Related Experiment Video
Updated: Jul 10, 2026
09:43
Using Optogenetics to Reverse Neuroplasticity and Inhibit Cocaine Seeking in Rats
Published on: October 5, 2021
Redefining the real problem in psychedelic trials: Why fighting the Lessebo matters more than blinding integrity
Laetitia Vanderijst1, Jean-Luc Faillie2, Thibault Mura3
1Laboratory of Medical Psychology and Addictology, Faculty of Medicine, Université libre de Bruxelles, Brussels, Belgium; Research Center for the Promotion of Health, Prosocial Behavior and Wellbeing, Faculty of Psychology, Université libre de Bruxelles, Brussels, Belgium.
The International Journal on Drug Policy
|July 8, 2026
Summary
Imperfect blinding in psychedelic trials is common but manageable. Focusing on managing disappointment, rather than perfect blinding, is key to ensuring reliable results and ethical research in mental health studies.
Area of Science:
- Psychopharmacology
- Clinical Trial Design
- Mental Health Research
Background:
- Blinding integrity is often imperfect in randomized controlled trials, particularly in psychedelic research.
- Concerns regarding imperfect blinding in psychedelic trials are often linked to expectancy bias and potential lessebo (negative placebo) effects.
- Patient-reported outcomes in mental health research face scrutiny due to perceived unreliability, compounded by limitations of clinician-rated scales and lack of biological markers.
Purpose of the Study:
- To re-evaluate the significance of imperfect blinding in psychedelic trials.
- To propose alternative strategies for maintaining trial validity and ethical feasibility.
- To address concerns about expectancy bias and lessebo effects in psychedelic research.
Main Methods:
- Analysis of blinding challenges in psychedelic and broader mental health research.
- Examination of the role of disappointment as a mechanism for lessebo.
- Proposal of enhanced clinical management strategies to mitigate disappointment.
Main Results:
- Imperfect blinding does not necessarily invalidate randomized trials; reasonable doubt of allocation is sufficient for internal validity.
- Disappointment, rather than solely pre-treatment expectation, is an underrecognized contributor to lessebo effects.
- Mitigating disappointment through structured psychoeducation, therapeutic alliance, and realistic preparation is proposed as a superior strategy to perfect blinding.
Conclusions:
- The focus in psychedelic trials should shift from achieving perfect blinding to effectively managing disappointment.
- Enhanced clinical management strategies can improve the ethical rigor, interpretability, and clinical utility of psychedelic research.
- Addressing disappointment proactively can mitigate expectancy bias and lessebo effects, strengthening the validity of psychedelic interventions.
Related Concept Videos
01:11Blinding
Blinding is a commonly used method of not telling participants which treatment a subject is receiving. Blinding is a critical part of a randomized control trial or RCT. It reduces the bias that affects the results. In an RCT, blinding is used in the form of a placebo. A placebo effect occurs when untreated subjects falsely believe they have received the treatment and report improved symptoms. A placebo or a dummy treatment is administered to subjects to negate the bias caused by such an effect.
01:27Hallucinogens and Psychedelics
Hallucinogens are psychoactive substances that profoundly alter perceptual experiences, generating unreal visual and sensory images. Often referred to as psychedelic drugs — a term derived from the Greek words "psyche" (mind) and "delos" (revealing) — these substances include marijuana and lysergic acid diethylamide (LSD), among others. These drugs vary in intensity and effects.
Marijuana, derived from the dried leaves and flowers of the hemp plant, contains delta-9-tetrahydrocannabinol (THC)...
Marijuana, derived from the dried leaves and flowers of the hemp plant, contains delta-9-tetrahydrocannabinol (THC)...
02:07Blind Procedures
Ideally, the people who observe and record the children’s behavior are unaware of who was assigned to the experimental or control group, in order to control for experimenter bias. Experimenter bias refers to the possibility that a researcher’s expectations might skew the results of the study. Remember, conducting an experiment requires a lot of planning, and the people involved in the research project have a vested interest in supporting their hypotheses. If the observers knew which child was...
01:22CNS Stimulants: Psychedelic Agents
Hallucinogens, also known as psychedelic drugs, are a class of substances known for their ability to alter perception, cognition, and emotions. Despite their profound effects on the mind, these drugs are non-addictive, setting them apart from many other abused substances. The mechanism of action of these drugs lies in their impact on the 5-HT2A receptor in the brain. Upon activation, this receptor couples to Gq-type G proteins, triggering a cascade that releases intracellular calcium. This...
01:26Psychosis: Goals of Pharmacotherapy
Antipsychotic drugs are a crucial treatment method for acute and chronic psychoses, bipolar illness, and behavioral disorders. The selection of these drugs depends on several factors, including the state of the disease, clinical judgment, possible drug interactions, and the patient's sensitivity to adverse effects. In immediate scenarios, such as delirium and dementia, short-term treatment with low doses of high-potency typical or atypical agents can effectively manage symptom exacerbation. For...
01:30Psychosurgery
Psychosurgery, the surgical alteration or permanent removal of brain tissue to alleviate severe psychological conditions, stands as one of the most radical and controversial treatments in the history of mental health care. Its development and application have evolved significantly, marked by dramatic shifts in scientific understanding and ethical perspectives.
Historical Development of Psychosurgery
In the 1930s, Portuguese neurologist Antonio Egas Moniz introduced a surgical procedure designed...
Historical Development of Psychosurgery
In the 1930s, Portuguese neurologist Antonio Egas Moniz introduced a surgical procedure designed...