© 2018 by Janelle E. Letzen, PhD

 
The Opioid Crisis
What is the Opioid Crisis?

A 2018 report from the UN showed that ~76% of recent substance abuse-related deaths around the world – especially in North America – were due to a class of drugs called opioids. This public health problem has been called “The Opioid Crisis.” The opioid crisis is often linked to chronic pain. Before reading below, some important things to keep in mind about pain and the opioid crisis are that: 1) not all chronic pain patients are addicted to/abuse opioids, 2) not all people with opioid addiction/abuse have chronic pain, & 3) some people have very real chronic pain and, unfortunately, addiction.

Society’s acceptance of opioids is often described as a pendulum, swinging between liberal and limited use. Let’s review these attitudes across time.

Have you ever seen The Wizard of Oz? There’s a scene when Dorothy et al. enter a field of flowers and become very sleepy. These flowers, called poppies, were used as a sleep aid and pain reliever because the sap contains opium, a narcotic. Substances associated with opium are morphine and heroin.

Click the play button!

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Swing 1: From ~1600-1700s, international opium trade was thriving. Opium became broadly available in the 1800s with commercial morphine production, sparking its popular use as a pain reliever for soldiers’ injuries and women’s menstrual cramps. For acute pain, opium seemed to reduce suffering. Its effects were much weaker in chronic pain, requiring stronger doses over time as tolerance/addiction grew. By the early 1900s, opium addiction was a global problem. 

 

Swing 2: In response, many countries banned opium. From the ~1910-80s, its use was criminalized, and medical education emphasized dangers of opioids to manage chronic pain in people without fatal diseases.

 

Swing 3: Pharma companies produced synthetic opiates over time. In the 1990s, these meds were marketed as a “safe” way to treat chronic pain and championed by some physicians who said negative effects were overstated. Opioid prescribing became liberal to emphasize reduction in patient suffering.

 

Swing 4: Mentioned above, opioids work best for acute, but not for chronic, pain. Tolerance to opioids builds with prolonged use, meaning more is needed to get an effect. Addiction can follow. It’s estimated that from 1999-2017, ~400,000 people in the US died from opioid-related complications. Opioid misuse/addiction were declared an epidemic in North America, resulting in some prescribing changes

 

How is Opioid Use Disorder Treated?

Did you know that subtypes of (non)prescription opioids can have diverging effects? For example, oxymorphone is an addictive pain reliever. By changing its chemical structure a bit, we get naloxone – a medication used to treat opioid overdose. These effects differ based on 1) the opioid receptor subtype that the chemical formulation binds to and 2) whether binding results in full/partial activation or full/partial blocking of the receptor.
 

Medication-Assisted Treatment opioid use sushi scienc
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Other opioids used to treat opioid-related consequences are methadone, buprenorphine, and naltrexone. For people with opioid use disorder (OUD; a clinical term that encompasses opioid addiction), the best approach is considered medication-assisted treatment (MAT). MAT combines regulated use of methadone, buprenorphine, and/or naltrexone with psychotherapy. Methadone – a mu-opioid full agonist – has been used longest. .How does it help with OUD? Methadone competes for the same receptors that common opioids (e.g., OxyContin, heroin) bind to, but it doesn’t trigger reward system activity as strongly (less euphoria).

This makes methadone less addictive than other opioids for some people. Once methadone takes up a receptor, other opioids can’t bind to it. As a result, a person taking methadone can stop using other opioids with reduced cravings and withdrawal symptoms compared to abruptly quitting. The latter is problematic because it often leads to relapse. Plus, methadone still acts as a pain reliever, if needed. The evidence for MAT is somewhat mixed: some studies show positive effects like reduced opioid-related mortality/crimes and improved quality of life, but others show moderate relapse rates, difficulty tapering, and risk of dependence. The consensus is that the benefits outweigh these risks. However, because use of MAT meds is often stigmatized, many people hesitate to even begin a programFor these reasons, pain researchers are focused on finding ways to replace opioid pain relievers.

Can Marijuana Substitute Opioids in Pain Management?

Advocacy for cannabis legalization is growing. But, the actual research on cannabis for chronic pain is only recently playing catch up to test pro-legalization claims. I tried to be an unbiased messenger of the available evidence, but I’m guessing what I have to share will not be popular…

Cannabinoids are compounds that bind to cannabinoid receptors in the brain. Remember how you can get opioids from your body’s own production or external forms? Similarly, our bodies make cannabinoids, and we can get them from external sources like cannabis sativa, purified forms (e.g., THC/CBD), or lab-made forms (e.g., dronabinol).

 

The findings below are from research approaches called systematic reviews (SR) and meta-analyses (MA), which

marijuana pain sushi science
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basically summarize available studies on a topic to provide big picture conclusions. A mix of external cannabinoids were included in these studies.

One SR/MA pooled results from 104 studies. Overall, there was no difference between cannabinoids vs. placebo in reducing patients’ pain by 50% and some benefit vs. placebo for 30% pain reduction. Importantly, they estimated that the number of people you would need to treat to PREVENT A BAD OUTCOME is 24 (called the number needed to treat). The number of people you would need to treat for one person to HAVE A BAD OUTCOME is 6 (number needed to harm). They concluded that cannabinoids are more likely to produce an undesired effect than pain relief.

These results were consistent with a SR/MA by Aviram et al. showing negligible differences between cannabinoid vs. placebo outcomes. They noted that cannabinoids had a small benefit vs. placebo for neuropathic pain specifically, a conclusion echoed by Allan et al. Yet, another SR/MA found that the potential harm outweighed potential benefits for neuropathic pain.

Some have argued that these results should be cautiously interpreted because not all SR/MAs separate out cannabinoid compounds or patient samples. On the other hand, some have warned that: “...we do not want to see a cannabis epidemic replacing that of opioids”.

References

[1] Smithsonian Magazine: “The Power of the Poppy: Exploring Opium through ‘The Wizard of Oz’”

[2] World Health Organization: “Opium Abuse and Its Management: Global Scenario”

[3] Smithsonian Magazine: “Inside the Story of America’s 19th-Century Opiate Addiction”
[4] Van Zee A. (2009). The promotion and marketing of oxycontin: commercial triumph, public health tragedy. American journal of public health, 99(2), 221-7.
[5] The Guardian: “The making of an opioid epidemic” [6] Rummans, T. A., Burton, M. C., & Dawson, N. L. (2018, March). How good intentions contributed to bad outcomes: the opioid crisis. In Mayo Clinic Proceedings (Vol. 93, No. 3, pp. 344-350). Elsevier. [7] US Center for Disease Control: “Understanding the Epidemic” [8] Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain — United States, 2016. JAMA 2016;315:1624-1645.

[6] United Nations Office on Drugs and Crime: World Drug Report 

[7] Sevarino KA, Kosten TR. Naltrexone for initiation and maintenance of opiate abstinence. In: Dean R, Bilsky EJ, Negus SS, eds. Opiate Receptors and Antagonists: From Bench to Clinic. New York, NY: Humana; 2009:227-245
[8] US CDC: Assessing and Addressing Opioid Use Disorder
[9] US FDA: Information about Medication-Assisted Treatment (MAT)
[10] Connery, H. S. (2015). Medication-assisted treatment of opioid use disorder: review of the evidence and future directions. Harvard review of psychiatry, 23(2), 63-75.
[11] Anderson, I. B., & Kearney, T. E. (2000). Use of methadone. The Western journal of medicine, 172(1), 43-6.
[12] Fullerton, C. A., Kim, M., Thomas, C. P., Lyman, D. R., Montejano, L. B., Dougherty, R. H., ... & Delphin-Rittmon, M. E. (2014). Medication-assisted treatment with methadone: assessing the evidence. Psychiatric services, 65(2), 146-157.
[13] Volkow, N. D., Frieden, T. R., Hyde, P. S., & Cha, S. S. (2014). Medication-assisted therapies—tackling the opioid-overdose epidemic. New England Journal of Medicine, 370(22), 2063-2066.
[14] Nosyk, B., Sun, H., Evans, E., Marsh, D. C., Anglin, M. D., Hser, Y. I., & Anis, A. H. (2012). Defining dosing pattern characteristics of successful tapers following methadone maintenance treatment: results from a population‐based retrospective cohort study. Addiction, 107(9), 1621-1629.
[15] Amato, L., Davoli, M., Ferri, M. M., & Ali, R. (2003). Methadone at tapered doses for the management of opioid withdrawal. Cochrane Database of Systematic Reviews, (2).
[16] Olsen, Y., & Sharfstein, J. M. (2014). Confronting the stigma of opioid use disorder—and its treatment. Jama, 311(14), 1393-1394.

[17] Fitzcharles MA, Eisenberg E. Medical cannabis: a forward vision for the clinician. Eur J Pain 2018;22:485–91.
[18] Häuser, W., Finnerup, N. B., & Moore, R. A. (2018). Systematic reviews with meta-analysis on cannabis-based medicines for chronic pain: a methodological and political minefield. Pain, 159(10), 1906-1907.
[19] US NIH: “NIH Research on Marijuana and Cannabinoids” [4] Stockings, E., Campbell, G., Hall, W. D., Nielsen, S., Zagic, D., Rahman, R., ... & Degenhardt, L. (2018). Cannabis and cannabinoids for the treatment of people with chronic noncancer pain conditions: a systematic review and meta-analysis of controlled and observational studies. Pain, 159(10), 1932-1954.

[20] Aviram, J., & Samuelly-Leichtag, G. (2017). Efficacy of Cannabis-Based Medicines for Pain Management: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Pain physician, 20(6), E755-E796.

[20] Allan, G. M., Finley, C. R., Ton, J., Perry, D., Ramji, J., Crawford, K., ... & Kolber, M. R. (2018). Systematic review of systematic reviews for medical cannabinoids: Pain, nausea and vomiting, spasticity, and harms. Canadian Family Physician, 64(2), e78-e94.

[21] Mücke, M., Phillips, T., Radbruch, L., Petzke, F., & Häuser, W. (2018). Cannabis‐based medicines for chronic neuropathic pain in adults. The Cochrane Library.