Opioid Use And Its Effect On The Brain

The serious health crisis in the United States today due to the opioid addiction epidemic is putting the country and its institutions in serious trouble.  The point is that these problems are not, at the moment, a feasible solution in the short term.

80% of the world’s opioid production, either through prescription or originating in the illegal market, is consumed in the United States. Health services cannot cope with the many deaths caused by opioid use.

It is estimated that around 200 people die every day in the country from opioid addiction.  But, what is more, a total number of deaths from this cause is already comparable to the deaths of American soldiers in the Vietnam War.

The data that is coming to us now about the high incidence of addiction that is generating the consumption of opioids such as OxyContin or morphic derivatives such as Fentanyl have triggered all the alarms. Statistics speak of addiction in more than 10% of patients only in the first five days of use.

This crisis has already been declared a “national public health emergency” in the United States. Therefore, below we are going to see what opioids are, how they act in the human brain and what studies are currently being carried out on the matter.

What are opioids

Opioids are pain relievers whose  active ingredients are extracted from the capsule of the opium plant. They are long-known natural substances found in poppy seed juice. In 1803 an opium alkaloid, morphine, was isolated; derivatives such as codeine and heroin were subsequently developed.

Opioids or narcotics are a strong pain reliever that is prescribed for acute or chronic pain, especially cancer-related pain. The problem is that there are many risks associated with its use, mainly the high rates of addiction that they are generating in patients. We say patients because many of those people who show addiction are people who were prescribed opioids after a surgical operation, an accident or a broken arm.

Until 1914 opium was legal in the United States but it was banned due to the high tolerance it generates and the serious withdrawal syndrome it causes. It is one of the most addictive drugs, since it reaches the brain very quickly. It produces a powerful effect of analgesia, drowsiness and gratifying sensations of pleasure.

There are three classes of opiate substances:

• Opium alkaloids, such as morphine (the prototypical opiate) and codeine.
• Semi-synthetic opioids, such as heroin and oxycodone.
• Fully synthetic opioids, such as pethidine and methadone.

How do they act in the brain?

All drugs of abuse activate the pathways of the brain’s reward system. This system comprises the ventral area of ​​the tegmentum, the nucleus accumbens, and the prefrontal cortex. The perception of pain involves the participation of various neural structures.

Through the afferent pathways, this substance reaches regions of the brainstem and diencephalon, including the thalamus and the periaqueductal gray matter. In addition, synapses occur in the thalamus, projecting to other areas such as the frontal lobe, the limbic system or the hypothalamus, mainly.

Opioids act on the afferent system (pathways by which the stimulus travels to the brain) but they also act on the efferent system (reverse pathway). They also activate the excitatory connections between the periaqueductal gray matter and the raphe nuclei. The pain stimulus is reduced by inhibiting GABA-containing interneurons.

What is being done to tackle the crisis generated by the use of opioids?

There are many fronts that this opioid consumption crisis has opened. There is a very important demand for assistance from people who have developed addiction to these drugs. In the absence of new prescriptions, these people are turning to the illegal market and replacing them with heroin, which is cheaper and easier to obtain.

Most notable is the work being done by the Mount Sinai research team in Florida. This research has focused on an intracellular network that controls the actions of opioids in the periaqueductal gray matter, as this network plays a very important role in the analgesic response.

These researchers managed to block the RGSz1 gene, responsible for encoding the negative modulator of opioid tolerance. The result was a significant reduction in pain with much lower doses of medication. In addition, a less rewarding effect was achieved, an important factor in the development of addiction.

The team is currently evaluating the opioids that are currently prescribed. They want to classify them for their abuse potential based on the RGS protein they activate. Their discoveries can be instrumental in the fight against this serious epidemic of opioid use.