Wednesday, March 28, 2018

Understanding the Mind - an Introduction to the Phenomenon of Placebo and Nocebo




Despite much recent intense study with some of the most remarkable scientific instruments and study methods yet devised for understanding brain function, much about the brain and mind remains mysterious. In understanding mood and psychiatric disorders, most study has focused on neuroanatomical and neurobiological factors that give rise to symptoms. We took a brief look at the basics of our brain anatomy and biology in neuroanatomy 101

When we think of ourselves, we generally think of our mind and not so much our brain. However, it is the brain that gives rise to the mind and, as we have been learning, it is deep brain regions that have so much "say" in our behaviours, actions, decisions, thoughts and so on. 

In this post, however, we are going to start looking at the power the mind can have over the brain; how thoughts, perceptions, beliefs, ideas and other apparent non-concrete phenomenon can produce amazing physiological changes in both the brain and body. 

As with all the topics I try to address, there is an enormous amount of present and past literature on today's topic and I can only hope to present a brief synopsis of what is known and, as is the purpose of this blog, how it applies to us mental health peeps. 

This is also going to be a difficult and probably somewhat controversial post as it will tread on some touchy ground for many if not all of us mental health peeps no matter our condition, our own experiences of it and our own treatment paths. 

Understanding the concepts placebo and nocebo is critical, however, for learning how mental perceptions will alter the physiology and outcomes of conditions like depression, bipolar, ADD/ADHD, anxiety and so on. It is also essential for a better understanding of how psychiatric medications may appear to work and how many other "treatments" may improve or appear to improve mental health outcomes or even physical health outcomes. 

Furthermore, it is also vital to understanding the damaging effects cognitive distortions or distorted thinking can have on our mental and physical health and why it's important to address these in our overall strategy for achieving better mental and physical health. 

As well, I'll also begin to tie these two concepts into our individual and subjective realities, how those are created and how we must learn to examine those and perhaps work to see them differently. 

Finally, if you have a clinical or professional interest in understanding psychiatric or mood disorders and all of their possible treatments this is yet another aspect of the human mind and brain that is absolutely essential to start learning to better understand. Without this you are for all intents and purposes lost at sea in trying to understand the vast puzzle that is the short and long term efficacy of any given course of treatments. 

That's a lot to get to in our limited space here today so let's dive in.


In his 2012 book Brain Wars, neuroscientist Dr Mario Beauregard introduces the chapter on placebo and nocebo with the sub-heading of "the power of belief to cure or kill". In a post on placebo in his award winning science blog Searching for the MindDr Jon Lieff writes that "mental activity, such as expectations, determine perception rather than just physical sensory information" and that "placebos demonstrate that perception alters physical health". 

These might appear to be astonishing - not to mention controversial - claims so we'd better first learn what each term means.


What is Placebo?


The word placebo comes from the Latin for "I will please". 

To begin to understand this important term and concept as it is used today, firstly we need to know that there are two ways to think of placebo; one is the placebo effect or response and the other is placebo medications or procedures for medical or medication trials. While what's going on in the brain is essentially or much the same, it's very important for our purpose here today to distinguish the differences in usages of the terms. 

Placebos in the field of medical or pharmaceutical trials is the use of a dummy pill or treatment to gauge the effectiveness of a new drug or treatment with the idea being that if the new treatment greatly outperforms the dummy pill or treatment - the placebo - then it's an effective treatment for a given medical or psychiatric condition via physiological means. If the new drug or treatment cannot outperform the placebo then it's judged (or should be) not an effective treatment in the sense that it has no actual physiological effect on the source of the condition (a tumour or the sources of a given pain for example). 

Placebo effect long predates the modern use of placebo medications or treatments in trials and could be from almost anything. 

As Beauregard stated, it comes from the power of belief or as Dr Lieff worded it, it is rooted in the power of our minds' perceptions and expectations and indeed our look today at placebo and nocebo effects in the mind and body are a look into the power of belief and mental perceptions and expectations of the mind, not to mention imagination

As for belief and what that means to the individual or a greater society or culture, Beauregard writes:
Belief, of course, is culturally specific. If you are an American believer in the power of Western medicine, a hypodermic needle, a striped capsule, or a sophisticated machine with several buttons may be the symbol of a powerful treatment. A member of a remote indigenous tribe might find the ingestion of a specific plant picked during the full moon much more credible. And regardless of the treatment, you may experience symptom relief. Because anything that enhances the credulity of a particular treatment will enhance the capacity of that treatment to evoke a placebo response. 

And by anything, that really could mean anything. As Beauregard further writes, "Mental processes and social contexts that facilitate faith and hope, positive expectations and feelings, motivation, and anticipation of improvement also appear to effect our brains, bodies, and behaviour". 

As Dr Lieff writes regarding placebo effect in Western society, "Placebos work through clinical rituals, symbols, and interactions with health care. The manner and explanations of doctors and other health care workers are also known to be a major aspect of the effect. It has long been noted that the manner in which doctors, therapists and nurses treat patients has a dramatic effect on whether they will improve or not".  

Not often seen in any discussion on placebo effect and the powers of belief and perception that creates the effect is the evolutionary basis for the powers of belief in the human mind. I introduced and somewhat addressed this in my post On Belief - an Introduction where I briefly outlined how the power of belief greatly ups a group's or individual's chance of survival and thus over the tens of thousands of years of our evolutionary development greater and greater capacity for belief became more and more a part of the neurobiological functioning in the human mind. 

And if we think back on the evolutionary history of homo sapiens, our species managed to survive and get by great injury or illness for many, many millenia before modern medicine. Not always, of course, but enough to survive. In the past when there were no means to treat injuries or diseases as there are today, almost the only way would have been through treatments in which the power of belief played the primary healing role (which we can see today by studying indigenous peoples and shaman administered treatments). 

Okay, that's a very brief introduction to placebo, let's now move on to nocebo. 


What is Nocebo?


As Beauregard (somewhat humorously) says, nocebo is placobo's "evil twin". It is Latin for "I will harm". Beauregard states that the term can be applied "whenever symptom aggravation follows negative beliefs and expectations without the administration of any inert treatment". As with placebo, a good deal of our modern medical understanding of the phenomenon comes from clinical trials of pharmaceutical drugs. Symptoms of side effects could arise from the negative beliefs and expectations of those even though the trial participants had received an inert substance (sugar pills are almost always used as the dummy pill). 

As another example, Beauregard reports that an average of twenty-five percent of participants in drug trials receiving the placebo will report negative symptoms associated with side effects for the trial medication (he then includes several case examples). In other words, what we are seeing here is, as Beauregard said regarding nocebo effect, "symptom aggravation following negative beliefs and expectations".

False positive medical test results such as X-rays and scans can also produce horrendous nocebo effects such as the case of a man who received a medical report indicating that he had widespread inoperable cancer of the esophagus. He displayed all the symptoms of the cancer and would eventually succumb to those symptoms and pass away. An autopsy, however, revealed that the report was based on false positive X-rays and in fact the level of cancer was very minor and should not have resulted in even much of an effect on health, let alone death. Again, in other words it was the patient's negative beliefs and expectations that created the deadly symptoms, not actual life threatening tumours. 

To return to indigenous peoples and nocebo effects of "curses", we'll look at an incident observed by a noted anthropologist studying a remote Australian aboriginal tribe. This involved the case in which a man accused of a tribal taboo had the tribe's shaman point a special bone at him and utter a curse:


The man who discovers he is being “boned” by the shaman is indeed a pitiful sight. He stands aghast, with his eyes staring at the treacherous pointer, and with his hands lifted as though to ward off the lethal medium, which he imagines is pouring into his body. His cheeks blanch and his eyes become glassy and the expression on his face becomes horribly distorted ... He attempts to shriek but the sound chokes off in his throat, and all that one might see is froth at his mouth. His body begins to tremble and the muscles twitch involuntarily. He sways backward and falls to the ground, and after a short time appears to be in mortal agony.

After a while he becomes very composed and crawls to his wurley (hut). From this time onward he sickens and frets, refusing to eat and keeping aloof from the daily affairs of the tribe. Unless help is forthcoming in the form of a counter charm administered by the village medicine man, his death is only a matter of a comparatively short time.

  • anthropologist Herbert Brooks in a 1925 account witnessed in his earlier observations of Australian tribes people


Nothing physically was done to the man nor were any poisons administered to him, only a simple bone pointed at him along with the utterance of some words. It was nothing more than the unquestioning belief in the omnipotent shaman's powers that created the deadly effect.

In one well known case study, a 26 year old male attempted suicide by taking what he assumed was an overdose of antidepressant pills. Along with other frightening symptoms, his blood pressure plunged to dangerously low levels. A friend rushed him to hospital where furious efforts were made to stabilize him. However, the patient had the pills as part of a clinical trial and in fact they were just dummy pills of sugar. When this was discovered and the patient informed, the dangerous symptoms cleared up within minutes. 


In 2012, the Technical University of Munich released one of the most thorough reviews of the literature on the nocebo effect in which they examined the underlying biological mechanisms and the problems these cause medical practitioner and clinicians. The conclusion: it is a surprisingly common and real phenomenon that should be taken seriously by the medical community on a daily basis. 


Okay, so those are some brief overviews as to what the terms placebo and nocebo mean and their outward effects. Let's now look a little deeper. 

As with so many leaps forward in medical understanding, some of the earliest known observations of the placebo response are from war zones. During WW II in a field hospital in Italy amidst a flurry of surgeries on injured soldiers, morphine supplies tragically ran short. With life saving surgeries imminent, a nurse assisting the anesthetist thought quickly and filled a syringe with a simple saline solution. Both the nurse and anesthetist carefully explained to the patient that he was receiving the powerful painkiller and the surgery proceeded with the patient remarkably experiencing little pain. 

That anesthetist, Dr Henry K. Beecher , would go on to publish the first known paper on the phenomenon The Powerful Placebo as well as becoming a leader in the field of its study (not to mention a highly respected leader in the field of medical ethics). 


The placebo effect or response can be so powerful that patients will report improving or disappearing symptoms of an illness or disorder even though it is clearly explained to them and that they clearly understand that they are taking the placebo of a trial medication; in other words, they knew they were taking only inert sugar pills. In an episode of the highly acclaimed Canadian Broadcasting Corporation series The Nature of Things called Brain Magic: The Power of Placebo, we also get some amazing examples and some in depth looks into how and why placebo works. In one portion of the program featuring Harvard Medical School's Ted Kaptchuk, a leading figure in the study of placebo effects, it recounts a study his department did on a new drug for Irritable Bowel Syndrome.

Eighty patients were involved; forty getting the active substance, forty getting a placebo. However, unlike a "blind" study, in which participants have no idea whether they're getting medications with active substances or a dummy placebo medication, in this study Dr Kaptchuk decided to make it an open label study - tell the placebo group openly, honestly and clearly that they were getting a placebo.

One woman who interviewed for the program had had Irritable Bowel Syndrome for twenty years and signed up for the trial because in her words she  "was desperate" and "willing to try anything". She describes how clear she was that she was getting a placebo and that she thought, "well, why not ... But I never, never, never thought it'd work".

As Kaptchuk recounts, "the important thing that we said was 'even if you have doubts, even if you think this is crazy, just take two pills twice a day. We think this will work'".

The woman followed the directions to a T and ... get this - after three days of knowingly taking a placebo her symptoms began to clear up. 

And that's not the most interesting part. In the end, twice as many patients who received the placebo pills reported significant improvement of symptoms as those who got the active ingredients. 

As Kaptchuk says in the program, "we got this incredible placebo response. We still can't believe it". 

The placebo effect is not limited to what sugar pills can do. In 2002 Dr Bruce Mosely, then of Baylor College of Medicine in Houston, Texas, received special (and rare) permission to investigate the effectiveness of placebo arthroscopic surgery for osteoarthritis of the knee. Three different procedures were performed on 160 patients; one third received the full normal arthroscopic repair, one third just a cleansing of the joint but no repair and another third in which only two incisions were made but no procedure at all was performed. All three groups went through the same pre and post operative procedures. 

Astonishingly, all three groups equally reported being pain free in a follow up two years later despite the nature of the study being revealed. 


So that's some very carefully and well conducted accumulation of powerful evidence. 


So what does this mean to us mental health peeps?

Several things. 

One, this has huge implications for the alleged efficacy of common antidepressants. This has long been a huge elephant in the room in every pharmaceutical company's boardroom. At no point since the release of the first antidepressant has any brand or formulation ever been able to outperform a placebo. This will require a separate post to better address this (and the literature on this is massively extensive), but the tragedy I've long seen (again, there is massive amounts of literature to support this) is that patients with serious underlying causes for their depressive symptoms will show initial improvement on antidepressants but then begin to decline over time. As I've said over and over again, there are many causes of depression and many of the symptoms that will simply not be addressed or "treated" by a simple pill (that can't even outperform placebos) that focuses on a tiny aspect of brain and body function. Thus literally tens of thousands of people become, as they say in the psychiatry business, "treatment resistant" and decline further and further. I have read dozens of case studies like these, talked to many people like this in psychiatric hospitals and since then interviewed many more. It is beyond heart breaking to see. 

But it's not just pharmaceutical drugs, it's any substance that becomes popular as an "effective treatment" for depression, anxiety or pain and so on. This means herbs of all kinds, so called homeopathic treatments, fancy looking treatments like "deep brain stimulation" (which I reported here failed to outperform sham treatments), you name it. 

It was always something that troubled me about looking for "cures" or "treatments" for mental health disorders; these desperate searches for some kind of magic bullet and the ongoing suffering because none of these ever actually address the true underlying causes of any one case. It was always heart breaking to me to see the hopes built up followed by the nearly inevitable let down and continued suffering made all the worse by yet another "failed treatment". 

I've argued this over and over again in many different posts; if we don't learn or recognize the underlying causes and work to address those, we will never escape the inner torment, the darkness, the pain, any of it. 

This has always been the biggest motivation for all my research of how brains work and how symptoms of so called "mental illnesses" are created. I wanted to know how everything worked in the brain, what caused any given symptom and most importantly how to address it and work on it with proven proactive methods that we can work on daily. 


Two, it gives us incredible real world well documented evidence into the power of the brain and body biology over the mind and the power of the mind over brain and body biology. Or in other words, the power of physiology over psychology and of psychology over physiology. Or to put it yet another way very, very important for us to understand - the power of suggestion, belief, perceptions, expectations, thoughts and yes, imagination can have over our physiology for both good or bad.  

As I've tried to hammer home in numerous pieces in this blog, there often is a very, very real brain and body physiology giving rise to the symptoms and mind phenomenon you experience. However, it is undeniable that it may well be mental experiences that create the physiology and this becomes a wicked cycle that is very, very hard to break with the mind influencing the brain and body physiology and the brain and body physiology influencing the mind and mental experiences (or conscious experience, as I like to say).

We must also be very clear about what placebo cannot do and what it does not mean. It does not shrink tumors, it does not heal broken bones or other wounds, it does not cure illnesses and conditions such as diabetes, heart disease, lung disease (and the list could run into the hundreds). It does not mean we can simply "will" ourselves to get better. 

Nor does it even remotely suggest that various conditions open to placebo effects are "all in your head" and no one who devotes their careers to studying these phenomenon would at all even imply that.

Dr Amir Raz of McGill University and noted authority in the studies of placebo responses firmly dispels these notions. 

As he explains, "Placebos instigate action, they change physiology. For real, not just for show". 

Some of this can be explained by how the brain creates anticipation based on memories of past events or experiences. Like many brain functions, they can be beneficial (this allows us to react quicker to danger, for example) or it may "trick us" by incorrectly anticipating something we "believe" will happen which in fact doesn't. This is part of what is known as the "conditioned response" which can be effectively demonstrated in numerous ways.

Kaptchuck puts it this way, "there are no pharmacological agents <in placebos> but the rituals and symbols of medicine activate neurotransmitters in relevant areas of the brain that change the experience of illness and alleviate symptoms."

An enormous body of evidence shows that placebo inducing treatments release the brain's natural endogenous opioids. The neurotransmitter dopamine is also heavily implicated which makes sense on a number of levels, chief of which is that it is this system that can keep us locked on to future hopeful targets and moving forward helping us block out obstacles (including negative mental states and pain). 

I strongly feel that both placebo and nocebo experiences would be very much tied into the harmful neurobiology of both acute and long term psychological stress with positive expectations mitigating the effects (placebo) or negative expectations, emotions, hopes, etc exacerbating them (nocebo). 


However, what we need to truthfully examine is the very real and powerful effect our thoughts, perceptions, expectations and even words have on our physical and mental health. 


When I started this whole journey back at the dawn of 2013 by thoroughly and honestly examining my own case history up until then, I felt strongly that some of my mental experience - particularly some of the dark hopelessness - may have been a result of the "expectations" I had had set by much of the literature I'd read stating the poor prognosis for those with my type of bipolar in my demographic (white male over 50 never diagnosed or treated) and the negative experiences of psychiatric and pharmacological care. 

When I came across and began study into the placebo and nocebo effects I felt I had the evidence that indeed some of my symptoms may have been nocebo effect and thus reversible. At that point I was also doing a lot of study into the power of belief and of the mind along with the interplay between brain, body and mind. 

"What if", I wondered "I could turn much of this around by learning to harness the power of my mind?" For this is what was very strongly suggested by the evidence from a great deal of the literature on belief, perceptions, expectations and placebo and nocebo and the findings of a sizable number of cognitive neuroscientists who investigate and research the power of mind. 

Over the ensuing years as I began to better and better understand the neurobiology and neuroanatomy of the brain and the interplay between brain, body and mind, the very real physiology of this in the brain and body became evident. 


So what, dear readers, am I suggesting here? 

What we allow in our minds matters. Undeniably so. The content of our thoughts, our beliefs, our expectations, our imagination, how we anticipate events absolutely makes a difference to our "mental health" (a term I feel is a very misleading and not very useful misnomer) and our physical health. 

What I am not suggesting is that defeating your symptoms is merely a question of "mind over matter". It is far from that simple. 

There is no way I could briefly describe or recount what a broken down wreck I was at the end of 2012 and again at the end of 2013 and few of those who know me today would believe it but everything I have accomplished in overcoming a long list of some of the worst symptoms there are involved in psychiatric disorders not to mention the brain damaging side effects of thirty months of psychiatric drug therapy came as a result of understanding the power of mind over our brains and bodies. 

All the daily habits I practice are to manage what is in my mind and any of the symptoms I may be experiencing at any one time. 

This is why I emphasize so much in so many posts how we must learn to control our thoughts and daily actions, not to mention how we view our selves and the world around us. 

This is why I worked so hard on meditation,  mindfulness meditation CBTmy brain training exercisesmusic therapy, being very aware of and careful of how my imagination is working, and to work very hard on common cognitive distortions.

In short, I work very hard daily on being very cognizant of what is in my head at any given point of the day and managing that quite simply because there is no doubt of the effects mind can have over brain and physical health. 


Now, you can learn to better understand this power within YOU or you can continue to be tossed at sea by these powers regardless of your willingness to accept these concepts or not (and the initial response of the vast majority of people both patients and professionals alike will be to deny these powers). 

Is it easy? 

No goddamned way. But that's life - it is not easy. 

Can you do it? 

I believe you can. 

It's a journey, it's a process and it takes time. And like all journeys no matter the personal difficulty and challenge, you move forward step by step, day by day.

But you're going forward in life regardless so you have nothing to lose by working on yourself and your mind. 

I know what you're thinking - "I'm not worth it". And I get that. I've been there countless times myself in brutally low ways. 

But ultimately that's not true. This is a conversation for a separate post but yes, 

YOU are worth it. 

Yes you are. 

Yes you can. 


Thank you as always for reading. 



Further reading resources:









McGill Talks Episode 7 - Prescriptions and Placebos

1 comment:

  1. Brad,
    Your work is phenomenal and I have tried to (continually) add your written works to my site without success.

    And today, the message below, Buddha's words regarding compassion, hit as if the Colorado skies opened up with 1000's of lightening bolts. Thank you!!

    ReplyDelete