicodin, fentanyl, and others. Ordinary side effects with narcotics/opioids include constipation, nausea, and drowsiness. For the millions who use long-term opioids for moderate to severe chronic pain, side effects often occur that go beyond the usual adverse effects. Changes occur within the endocrine system and immune system. Even cancer risk may increase with use of these medications.

Opioids affect numerous tissues as opioid receptors are primarily found in the brain and peripheral nervous system. These receptors are also found in the lungs, spleen, liver, small and large intestine, adrenals, kidneys, testes, ovaries, uterus and several types of immune cells.

Opioids Change the Endocrine System

Research shows that major endocrine changes occur with opioid intake. These medications affect the hypothalamic-pituitary-gonadal (HPG) axis and the hypothalamic-pituitary-adrenal (HPA) axis. When it affects the HPG axis, it creates opioid-induced androgen deficiency. (OPIAD) Opioid-induced androgen deficiency was described in the medical literature about 40 years ago, yet many may not know about this risk even today.

Sex Glands Affected

Opioid-induced androgen deficiency occurs as the result of opioids dysregulating neuroendocrine signals from the brain to the sex glands – testes and ovaries. Production of androgen hormones declines. Androgen hormones are naturally found in men and women. Men have much higher amounts of androgen production than women. Androgen hormones include testosterone, DHEA, DHT and others.

Loss of androgen function in the body from opioid intake results in decreased libido or loss of interest in sex, fatigue, osteoporosis, osteopenia, loss of menstrual cycle for women, and erectile dysfunction in men. It may even cause impaired cognitive function, mood disorders, and infertility. Studies show that 53 to 90 percent of male patients experience androgen deficiency with opioid use.

Women who consume opioids were found to have 48 to 57 percent less testosterone, estradiol, and DHEA. Daily intake of 100 mg or more of morphine or morphine equivalents for more than a few weeks induced OPIAD. Even a single dose of 30 mg of morphine such as after surgery has been shown to decrease testosterone production.

Adrenal Glands Affected

The July 2018 journal Mayo Clinic Proceedings recently reported adrenal insufficiency may occur in the 9 to 29 percent of patients receiving long-term opiate therapy. Opioids may interfere with the natural production of the adrenal hormones cortisol and DHEA causing adrenal insufficiency.

Adrenal insufficiency in chronic pain patients is poorly recognized. Even in those who don’t use opioids, adrenal insufficiency is often hard to identify and diagnose within the medical system. Adrenal insufficiency occurs because opioids inhibit the communication pathway between the brain to the adrenal glands or hypothalamic-pituitary-adrenal (HPA) axis. The pathway is blocked from doing its job which prevents the adrenal glands from releasing cortisol and other adrenal hormones.

Adrenal insufficiency symptoms include fatigue, muscle weakness, blood sugar dysregulation, poor appetite, depression, irritability, loss of libido, nausea, craving salty foods, sweating, and other symptoms. Many of these symptoms are often ignored and are attributed aging, stress, or just never having recovered after an injury or surgery.

Immune System and Gut Affected by Opioids

Cellular and human studies show that opioids have powerful negative effects on the immune system. Opioids dampen several immune responses which contributes to pain relief but simultaneously impairs immune function. Opioid use is likened to a double-edge sword for the immune system.

Opioids decrease the activity of natural killer (NK) cells. This adverse effect causes suppression of the natural killer cell activity. Natural killer cells are a type of lymphocyte or white blood cell that is at the front line of immune defense. Their job is to reject or “kill” tumor and virally infected cells. NK cells interact with cells throughout the body and help control inflammation and autoimmune disorders.

Several other changes occur with the immune system leading to suppression of immune activity and altered gut structure. T-cell and macrophages are impaired which affects infection risk and defense activity. The lining of the gut barrier is weakened creating increased risk of intestinal permeability or Leaky Gut Syndrome.

Research published February 2018 shows that morphine/opioid intake causes distinct adverse changes in the gut. Even one day of opioid use has been shown to shift the gut flora in a negative manner. This shift in gut flora is considered the cause of the common symptoms of nausea, constipation, etc. Morphine and opioids increase the number of bad bacteria in the gut, suppress the beneficial bacteria that help the brain with stress management. Bile acids and detoxification processes were found to also be significantly impaired. The study recommended the need to maintain healthy gut flora and balance if using opioids. Clearly this study shows a marked change in gut health.

This information is essential for those even with short-term use with outpatient surgery, colonoscopy, or other procedures that may use opioids. Long-term medication use and those who have dysbiosis and Leaky Gut Syndrome due to other underlying concerns will likely find that the gut problem is locked in and more difficult.

Another consequence of opioid-induced immune suppression is the effect on some viruses. Opioids can cause activation of several viruses and subsequently worsen disease pathology. In HIV patients, opioid use worsens the toxicity of the HIV virus within the body and central nervous system. It even limits the ability of the nervous system to recover from the toxic damage.

Hepatitis C, which is a virus that affects the liver, worsens with chronic opioid use and abuse. Opioids increase oxidative stress in the immune system which worsens the disease process of hepatitis C.

Opioid receptors occur also in the lung, which may lead to increased risk of certain types of lung infections like common community-acquired pneumonia. In a population-based case-control study of adults age 65 to 94, researchers identified that opioid users had a higher risk of pneumonia after exposure to the influenza virus due to opioid-induced immune suppression.

Other research shows that opioid use prevents the ability of the white blood cells to protect against the herpes virus, HSV-1. It can even cause the virus that is dormant in the body to reactivate. Medical literature shows that patients given epidural morphine after cesarean or C-section had a higher prevalence of HSV-1or caused the oral herpes to reactivate.

Morphine and Cancer

Individuals who are fighting cancer need to be aware of a potential double-edge sword with morphine/opioid use. Medical literature provides helpful, yet controversial and even contradictory, findings for morphine and its effect on cancer. Some studies have revealed that opioids may promote cancer growth in some types of cancer. Discuss these concerns with your medical providers before taking any action in using or stopping these medications. Much more research needs to be done and individual treatment needs must be appropriately managed. Here are some recent findings that indicate increased risk.

Cellular studies in 2015 demonstrated that angiogenesis (blood vessel growth) and triple negative breast cancer cells grew when exposed to therapeutic levels of morphine. Thus, breast cancer progressed.

January 2018 research shows that surgical patients treated with opioids and ‘volatile’ anesthetics like ketamine, had greater loss of natural killer cell activity, more immune suppression, and greater recurrence of some cancer types.

More Americans suffer from moderate to severe chronic pain 2 than cancer, heart disease, and diabetes combined. The information brought here is meant to help individuals see that their health may have negatively changed due to the medication’s side effects rather than coincidental or the consequence of age. Chronic pain management patients need a team approach with appropriate drug management and other modalities.