Exosomes & the Placebo Effect

How is the Placebo Effect possible? or the Nocebo Effect? How could someone think themselves well, or sick? How could a voodoo curse or other negative thought cause someone to die even, for no apparent reason? Magic? or biology?


Hold that thought.


The power of belief is quite magical, whether Christmas cheer, or the kiss from momma on the boo-boo.

Continuation of a series:

  • Placebo and Nocebo Effects and COMT gene alleles. - our dopamine level seems to affect whether we will be more or less likely to have a placebo response, and our dopamine level is effected by alleles the COMT gene. Some people will produce more dopamine than others (on average) based on the allele type of their COMT gene.

  • Kindness is the best placebo. - continues the discussion of dopamine and the placebo and nocebo effects with a focus on the language health professionals might use and how it may be harmful without their realizing - warning of specific negative side effects may increase the likelihood of the person experiencing them. Trauma patterns in childhood or later in life may also involve a repetitive nocebo effect having occurred - say something or someone is bad often enough and the person or child may grow to believe it.

Repetition of the positive or negative message may add to the strength of a placebo or nocebo response - and repetition of new messages is needed to build new habits or beliefs. Change requires the repetitive practice in order for the brain to lay down new nerve pathways and remove unused ones. So it is important to stop thinking about the old stuff you want gone. The very act of thinking about it is keeping it an actively used brain pathway, like a line of Domino's falling, being rebuilt, and knocked over again, every time it happens the pathway is strengthed. The next post in my series does not directly mention the placebo/nocebo theme but it is a resource page about habit change - and needs this introductory paragraph added perhaps (note to self).


Placebo Effect - Magic? or Biology?


I am going with biology - exosomes may be the explanation.


Exosomes are tiny packets of information chemicals (messenger and microRNA, along with proteins and lipids) that one cell can produce and send out into the body - where they selectively can choose other cell types to enter and release the message chemicals which can then change certain sequences of that cell's genes to be either on or off depending on the message. (1)


"It is only recently that these extracellular vesicles, [exosomes, were found to be] functional vehicles that carry a complex cargo of proteins [2], lipids [3], and nucleic aids [2, 4, 5], be capable of delivering these cargos to the target cells they encounter, which may ultimately reprogram the recipient cells distal from their release. Thus, exosomes represent a novel mode of intercellular communication, which may play a major role in many cellular processes, such as immune response [6], signal transduction [7], antigen presentation [8]." (1)


The proteins and lipids could form the outer membrane containing the RNA. MicroRNA are tiny pieces of code that can affect the methylation status of our cell's genes - turning them either on or off - methylated is inactive, off for any transcription of new messenger RNA which are what proteins are transcribed from - like a computer code kind of. The surface of the exosome packet could be marked with surface glycoproteins that can recognize another specific surface marker glycoprotein on other cells -possible in a far away location within the body. Biology makes magic seem possible - or biology seems fairly magical at least.


How would thinking positively or negatively about something create specific exosomes?

That is not known. This is a new idea that is not really in research stages yet. Exosomes are being studied though, and the idea of their being a causal agent of the placebo effect has been suggested. (2) How could we test the theory? It would be an unethical research design to study the nocebo effect on purpose, "First do no harm", but a study looking at the placebo effect and the power of positive messages might be possible. Check the patient's exosomes before and after the positive messages are given, and see if there is a difference in any of the exosomes. That would not be easy to do, though. Exosomes are very tiny. (1)


"However, challenges exist not just in exosome isolation, but rather in rapid and accurate quantification of exosomes with minimal sample preparation, to allow detection of tiny pathological changes of disease." (1)


The specific messages of the exosomes would need to be identifiable as well as finding the little things in the first place.


In the meantime, thinking positively, and trying to set aside worries and negative thoughts, seems like a safe bet.


History of the term 'placebo'.

A blog series about exosomes includes a history lesson about the word placebo and its change in meaning over time, Blog 26. The Placebo Effect. (3)


Initially in medical care the word placebo was chosen based on it's Latin meaning "I will please" and the medication that was given was considered nontherapeutic, simply pain relieving and were based on opium or cannabis preparations - neither of which would be inactive. Both opiates and cannabinoids actively treat pain - which would be providing hospice care for the end-stage of life. Then there was a transition to the clinical trial use of the word to mean an inert "sugar pill" placebo. The third meaning refers to the mind-body connection of thinking positively to get positive results and avoid negative thinking. The third seems to most accurately reflect the body's true ability to do self healing or self-harm based only on external discussion or internal worries or positive visualization. (3)


The author, Ed Park, MD, is a doctor who uses exosomes for the treatment of pain and his work was challenged as being only helpful due to a placebo effect. He suggested that is not possible - exosome treatment is doing something to the body to reduce the pain. (3) Interestingly - they may both be right. Dr. Park may be an early adopter of our own mechanism of action for a placebo or nocebo effect - exosomes containing RNA that can go to specific types of cells and reset their genes to perform different actions, or to stop an action.


Dr. Park may be able to harness the biology of exosomes and possibly the power of our placebo effect, but for us - we need to do our own magic. Our own positive thoughts about our ability to self heal, defend against pathogens and other toxins, may help us to do so! But we also need positive diet and lifestyle habits - thinking about it doesn't get a meal on the table.


"You can't do anything about the length of your life, but you can do something about its width and depth." - Evan Esar

-quote via Pat McDaniel, (@wise_insights4u)


Disclaimer: Opinions are my own and the information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes.


Reference List

  1. Zhang Y, Liu Y, Liu H, Tang WH. Exosomes: biogenesis, biologic function and clinical potential. Cell Biosci. 2019;9:19. Published 2019 Feb 15. doi:10.1186/s13578-019-0282-2 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6377728/

  2. Dr. Grouf, "might have rna mediated, exosomal metabolic effects" https://twitter.com/DGrouf/status/1405387766133932032?s=20

  3. Ed Park MD, Blog 26. The Placebo Effect, Jan 14, 2020, rechargebiomedical.com https://www.rechargebiomedical.com/exosomes-blog-26-the-placebo-effect/