The scourge of fentanyl: How the devastating drug affects the body

Overdose deaths of this opioid have increased by more than 90% in three years in the United States

Two fentanyl users in Tijuana (Mexico), in October 2022.
Two fentanyl users in Tijuana (Mexico), in October 2022.Salwan Georges (The Washington Post / Getty)

In the last decade, the recreational use of fentanyl has increased considerably, which has taken and continues to take a heavy toll on the United States. In a matter of three years, overdose deaths from the opioid have increased by more than 90%. In 2021, some 70,000 deaths were attributed to fentanyl in the country.

But it is no longer an exclusively American phenomenon. For example, according to the statistics from Spain’s National Plan on Drugs (EDADES 2022), 15.8% of the population aged between 15 and 64 admit to having taken prescription or non-prescription opioid analgesics on some occasion. Specifically, the consumption of fentanyl has increased from 3.6% in 2020 to 14% in 2022.

What’s more, it should be noted that the drug is often combined with alcohol, heroin or methadone, which increases its effects and, consequently, addiction to the drug or even death.

More addictive, toxic and cheap

Fentanyl belongs to the opioid category of drugs (which can be of natural or synthetic origin), which are one of the most powerful pain relievers available to humankind. The natural substance, known as opium, is obtained from the Papaver somniferum plant — better known as opium poppy — whose use has been known since ancient times.

Despite being very useful drugs in medicine, the black market for synthetic opioids has grown rapidly in recent years. It has become the latest trend in the world of psychoactive substances. These narcotic compounds have properties similar to morphine and heroin, but have greater addictive potential and toxicity. They are also cheaper to manufacture and, therefore, cheaper for the consumer, increasing the risk of overdose.

Among these new laboratory drugs, fentanyl stands out, as it is 50 times more powerful than heroin. Synthesized for the first time in 1960 by the Belgian physician and researcher Paul Janssen, it has been used as an intravenous analgesic since 1963. But in the 1970s and 1980s, it began to be consumed for other purposes.

How it affects the brain

The human body contains more than 20 endogenous opioid peptides, such as endorphins, enkephalins and dynorphins. They act through specific receptors and allow synthetic substances such as fentanyl to locate specific places to produce their effects. Within the central nervous system, these compounds stimulate what we know as the brain’s reward system. This circuit comprises different structures — the prefrontal cortex, ventral tegmental area, nucleus accumbens — and is responsible for regulating pleasure, memorizing stimuli from our environment, facilitating learning and controlling our behaviors.

The drugs stimulate this system to such a high degree that they cause neuroadaptations (brain changes) and promote tolerance (increasing doses will be needed to achieve the desired effects), dependence, addiction and withdrawal syndrome.

The pleasurable or reinforcing effect produced by fentanyl depends on the mesolimbic dopamine system, the pathways used by the neurotransmitter dopamine to distribute itself in the brain. However, after continued consumption, the first neuroadaptations begin to take place. These affect the dorsal striatum, a region involved in the formation of habits.

Demand for the drug

If consumption is interrupted, it triggers a negative emotional state that activates the stress circuit. As a result, the release of the noradrenaline neurotransmitter rises, the amygdala is turned on and levels of the corticotropin-releasing factor, a hormone related to emotional stress, also increase.

This whirlwind of reactions causes symptoms linked to the activation of the autonomous nervous system, whose function is to regulate the activity of the internal organs — heart, liver, reproductive organs, sweat glands, etc. — to adapt to the demands of the environment. These organs produce tremors, sweating, vomiting and tachycardia, i.e. the symptoms that come with withdrawal syndrome when the consumption of the drug is stopped.

In addition, the desire to obtain and consume the substance is related to the neuroadaptations in the cerebral cortex, the hippocampus and the amygdala, which intensify the feeling when receiving signals associated with consumption.

All these transformations promote addiction, a chronic disease, which makes giving up fentanyl an increasingly difficult task. The body thinks it needs the drug in order to function.

Concepción Blasco Ros is a doctor in Psychobiology, University of Valencia. Sandra Montagud Romero is a PhD assistant professor, University of Valencia

This article was originally published on The Conversation.

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