The vaccine is safer than driving your car, but can the power of your mind make it deadly?

How a relatively unknown medical phenomenon may actually cause the side effects anti-vaxxers have been stubbornly convincing themselves of. And how this could pose a major threat to public health.

Nov 17, 2021

Most people reading this article will be familiar with the term placebo effect. The widespread medical phenomenon that is so powerful and prevalent, that all major clinical trials everywhere in the world have to factor it in during their evaluation of a new medicine.

You may have also heard of such a thing as a double-blind, randomised, placebo-controlled trial - this means that the trial is being conducted in a scenario where neither the patient nor the doctor know which dose of ‘therapeutic’ being administered is the actual compound and which is the placebo or sham substance.

This ensures that there is no bias or subtle unconscious hinting on behalf of the prescribing physician during the trial, ever.

Yet even with such precautions, most medications will struggle to beat the placebo during these trials. In fact, the only class of drugs that has ever managed to beat the placebo in every single clinical trial setting, are a class of drugs known as antimicrobials, this includes the fungal derived penicillin and other antibacterial agents commonly known as antibiotics. To reiterate, most drugs and yes, this includes vaccines, struggle to perform better than the placebo in many trials conducted to date.

The human brain is the most complicated object in the known universe

So what does this mean? It shows how unbelievably powerful the human brain actually is. In one of the more fringe medical subjects that I have been privileged to study in my life, psychoneuroimmunology, this phenomenon is almost exclusively studied. The pursuit of figuring out how the brain, the nervous system, the immune system and our small intestine all function together harmoniously to protect us from outside harm, is a highly complex and intricate study of medicine.

The only thing more complex on planet Earth than the human immune system, is the human brain. On top of this, the 39 trillion microorganisms that inhabit the human body, mainly in the small intestines, also factor into this regulation of the immune system, by interacting in complex and often as yet incomprehensible ways with the near 7 trillion nerve cells that occupy a typical human’s central nervous system.

So just factoring these numbers into a standard equation, it becomes apparent how intricate the interactions and cellular signalling cascades can be. Interactions that happen every second in the 30 trillion human cells that exist on top of the 39 trillion microorganisms and 7 trillion nerve cells in our body. These numbers are so vast and the potential amount of interactions so high and unfathomable, that many molecular biologists and medical researchers shun this area of investigation completely. And understandably so, it is just far too complex an array of biochemical processes to be made sense of meaningfully.

The University of Auckland in New Zealand has been running a postgraduate course in psychoneuroimmunology since the mid 2000s, spearheaded by the legendary scientist Professor Roger Booth. It was here that I got to investigate and study the phenomenon of the placebo effect and specifically the impact stress has on the immune system via the hormone cortisol that has deleterious effects on many immune cells. If you have ever had a bad allergic reaction to something, chances are that the physician prescribed you corticosteroids, which in essence mimic cortisol and switch off many genes responsible for allergy and inflammation.

What on earth is the nocebo?

But in this article, it was neither stress nor the placebo effect that I wanted to highlight. I wanted to bring people’s attention to a much lesser known medical phenomenon, one called the nocebo effect. It comes from the Latin word “nocere” which means “harm” and the word “nocebo” literally translated, means “I do harm.”

The nocebo effect is essentially the exact opposite of the placebo, it occurs when a human being believes that a certain medication or therapeutics will have negative or adverse side effects when ingested or injected.

“Negative expectations tend to be formed much faster than positive expectations and this has an evolutionary reason — our bodies are programmed to protect us from adverse events.”

Says University of Maryland neurophysiologist Luana Colloca - and this is the reason why the nocebo effect is a lot more dangerous than people initially suspect.

Most people are acutely unaware of the phenomenon altogether, including medical doctors and people who work in the field of healthcare. It is also often completely ignored in clinical trial settings and general medical practice, and is clear that this has to change.

Adverse events reported during a clinical trial where the patient takes a placebo, are not that uncommon. The potential negative repercussions this can have now during this pandemic and the resultant vaccination drive that is being scaled out all over the world in an unprecedented way, can be catastrophic if not addressed properly. Especially when combined with the widespread misinformation campaign regarding wholly unsubstantiated claims of potential side effects of this vaccine.

Some of the greatest work investigating the nocebo effect was done by University of Hull neuroscience researcher Giuliana Mazzoni. You may be familiar with the rubber hand illusion often used by stage magicians to show autosuggestion, whereby a person is conditioned to believe that a fake hand is their own, and then a whole well of tricks is performed on the fake hand and the person believes it is their real hand. Well, Mazzoni used this technique in a 2017 study to investigate the nocebo effect in regards to human pain perception, in the context of such diseases as fibromyalgia. And her findings were remarkable. In short, conditioning is real and the human brain can be convinced of nearly anything.

The evil twin

The nocebo effect has been referred to as the placebo effect’s evil twin, and it is not something to take lightly. There are in fact multiple reports of serious physical and mental harm caused by this irrational disbelief and fear of even common medicines and their side effects.

It is so deep rooted that studies from Finland have shown that certain generic medications that “look cheaper'' lose their efficacy when patients see the packaging. These studies were replicated in a 2017 study regarding “sham” analgesic creams used by patients, where the patients were told that the cheaper looking creams “may cause more pain” - and lo and behold the results showed that it did.

The dissemination of irrational adverse effects through widespread “media storms” can have huge impacts on the prevalence of nocebo effects in a population. This became relevant in 2013, when the British media started highlighting the adverse events of particular cholesterol lowering drugs called statins. What followed was 200 000 patients discontinuing the treatment and most of these due to these widely reported side effects. This peculiar outcome was largely attributed to the nocebo effect.

The nocebo effect can also kill

In some cases the nocebo effect has even been attributed to killing people. In the 1970s there was a medical case that showed a patient dying of cancer who had been told that they only had 3 months to live. In the resulting autopsy they discovered that the cancer had been misdiagnosed and couldn’t have caused this early death. This may sound like voodoo, but this case is widely known and has been noted in the medical literature1.

As well as another unusual study outcome from 2017, this time with antidepressants, where a 26 year old patient enrolled in a clinical trial, attempted to take their own life through overdose, initially showing signs of severe hypotension and other symptoms, only to be admitted to hospital and be told that they had been receiving placebo pills all along. The symptoms quickly disappeared.

Professor Christian Büchel, a German neuroscientist from Hamburg University, puts it bluntly:

“Unfortunately, the nocebo effect has a huge impact on clinical outcomes, I think maybe more than the placebo effect,”

Büchel has been using MRI scans to further understand the biomechanics of the nocebo effect. In terms of pain reduction and increase in terms of the 2017 cream study mentioned above, Büchel found changes at multiple levels of neurobiology happening in the brain’s sub-cortex and cortex as well as the spinal cord. Areas that have been previously mapped to be involved in pain modulation, including the periaqueductal gray (PAG),an area of the brain thought to be the main modulation centre for pain. So the phenomenon is real.

Now you can probably guess where I am going with this in terms of the widespread anti-vaccination sentiment that currently exists and is spreading everywhere on the planet.

Misinformation regarding inflated claims of myocarditis in vaccine recipients are one thing, but many fringe groups are falsely and hysterically reporting mass casualties all over the world in often very professional videos and articles - that attribute death to the covid vaccination.

Antivax propaganda is professional and psychologically targeted

There is one particularly misleading and nefarious instagram video which appears to attribute all of these random deaths in athletes around the world to the vaccine. I won’t share this video as I don’t like propelling such information, but it is out there and it is pretty compelling and scary the way they have professionally framed all of these unconnected deaths and concluded that the covid vaccine was the culprit.

I mean, I consider myself fairly rational with a good grip on reality, but even I had to do a double take after watching the video of these people “connecting the dots.” There is so much misinformation out there and since publishing my article targeting people sitting on the fence, I have been answering queries and emails from people all over the world, mostly worried about family members or children who have been sucked down the rabbit hole.

The Rabbit Hole Resistance

The place I call home, Golden Bay is probably one of the least vaccinated areas of the country because this place attracts a lot of people who defy authority, seeing themselves divinely selected light workers and freedom fighters and let’s face it a high proportion of them suffer from narcissistic personality disorder and as such we should really feel sorry for them as it is a very real and frightening psychological condition. It is hard to reason with these people as they suffer from cognitive dissonance and confirmation bias - two guaranteed symptoms of ignorance and mental blinkeredness.

One thing that has helped is a facebook group started by the German Kiwi journalist Anke Richter and her friends, called Rabbit Hole Resistance which is a worldwide collection of rational people (at this point in time numbering 1600 concerned global citizens) who are dealing with loved ones and acquaintances who have been pulled down into the rabbit hole of antivax conspiracies. In our community, we have splintered regionally into a group that helps each other deal with the obvious repercussions of living in an area that has a high proportion of antivax sentiment.

Because let’s face it, it is by now well established that even though the media may portray vaccination as essential, many of the antivax belief holders are very vocal and in certain parts of the country definitely outnumber and out-voice the people who are trying to do the right thing by getting vaccinated.

12 social media personalities control the majority of all the misinformation online

Yes, you read that right, just twelve. The “Antivax Anti-disciples” or as the founder of the Center for Countering Digital Hate, Imran Ahmed calls them, the Disinformation Dozen. Ahmed recently wrote a paper that outlined the existence of “12 spirituality gurus” and his calculations showed that the bulk of all (65%) misinformation on Facebook stems directly from these people.

So the good news is that Ahmed’s work caught the attention of the Speaker of the House Nancy Pelosi and Zuckerberg has announced that they have launched an internal investigation into the matter.

The bad news is that misinformation is still incredibly prevalent.

Two of the main culprits who are incredibly popular among new age people, counting millions of followers among their “disciples” - who have been continuously spreading mistrust and flat out false information regarding th vaccine are Charles Eisenstein and Russel Brand.

Now I won’t go into much detail about how these two have seriously lost my respect over the last two years with their cowardly stance on the covid vaccination during this pandemic and their irresponsible spreading of misinformation and mistrust over their various social media platforms that are absorbed by millions of people around the globe, no I won’t subject you to that, instead I would urge you to listen to these two podcast episodes by the amazing and super well researched Conspirituality podcast team:

This episode (the interview is split into two episodes so make sure you listen to both) completely dismantles Charles Eisenstein and this one, puts Russell Brand in his rightful spot, at the bottom of the barrel.

There is hope

In terms of all of the antivaxers who have fallen down the rabbit hole, where the nocebo effect may affect the clinical outcome of a vaccine should they potentially get one - which is seeming ever more likely now that the vaccine certificates have been rolled out in NZ and most jobs state vaccination as a requirement - a very important question arises, can these people be helped? In other words can the potential nocebo effect be either prevented or even, reversed?

Well, the initial good news is that there is evidence that the effect can be reversed and even better, changed into a placebo effect. One particular study that looked at the sensation of itching connected to looking at a coloured dot on a screen, showed that certain conditioning behaviours can bring a test subject to revert feelings of a nocebo into a placebo.

The only question here remains, who will re-condition these people and will they be willing to let themselves undergo potential psychological screening? Short answer is probably no. What will convince them?

You can probably answer that for yourselves.

In summary the basic question is not around efficacy of vaccines but the real and/or perceived side effects, which could be reported and documented - potentially showing vaccines more negatively than what they "really" are - simply because of this nocebo effect. A recent study published in the Lancet analysed a number of clinical trials comparing side effects for vaccine and placebo groups and found that a substantial portion (over half in some cases) of reported adverse events are unrelated to the vaccine and are likely nocebo effects2.

Can this be measured and validated further? That is the question.

Please contact me if you are willing to collaborate.

Reference List

Meador C K. Hex death: voodoo magic or persuasion? South Med J 1992;85;244–247.

Reeves RR, Ladner ME, Hart RH, Burke RS. Nocebo effects with antidepressant clinical drug trial placebos. Gen Hosp Psychiatry 2007;29:275–277. doi: 10.1016/j.genhosppsych.2007.01.010

F. Benedetti, M. Amanzio, S. Vighetti, G. Asteggiano, The biochemical and neuroendocrine bases of the hyperalgesic nocebo effect. J. Neurosci. 26, 12014–12022 (2006).

J. Kong, R. L. Gollub, G. Polich, I. Kirsch, P. Laviolette, M. Vangel, B. Rosen, T. J. Kaptchuk, A functional magnetic resonance imaging study on the neural mechanisms of hyperalgesic nocebo effect. J. Neurosci. 28, 13354–13362 (2008).

Abramson JD, Rosenberg HG, Jewell N & Wright JM. Should people at low risk of cardiovascular disease take a statin? BMJ 2013;347:f6123. doi:10.1136/bmj.f6123 pmid:24149819

Coleshill MJ, George DN & Mazzoni G. Placebo analgesia from a rubber hand. J Pain 2017;18:1067–1077. doi: 10.1016/j.jpain.2017.04.004

Nikiphorou E, Kautiainen H, Hannonen P et al. Clinical effectiveness of CT-P13 (Infliximab biosimilar) used as a switch from Remicade (infliximab) in patients with established rheumatic disease. Report of clinical experience based on prospective observational data. Expert Opin Biol Ther 2015;15:1677–1683. doi: 10.1517/14712598.2015.1103733

Matthews A, Herrett E, Gasparrini A et al. Impact of statin related media coverage on use of statins: interrupted time series analysis with UK primary care data. BMJ 2016;353:i3283. doi: 10.1136/bmj.i3283

Abrahamson JD, Rosenberg HG, Jewel N, et al. 2013. Should people at low risk of cardiovascular disease take a statin? British Medical Journal 347: f6123. DOI: https://doi.org/10.1136/bmj.f6123

Nikiphorou E, Kautiainen H, Hannonen P, et al. 2015. Clinical effectiveness of CT-p13 (infliximab biosimilar) used as switch from Remicade (infliximab) in patients with established rheumatic disease. Report of clinical experience based on prospective observational data. Expert Opinion on Biological Therapy 15(12): 1677–83. DOI: 10.1517/14712598.2015.1103733

Zhang H, Plutzky J, Shubina M & Turchin A. Continued statin prescriptions after adverse reactions and patient outcomes: a cohort study. Ann Intern Med 2017;167:221–227. doi: 10.7326/M16-0838

Gupta A, Thompson D, White A et al. Adverse events associated with unblinded, but not with blinded, statin therapy in the Anglo-Scandinavian Cardiac Outcomes Trial—Lipid-Lowering Arm (ASCOT-LLA): a randomised double-blind placebo-controlled trial and its non-randomised non-blind extension phase. Lancet 2017;389:2473–2481. doi: 10.1016/S0140-6736(17)31075-9

Tinnermann A, Geuter S, Sprenger C et al. Interactions between brain and spinal cord mediate value effects in nocebo hyperalgesia. Science 2017;358;105–108. doi: 10.1126/science.aan1221

P. Enck, U. Bingel, M. Schedlowski, W. Rief, The placebo response in medicine: Minimize, maximize or personalize? Nat. Rev. Drug Discov. 12, 191–204 (2013).

F. Eippert, U. Bingel, E. D. Schoell, J. Yacubian, R. Klinger, J. Lorenz, C. Büchel, Activation of the opioidergic descending pain control system underlies placebo analgesia. Neuron 63, 533–543 (2009).

Brasil R. 2018. Nocebo: the placebo effect’s evil twin. The Pharmaceutical Journal 300(7911): 05. DOI: 10.1211/PJ.2018.20204524 https://pharmaceutical-journal.com/article/feature/nocebo-the-placebo-effects-evil-twin

Abrahamson JD, Rosenberg HG, Jewel N, et al. 2013. Should people at low risk of cardiovascular disease take a statin? British Medical Journal 347: f6123. DOI: https://doi.org/10.1136/bmj.f6123

Tinnermann A, Geuter S, Sprenger C, et al. 2017. Interactions between brain and spinal cord mediate value effect in nocebo hyperalgesia. Science 358(6359): 105–8. DOI: 10.1126/science.aan1221 (accessed 22 January 2019).

Medsafe. 2018. Brand switches in New Zealand (presented at the 175th meeting of the Medicines Adverse Reaction Committee) 30 October 2018. URL:

www.medsafe.govt.nz/committees/MARC/reports/175-Brand%20Switches%20in%20New%20Zealand.pdf

Planès S, Villier C and Mallaret M. 2016. The nocebo effect of drugs. Pharmacology Research & Perspectives 4(2): e00208. www.ncbi.nlm.nih.gov/pmc/articles/PMC4804316/