Trial reportPsychopharmacology2011
Interaction between expectancies and drug effects: an experimental investigation of placebo analgesia with caffeine as an active placebo.
Trial report in Psychopharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 3 syntheses or guidelines pooled it, 53 citations in OpenAlex.
- Effectiveness of ketamine-assisted psychotherapy as a treatment for treatment-resistant depression: a systematic review.Psychopharmacology · 2026Pooled it
- Impact of active placebo controls on estimated drug effects in randomised trials: a systematic review of trials with both active placebo and standard placebo.The Cochrane database of systematic reviews · 2023Pooled it
- How do they add up? The interaction between the placebo and treatment effect: A systematic review.British journal of clinical pharmacology · 2022Pooled it
- Effect of the oral intake of astaxanthin on semen parameters in patients with oligo-astheno-teratozoospermia: a randomized double-blind placebo-controlled trial.Radiology and oncology · 2020Trial
- Inverted Perceptual Judgment of Nociceptive Stimuli at Threshold Level following Inconsistent Cues.PloS one · 2015Trial
- Durability of improvement in post-traumatic stress disorder symptoms and absence of harmful effects or drug dependency after 3,4-methylenedioxymethamphetamine-assisted psychotherapy: a prospective long-term follow-up study.Journal of psychopharmacology (Oxford, England) · 2013Trial
- Distinguishing caffeine expectancy from pharmacological effects: a comparative review of experimental designs with future directions.Frontiers in physiology · 2026Review
- Photophysical Properties of Sinapic Acid and Ferulic Acid and Their Binding Mechanism with Caffeine.Journal of fluorescence · 2025Article
- Can oral caffeine decrease postoperative opioid consumption following posterior spinal fusion in adolescent idiopathic scoliosis? A randomized placebo-controlled trial.North American Spine Society journal · 2025Article
- The Effect of Singular Nonverbal Behaviours of Experimenters on Pain Reports.Journal of pain research · 2024Article
- Harnessing placebo: Lessons from psychedelic science.Journal of psychopharmacology (Oxford, England) · 2023Review
- Systematic manipulation of experimenters' non-verbal behaviors for the investigation of pain reports and placebo effects.Frontiers in psychology · 2023Article
- Cutoff criteria for the placebo response: a cluster and machine learning analysis of placebo analgesia.Scientific reports · 2021Article
- Article
- Positive expectations predict improved mental-health outcomes linked to psychedelic microdosing.Scientific reports · 2021Article
- Classical conditioning of antidepressant placebo effects in mice.Psychopharmacology · 2020Article
- Drug-Placebo Additivity in Randomized Clinical Trials.Clinical pharmacology and therapeutics · 2019Article
- Does Sex/Gender Play a Role in Placebo and Nocebo Effects? Conflicting Evidence From Clinical Trials and Experimental Studies.Frontiers in neuroscience · 2019Review
- The Role of Tactile Stimulation for Expectation, Perceived Treatment Assignment and the Placebo Effect in an Experimental Nausea Paradigm.Frontiers in neuroscience · 2019Article
- A systematic review of sex differences in the placebo and the nocebo effect.Journal of pain research · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
rationaleIn a randomised placebo-controlled clinical trial it is assumed that psychosocial effects of the treatment, regression to the mean and spontaneous remission are identical in the drug and placebo group. Consequently, any difference between the groups can be ascribed to the pharmacological effects. Previous studies suggest that side effects of drugs can enhance expectancies of treatment effects in the drug group compared to the placebo group, and thereby increase placebo responses in the drug group compared to the placebo group.
objectivesThe hypothesis that side effects of drugs can enhance expectancies and placebo responses was tested.
methodPainful laser stimuli were delivered to 20 healthy subjects before and after administration of a drink with 0 or 4 mg/kg caffeine. The drink was administered either with information that it contained a painkiller or that it was a placebo. Laser-evoked potentials and reports of pain, expectancy, arousal and stress were measured.
resultsFour milligrammes per kilogramme of caffeine reduced pain. Information that a painkiller was administered increased the analgesic effect of caffeine compared to caffeine administered with no drug information. This effect was mediated by expectancies. Information and expectancies had no effect on pain intensity when 0 mg/kg was administered.
conclusionThe analgesic effect of caffeine was increased by information that a painkiller was administered. This was due to an interaction of the pharmacological action of the drug and expectancies. Hence, psychosocial effects accompanying a treatment can differ when an active drug is administered compared to a placebo.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.