The Role of Science in Addiction

SPECIAL REPORT
From the New England Journal of Medicine
May 31, 2017
By Nora D. Volkow, M.D, and Francis S. Collins, M.D., Ph.D.

Opioid misuse and addiction is an ongoing and rapidly evolving public health crisis, requiring innovative scientific solutions. In response, and because no existing medication is ideal for every patient, the National Institutes of Health (NIH) is joining with private partners to launch an initiative in three scientific areas:

  1. developing better overdose-reversal and prevention interventions to reduce mortality, saving lives for future treatment and recovery;
  2. finding new, innovative medications and technologies to treat opioid addiction; and
  3. finding safe, effective non-addictive interventions to manage chronic pain.

Overdose-Reversal Interventions

Every day more than 90 Americans die from opioid overdoses. Death results from the opioid’s antagonistic effect on brainstem neurons that control breathing. In other words, the victim succumbs to respiratory failure. Naloxone can be used effectively to reduce the effect of opioid intoxication, thereby reversing the overdose, if it is administered in time. Although naloxone has saved tens of thousands of lives, overdoses frequently occur when no one else is around, and often no one arrives quickly enough to administer it.

Overdose fatalities have also been fueled by the increased availability of very powerful synthetic opioids such as fentanyl and carfentanil (50-100 times and 5,000-10,000 times more potent than heroin respectively). Misuse or accidental exposure to these drugs (e.g., when laced in heroin) is associated with very high overdose risk, and naloxone doses that can often reverse prescription-opioid or heroin overdoses may be ineffective. New and improved approaches are needed to prevent, detect and reverse overdoses.

Treatments for Opioid Addiction

The partnership will also focus on opioid addiction (the most serious form of opioid use disorder), which is a chronic, relapsing illness. Abundant research has shown that sustained treatment over years or even a lifetime is often necessary to achieve and maintain long-term recovery. Currently, there are only three medications approved for treatment: methadone, buprenorphine, and extended-release naltrexone. These medications, coupled with psychosocial support [such as rehab and 12-step programs] are the current standard of care for reducing illicit opioid use, relapse risk, and overdoses, while improving social function. There is a clear need to develop new treatment strategies for opioid use disorders. New pharmacologic approaches aim to modulate activity of the reward circuitry of the brain.

Non-Addictive Treatment for Chronic Pain

The third area of focus is chronic pain treatment: over-prescription of opioid medications reflects in part the limited number of alternative medications for chronic pain. Thus, we cannot hope to prevent opioid misuse and overdose without addressing the treatment needs of people with moderate-to-severe chronic pain. Though more cautious opioid prescribing is an important first step, there is a clear need for safer, more effective treatments.

Foremost is the plan to develop formulations of opioid pain medication with built-in abuse deterrent properties that are more difficult to manipulate for snorting or injecting, the routes of administration most frequently associated with misuse because of their more immediate rewarding effects. Such formulations, however, can still be misused orally and still lead to addiction. Thus, a more promising long-term avenue to addressing pain treatment will involve developing a powerful non-addictive analgesic. There are some fascinating x-ray crystallography studies going on that look promising.

Non-pharmacologic approaches being explored today, including brain-stimulation technologies such as high-frequency repetitive transcranial magnetic stimulation (rTMS, already FDA-approved for depression), have shown efficacy in multiple chronic pain conditions. At a more preliminary stage are viral-based gene therapies and transplantation of progenitor cells to treat pain. NIH researchers are investigating the use of gene therapy to deliver a potent anti-inflammatory protein directly to painful sites. Pre-clinical studies show powerful and long-lasting effects in reducing pain without side effects such as numbness, sedation, addiction, or tolerance.

Public-Private Partnerships

In April 2017, the NIH began discussions with pharmaceutical companies to accelerate progress on identifying and developing new treatments that can end the opioid crisis. Some advances may occur rapidly, such as improved formulations of existing medications, opioids with abuse-deterrent properties, longer-acting overdose-reversal drugs, and repurposing of treatments approved for other conditions. Others may take longer, such as opioid vaccines, and novel overdose-reversal medications. For all three areas, the goal is to cut in half the time typically required to develop new safe and effective therapeutics.

As noted throughout the history of medicine, science is one of the strongest allies in resolving public health crises. Ending the opioid epidemic will not be any different. In the past few decades, we have made remarkable strides in our understanding of the biologic mechanisms that underlie pain and addiction. But intensified and better-coordinated research is needed to accelerate the development of medications and technologies to prevent and treat these disorders. The scope of the tragedy of addiction and overdose deaths plaguing our country is daunting. The partnership between NIH and others will take an all hands on deck approach to developing and delivering the scientific tools that will help end the opiate epidemic in America and prevent it from reemerging in the future.

References

Volkow, N. and Collins, F. (May 31, 2017). “The Role of Science in Addressing the Opioid Crisis.” The New England Journal of Medicine. DOI: 10.1056/NEJMsr1706626

Volkow, L. (May 31, 2017). “All Scientific Hands On Deck to End the Opioid Crisis.” [Web blog comment]. Retrieved from : https://www.drugabuse.gov/about-nida/noras-blog/2017/05/all-scientific-hands-deck-to-end-opioid-crisis

Fentanyl Becomes Deadly Force

Some Excerpts taken from an article By Eric Scicchitano
The Daily Item
July 10, 2017

Fentanyl

The deadly heroin and opioid epidemic is expected to become even deadlier with the increasing presence of Fentanyl in America. According to the DEA, Fentanyl is 50 to 100 times more powerful than morphine, and substantially more potent than heroin. As little as 2 grams of Fentanyl can be deadly. Alarmingly, it is fast becoming the most prevalent active ingredient in counterfeit drugs like Adderall, Xanax, and OxyContin being sold on the streets. During the first quarter of 2017, heroin combined with Fentanyl was detected in 61% of opioids seized for evidence and inspected in DEA labs. It is also frequently laced into marijuana and smoked.

The DEA’s Philadelphia Division warns that Fentanyl is on the rise, with seizures of shipments more than doubling from 167 kilos in 2015 to 365 kilos in 2016. Investigators are trying to determine if an outbreak of Fentanyl is responsible for 51 overdoses which occurred in Williamsport (Pennsylvania) in forty-eight hours. [See my post 51 overdoses in 48 hours] Three of those cases ended in death. According to the National Institute on Drug Abuse (NIDA), heroin and opioids killed an estimated 280,000 people nationwide between 2002 and 2015. Based upon preliminary figures put together through state coroners, more than 4,800 people died of an overdose in Pennsylvania last year. Experts are concerned that the next chapter in the opioid crisis could dwarf what we’ve seen so far. Their concern is based on the proliferation of Fentanyl.

Fentanyl Deaths Map

Let’s take a few moments to discuss Fentanyl. It is a man-made (synthetic) opioid, meaning it is manufactured in a laboratory, but it acts on the mu-opioid receptors in our brain and spinal column in the same manner as the morphine molecule found naturally in opium. Typically, these receptor sites are meant for naturally-occurring endorphins, our “feel good” chemical released by the pituitary gland. Fentanyl is usually prescribed to patients suffering from intractable cancer-related pain and, in some cases, debilitating back pain. My father was given Fentanyl patches for compression fractures near the end of this life. Initially, it was believed Fentanyl would not be abused. Unfortunately, addicts decided to start opening the patch in order to scrape out the medicine and abuse it.

Fentanyl Mapping.gif

As if that were not enough, Fentanyl is being illegally manufactured in labs (primarily in China). It is produced in powder form, and is also pressed into pills, and smuggled into the United States. These knock-off pills are catching users off guard. Fentanyl is 50 to 100 times more powerful than morphine. DEA and border patrol seized more than 10,000 counterfeit pills containing Fentanyl in 2015. An amount as small as 2 milligrams can be deadly. First responders and ER physicians have to use extreme caution in order to avoid accidental exposure. According to the article in The Daily Item, an Ohio police officer accidentally overdosed in May of this year after brushing Fentanyl powder from his uniform during an arrest.

After the recent overdose surge in Lycoming County (Pennsylvania), Todd Owens, Mount Carmel police chief and head of the Northumberland County Drug Task Force, advised first responders to take measures to protect themselves. Chief Owens said his own department stocks medical masks, coveralls and heavy-grade gloves in their cruisers to be worn in the event they encounter heroin.

Heroin Fentanyl and Carfentanil Pics

The above is an illustration of potency betwen heroin, Fentanyl, and Carfentanil.

Carfentanil

Carfentanil is an extremely powerful derivative of Fentanyl. While Fentanyl is up to 100 times more potent than morphine, Carfentanil is 100 times more powerul than Fentanyl. In other words, it is 10,000 times more powerful than morphine. It is not approved for use in humans; rather, it is used in veterinary medicine to sedate large animals, primarily elephants. Yes, elephants! Carfentanil is so powerful that when veterinarians handle it, they use protective gear to avoid breathing it in or absorbing it through their skin. The amount of Carfentanil that can be safely administered to a human is 0.1 mg., compared to 13 mg. needed to sedate an elephant. It is obviously rather easy for an addict to accidentally take too much Carfentanil.

Interestinly, there are no statistics showing Carfentanil leading to addiction. That’s because even in the case of a seasoned addict a dose the size of a grain of salt can rapidly lead to an overdose and death. Frighteningly, drug dealers have begun cutting heroin with Carfentanil because it is extremely cheap to acquire. Even more disturbing is the fact that addicts in search of the ultimate high are deliberately trying this deadly drug. Rangers at Yellowstone National Park have recently begun issuing warnings to avoid eating the meat of bison killed in the park because the bison might have been sedated with Carfentanil for tagging or medical treatment. The drug can easily enter the bloodstream of those who eat the bison meat. It is most chilling to note that Carfentanil rapidly latches on to the mu-opioid receptors in humans, causing overdose almost immediately.

Moving Forward

Fentanyl moved up the rankings, from the 9th most common drug involved in overdose deaths in 2013, to the 5th most common drug involved in overdose deaths in 2014. The singer-songwriter Prince died of an overdose of Fentanyl in April 2016, according to officials in Minnesota. Philip Seymour Hoffman, a very successful indie film star (and one of my favorites), died of a heroin overdose on February 2, 2014. Although he had a drug problem while in college, he was clean for twenty years. No doubt his system was not able to handle the strength of today’s heroin.

Reports from the Centers for Disease Control (CDC) and the Food and Drug Administration (FDA) showed that deaths from heroin more than tripled during a five-year period, from 3,020 deaths in 2010, to 10,863 deaths in 2014. These deaths are yet another symptom of the broader epidemic of opioid addiction. Just as deaths from AIDS are due to untreated HIV, deaths from overdose are frequently due to untreated addiction. I know of many addicts attending 12-step meetings who are positive for hepatitis-C secondary to sharing needles while injecting heroin. Prince’s death is a reminder that opioid addiction is a disease that can and does affect people from all economic classes and all walks of life.

References

Scicchitano, E. (July 10, 2017). Fentanyl Becomes Deadly Force. Daily Item. Sunbury, PA.

Wakeman, S. (Aug. 5, 2016). Fentanyl: The Dangers of this Potent “Man-Made” Opioid. [Web Blog Comment.] Retrieved from: http://www.health.harvard.edu/blog/fentanyl-dangers-potent-man-made-opioid-2016080510141

Rettner, R. (Dec. 20, 2016). Deaths From Fentanyl Overdoses Double in a Single Year. LiveScience.com. Retrieved from: https://www.livescience.com/57268-fentanyl-overdose-deaths-double.html