Globally, opioid overdose deaths are more common than you think. It is one of the most important public health concerns, having adverse implications on individuals, families and societies worldwide. Widespread misuse of prescription opioids, drug abuse due to prevalence of illicit drugs like heroin, and the blooming of synthetic opioids, have all led to an opioid crisis.
Opioids, including natural opiates like morphine and codeine, are derived from the latex of the unripe seed pods of the poppy plant (Papaver somniferum). This plant produces alkaloids such as morphine, codeine, thebaine, and papaverine, which act on brain receptors to produce analgesic and sedative effects.
Commonly used for the treatment of pain, their non-medical misuse and use without medical supervision can lead to opioid dependence and other health problems.
What happens in opioid overdose
Opioid use can lead to death due to the effects of opioids on the part of the brain which regulates breathing. According to the WHO, an opioid overdose can be identified by a combination of three signs and symptoms:
pinpoint pupils
unconsciousness
difficulties with breathing
Risk factors for opioid overdose
There are a number of risk factors for opioid overdose. The WHO says, these are:
having an opioid use disorder
taking opioids by injection
resumption of opioid use after an extended period of abstinence (e.g. following detoxification, release from incarceration, cessation of treatment)
using prescription opioids without medical supervision
high prescribed dosage of opioids
using opioids in combination with alcohol and/or other substances or medicines
having concurrent medical conditions such as HIV, liver or lung diseases or mental health conditions
New research
However, researchers at the National Institutes of Health (NIH) have recently discovered a potent new opioid compound that may provide excellent pain relief without the harmful side effects usually associated with such medications, potentially mitigating these dangers. The findings were published in Nature.
The NIH team focused on nitazenes, a family of synthetic opioids that were first created in the 1950s but later discontinued because of their tremendous potency and related dangers.
Rather than completely discarding these substances, researchers re-examined them to see whether their analgesic qualities could be preserved while lessening their negative effects. Their answer appears to be yes.
The discovery from FNZ to DFNZ
Using cutting-edge imaging methods, the researchers first examined a substance known as FNZ and tracked its passage through the brain. Although FNZ only momentarily penetrated the brain, its analgesic effects persisted for considerably longer, prompting researchers to investigate more.
This led them to DFNZ, another substance produced by the body.
What they discovered was surprising. Although DFNZ functioned considerably differently from conventional opioids, it proved to be a very efficient pain reliever. “Our goal was to study the profile, or pharmacology, of these drugs,” said Michael Michaelides, Ph.D., senior author and NIDA investigator. “We wanted to decrease the potency and create a potential therapeutic. What we discovered exceeded our expectations.”
Strong pain relief, without dangerous side effects
DFNZ demonstrated potent and sustained pain alleviation in animal experiments. However, in contrast to widely used opioids, it did not seem to induce respiratory depression, which is a significant contributing factor to lethal overdoses.
Its safety profile after repeated use was even more remarkable. Because the medication did not cause tolerance, its efficacy did not wane with time. With the exception of occasional mild irritation, it did not cause dependence or severe withdrawal symptoms.
Given that these effects are practically expected with traditional opioids, these findings are quite noteworthy.
A different kind of “reward” response
Opioids' potential for addiction, which is frequently caused by how they alter the brain's reward system, is one of the main worries. In order to test this, the researchers looked at whether the animals would consistently seek out the medication. The animals did self-administer DFNZ, but when the medication was taken away, their conduct rapidly changed. They gave up looking for it.
In contrast, drug-seeking behaviour usually continues even after the drug is no longer available when it comes to narcotics like heroin, morphine, or fentanyl.
The way DFNZ interacts with brain chemistry could be the cause. DFNZ causes a slower, more regulated release of dopamine than conventional opioids, which cause quick surges associated with euphoria and addiction. This could lessen the chance of developing intense drug cravings.
“DFNZ has an unprecedented pharmacology for an opioid,” Michaelides said. “It is a potent and high-efficacy analgesic, but in certain contexts it resembles partial agonists, drugs that activate the receptor with low efficacy, which is what scientists think is needed for safety. Its capacity to be administered at therapeutic doses without producing respiratory depression is very important."
Because of its distinct profile, researchers think it may be able to treat opioid use disorder in addition to being a better analgesic.
What follows
The research is still in its early phases, but the results are encouraging. The medication has only been tried on animals thus far.
Before requesting permission to start human trials, the NIH team intends to carry out additional research. If they prove effective, DFNZ may eventually be applied in a variety of contexts, including addiction treatment, chronic pain management, and post-surgical care.
A cautious but hopeful step forward
Experts advise caution for the time being. Many medications that show promise in preliminary research do not necessarily convert into human treatments that are both safe and effective. However, a medication that may provide potent relief without the typical hazards of addiction and overdose has long been a distant dream.