HARNESSING THE PLACEBO EFFECT: A PROMISING METHOD FOR CURBING THE OPIOID CRISIS?

In 1980, the New England Journal of Medicine published a five-sentence letter [1], which has been cited widely, perhaps erroneously, as suggesting that prescription opioids are rarely addictive [2]. Forty years later, North America is facing an opioid epidemic attributed largely to the over-prescription of opioids for treating pain [3,4]. Developing non-addictive analgesics is an imperative for public health. The National Institutes of Health (NIH) recently launched the HEAL (Helping to End Addiction Long-term) initiative, which allocates an additional 500 million dollars in fiscal year 2018 to combat the opioid crisis, including research on enhanced methods of pain management [5]. As this work develops, we should not forget about the efficacy of an unusual, but well-supported treatment for pain: the placebo.

Throughout history, the placebo effect has been a well-documented source of the effectiveness of medical treatments [6]. Placebos relieve self-appraised symptoms, including pain [7,8]. Analgesic properties of placebos were observed more than 60 years ago, when Henry Beecher gave saline injections to wounded soldiers in World War II after his morphine supply was exhausted [9]. A recent meta-analysis found that placebos were associated with very large decreases in pain among healthy volunteers and patients [10]. Placebo analgesia is partially reversed by the opioid antagonist naloxone, suggesting that placebo pain-relievers enhance endogenous opioid production [11]. Neuroimaging studies have observed similar brain activation in response to both real and placebo opioids [12], which demonstrates commonalities in the biological mechanisms of placebo and opioid pain relief.

Readers might wonder how placebos could be adapted clinically, given legitimate concern over patient deception, typically viewed as inherent to placebos. However, as early as 1965 there was evidence that placebos might be effective even when patients knew they were taking placebos [13], and the first randomized clinical trial supporting the efficacy of open placebos was published in 2010 [14]. There is now mounting evidence among several clinical populations that open placebos are indeed effective [15]. Furthermore, deceptive placebos are not associated with more pain relief than open placebos, so long as participants in the latter group are told why placebos might work [16]. Recently, open placebos were tested as an adjunctive therapy to treatment as usual for chronic lower back pain patients. Placebos were associated with large reductions in pain intensity and disability (Hedge’s gs = 0.74–0.76) [17]. Although patients on opioids were excluded, this study indicates that it might be possible to use placebos as an opioid-sparing treatment. Therefore, more work is needed to determine whether open placebos could be applied to opioid misuse prevention. Doing so will require researchers and clinicians to view placebo effects as intrinsically effective, rather than nuisance factors accounted for in control conditions.

As the development of novel, non-addictive pain management drugs accelerates, we should consider the potential role of placebos in addressing the opioid epidemic. While this suggestion might sound more like quackery than good medicine, it is actually based upon an emerging field of placebo research. If open placebos reduce pain safely and effectively, then they should be tested as an adjunct to, or substitute for, prescription opioids.