A brand-new opioid compound known as PZM21 prevents patients from experiencing a high while effectively eliminating pain. Does this mean future prescription painkillers will be less likely to drive opioid addiction?

PZM21 Addiction Resistant Opioid


  • Scientists at UC San Diego may have found a drug to kill pain without increasing risk for opioid addiction.
  • A new drug called PZM21 could make your painkiller prescription safer.

Opioids have caused an epidemic of addiction and overdose worldwide. In fact, an estimated half a million people died from opioid overdose between 2000 and 2014 in the US alone, and one-fifth of those fatalities are thought to have resulted from prescribed painkillers.

So far, pharmaceutical companies have addressed the problem by making their drugs increasingly abuse-deterrent – designing them to be difficult to crush, which prevents snorting or injecting. But the fact remains that many opioids are still abused simply by swallowing. Now, however, a new company called Epiodyne thinks it may have the solution.

Epiodyne, formed by researchers at the University of San Diego, is currently developing PZM21, a compound that works to relieve pain effectively without giving users a ‘high’. Though PZM21 is still in its early stages of testing, current findings based on lab mice testing make the future of the drug look promising.

Of course, PZM21 is not going to eliminate all forms of opioid abuse worldwide, and those already struggling should seek professional opioid addiction treatment. However, it may be able to address the epidemic by making prescribed opioids, such as fentanyl and codeine, less dangerous and less addictive. But how exactly does PZM21 differ from other opioids? First, it is important to understand what makes more traditional forms of opioids so dangerous in certain situations.

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Effects of Opioid Abuse

The most famous illicit opioid is heroin, a drug that has caused countless deaths over the years and is extremely addictive. However, an increasing number of people are getting addicted to prescribed opioids such as codeine and fentanyl, a drug thought to be 10,000 times stronger than morphine.

Opioids are so addictive because they cause a surge in the release of dopamine, the chemical responsible for powerful emotions such as desire and pleasure. When people abuse opioids, their brain’s natural levels of dopamine are altered, and it can become difficult to sustain happiness without further opioid use. More dangerously, opioids can work to reinforce addictive behaviour, meaning users will often have a desire to repeatedly take the drug.

While opioids can effectively eliminate pain, abusing them results in some users constantly trying to attain the same level of euphoria time and time again. An overdose of these drugs can cause brain damage, coronary arrest, comas and even death. Indeed, 69,000 people die every year from opioid overdose worldwide according to the Worldwide Health Organisation.

Most pharmaceutical companies are currently focusing their efforts on making their drugs more difficult to abuse by making them difficult to grind and snort or ‘melt’ and inject. However, with opioid-related fatalities still on the rise, these efforts seem to be futile. The answer may lie in preventing future opioid painkillers from causing a huge dopamine release.

PZM21 Could Make Opioids Safer

Dr Brian Shoichet, the chief scientist behind PZM21, thinks his team’s new compound might be the answer to removing the dangers associated with modern-day prescription opioids. Essentially, PZM21 is an opioid that works to eliminate pain but is absorbed too slowly for the brain to release a surge in dopamine, the key chemical that makes opioids so addictive.

Says Dr Shoichet: “What we know is that mice don’t seem to like it, meaning they don’t go back for more if given the choice. That gives us hope that it might not be addictive.” Lab mice are often used to test a new drug’s addictiveness, and the fact that they do not return for more when exposed to the drug after prolonged use makes the results look extremely promising.

However, PZM21 has yet to be tested on humans, and there is always a concern that testing will never even reach that stage. According to Pinar Karaca-Mandic, a health policy researcher at the University of Minnesota, most new drugs have about a one in 10 chance of reaching human trials, but PZM21 is a hopeful candidate because it appears to have no effect on breathing or reflex pain.

Results so far show that the new compound developed by Dr Shoichet and his team only eliminates affective pain, the type which is felt constantly such as back or neck ache. Reflex pain is felt immediately, for example, when you touch a hot stove. Dr Shoichet pointed out that pain-relieving drugs are not beneficial if they prevent people from detecting a hot stove due to being ‘doped up’.

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NKTR-181, an Alternative Painkiller to PZM21

PZM21 is not the only drug being developed to address the opioid overdose epidemic, though it does look to be the most promising at this stage. NKTR-181 was first tested on humans in February 2015, and it appears that it too does not result in users experiencing a high. Current findings show that NKTR-181 is indistinguishable from a placebo among recreational drug users, though it does not possess the benefits of preventing users from feeling reflex pain or slow breathing.

However, authorities still seem to be focusing their efforts on making currently available drugs abuse-deterrent, with the US government currently commissioning the development of 30 of such drugs. But with users still able to experience a high by swallowing these opioids in large quantities, some experts think the opioid epidemic could remain a huge problem.

Opioid Addiction Treatment

Hopefully, we will start seeing opioids become less addictive as time progresses, thanks to modern innovations such as PZM21 and NKTR-181.  But those already suffering from addiction may migrate to more dangerous illicit drugs like heroin in order to achieve the same high they became familiar with when consuming prescription opioids. Fortunately, there is help available.

If you or anybody you know is suffering from addiction, we are here to help. At The Cabin Singapore, top minds in the addiction treatment field provide a holistic and effective rehab programme. Our outpatient model allows you to fit treatment around your normal schedule, meaning you can continue to work and spend time with your family while receiving a high level of care. We understand that addiction is a condition, not a crime, and we have the resources to help you beat addiction for good. For further information, contact us today.