The rising need for non-addictive pain medication can be largely attributed to the opioid crisis prevailing in the US. Out of 72,000 Americans dying in 2017 from drug overdose, at least 2/3rd is related to opioid use.
Seeking fast relief from pain is one of the most common reasons for a doctor visit. None can deny that. Although there are a number of pain-relieving medications, about 20% of patients are prescribed opioids. You may hear doctors calling it an opiate or a narcotic. These are mainly prescribed to treat severe pain caused by a fractured bone or a major surgical procedure.
Opioids are derived from poppy seeds. Morphine, codeine, oxycodone and hydrocodone are commonly used opioids for pain management. Medications prescribed to treat a range of painful situations starting from simple headaches, menstrual cramps to migraine, cluster headache etc. which are mostly non-opioids readily available over the counter and have relatively low health risks.
Why opioids are dangerous?
Opioids are no doubt effective pain medications but may lead to dangerous consequences. Overuse may cause death and long-term use can lead to opioid addiction. Opioids are powerful drugs as they follow a special mechanism of functioning by getting attached to a specific receptor of the brain, spinal cord and gastro-intestinal tract. These substances alter the path of experiencing pain.
Narcotic abuse from opioids:
Opioids taken as prescribed for a short time do not pose any risk but apart from pain management, it gives the feeling of euphoria or well-being. This leads to narcotic abuse when the user misuses the drug or consume in a manner not recommended by the physician. The person might:
- Take a higher dose of opioid medication
- Take other’s prescription to treat pain and gradually get addicted to it.
- Take opioid to get the ‘high’ feel.
People resorting to these actions develop Opioid Use Disorder (OUD) when they are unable to cut down the intake or control themselves from using it. People may also show withdrawal symptoms similar to other habit-forming substances.
OUD is a validated clinical condition where a physician’s intervention is required to get rid of painkiller addiction. In 2015, approximately 2 million Americans suffered from opioid related substance abuse.
Non-addictive pain medications are recommended for chronic pain management:
Considering the addictive nature and other dangerous side effects of opioids, over-the-counter non-addictive pain medications and natural treatments are safer for chronic pain management. These are:
- NSAIDs (Non-steroidal anti-inflammatory drugs) like acetaminophen, ibuprofen etc.
- Physical exercises, massage, acupuncture or counseling
- Steroid injections, radiofrequency ablation, neuromodulation
- Anti-seizure drugs
Natural treatments are the safest in chronic pain management with zero side effects but adherence to the treatments is crucial. Many people seeking quick pain relief prefer pain medications many of which do not work well owing to prolonged use.
Non-addictive pain medications are quite effective in managing moderate pain related to arthritis and other conditions of bone degeneration, but it may not be that effective in managing pain from cancer or other orthopedic disorders especially in fractures. Opioids are better options in such cases but the risk of overdose and addiction should be considered as well.
Addressing the opioid crisis:
Despite serious efforts of pharmaceutical and biotech industries could not translate the preclinical findings of new ways of pain management into new drugs. These were expected to address the opioid crisis and benefit patients in a better manner, but they could not see the light of success.
Scientists follow a targeted approach to developing non-addictive pain medication using advanced tools like biomarkers, subjective and objective measures in phenotyped populations.
This can be considered as a potentially useful drug development strategy. The subpopulation is more likely to respond to the drug but if the compound does not effectively address the specific aspect of a specific disease. This makes it prone to be used in a general way, which may carry certain risks.
Preclinical models also fail to predict the clinical efficacy owing to a number of reasons. Preclinical studies may also fail to detect serious adverse effects of drugs which get revealed in clinical studies. Tools may help in assessing the efficacy during clinical trials but adequate compliance measures is a must that would help in avoiding failures in the clinical trial.
People with different genetic makeup differ in pain sensitivity and responsiveness. Advanced modes of drug development in pain killers are adopting a multidimensional approach in collaboration with the Precision Medicine Initiative that would help in creating a safer medication in pain management.
Is AT- 121 the Holy Grail of non-addictive pain medication?
In a recent breakthrough, scientists have discovered a new drug AT-121 that will not lead to painkiller addiction. The study was conducted in 15 adult Rhesus monkeys and it was found the effect of this drug is similar to morphine requiring only 1% of the morphine dosage.
Most importantly, the monkeys did not develop any dependence on the drug. This was observed when they were allowed to self-administer AT- 121 but they refrained from doing it. The drug neither gave the euphoric feeling nor didn’t it appear to cause any breathing distress that is normally observed with long-term opioid use.
Opioid-related deaths are mainly caused by suppression of respiration owing to drug overdose.
How AT-121 acts?
AT- 121 acts against both mu-opioid and nociceptin receptors. Normally, opioids act only against the mu-opioid receptor that makes it an effective painkilling medication but causes euphoria. The drug’s interaction with the nociceptin receptor is the key to make it a non-addictive pain medication as it effectively blocks substance-dependence related side effects.
The rhesus monkeys in the above study who were given oxycodone continued dosing themselves with the drug. When oxycodone was replaced by AT-121, a decline in the signs of addiction was observed.
Apart from reducing side effects, the two-pronged attack of AT-121 on mu and nociceptin receptors makes it a more effective painkiller than opioids. AT-121 is yet to pass human clinical trials. If the drug can live up to its promise with humans, it can make a huge difference in pain management providing an effective solution in non-addictive pain medication.
However, moving ahead lots of consideration need to be given when a drug follows an innovative pathway. Success in small clinical trials may not assure efficacy and can be risky. It also needs to substantiate that what type of pain can be managed with this new drug. The crux of the matter is practicing safety medication irrespective of the class of drugs.