How Placebo Effects Work to Change Our Biology & Psychology

Placebo Effects (00:00:00)

• Placebo effects are not simply psychological or the power of the mind over matter.
• Placebo, nobo, and belief effects actually change the way biology and physiology work.
• Neural circuits in the brain are dedicated to how expectations of what will happen change core biological functions.
• Placebo effects can modify heart rate, blood pressure, and the release of neuromodulators like dopamine and adrenaline.
• Placebo effects can work alongside traditional drug treatments or behavioral treatments to change how the brain and body work.
• Placebo, nobo, and belief effects have powerful impacts on physiology separate from their use as controls in clinical studies.
• Some researchers believe that these effects should be leveraged as their own unique treatment for various diseases.

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Placebo, Nocebo vs. Belief Effect, Prefrontal Cortex (00:07:24)

• The placebo effect occurs when an inert substance or treatment improves symptoms or performance due to the patient's belief in its effectiveness.
• The nocebo effect occurs when an inert substance or treatment worsens symptoms or performance due to the patient's negative expectations.
• Belief effects involve specific knowledge changing expectations and leading to specific physiological or psychological outcomes.
• The prefrontal cortex, a complex brain region, plays a crucial role in the placebo effect by integrating present context, past memories, and future goals to influence basic physiological functions.
• The prefrontal cortex communicates with areas of the brain stem, controlling functions like breathing, and with deeper brain areas like the hypothalamus, which regulates primitive functions.

Dopamine, Placebo & Parkinson’s Disease; Placebo Controls (00:14:03)

• Placebo effects can significantly alter dopamine levels in the brain, even in the absence of any active chemical compounds.
• Parkinson's patients and healthy individuals both exhibited increased dopamine release when given a placebo drug, as observed through brain imaging.
• The placebo effect reduces the binding of raclopride to dopamine receptors, indicating heightened dopamine release.
• While placebos have genuine biological effects, their dopamine-increasing impact is generally weaker compared to actual dopamine-boosting drugs.
• The strength of the expectation effect, which drives the placebo effect, varies among individuals and diminishes when people realize they're taking a placebo.
• Placebo effects serve as a measure of expectation in drug trials, emphasizing the influence of beliefs on drug outcomes.
• The specificity of placebo effects raises questions about the role of beliefs in shaping drug effects, even when the precise drug mechanism is unknown.

Hormone Release & Placebo Effect, Paired Associations (00:21:36)

• The placebo effect can have specific biological effects, such as altering hormone levels, even in the absence of an active treatment.
• Injections of an inert saline solution can lead to changes in hormone levels similar to those caused by an actual drug, demonstrating the power of the placebo effect.
• The brain and body form associations between receiving an injection and the expected hormonal changes, leading to the placebo effect, despite the ancient nature of the hormonal systems involved.
• The brain simplifies information and forms predictions, often subconsciously, which can have significant effects on internal processes like hormone release.

Conditioning Effect & Insulin; Pavlovian Response (00:28:52)

• The smell of certain foods can lead to the release of insulin due to classical conditioning.
• Insulin is a hormone that regulates blood glucose levels.
• Experiments have shown that a neutral stimulus (e.g., a bell or buzzer) paired with food consumption can lead to a conditioned insulin response.
• This demonstrates the strong modifiability of the placebo effect according to context.
• The prefrontal cortex plays a role in the anticipation of the placebo effect by integrating various environmental cues.
• Classical conditioning, as described by Pavlov, involves inducing a response (e.g., salivation in dogs) through a stimulus unrelated to the natural trigger.

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Context & Expectations; Placebo Effect & Brain (00:34:17)

• The placebo effect is influenced by the context and expectations surrounding a treatment, including the brand name, color, and invasiveness of the placebo.
• The more invasive or complex a placebo appears, the greater the placebo effect.
• Medical devices or machines can have a significant placebo effect, even if they are not doing anything specific to the biological system.
• The placebo effect works by activating specific neural circuits in the prefrontal cortex, which then communicate with other areas of the brain and body through neurotransmitter release and electrical activity in neurons.
• The belief and expectations associated with a treatment have real effects on the body through true biological circuitry, even though the treatment itself may not have any specific biological impact.

Cancer, Mind-Body Practices; Placebo Effects & Limits (00:40:51)

• Placebos can reduce the discomfort of cancer treatments like chemotherapy or radiation therapy, such as reducing pain and nausea.
• Placebos cannot reduce the size or eliminate tumors.
• Mind-body techniques like meditation, sleep, and social support can improve cancer treatment outcomes by reducing inflammation and stress hormones.
• These improvements are not placebo effects but real effects due to reduced inflammation and stress hormones.
• Real effects also include drugs, radiation, chemotherapy, immunotherapy, and devices known to reduce tumor size or eliminate cancerous tumors.
• Placebo effects are based on knowledge, belief, and expectation about a treatment's outcome.
• Placebos do not directly act on tumors to reduce their size or eliminate them.

Asthma, Specificity & Placebo Effects (00:44:54)

• A study from Dr. Ted Kaptchuk's Lab at Harvard Medical School showed the power and limitations of placebo effects.
• Asthmatic patients were taken off their medication for a short time and experienced breathing challenges and discomfort.
• One group received no treatment, another received a placebo, and the third received a drug to improve asthma symptoms.
• The drug group had improved breathing and reduced discomfort, as expected.
• The placebo group also experienced reduced discomfort, but their breathing patterns didn't change.
• This demonstrates that placebo effects are powerful but specific, not eliminating conditions like asthma completely.
• Placebo effects can effectively reduce discomfort associated with breathing challenges but don't restore normal breathing patterns.
• The prefrontal cortex and expectations can have significant effects on pain, dopamine, and various brain and body systems, but they are not omnipotent.

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Nicotine & Dose-Dependent Placebo Effects (00:49:03)

• A study led by Dr. Michael C. Treadway found that nicotine-related beliefs can induce dose-dependent responses in the human brain.
• Participants vaped nicotine and were told they were ingesting a low, medium, or high concentration of nicotine, but everyone received the same amount.
• Those who believed they received a higher concentration performed better on a cognitive task, demonstrating the power of the placebo effect.
• Brain imaging revealed increased activity in a specific brain region related to nicotine and cognitive functioning in those who believed they received a higher nicotine concentration.
• Placebo effects are real and their magnitude corresponds to the degree of expectation, inducing not only psychological but also physiological changes, such as alterations in brain activity.
• The extent of placebo effects depends on the modifiability of the desired outcome by knowledge and expectation.
• While placebo effects have limitations and cannot be used to eliminate severe conditions like tumors, they offer valuable insights into the mind-body connection and the power of belief.

Placebo Effects vs. Belief Effects, Food & Mindset (00:55:31)

• Belief effects can significantly influence the outcomes of drug treatments and behavioral interventions.
• Mindset, encompassing beliefs, prior knowledge, and additional information, plays a crucial role in determining outcomes.
• Dr. Alia Crum's study revealed that individuals who believed they were consuming a high-calorie milkshake experienced a steeper reduction in the hunger hormone ghrelin compared to those who thought they were consuming a low-calorie milkshake, despite both groups consuming the same 380-calorie milkshake.
• Our beliefs about food can strongly impact the hormonal responses associated with consuming those foods.

Exercise & Belief Effects (01:01:02)

• A study on belief effects and mindsets examined the impact of beliefs on exercise outcomes.
• Dr. Alia Crum's advisor suggested that the positive effects of exercise might be due to placebo effects.
• The study involved hotel service workers who were divided into two groups.
• One group was told that their job activities were beneficial for their health, while the other group was informed that their daily activities constituted exercise.
• The group that believed their activities were exercise experienced improvements in health metrics such as reduced blood pressure, lower resting heart rate, and decreased body weight.
• This supports the idea that mindsets and beliefs can influence exercise outcomes.

Placebo Effect, Brain & Stress Response (01:04:08)

• The prefrontal cortex, a prediction machine that sets expectations based on context, can influence various physiological responses through neural circuits that extend to the hypothalamus, brain stem, and periphery.
• Activation of specific neurons in the dorsal medial hypothalamus can change blood pressure and cause vasoconstriction in the periphery.
• The placebo effect involves a chain of neural circuits that starts in the prefrontal cortex and extends to the hypothalamus, brain stem, and periphery.
• Studies are revealing the precise neural pathways that connect higher brain areas associated with thought and context to deeper brain structures involved in the stress response.
• The prefrontal cortex, highly elaborated in humans, exhibits a high degree of specificity in its sub-areas and connections.

Individual Variation, Genetics & Placebo Effect (01:11:18)

• The placebo effect can vary significantly between individuals and across studies.
• Approximately 30% of individuals show a robust placebo effect, while the remaining 70% show a less robust effect.
• Certain genes, such as the CT gene, which encodes for the enzyme catechol-O-methyl transferase (COMT), have been found to correlate with the strength of the placebo response.
• COMT is involved in regulating dopamine, epinephrine, and norepinephrine, which are neurotransmitters associated with motivation, focus, and movement.
• Individuals with variations in the CT gene show corresponding variations in their placebo response to certain conditions.
• The levels of these genes and the degree to which an individual experiences the placebo effect are strongly correlated.
• The placebo effect has a real biological substrate, involving anatomical pathways, hormonal pathways, and neurotransmitters.

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