Do Pain Patients Really Get High on Rx Opioids?

By Roger Chriss, PNN Columnist

The standard narrative of the opioid crisis is built on the idea that people feel euphoria or get “high” when exposed to opioids and almost immediately become addicted. Some assert that opioid medications should have no role outside of trauma, surgical, palliative and end-of-life care due to their high risk and side effects.

But reality is more complex.

Euphoria is widely believed to be inevitable with opioids, and increases the risk for misuse and addiction. But in fact, euphoria is not common.

"I think that the notion that opioids [always] cause pleasure is a myth," Siri Leknes, principal investigator at the University of Oslo in Norway, told Live Science.  "I think it's especially important to point out that opioids do not reliably cause pleasure or relief of subjective stress and anxiety in the lab or in stressful clinical settings."

Leknes’ research found that patients receiving remifentanil – a potent, short-acting synthetic opioid -- felt high, but the experience was unpleasant.

"Not everyone experiences the same level of euphoria from opioids, and not everyone that uses opioids will develop an addiction or opioid use disorder,” says Brian Kiluk of Yale School of Medicine.

Major cognitive side effects are often thought to be inevitable with opioids. But a review of 10 clinical studies on older adults with chronic pain found that most “demonstrated no effect of opioid use on cognitive domains.” Only at high daily doses did opioids worsen memory, language and other cognitive skills.

In other words, long-term opioid therapy may cause side effects at doses well above what most people ever receive and beyond thresholds recommended by the CDC and state governments.

The risks of overdose are similarly nuanced. For instance, a study on opioids and mortality looked at a nationally representative sample of over 90,000 people, among whom 14% reported at least one opioid prescription. There were 774 deaths during the study period, with the death rate slightly higher among those taking opioid prescriptions.

However, after adjusting for demographics, health status and utilization, the authors concluded there was “no significant association” between opioids and sudden death. “The relationship between prescription opioid use and mortality risk is more complex than previously reported, meriting further examination," they said.

On the efficacy of opioid therapy, a major review in Germany looked at 15 studies with 3,590 patients with low back, osteoarthritis and neuropathic pain. The quality of evidence was low, but the authors concluded long-term opioid use was appropriate for patients who experience “meaningful pain reduction with at least tolerable adverse events."

Pain Patients Used As ‘Guinea Pigs’

Instead, we have an intense focus on prescribing statistics. States like Minnesota tout a 33% decrease in opioid prescribing for Medicare patients, while ignoring how those poor and disabled people are faring.

“My cat gets better pain management than I do after surgery,” one man wrote to state health officials.

In Ohio, opioid prescriptions have declined by 41% since 2012. Some wonder if the cutbacks went too far.

“There needed to be an adjustment and maybe it did go overboard a bit. I feel bad for the people in chronic pain because they're going to be the guinea pigs for how we get it back to the middle," Ernest Boyd, executive director of the Ohio Pharmacists Association, told the Akron Beacon Journal

So the medical needs of people with cancer, sickle cell disease and other chronic painful conditions are going unmet. And some doctors are even avoiding such patients entirely.

Naturally, there is a need to safeguard the entire opioid supply chain, and to carefully screen and monitor people on any form of opioid therapy. But we also need to track the rapidly evolving policy landscape surrounding prescription opioids to make sure that pain patients with chronic medical needs are being not harmed.

Roger Chriss lives with Ehlers Danlos syndrome and is a proud member of the Ehlers-Danlos Society. Roger is a technical consultant in Washington state, where he specializes in mathematics and research.

New Opioid Painkiller Has Less Abuse Potential

By Pat Anson, Editor

A new opioid medication being developed by Nektar Therapeutics for the treatment of moderate to severe chronic pain has significantly less abuse potential than oxycodone -- even at high doses – according to the results of a new clinical study.

The investigational oral drug – known as NKTR-181 -- is the first analgesic opioid designed to reduce side effects such as euphoria, which can lead to abuse and addiction.

In a small study involving 54 recreational drug users, NKTR-181 had significantly less “drug liking” than oxycodone in the first hours of use. The dosage given to the study participants ranged from a maximum therapeutic dose of 400mg of NKTR-181 to a “supratherapeutic” dose that was 3 to 12 times higher than common doses of oxycodone.

"It is clear from our new study results that NKTR-181 is highly differentiated in this respect from oxycodone, which is a choice drug of abuse.  Further, and critically important in the context of this public health emergency, NKTR-181's less rewarding properties and strong analgesia are inherent to its novel molecular structure and independent of any abuse-deterrent formulation,” said Ivan Gergel, MD, Senior Vice President and Chief Medical Officer of Nektar. 

“Many patients do not receive adequate pain relief because they fear taking conventional opioids, including abuse-deterrent formulations, because of their potential for abuse and addiction.  We believe NKTR-181 is a transformational pain medicine that should significantly advance the treatment of chronic pain and could be a fundamental building block in the fight against prescription opioid abuse.”

nektar therapeutics

In March, NKTR-181 received “fast track” designation from the Food and Drug Administration -- a status that allows for an expedited review of the drug – after Nektar reported positive results from a Phase 3 study of over 600 patients with chronic back pain.  Pain scores dropped by an average of 65% in patients taking NKTR-181 twice daily.

The molecular structure of NKTR-181 is designed to have low permeability across the blood-brain barrier, which slows its rate of entry into the brain – thus reducing the “high” or euphoric effect. Many pain sufferers say they do not get high or experience euphoria from opioid medication, but drug makers and regulators are working to develop painkillers with less risk of abuse and addiction.  

"Getting very high, very fast, is a mark of conventional high-risk, abused opioids," said Jack Henningfield, PhD, vice president at Pinney Associates and adjunct professor at The Johns Hopkins University School of Medicine. "NKTR-181 represents a meaningful advance in the treatment of pain as the first opioid analgesic with inherent brain-entry kinetics that avoids this addictive quality of traditional opioids. This prevents the rapid 'rush' that abusers seek during the critical period immediately after dosing. Importantly, these properties of NKTR-181 are inherent to its molecular structure and are not changed through tampering or route of administration." 

Because NKTR-181 produces less euphoria, Nektar believes it should be scheduled as a Class III or Class IV controlled substance, a less restrictive schedule than Class II medications, a category that includes oxycodone, hydrocodone and many other opioids.

Nektar is a research-based biopharmaceutical company that discovers and develops new drugs for which there is a high unmet medical need. It has a pipeline of new investigational drugs to treat cancer, auto-immune disease and chronic pain.