Harnessing placebo effects to regulate emotions

The placebo effect
Placebo effects work through two interrelated mechanisms: expectations and learned 
associations (Ashar et al., 2017). In the placebo context, expectations refer to the probability of 
an intended beneficial effect. Expectations are typically induced through verbal suggestions. For 
3 example, Koban et al. (2017) told participants experiencing a break-up that they would receive a 
nasal spray that would reduce their negative emotions when looking at pictures of their expartner. On the other hand, learned associations are automatic responses to stimuli or procedures. 
In the placebo context, learned associations refer to pairing a beneficial effect with a placebo 
object or procedure. For example, Petrovic et al. (2005) intravenously delivered an anxiolytic to 
participants before viewing distressing images. Participants paired the intravenous drip with 
feeling less negative when looking at these pictures. In the next session, they received a saline 
intravenous drip with the verbal suggestion it was the same anxiolytic.
Whether through expectations or learned associations, placebos appear to exert their 
effects automatically and with minimal cognitive effort (Braunstein et al., 2017). Buhle et al. 
(2012) examined whether engaging executive function would interfere with placebo effects on 
pain. The placebo reduced pain experience even when the person simultaneously completed a 
working memory task. Notably, the placebo did not interfere with cognitive performance, 
suggesting that it did not require extra mental resources to exert its effects. In an fMRI study 
comparing placebos with cognitive reappraisal (i.e., a strategy that requires more cognitive 
effort), placebos led to less dorsolateral prefrontal cortex (dlPFC) activation, a brain region 
associated with selective attention, working memory, and holding active appraisals (Schienle et 
al., 2017).

How can placebos regulate emotions?
There is substantial evidence that expectation-based placebos can effectively regulate 
emotions (Geers et al., 2021). In these paradigms, participants are deceptively told they will 
receive a treatment to reduce their negative emotions before undergoing a distressing task. In 
laboratory studies, placebos reduced the experience of distress from negative emotional images 
4 (Schienle, Übel, & Scharmüller, 2014; Schienle, Übel, Schöngaßner, et al., 2014), sad movie 
clips (Glombiewski et al., 2019) and memories (Rebstock et al., 2020), the threat of shock 
(Meyer et al., 2015; Meyer et al., 2019), and a speech task (Abrams et al., 2001). Some evidence 
shows placebos can impact autonomic measures associated with emotional responses. For 
example, participants who received a placebo nasal spray showed reduced skin conductance 
levels when anticipating painful shocks (Meyer et al., 2015). These studies suggest that placebos 
influence subjective and objective emotional distress measures.
Much of what we know about neural systems associated with placebo effects come from 
pain analgesia studies. However, there is evidence that placebos also influence neural measures 
such as BOLD fMRI signals (Koban et al., 2017; Petrovic et al., 2005; Schienle, Übel, 
Schöngaßner, et al., 2014) and electrocortical activity (Meyer et al., 2015; Schienle et al., 2020)
in emotion regulation contexts. Collectively, these studies show placebos down-regulate brain 
regions involved in emotional experience (e.g., insula, amygdala). Nevertheless, more research is
needed to understand the unique neural systems consistently associated with placebos regulating 
emotions.
Placebos are also effective in regulating acute emotional distress in clinical samples, 
including those with social anxiety disorder (Abrams et al., 2001), spider phobia (Gremsl et al., 
2018), and depression (Haas et al., 2020). The regulatory effects of placebos also extend to
reducing affective symptoms. Meta-analytic findings show that placebos decrease anxiety 
(Bandelow et al., 2015) and depression symptoms (Khan et al., 2012). It should be noted, 
however, that active treatments such as SSRIs still outperform placebos (Cipriani et al., 2018), 
albeit with important moderators. For example, Fournier et al. (2010) showed that placebos 
5 performed just as well as antidepressants for patients with mild to moderate depression; 
antidepressants only outperformed placebos for patients with very severe depression.
In summary, placebos effectively regulate acute bouts of emotional distress for both nonclinical and clinical samples. The positive effects in clinical samples are noteworthy since people 
with affective disorders often have difficulties regulating their emotions (Sheppes et al., 2015). 
Moreover, placebos can reduce mild and moderate affective symptoms, which open-up their 
clinical application across the full spectrum of people struggling with emotional problems.

Addressing the ethical dilemma of placebos: Introducing placebos without deception
Placebos are remarkably effective in regulating emotions, with 25+ studies showing 
positive effects with medium to large effect sizes (Ashar et al., 2017; Geers et al., 2021). 
However, to get placebos to work, participants are deceived into believing they are taking an 
active treatment. On the one hand, placebos can effectively regulate emotions. But on the other 
hand, people must be deceived to activate their regulatory effects, creating an ethical dilemma. 
Fortunately, there is growing evidence that placebos can work without deception (i.e., nondeceptive placebos or open-label placebos) by honestly leveraging expectations through verbal 
suggestions. In non-deceptive placebo studies, participants are educated about the placebo effect, 
how it can lead to beneficial outcomes in some contexts, how positive expectations can help but 
are not crucial, and that taking the placebo object as prescribed is important. Using this 
educational approach that uses a combination of readings, videos, and instructions from an 
experimenter, there is growing evidence that non-deceptive placebos can regulate emotions like 
their deceptive counterparts. 

In laboratory settings, non-deceptive placebos reduced the experience of self-reported 
distress from negative emotional images (Guevarra et al., 2020; Schienle et al., 2022) and self-referential sentences with sad music (Hahn et al., 2022). Hahn et al. (2022) also measured heart 
rate. They found null effects, casting doubt on whether self-reported results reflect genuine 
regulation effects or are a product of response bias. After all, directly telling participants that the 
non-deceptive placebo may reduce their negative emotions increases demand characteristics and 
response bias concerns. Guevarra et al. (2020) and Schienle et al. (2022) addressed these 
concerns by showing that non-deceptive placebos reduced neural measures associated with 
emotional distress (late positive potential; LPP).

It is worth noting that one study did not show positive non-deceptive placebo effects. 
Friehs et al. (2022) randomly assigned participants into five groups (control, two deceptive 
placebo groups, and two non-deceptive placebo groups) before watching a sad film. They found 
decreases in sadness for deceptive placebos but not for their non-deceptive counterpart. Their 
null findings may have to do with their manipulation. Previous studies relied on a combination of 
reading materials with experimenter instructions (Guevarra et al., 2020), videos with 
experimenter instructions (Schienle et al., 2022), and oral presentations from an experimenter 
(Hahn et al., 2022). Friehs et al. (2022) instructed participants to read about placebo effects and 
self-administer a nasal spray. Although this reading manipulation may be sufficient for deceptive 
placebos, it may not be an optimal manipulation for non-deceptive ones. These studies suggest 
that non-deceptive placebos can regulate emotions; however, their effectiveness may be 
dependent on the features of the manipulation. Future studies should systematically examine 
what contextual features of the manipulation are important such as the experimenter’s presence, 
mode of information delivery, audio/visual cues, or type of placebo object. 

Outside the lab, non-deceptive placebos have helped manage daily stressors and 
chronically stressful periods. El Brihi et al. (2019) showed that taking non-deceptive placebo pills for five days reduced emotional distress and physical symptoms and improved mental wellbeing and sleep quality. During chronic stress periods, non-deceptive placebos manage students’
test anxiety for two to three weeks (Kleine-Borgmann et al., 2021; Schaefer et al., 2019). 
However, there is insufficient evidence that non-deceptive placebos are effective in affect-related 
disorders. We are aware of two small sample studies (n < 20 per group) that showed trending but 
non-significant decreases in depression symptoms (Kelley et al., 2012; Nitzan et al., 2020). 
Future large-scale RCTs should examine if non-deceptive placebos can reduce affective 
symptoms in clinical samples.

Fundamental questions and directions for future research
Harnessing placebo effects to regulate emotions raises many questions. We have 
identified directions for future research throughout this chapter, and we highlight some more key 
questions here. To harness placebo effects to regulate emotions, examining the efficacy and 
understanding the mechanisms of non-deceptive placebos is essential. Although interrelated, we 
divide this section into basic and translational science implications.

Basic science questions
First, what are placebos doing phenomenologically when regulating emotions? An 
expectation-based placebo is an appraisal-type strategy that may broadly help interpret an 
upcoming emotional situation as less severe. Indeed, Guevarra et al. (2020) show that nondeceptive placebos impact neural measures (sustained LPP) involved in the appraisal stages of 
emotional processing. Yet, taking a pill or nasal spray that people believe will reduce their 
emotional reactions versus having people cognitively reappraise a situation to reduce their 
emotional reactions are phenomenologically distinct. Future studies should directly compare non-deceptive placebos with other appraisal-type strategies to understand important similarities 
and differences in efficacy, underlying neural mechanisms, and cognitive cost.
Second, how reliable and robust are non-deceptive placebo effects in regulating 
emotions? Although three lab studies showed positive results, one did not. We pointed out that 
this may have to do with features of the non-deceptive placebo manipulation. A related question 
is how to leverage associative learning mechanisms to enhance non-deceptive placebo effects. In 
the deceptive placebo literature, placebos that rely on expectations and learned associations 
produce the most reliable and robust effects. Presumably, non-deceptive placebos that leverage 
both mechanisms will also produce the strongest effects. More research is needed that 
systematically manipulates different contextual features such as the source of information, mode 
of information delivery, type of mechanism, and type of object in non-deceptive placebo 
research. non-deceptive placebos with other appraisal-type strategies to understand important similarities 
and differences in efficacy, underlying neural mechanisms, and cognitive cost.
Second, how reliable and robust are non-deceptive placebo effects in regulating 
emotions? Although three lab studies showed positive results, one did not. We pointed out that 
this may have to do with features of the non-deceptive placebo manipulation. A related question 
is how to leverage associative learning mechanisms to enhance non-deceptive placebo effects. In 
the deceptive placebo literature, placebos that rely on expectations and learned associations 
produce the most reliable and robust effects. Presumably, non-deceptive placebos that leverage 
both mechanisms will also produce the strongest effects. More research is needed that 
systematically manipulates different contextual features such as the source of information, mode 
of information delivery, type of mechanism, and type of object in non-deceptive placebo 
research.

Translational science applications
In terms of translational science questions, we highlight two future directions. First, 
related to the assumption that non-deceptive placebos may work automatically and with less effort, it is important to examine if they can work for people who have difficulties with selfregulation and for instances where self-regulation is difficult. For example, studies can examine 
if non-deceptive placebos can be effective for younger people with underdeveloped selfregulation capacity or for people with self-regulation impairments, such as those with affective 
disorders. Moreover, research can investigate if non-deceptive placebos can work when a person 
is fatigued or stressed. A second question is can non-deceptive placebos help manage clinical levels of anxiety 
and depression. Ethical issues must be considered since people with affective disorders should 
receive the best treatment. One way around this issue is to first test non-deceptive placebos in 
samples experiencing subclinical, mild, or moderate levels of anxiety and depression. Another 
way to conduct studies in clinical samples is to use non-deceptive placebos as co-interventions. 
For example, future studies can randomly assign people with mild to moderate affective 
symptoms to a CBT-only group or a CBT with non-deceptive placebos group. Large-scale RCTs 
are needed to determine efficacy, feasibility, and long-term effects.

Conclusion
Placebos are remarkably effective in managing a host of clinical disorders and nonclinical symptoms (Ashar et al., 2017; Benedetti, 2021). But the ethical dilemma that deception 
is necessary for placebos to work has prevented their widespread use. In a promising new twist, 
there is evidence that placebos can still work without deception. We are beginning to accumulate 
evidence that non-deceptive placebos can help regulate acute emotional episodes and manage 
chronically stressful periods. This opens up using an alternative strategy in which people can 
outsource regulating their emotions to non-deceptive placebos. Although in its infancy, we believe harnessing the regulatory effects of placebos without deception represents an exciting 
direction in emotion regulation research.