Taking a placebo knowingly still improves stress and memory

By Dr. Liji Thomas, MDReviewed by Lauren HardakerMar 30 2026

Taking a placebo, while knowing it’s a placebo, may still ease stress and sharpen memory in older adults, offering a surprising and ethical path to support healthy aging. 

Study: Placebo mechanisms in aging: A randomized controlled trial comparing deceptive and open-label placebos on psychological, cognitive, and physical functioning in older adults. Image credit: Lanevskyi/Shutterstock.com

A randomized trial in healthy older adults, published in the International Journal of Clinical and Health Psychology, found that open-label placebos were associated with reduced stress and modest improvements in memory and physical performance.

Can placebos work even when people know?

A placebo is “an inert treatment presented as active”, according to the definition used by these authors. In medical history, placebo effects have been researched by offering an inert treatment as if it were an active intervention. This presumes that the patient's belief is necessary for the effect to occur. However, more recent literature suggests the contrary.

That is, if the placebo effect is satisfactorily explained as involving mind-body interactions, open-label placebos exert effects on patients as strong as deceptive placebos across multiple clinical and experimental parameters. Psychologists attribute this to patients’ expectations, which operate through psychological, contextual, and expectancy-driven processes to fulfil them.

Conversely, negative expectations, beliefs, and societal influences regarding aging often determine how an individual ages, including psychological well-being, physiological responses, and functioning. Thus, expectancy may drive health outcomes with a placebo. This remains under-researched among healthy older adults, except in specific conditions such as osteoarthritis-associated knee pain.

The authors here extended previous knowledge by using two different placebo procedures to examine the impact on functioning in multiple areas in healthy older adults.

Comparing known versus a deceptive placebo

The study included 90 healthy older adults, randomized to receive one of the following for the three-week study period: no intervention (controls), a deceptive placebo (stated to be a multivitamin supplement to improve well-being and functioning), or an open-label placebo (stated to be such but capable of producing psychological benefit reflected as physical improvement).

At baseline, participants reported measures of perceived stress, mental well-being, tiredness, optimism, sleepiness, and self-efficacy, as well as stereotyped aging characteristics. They performed tests of memory, selective attention, and physical function.

Both the self-assessment and the testing were repeated after the study period. The authors suspected that both placebo groups would show evidence of benefit, but this would mainly involve states that rapidly respond to expectancy (such as perceived stress and performance measures) rather than trait-like areas, including self-efficacy and optimism, which are more stable over time.

The open-label placebo group shows the clearest between-group effects in key outcomes

Between-group comparisons

Post-intervention, the group that knowingly received a placebo reported lower perceived stress than both other groups. No significant difference in perceived stress was observed between the deceptive placebo and control groups.

Short-term memory was higher in the open-label placebo group than in the controls, but not when compared to the deceptive placebo group or when the latter was compared to the control group. No significant between-group differences were observed for selective attention (Stroop test), despite improvements over time across all groups.

Pre- to post-intervention differences

Within each group, self-reported parameters remained unchanged. Cognitive performance increased from before to after the intervention in both placebo groups. A cognitive inhibition task showed improvement in all groups, including controls, suggesting a likely practice or habituation effect rather than a placebo-specific effect.

Physical functioning improved in both placebo groups, but more significantly in the open-label group, in within-group analyses, although no significant between-group differences were observed at post-intervention.

Overall, these findings suggest a potential role for expectancy-related mechanisms alongside practice effects, rather than the placebo effect alone. Even so, the greater improvement in the open-label group may support the theory that improved outcomes result from believing that an intervention has a useful purpose, even in an objectively measured area like physical functioning.

Placebo interventions were associated with modest changes in functioning

In this study, modest cognitive and physical improvements were observed in both placebo groups, though the effects were more marked in the open-label placebo group. The between-group differences, particularly those favoring the open-label placebo group, present the strongest evidence for placebo effects.

These findings agree with the existing literature, suggesting that the placebo effect operates regardless of whether the substance is known to be a placebo, although effects appear to depend on the specific outcome and analytical comparison used.

Mechanisms underlying the placebo effect

The authors cite several possible mechanisms driving the placebo effect, including the expectation of treatment benefit, improved regulation of thoughts, feelings, and behaviors, enhanced mind–body interactions, and the provision of a credible explanation for the treatment. 

The open-label method, supported by a credible explanation, could have fostered greater trust, thereby improving their ability to respond to the intervention. Alternatively, or in addition, they might have felt more in control over their health and acted accordingly. This has been associated with greater resilience and healthier aging.

The deceptive placebo group might have perceived the intervention as a supplement of doubtful efficacy. This hypothesis needs to be explored, though both placebo groups reported confidence in the intervention's effectiveness before and after the study period. However, treatment expectations were assessed informally rather than through standardized measures, limiting conclusions about the mechanisms involved.

Study limitations

The study has several limitations. It has a small sample size and excludes older adults on medication, limiting generalizability. There was no baseline cognitive screening, which may affect placebo responsiveness. Objective markers such as serum cortisol or heart rate variability were not included. The study was not preregistered. Multiple outcomes were tested, increasing the risk of false-positive findings despite statistical correction. 

Larger studies needed to confirm placebo effects

Future studies should use larger, more diverse samples and objective methods to capture treatment expectations, rather than the qualitative discussions used here. Mechanistic research should be prioritized in this field.

They should also use other measures of credibility (whether the participants believed the description of the intervention given to them), adherence, and what the participants believed to be the purpose of the study. Of course, in this case, the open-label group knew what the study aimed to do, which may have influenced their responses in an effort to fulfill the perceived requirements.

The open-label placebo group showed improvement at least as great as that seen with a deceptive placebo, suggesting that, contrary to the traditional view, placebos may have observable effects on some objective outcomes, although these effects were modest, context-dependent, and should be interpreted cautiously. If validated in larger studies, this could represent a scalable, inexpensive treatment framework for older adults across multiple settings.

“These findings suggest the potential of open-label placebos as a promising, ethically acceptable approach for supporting healthy aging,” while remaining preliminary and requiring further confirmation of mechanisms, durability, and generalizability.

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