Opioid overdose: Signs and reasons of overdose

Opioids are well-known pain-relieving agents. They reduce pain perception by inhibiting the damaged cells from releasing pain messages. The neurons now will have no messengers to process and sense pain resulting in pain relief. However, many people worldwide are addicted to opioids and are victims of overdose. The significant sign of opioid overdose is respiratory depression. The opioid fentanyl is 100 times more effective than drugs like morphine and heroin.

Neurobiology behind opioid addiction

If you or your loved ones are victims of overdose, you should understand the neurobiology behind it. This explains why you or your friends are not “bad,” rather victims of biological effects. The force behind overdose is addiction. It makes you “want more” though it’s harmful. When you take opioids, they reach your brain because they are neural targeting agents. The drug binds to opioid receptors in the brain and release dopamine from the VTA and NAs.

Dopamine gives you the sense of pleasure and motivates you to seek the same experience again. This doesn’t mean dopamine is encouraging you to take the same drug or do the same activity. Learning and memory, which are the roles of surrounding brain parts, urge you to do the same activity for the same intense experience. With this continuous pattern, you fall into the cycle of addiction.

The brain slows down and decreases their production to compensate for the elevated levels of opioid and dopamine receptors. As a result, the addict will have to take vast amounts of the drug for the satisfying intense experience– tolerance. Dependence is apparent in later stages.

The basic idea behind tolerance and dependence is that the abuser alters the physiological baseline– high is the new normal.

Before opioid exposure, the dopamine levels are at a steady-state for a spontaneous sense of pleasure. Due to excess intake, the DA releases reduce though the addict performs normally pleasurable activities without any opioid intake.

What happens with an opioid overdose?

The pathway that explains how opioid overdose affects you involves the role of locus coeruleus (LC). When opioid molecules bind to receptors in the LC, the production of noradrenaline (NA) reduces. Opioids attack the converting enzyme, which converts ATP to cAMP, which triggers NA release.

This inhibition process prevents NA from performing its normal wakefulness activities and maintaining breath rate and blood pressure. As a result, the hyperactive NA neurons increase NA release, making the consumer feel more or less normal. This process generally rests if there is no further drug use for a few days or weeks.

Prolonged and excessive drug use intensifies this compensation activity. When the addict suddenly stops the intake, due to the excess precursors and enzyme levels, the production of cAMP and NA release is enormous, resulting in the withdrawal symptoms. These symptoms include anxiety and jitters. A sudden overdose of NA can lead to high blood pressure, stroke, or even death.

What are the signs of an opioid overdose?

Respiratory depression is the most important diagnostic sign of opioid overdose. If given to opioid sensitive patients, it can result in rapid respiratory decline and distress. Disturbing and low breath rate (also in apnea) when the person is not in sleep is a potent signal. 

The oxygen saturation reduces to less than 90%, also suggesting carbon dioxide accumulation. Pulmonary edema is apparent in the later stages due to stress on the thoracic cavity. This condition may also worsen, leading to acute lung failure.

Gut lining complications are evident due to indigestion and renal failure. Hypothermia is also a sign due to misguided attempts of reversing intoxication. Additionally, lying idle for a long time due to stupor can lead to muscle complications and subsequent compartment syndrome.

All other signs are similar to typical drug poisoning and are not consistently present to diagnose an opioid overdose. Besides, constriction of pupils (miosis) accompany the condition but is insufficient for diagnosis (also a consequence of poisoning and sedation). Also, the doctor also checks for fentanyl patches.

Can opioids relieve depression? Can it be a reason for addiction?

Antidepressants can treat minimal neuropathic pain; similarly, opioids are neuromodulators and can treat depression upto a significant level. 

Depression suggests a lack of pleasure, opioid dysfunction, and endorphin deficiency, which solves the relation. 

Endorphins are endogenous opioids, which also bind to mu-opioid receptors. Other studies also indicate that mu receptors are involved in emotions and mood, along with delta and kappa opioid receptors. However, you should understand that opioids are not potential treatments of depression, and withdrawal can elevate depression symptoms.

  • Mu agonist relieve depression and increase tolerance
  • Delta agonists improve mood
  • Kappa agonists worsen depression

Opioids also increase the level of cortisol (the stress hormone). This may lead to their consumption in the first place or the reason for subsequent addiction.

What are the potential treatments for opioid overdose?

Drugs used to treat opioid overdose attach to the mu receptors and work more or less in the same fashion. The duration difference makes these drugs potential medications.


Unlike other drug treatments, methadone has a lasting effect (for days). It may cause dependence, but its activity produces minimal tolerance and alleviates cravings. Its therapy can also normalize the hormone disruptions (for example, cortisol). It reduces relapse and encourages patients to focus on personal and professional life. 

Stopping this medication before completing the dosage may increase the risk of relapse. Its longer active derivative is LAAM. However, cardiovascular concern limits its use. The dose is subjective.


Naltrexone avoids relapse only after complete detoxification; else it increases the risk of withdrawal. It takes control of the opioid receptors and prevents unnecessary stimulations. The subjective dosage will not drive any motivation towards opioid use. Naltrexone, when used in combination with clonidine, helps in spontaneous detox and suppresses the excess NA.

What are the different ways of prevention?

The primary reason for overdose is the ease of access. You and the doctor should carefully monitor your friends’ access to the drug via multiple sources– Make sure you limit their exposure to excessive opioids quantities. The painkillers of relatives on opioid treatments are easy access. Doctors should monitor the drug levels and identify patients who may receive them from inappropriate sources.

Finally, the consumer should understand that opioids do not relieve all kinds of pain. Moreover, they are lethal when consumed inappropriately.

Related: Pain relief strategies: How does your psychology influence the experience?

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