Opioid Mechanism Of Action: How Do Opioids Work In The Brain & Body?

Last Updated: May 5, 2020

Reviewed by Michael Espelin APRN

Opioids are pain-relieving substances that can come from natural sources or are produced synthetically. The use of opioids for pain can be traced back to centuries. Opioid mechanism of action is generally the same regardless of what kind of medicine it is and how it is obtained. Read further to find out about the opioids mechanism of action, how opioids work, and the various types of opioid receptors.

Opioid Mechanism Of Action

Opiates are naturally obtained from the opiate poppy plants in Africa and Asia. They can also be synthetically produced using chemicals into the various types of synthetic and semi-synthetic opioid painkillers. The poppy plant had been used for its pain-relieving and sleep-inducing properties for centuries. According to this study about pain pharmacology, chronic pain has an incidence of about 20-25% worldwide.

young woman taking prescription pill.

Exogenous And Endogenous Opioids

These medications are considered one of the primary classes of drugs to treat pain. Those synthetic opiates that are not naturally produced by the body are called exogenous opioids. The primary purpose of them is to offer pain relief by blocking or reducing the pain signals in the brain and spinal cord.
Mechanism of action of opioids includes working in the central and peripheral nervous systems. The brain produces endogenous opioids which include endorphins and enkephalins.
They attach with opioid receptors in the body and help reduce the release of neurotransmitters sending pain signals to the brain. These endogenous opioids are produced in small quantities in the body for a short duration. Exogenous opioids can then be administered to treat severe or chronic pain. The main effect of these drugs in the central nervous system is in the spinal cord. In the peripheral nervous system, their main function is in the peripheral tissues and the gastrointestinal tract. This function of opiates in the peripheral nervous system results in inflammation reduction along with pain relief. Opioid-induced constipation is the result of its effect on the submucous plexus in the wall of the gut.
Opioids mechanism of action is quite similar to that of Cannabidiol (CBD) which acts on cannabinoid receptors in the peripheral and central nervous system and the brain. Based on the latest research, CBD and opioids can be considered to be substitutes of each other. However, more research is required on this matter to prove the efficacy of the use of CBD instead of opiates. CBD is also being used now to treat opiate addiction and to manage the related withdrawal symptoms.

Opioids Mechanism Of Action Through The Pain Pathways

The Opioid analgesic effect works by affecting the brain receptors in the pain pathways. According to this study about opiates and pain, several endogenous opioid peptides and their receptors are located in the pain pathways. Local application of them at those critical points can result in the modulation of the response to pain.

What Are Opioid Receptors?

The human brain and body have opioid receptors at various key points. There are three main types of them, as described in the study about the opioid pharmacology:

  • Delta opioid receptors
  • Kappa opioid receptors
  • Mu opioid receptors

These receptors are located on the neuronal cell membranes. Each receptor attracts a different type of drug, but the general mechanism of action is the same. They act on these receptors as agonists, antagonists, or partial antagonists. Most of them bind to the Mu-opioid receptors in an agonist action to offer the desired result of analgesia.

Opioids Work In The Brain And Body

When pain is caused as a result of potential or actual tissue damage, primary sensory neurons transmit the pain signals to the brain. Opiates work by attaching with the brain receptors. They inhibit the release of neurotransmitters from the primary afferent terminals in the spinal cord as well as activate the descending inhibitory controls in the brain. This results in the sensation of pain relief as well as a relaxing and sedative effect.
When these meds are taken, they work in two major ways in the brain and the body: on the presynaptic nerve terminal and the postsynaptic neurons. Opioids MOA includes inhibiting the release of neurotransmitters as part of its presynaptic action, thus inhibiting pain signals to reach the brain. However, this action can also act on the excitatory neurons, which are then inhibited by the postsynaptic action of opioids. Depending on the various kinds of neurons in the body and the different opioid receptors, different medications are taken to achieve the desired result.

When Opioids Will Start Acting?

Several methods of administration are typically used with opioids which include the following:

  • Oral tablets
  • Nasal spray
  • IV line
  • Intramuscular shot
  • Suppository
  • Skin patch
  • Shot into the spinal cord.

These drugs are usually fast-acting drugs with the analgesic effects starting within 15 to 20 minutes. There are different types of these painkillers depending on the duration for which their effects last and its onset speed. These include the rapid onset, short-acting, and long-acting ones. The short-acting meds can provide pain relief for 3 to 4 hours, whereas the mechanism of action of long-acting pills can offer pain relief for a good 8 to 12 hours.

woman waiting opioids to act

How long opioids stay in urine depends on several factors which include the type of drug used, the dose consumed, metabolism rate, weight and gender of the individual, and some other factors. But generally, this can range anywhere from 1 to 7 days.

Beating The Opiate Abuse And Addiction

Why do people abuse opioids? While being one of the best analgesic agents, their mechanism of action tend to cause physical dependence if used for a long duration. Opioids effects on the brain also include a feeling of “high” and sedation which makes it a cause for abuse. Patients’ bodies become tolerant to it with prolonged use which results in them taking higher doses at more frequent intervals.

Rehab comprises several phases through which a patient’s body is rid of addiction. This includes detoxification step, medically-assisted treatment, behavioral and psychological therapies, and other modes of treatment.
The usual opioid withdrawal timeline is anywhere between 6 hours to a month with the withdrawal symptoms peaking at 72 hours. A good rehabilitation center can help patients manage withdrawal symptoms and help them achieve sobriety. They also offer aftercare support programs to prevent relapse. With proper addiction treatment and support from family, friends, and loved ones, addiction to opiates can be successfully beaten.

Page Sources

  1. Kanjhan R, Opioids and Pain, https://www.ncbi.nlm.nih.gov/pubmed/8582088
  2. Diego Fornasari, Pain Pharmacology: Focus On Opioids, 2014, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4269136/
  3. Hasan Pathan, John Williams, Basic Opioid Pharmacology: An Update, 2012, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4590096/

Published on: September 17th, 2019

Updated on: May 5th, 2020

About Author

Peter J. Grinspoon, MD

Dr. Peter Grinspoon is an experienced physician with long-term clinical practice experience. As a former analgesic addict, Dr. Grinspoon knows precisely how important it is to provide patients with effective treatment and support. Medical writing for him is the way to communicate with people and inform them about their health.

Medically Reviewed by

Michael Espelin APRN

8 years of nursing experience in wide variety of behavioral and addition settings that include adult inpatient and outpatient mental health services with substance use disorders, and geriatric long-term care and hospice care.  He has a particular interest in psychopharmacology, nutritional psychiatry, and alternative treatment options involving particular vitamins, dietary supplements, and administering auricular acupuncture.


Leave a comment