Over the past decade, recreational use of fentanyl has increased substantially, which has taken and continues to take a heavy toll in the United States. Within three years, opioid overdose deaths increased by more than 90 percent. In 2021, about 70,000 deaths were attributed to fentanyl in the country.
But it is no longer an exclusively American phenomenon. For example, according to statistics from the Spanish National Plan on Drugs (EDADES 2022), 15.8% of the population aged between 15 and 64 admit to having taken opioid analgesics with or without a prescription on occasion. Specifically, the use of fentanyl increased from 3.6% in 2020 to 14% in 2022.
Furthermore, it should be noted that the drug is often combined with alcohol, heroin or methadone, which increases its effects and, consequently, drug addiction or even death.
More addictive, toxic and cheap
Fentanyl belongs to the category of opioid drugs (which can be of natural or synthetic origin), which are one of the most powerful painkillers available to mankind. 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 similar properties to morphine and heroin, but have greater addictive potential and toxicity. They are also cheaper to produce and, therefore, cheaper for the consumer, increasing the risk of an overdose.
Standing out among these new laboratory drugs is fentanyl, 50 times more potent than heroin. Synthesized for the first time in 1960 by the Belgian doctor 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 target 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 includes several structures: the prefrontal cortex, the ventral tegmental area, the nucleus accumbens and is responsible for regulating pleasure, memorizing stimuli from our environment, facilitating learning and controlling our behaviors.
Drugs stimulate this system to such a high degree that they cause neuroadaptations (brain changes) and promote tolerance (increasing doses will be required to achieve the desired effects), dependence, addiction, and withdrawal syndrome.
The pleasurable or strengthening 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 occur. These affect the dorsal striatum, a region involved in habit formation.
Application for the drug
If consumption is stopped, a negative emotional state is triggered which activates the stress circuit. As a result, the release of the neurotransmitter norepinephrine increases, the amygdala is activated, and levels of corticotropin-releasing factor, a hormone related to emotional stress, also increase.
This whirlwind of reactions causes symptoms related to the activation of the autonomic nervous system, whose function is to regulate the activity of the internal organs of the heart, liver, reproductive organs, sweat glands, etc. to adapt to the demands of the environment. These organs produce tremors, sweating, vomiting and tachycardia, that is, the symptoms that accompany the withdrawal syndrome when the consumption of the drug is stopped.
Furthermore, the desire to obtain and consume the substance is related to neuroadaptations in the cerebral cortex, hippocampus and amygdala, which intensify the sensation when cues associated with consumption are received.
All of these transformations promote addiction, a chronic disease, which makes giving up fentanyl an increasingly difficult task. The body thinks it needs the drug to function.
Concepcin Blasco Ros is doctor in Psychobiology, University of Valencia. Sandra Montagud Romero is PhD assistant professor, University of Valencia
This article was originally published in The Conversation.
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