Placebo & NOcebo

2023

Feb 28

The history of placebo likely goes as far back in history as we do but the first documented medical placebo occurred in 1796 when a Dr. Elisha Perkins began marketing a new healthcare product called the "Perkins Tractor". Heralded as a medical breakthrough the tractor was nothing other than two metal sticks one made of iron and the other brass. Simply touching these sticks to the patient was rumored to cure all sorts of health problems. As people tend to do, they deferred to the science at the time and Dr. Perkins would become very wealthy selling overpriced metal rods to many physicians, even George Washington would pick up a pair. According to Dr. Perkins the unique metal composition of the tractor yielded the medical benefits.

Not everyone was a believer however, the Connecticut Medical Society to which Dr. Perkins belonged would give him the boot and many other skeptical physicians would begin experimenting with the tractors. A Dr. John Haygarth was treating patients with rheumatic disorders and decided to try and use a wooden stick in place of the metal tractor. He observed similar results no matter what substance the stick was constructed of and determined that Dr. Perkins' product was a sham. This would become the first documented case of the placebo effect. Dr. Haygarth would publish a book on the subject entitled On the Imagination as a Cause & as a Cure of Disorders of the Body.

Haygarth would go on to become a celebrated physician, Perkins on the other hand would be run over directly by a karma train when he traveled to New York city during a smallpox outbreak hoping to test his new antiseptic, a combination of vinegar and salt water. The antiseptic was a failure and Perkins himself would catch smallpox and die a month later.

Pacemaker studies provide an interesting view of the phenomenon. Proving that pacemakers worked would require studies comparing it to placebo. That is easy to do with say a drug when you never know what is in the pill provided, gets tougher when you need to surgically implant something. The solution is everyone is getting a pacemaker but we're only going to turn on half of them. Eyebrows were raised when improvements were seen across both groups. As late as 2012 a Cochrane review would be ambivalent calling for larger higher quality trials to be conducted. Recent studies have shown a small to moderate benefit over placebo but it's still closer than you would expect.

Perhaps the best documentation for the power of the placebo effect comes from the eighties when 74 patients after dental surgery were randomly assigned to receive either morphine or normal saline. It yielded some surprising results like the average pain being independent of the morphine dose administered. The placebo was as effective as 4 to 6 milligrams of morphine. With higher doses the morphine would prove to be the superior analgesic as you would expect, but the placebo put up a good fight.

For a short time, doctors were able to prescribe placebo or sugar pills for patients. Physicians had the option of prescribing something completely inert and safe for their patients who demanded medication. While it may have been more to placate the patient than treat a disease there is no way to prescribe an inert substance like that today. Instead, doctors tend to use actual drugs going off label for instance or simply prescribing medications they know are safe even if they think them unnecessary. They do this because patient expectations matter and having a positive attitude about a potential treatment can make it that much more effective.

The placebo effect is very real and for that reason most in medicine are careful to use it as a tailwind instead of fighting against it. Cautious optimism is always preferred to pessimistic nihilism. When the placebo effect works in reverse, we call it a nocebo. While we try to harness the placebo for our benefit the nocebo should be avoided at all costs. Nocebo does not get the attention of its more positive counterpart because ethically it should never happen but there are two good reasons for the nocebo to break into the mainstream consciousness sometime soon. The first is the movie Nocebo a decent psychological horror flick starring Eva Green, the former Bond girl from Casino Royale. It is worth a watch and strangely enough popped in my shudder watch list a few hours after finishing this piece. The second reason is because the nocebo effect is the perfect scapegoat.

The mRNA vaccines have hit a speed bump in their PR campaign, between VAERS, VSAFE, a recent Rasmussen poll and increasingly vocal vaccine injured patients, people suspect there is something going on. Since the government must start from the conclusion that their products are not the problem, the next best argument for them is the nocebo effect. Studies are already coming out concluding that adverse events from vaccination can be reduced with what they call “positive information framing”. In Canada “Altruism-Eliciting video intervention” is being studied to make young people more amenable to vaccination. A recent paper on vaccine anaphylaxis argues that the mRNA shots have a similar rate of anaphylaxis as other vaccines but offers stress related and nocebo effects as potential sources of the public misconception.

Providing positive propaganda to people before giving them their injection is not exactly what I would call informed consent, but it is at least keeping the placebo effect pointed in the right direction. The effect is real enough to make sure it is in your favor and the nocebo effect is good enough to blame the vaccines shortcomings on. The problems were not unexpected side effects and suspicious quality control. You see the problem was your lack of faith, which the government finds disturbing. Framing it in this light freedom of speech and bodily autonomy stood no chance against certain forces' determination to prevent a nocebo effect on their precious.

At the same time, they were also coordinating the greatest nocebo campaign in history against off label treatments like ivermectin, hydroxychloroquine, fluvoxamine, famotidine, and even vitamin D. The FDA would go so far as to openly mock sick people for seeking a cure that their doctor prescribed. Physicians wishing to share their success with the medications were silenced and shunned. Only profitable meds whose name rhymes with covid are the acceptable forms of treatment. Even if all the potential benefits of ivermectin were due to nothing more than the placebo effect this still makes their actions asinine and lacking common decency.

If you wanted a little more insight into the ivermectin debate Sharyl Attkisson has an interesting interview with patients who after failing to get their prescription filled downed the actual horse paste and recovered. She also speaks with a pharmacist who argues that the doses being prescribed are unsafe, not the pharmacologic hill I want to make a stand on but a good job by Sharyl to find someone to argue the other side. Ivermectin is weight based so higher doses should be no surprise especially when the patient population most are concerned with are not skinny sallies.

https://sharylattkisson.com/2023/02/after-hours-dr-vs-pharmacist-the-power-to-prescribe-podcast/

Jacob Hyatt Pharm D.
Father of three, Husband, Pharmacist, Realtor, Landlord, Independent Health and Medicine Reporter
www.pharmacoconuts.com

www.jeffersongroverva.com

@Hyattjn

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Further Reading and References
https://archive.org/details/b21514859 (Haygarth's book)
https://archive.org/details/2566066R.nlm.nih.gov/page/n15/mode/2up (Perkins original study)
https://www.psychiatria-danubina.com/UserDocsImages/pdf/dnb_vol26_no2/dnb_vol26_no2_100.pdf
https://countway.harvard.edu/news/backblog-elisha-perkins-metallic-tractors
https://www.founderoftheday.com/founder-of-the-day/perkins

https://sitn.hms.harvard.edu/flash/2016/just-sugar-pill-placebo-effect-real/

https://pubmed.ncbi.nlm.nih.gov/7279424/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094451/

https://pubmed.ncbi.nlm.nih.gov/10190407/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360382/