Opioid Abuse in Chronic Pain by N. Volkow – repost

Opioid Abuse in Chronic Pain — Misconceptions and Mitigation Strategies — NEJM – N Engl J Med 2016;   Nora D. Volkow, M.D., and A. Thomas McLellan, Ph.D.

The urgency of patients’ needs, the demonstrated effectiveness of opioid analgesics for the management of acute pain, and the limited therapeutic alternatives for chronic pain have combined to produce an overreliance on opioid medications in the United States,

Given the lack of clinical consensus and research-supported guidance, physicians understandably have questions about whether, when, and how to prescribe opioid analgesics for chronic pain

Why Opioid Medications Are Diverted and Abused  

Mu-opioid receptors are densely concentrated in brain regions that regulate pain perception (periaqueductal gray, thalamus, cingulate cortex, and insula), including pain-induced emotional responses (amygdala), and in brain reward regions (ventral tegmental area and nucleus accumbens) that underlie the perception of pleasure and well-being.

This explains why opioid medications can produce both analgesia and euphoria.

What all the officials do NOT understand is that pain patients, if using opioids properly, do not get the feeling of euphoria that abusers enjoy. (See Opioids, Endorphins, and Getting High)

For a patient in chronic pain, even mild levels of pain can trigger the learned associations between pain and drug relief, which are manifested as an urge for relief. Such a conditioned urge for relief from even mild pain can lead to the early, inappropriate use of an opioid outside prescribed scheduling.

Again, because pain patients don’t get euphoria, the only pleasure is the pain relief.

Opioid-Induced Tolerance and Physical Dependence

There is lingering misunderstanding among some physicians about the important differences between physical dependence and addiction

I’m glad that someone in a position of high authority (Director of NIDA) realizes that there is a difference, even as PROP is doing their best to obfuscate this fact.

The repeated administration of any opioid almost inevitably results in the development of tolerance and physical dependence. These predictable phenomena reflect counter-adaptations in opioid receptors and their intracellular signaling cascades

In contrast, addiction will occur in only a small percentage of patients exposed to opioids.

This is certainly not the view that PROP is pushing. Their insistence that dependence = addiction is merely propaganda.

Addiction develops slowly, usually only after months of exposure, but once addiction develops, it is a separate, often chronic medical illness that will typically not remit simply with opioid discontinuation and will carry a high risk of relapse for years without proper treatment.

The molecular processes responsible for addiction are also distinct from those underlying tolerance and physical dependence, and so are the clinical consequences.

Physical dependence underlies the physiological adaptations that are responsible for the emergence of withdrawal symptoms on the abrupt discontinuation of opioids.

Withdrawal symptoms (e.g., piloerection, chills, insomnia, diarrhea, nausea, vomiting, and muscle aches) vary appreciably in severity (from not noticeable to quite uncomfortable) and duration (1 to 14 days) on the basis of the type, dose, and duration of opioid prescribed

In the context of chronic pain management, the discontinuation of opioids requires dose tapering in order to prevent the emergence of such withdrawal symptoms.

This implies that doctors and even medical organizations are committing malpractice in releasing their pain patients from opioid therapy without careful tapering.

In some patients, the repeated use of opioids can also lead to hyperalgesia, which is a state of heightened pain sensitivity. In the clinical context, hyperalgesia can lead to inappropriate increases in opioid doses, which further exacerbate rather than ameliorate pain. In the case of hyperalgesia, dose tapering or tapering to discontinuation is a better pain-relief strategy.

Unfortunately, Volkow is still spreading the “hyperalgesia” trope, which has never been proven in humans.

Unlike tolerance and physical dependence, addiction is not a predictable result of opioid prescribing.

Addiction occurs in only a small percentage of persons who are exposed to opioids — even among those with preexisting vulnerabilities.

This contrasts with the scenario that PROP is broadcasting, which insists that taking opioids for any reason always leads to addiction.

Older medical texts and several versions of the Diagnostic and Statistical Manual of Mental Disorders (DSM) either overemphasized the role of tolerance and physical dependence in the definition of addiction or equated these processes (DSM-III and DSM-IV).

However, more recent studies have shown that the molecular mechanisms underlying addiction are distinct from those responsible for tolerance and physical dependence,…

This implies that there is a method to determine whether a patient has an addiction or not. If so, why isn’t it being applied to the endless debate of addiction (a mental disorder) versus dependence (a physical disorder)?

…in that they [mechanisms underlying addiction] evolve much more slowly, last much longer, and disrupt multiple brain processes.

Cardinal features of addiction include a pronounced craving for the drug, obsessive thinking about the drug, erosion of inhibitory control over efforts to refrain from drug use, and compulsive drug taking (DSM-5)

Clinical studies have also shown that the ability of opioids to produce addiction is genetically modulated, with heritability rates similar to those of diabetes, asthma, and hypertension

For these reasons, we do not know the total dose or the duration of opioid administration that will reliably produce addiction.

NIDA may admit they don’t know, but PROP is certain that any opioids taken for any reason literally cause addiction.

This is wrong in so many ways, but I think the basic point that’s simple to understand is that addiction is mostly a mental disorder while dependence is mostly a physical disorder.

Yet, the myth that opioids=addiction stubbornly remains embedded in America’s “common knowledge” thanks to copious media, recovery industry, and government propaganda.

The anti-opioid PROP has so much influence that the CDC acted on its behalf by issuing anti-opioid guidelines unsupported by science, blending the interests of the recovery industry with a high-level government agency dedicated to the public welfare.

However, we do know that the risk of opioid addiction varies substantially among persons, that genetic vulnerability accounts for at least 35 to 40% of the risk associated with addiction,62-64 and that adolescents are at increased risk because of the enhanced neuroplasticity of their brains and their underdeveloped frontal cortex, which is necessary for self-control.

In a person with an opioid addiction, discontinuation of the opioid will rapidly reverse the tolerance and physical dependence within days or a couple of weeks. In contrast, the underlying changes that are associated with addiction will persist for months and even years after the discontinuation of opioids

This finding is clinically relevant, because after abstinence from opioids, addicted patients are particularly vulnerable to overdosing: their intense drive to take the drug persists, but the tolerance that previously protected them from overdosing is no longer present. These effects explain the high risk of overdosing among persons with an opioid addiction after they have been released from prison or from a detoxification program

Approximately 7 to 10% of diversion occurs among patients who feign pain to acquire prescribed opioids, usually with the goal of maintaining their addiction, and who will often attempt to acquire opioids from multiple physicians (doctor shopping).

Even though 90%-93% of pain patients are NOT feigning pain, they are being forced off opioids because of the few who are.

For many years, it was believed that pain protected against the development of addiction to opioid medications.

This is because pain patients generally don’t feel euphoria, only pain relief, and it’s the euphoria that tempts people to take too much and become addicted.

Rates of carefully diagnosed addiction have averaged less than 8% in published studies, whereas rates of misuse, abuse, and addiction-related aberrant behaviors have ranged from 15 to 26%.

A noteworthy fact is that aberrant behaviors also include taking LESS pain medication than prescribed.


Although there are no simple solutions, we recommend three practice and policy changes that can reduce abuse-related risks and improve the treatment of chronic pain.

Below are 3 recommendations she urges:

Increased Use of Science-Supported Prescribing and Management Practices

Better results can be obtained by using the most contemporary guidelines for pain management

This claim is simply absurd. Nothing works as well as opioids for pain.

Increased Medical School Training on Pain and Addiction

If medical schools teach the kind of nonsense being promulgated by NIDA, the DEA, and PROP, pain patients will only suffer more.

Increased Research on Pain  

This is the only point on which pain patients can agree, yet most research seems to be about addiction or the dangers of opioids instead of pain.

If the NIH would fund more pain studies, including some that investigate the effectiveness of opioids, perhaps we can find a way out of this mess.

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