March 4, 2024 • 1hr 18min

How Placebo Effects Work to Change Our Biology & Psychology

Huberman Lab

This episode explores the incredible power of placebo effects, nocebo effects, and belief effects. These phenomena illustrate how our brain's expectation of what will happen can actually change what does happen, independent of any active drug or treatment.

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Key Takeaways

Placebo effects are when an inert substance or behavioral treatment leads to improvement in symptoms or performance. Nocebo effects are when an inert substance or treatment leads to worsening of symptoms or performance.
Belief effects are when specific knowledge changes your expectation about what will happen, leading to that specific outcome.
Placebo, nocebo, and belief effects all work by changing expectation, which is driven by the prefrontal cortex of the brain.
The prefrontal cortex is a prediction machine that evaluates context and activates or suppresses other neural circuits to shape bodily functions like heart rate, blood pressure, hormone release, and more (12:01)
"Placebo effects are real, and placebo effects scale with the degree of expectation that one has...Whether or not that occurs is going to depend a lot on what sorts of quote unquote effects we are expecting." - Andrew Huberman (54:08)
Placebo effects have limits - they can reduce discomfort from cancer treatments but cannot eliminate tumors, for example (42:06)
Beliefs and mindsets can impact very basic physiological functions like insulin response to foods and health benefits of exercise (58:09)

Introduction

This episode explores the incredible power of placebo effects, nocebo effects, and belief effects. These phenomena illustrate how our brain's expectation of what will happen can actually change what does happen, independent of any active drug or treatment.

While placebo effects may seem like the power of mind over matter, they actually involve real, measurable biological changes driven by specific neural circuits. By the end, you'll understand the mechanisms behind these effects and how to leverage them for your mental and physical health.

Topics Discussed

Defining Placebo, Nocebo & Belief Effects (8:01)

Placebo effects: When an inert substance/treatment improves symptoms or performance
Nocebo effects: When an inert substance/treatment worsens symptoms or performance
Belief effects: When specific knowledge changes expectation, leading to that outcome
All of these work by changing expectation, driven by the prefrontal cortex

Placebo Effects on Dopamine & Parkinson's (16:02)

Parkinson's involves degeneration of dopamine neurons; drugs like L-dopa aim to increase dopamine
In studies, Parkinson's patients given a placebo showed increased dopamine release in the brain
Simply being told a placebo will increase dopamine leads the brain to release more dopamine
Shows placebo effects have real biological underpinnings, not just psychological

Specificity of Placebo Effects on Hormones (22:03)

Study measured effects of placebo injection after taking a real drug (sumatriptan)
Sumatriptan increased growth hormone & decreased cortisol; then placebo injection alone did the same
Even when told placebo would have the opposite effect, subjects still showed same hormone changes
Brain formed an association between injection and specific hormonal response

Classical Conditioning & Insulin Response (30:04)

Smell of food alone can trigger insulin release due to past pairing of smell with insulin response from eating
In Pavlov's famous experiments, a bell paired with food caused dogs to salivate to bell alone
Shows how stimuli unrelated to food can evoke conditioned hormonal responses through learning/expectation

Factors Influencing Placebo Effect Magnitude (36:05)

Perceived quality: Branded or well-packaged placebos have stronger effects than generic ones
Pill color: Blue linked to sleep, red to stimulation, yellow to anti-depressant effects in studies
Route of delivery: Capsules > tablets; injections > oral; elaborate delivery methods > simple ones
Brain associates higher complexity & invasiveness with bigger expected effects

Limits of Placebo Effects (42:06)

Placebos can reduce side effects of cancer treatment but cannot shrink tumors themselves
In asthma, placebos reduced discomfort of symptoms but did not improve objective lung function
Prefrontal belief circuits have many outputs but are not omnipotent; they connect to primitive regulatory areas but not everywhere

Belief Effects & Nicotine Dose Expectancy (50:08)

Study told subjects they got low, medium or high nicotine dose in vape; all got same dose
Belief in higher dose led to better performance on attention task and more activity in brain's nicotine-responsive areas
Shows belief effects scale dose-dependently and involve real neurobiological changes, not just subjective perception

Mindsets & Physiological Impacts (56:09)

In "mind over milkshakes" study, believing a shake was indulgent & high-calorie led to greater drops in hunger hormones vs believing it was sensible & low-calorie (despite same actual content)
Hotel workers told their work was good exercise showed greater health improvements than those just told it was important work
Primitive hard-wired functions like hunger and health impacts of movement are still shaped by higher-order cognition about meaning & expectancies

Brain Circuits Mediating Belief & Stress Physiology (1:06:10)

Study traced a pathway from rat prefrontal cortex to hypothalamus to brainstem to body
Activation of this top-down circuit elicited cardiovascular & temperature stress responses
Analogous human studies show how abstract thought centers modulate primitive survival physiology
Helps explain how beliefs/expectations alone (placebo effects) can potently shape clinical outcomes

Genetic Influences on Placebo Response (1:12:10)

~30% of people tend to show strong placebo effects, 70% more modest; relatively stable individual trait
COMT gene, which regulates dopamine & other catecholamines, linked to variation in placebo response
Further evidence that placebo effects are not imaginary but grounded in biological predispositions

Conclusion

This episode illuminates the incredible power of the mind to shape physical reality through placebo and belief effects. While these effects arise from our conscious expectations, they are not imaginary - they involve measurable changes in brain activity, hormone levels, and clinical outcomes.

The prefrontal cortex acts as a prediction machine, evaluating context and activating bodily control centers to align physiology with expectations. This top-down circuit can modulate everything from Parkinson's symptoms to hunger hormones to the health impacts of physical activity.

However, placebo effects also have limits and show individual variability. They are constrained by the actual architecture of mind-body connections and influenced by genetic factors. Understanding these nuances allows us to harness the power of belief in an evidence-based manner.

Ultimately, these effects underscore a key insight: Our mindsets and expectations are not idle thoughts but architects of our lived reality. As Dr. Huberman puts it, "The belief effects, the expectations, are real. They are having effects through true biological circuitry."