Caffeine and Placebo Expectation

2007 ◽  
Vol 21 (2) ◽  
pp. 91-99 ◽  
Author(s):  
Yunfeng Sun ◽  
Yinling Zhang ◽  
Ning He ◽  
Xufeng Liu ◽  
Danmin Miao

Abstract. Caffeine placebo expectation seems to improve vigilance and cognitive performance. This study investigated the effect of caffeine and placebo expectation on vigilance and cognitive performance during 28 h sleep deprivation. Ten healthy males volunteered to take part in the double-blind, cross-over study, which required participants to complete five treatment periods of 28 h separated by 1-week wash-out intervals. The treatments were no substance (Control); caffeine 200 mg at 00:00 (C200); placebo 200 mg at 00:00 (P200); twice caffeine 200 mg at 00:00 and 04:00 (C200-C200); caffeine 200 mg at 00:00 and placebo 200 mg at 04:00 (C200-P200). Participants were told that all capsules were caffeine and given information about the effects of caffeine to increase expectation. Vigilance was assessed by a three-letter cancellation test, cognitive functions by the continuous addition test and Stroop test, and cardiovascular regulation by heart rate and blood pressure. Tests were performed bihourly from 00:00 to 10:00 of the second day. Results indicated that C200-P200 and C200-C200 were more alert (p < .05) than Control and P200. Their cognitive functions were higher (p < .05) than Control and P200. Also, C200-P200 scored higher than C200 in the letter cancellation task (p < .05). No test showed any significant differences between C200-P200 and C200-C200. The results demonstrated that the combination of caffeine 200 mg and placebo 200 mg expectation exerted prolonged positive effects on vigilance and cognitive performance.

2007 ◽  
Vol 102 (6) ◽  
pp. 2092-2097 ◽  
Author(s):  
Matthew V. Dzurik ◽  
André Diedrich ◽  
Bonnie Black ◽  
Sachin Y. Paranjape ◽  
Satish R. Raj ◽  
...  

Substance P (SP) is a peptide neurotransmitter identified in many central and peripheral neural pathways. Its precise role in human physiology has been difficult to elucidate. We used the selective neurokinin 1 (NK1) antagonist aprepitant as a pharmacological probe to determine the role of endogenous SP in human cardiovascular regulation. We performed a randomized, double-blind, placebo-controlled, crossover trial in healthy subjects. Blockade of endogenous NK1 receptors reduced resting muscle sympathetic activity 38% ( P = 0.002), reduced systemic vascular resistance by 25% ( P = 0.021), and increased cardiac index by 47% ( P = 0.006). This constellation of changes did not, however, alter either blood pressure or heart rate in the supine position. NK1 antagonism also raised orthostatic heart rate change by 38% ( P = 0.023), although during the incremental postural adjustment on the tilt table neither heart rate nor blood pressure was altered significantly. Despite a mildly attenuated vagal baroreflex with SP blockade, the depressor and pressor responses to nitroprusside and phenylephrine did not differ compared with placebo, suggesting other compensatory mechanisms. NK1 blockade manifests as a decrease in muscle sympathetic nerve activity and systemic vascular resistance. Our study suggests SP exerts a tonic enhancement of sympathetic outflow to some cardiovascular structures via its modulation of the NK1 receptor. Most likely, this ubiquitous neurotransmitter exerts effects at multiple sites that, in the aggregate, are relatively well compensated under many circumstances but may emerge with perturbations. This study is consistent with a role for SP afferents in supporting peripheral vascular resistance.


2009 ◽  
Vol 23 (3) ◽  
pp. 104-112 ◽  
Author(s):  
Stefan Duschek ◽  
Heike Heiss ◽  
Boriana Buechner ◽  
Rainer Schandry

Recent studies have revealed evidence for increased pain sensitivity in individuals with chronically low blood pressure. The present trial explored whether pain sensitivity can be reduced by pharmacological elevation of blood pressure. Effects of the sympathomimetic midodrine on threshold and tolerance to heat pain were examined in 52 hypotensive persons (mean blood pressure 96/61 mmHg) based on a randomized, placebo-controlled, double-blind design. Heat stimuli were applied to the forearm via a contact thermode. Confounding of drug effects on pain perception with changes in skin temperature, temperature sensitivity, and mood were statistically controlled for. Compared to placebo, higher pain threshold and tolerance, increased blood pressure, as well as reduced heart rate were observed under the sympathomimetic condition. Increases in systolic blood pressure between points of measurement correlated positively with increases in pain threshold and tolerance, and decreases in heart rate were associated with increases in pain threshold. The findings underline the causal role of hypotension in the augmented pain sensitivity related to this condition. Pain reduction as a function of heart rate decrease suggests involvement of a baroreceptor-related mechanism in the pain attrition. The increased proneness of persons with chronic hypotension toward clinical pain is discussed.


2001 ◽  
Vol 6 (1) ◽  
pp. 15-25 ◽  
Author(s):  
Harald Walach ◽  
Stefan Schmidt ◽  
Yvonne-Michelle Bihr ◽  
Susanne Wiesch

We studied the effect of experimenter expectations and different instructions in a balanced placebo design. 157 subjects were randomized into a 2 × 4 factorial design. Two experimenters were led to expect placebos either to produce physiological effects or not (pro- vs. antiplacebo). All subjects except a control group received a caffeine placebo. They were either made to expect coffee, no coffee, or were in a double-blind condition. Dependent measures were blood pressure, heart rate, well-being, and a cognitive task. There was one main effect on the instruction factor (p = 0.03) with the group “told no caffeine” reporting significantly better well-being. There was one main effect on the experimenter factor with subjects instructed by experimenter “proplacebo” having higher systolic blood pressure (p = 0.008). There was one interaction with subjects instructed by experimenter “proplacebo” to receive coffee doing worse in the cognitive task than the rest. Subjects instructed by experimenter “antiplacebo” were significantly less likely to believe the experimental instruction, and that mostly if they had been instructed to receive coffee. Contrary to the literature we could not show an effect of instruction, but there was an effect of experimenters. It is likely, however, that these experimenter effects were not due to experimental manipulations, but to the difference in personalities.


1985 ◽  
Vol 69 (5) ◽  
pp. 533-540 ◽  
Author(s):  
Gianfranco Parati ◽  
Guido Pomidossi ◽  
Agustin Ramirez ◽  
Bruno Cesana ◽  
Giuseppe Mancia

1. In man evaluation of neural cardiovascular regulation makes use of a variety of tests which address the excitatory and reflex inhibitory neural influences that control circulation. Because interpretation of these tests is largely based on the magnitude of the elicited haemodynamic responses, their reproducibility in any given subject is critical. 2. In 39 subjects with continuous blood pressure (intra-arterial catheter) and heart rate monitoring we measured (i) the blood pressure and heart rate rises during hand-grip and cold-pressor test, (ii) the heart rate changes occurring during baroreceptor stimulation and deactivation by injection of phenylephrine and trinitroglycerine, and (iii) the heart rate and blood pressure changes occurring with alteration in carotid baroreceptor activity by a neck chamber. Each test was carefully standardized and performed at 30 min intervals for a total of six times in each subject. 3. The results showed that the responses to any test were clearly different from one another and that this occurred in all subjects studied. For the group as a whole the average response variability (coefficient of variation) ranged from 10.2% for the blood pressure response to carotid baroreceptor stimulation to 44.2% for the heart rate response to cold-pressor test. The variability of the responses was not related to basal blood pressure or heart rate, nor to the temporal sequence of the test performance. 4. Thus tests employed for studying neural cardiovascular control in man produce responses whose reproducibility is limited. This phenomenon may make it more difficult to define the response magnitude typical of each subject, as well as its comparison in different conditions and diseases.


2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Ana Ellen Queiroz Santiago ◽  
Adriana Machado Issy ◽  
Rioko Kimiko Sakata

Objectives. The aim of this study was to assess the effects of clonidine on intraoperative analgesia, sedation, intraocular and blood pressure, arrhythmia, and ischemia.Methods. Forty patients undergoing cataract surgery were allocated into two groups. They were monitored with Holter machine, the pupil was dilated, and 30 minutes later, 20 patients received clonidine (4 µg/kg), while the other 20 patients were given a 0.9% saline intravenously. Twenty minutes later, 2% lidocaine gel was applied. There were assessed intraoperative analgesia, intraocular pressure, blood pressure, heart rate, and the occurrence of arrhythmias and myocardial ischemia.Results. Pain intensity was lower in G1 during the phacoemulsification, irrigation, aspiration, and intraocular lens implantation. The HR and BP were lower with clonidine. The IOP was lower with clonidine after 15 minutes and at the end of the surgery. Sedation was higher with clonidine. The incidence of arrhythmia was lower at the end of surgery with clonidine. The incidence of myocardial ischemia did not differ between the groups.Conclusions. Clonidine (4 µg/kg) before a phacoemulsification reduced the intensity of pain during cataract surgery. It also induced sedation, reduction of BP, HR, and incidence of arrhythmia at the end of the surgery, and did not alter myocardial ischemia. This trial is registered with Clinicaltrials.govNCT01677351.


1985 ◽  
Vol 30 (2) ◽  
pp. 106-110 ◽  
Author(s):  
D. J. Webb ◽  
M. J. Hutcheson ◽  
M. P. Robertson ◽  
G. D. Murray ◽  
A. R. Lorimer ◽  
...  

In a 12-week double-blind randomised study the efficacy of atenolol and a new longer-acting formulation of trimazosin were compared when given once daily in patients with mild to moderate hypertension. Two parallel groups, each consisting of 18 patients, were studied. At randomisation the two groups were well matched for age and sex distribution. They were also well matched for blood pressure, pulse rate and body weight; these latter measurements were recorded at regular intervals during the 12 weeks of study. Atenolol produced substantial reduction in both systolic and diastolic blood pressure, and in heart rate, during 12 weeks of treatment. This therapeutic effect was maintained until the next dose after 24 hours. Trimazosin, by comparison, failed to reduce either systolic or diastolic pressure, or to alter heart rate. Side effects were minor with both agents and compliance with treatment was good. Atenolol caused significant elevation of plasma concentration of triglyceride, with reduction in high density lipoprotein concentration when compared with trimazosin. In conclusion, atenolol was confirmed as an effective agent for the treatment of mild to moderate hypertension. By comparison trimazosin in the longer-acting formulation was ineffective in this study. However, trimazosin may still find a place in treatment if used at higher dose.


Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Brianna K Bruggeman ◽  
Katharine E Storo ◽  
Haley M Fair ◽  
Andrew J Wommack ◽  
James M Smoliga ◽  
...  

Intro: Glutathione is endogenous within human plasma, erythrocyte lysate and is also bound to the protein within plasma. Glutathione mediates redox chemistry and prevents oxidative damage within and around cellular components via reduction of reactive species (e.g. reactive oxygen, nitrogen, or sulfur species). Polyphenols and antioxidants have been shown to improve NO bioavailability which may reduce long term incidence of endothelial dysfunction. Less is known about whether changes in antioxidant capacity augments the risk of developing hypertension. Hypothesis: We hypothesized that acute glutathione supplementation would decrease arterial stiffness and reduce both brachial (bBP) and central blood pressure (cBP) in healthy male and female volunteers. Methods: Six males and six females (25 ± 3 and 22 ± 1 years, respectively) participated in a randomized, double blind, placebo controlled, crossover protocol. On two visits separated by 1 week, following a 12-hour fast, participants consumed either a placebo or glutathione (negligible and 200 mg, respectively) supplement via 90 second sublingual absorption which was then swallowed. Concentrations of oxidized (GSSG) and reduced glutathione (GSH) were spectrophotometrically measured in plasma (protein-bound) and erythrocyte lysate using a kinetic, enzymatic assay. Arterial stiffness was measured via pulse wave velocity (PWV) using applanation tonometry, and cBP was determined non-invasively using pulse wave analysis. All data were recorded before supplementation (baseline) and at 10, 30, 60 and 120 minutes post-consumption. Results: Linear mixed effect models revealed a significant (p<0.01) increase in total glutathione (GSH+GSSG) in the supplement group compared to placebo across all post-supplementation time points with the greatest increase occurring at 120 minutes (mean 99.0; 95%CI: 7.9,190.1). At 120 minutes post-consumption, no difference was present between glutathione and placebo groups for PWV (5.86 ± 1.19 and 6.08 ± 1.25 m/s, respectively; p=0.43), resting heart rate (52.95 ± 3.55 and 55.83 ± 6.36, respectively; p=0.16), systolic bBP (123.05 ± 12.75 and 123.13 ± 14.52 mmHg; p=0.22), diastolic bBP (71.81 ± 7.87 and 74.21 ± 6.53; p=0.48), systolic cBP (108.05 ± 10.45 and 108.68 ± 11.14 mmHg, respectively; p=0.11) and diastolic cBP (72.03 ± 7.82 and 74.94 ± 6.42 mmHg, respectively; p=0.46). Conclusion: Young healthy males and females experienced an increase in circulating humoral antioxidants in response to glutathione supplementation. However, supplementation had minimal effects on resting hemodynamics. Future research should examine glutathione supplementation’s effect in participants with decreased antioxidant capacity and increased oxidative stress including patients with known disease such as hypertension or peripheral artery disease.


2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Tian Shen ◽  
Guoqiang Xing ◽  
Jingfen Zhu ◽  
Yong Cai ◽  
Shuxian Zhang ◽  
...  

Background. Uncontrolled blood pressure is the leading cause of mortality and disability due to associated cerebral and cardiovascular diseases and kidney failure. More than one-third of the old adult population have hypertension or prehypertension and many of their blood pressure are poorly controlled. Objective. We hypothesized that plant extracts-based antioxidants may benefit those with prehypertension/hypertension. Method. One hundred age- and gender-matched healthy older adults were randomly assigned to receive HyperBalance capsules (n=50) or placebo (n=50) at Tang-Qiao Community Health Service Center, Shanghai. Blood pressure and severity scores of hypertension treatment-related symptoms (dizziness, headache, ringing/buzzing in ears, rapid heart rate, and chest tightness) were evaluated before and after the 12-week intervention. Results. Ninety-eight people completed the study, with 2 dropouts in the placebo group before the end of the study. Forty-one subjects (82%) of the HyperBalance group and 40 subjects (83.3%) of the placebo group had prehypertension (systolic blood pressures (SBP) between 130-139 and diastolic blood pressure (DBP) between 85-89mmHg), and 9 subjects (18%) in the HyperBalance group and 8 subjects (16.7%) in the placebo group had hypertension (≥140/90mmHg) before the intervention. HyperBalance significantly (P<0.01) reduced SBP from 136.18±4.38 to 124.14±3.96 mmHg and reduced DBP from 82.45±2.91 to 80.24±2.41mmHg, respectively, and reversed all 9 hypertension people to normotension or prehypertension state, whereas the placebo moderately reduced SBP from 135.79±4.22 to 132.35±4.656mmHg and reduced DBP from 82.90±3.07 to 82.27±3.01mmHg. All symptom severity scores became significantly lower in the HyperBalance group than in the placebo group after HyperBalance intervention: dizziness (0.82±0.44; vs 2.02±0.64, P<0.01); headache (0.46±0.50; vs 1.81±0.61, P<0.01); ringing/buzzing in ears (0.44±0.50; vs 1.04±0.29, P<0.01); and rapid heart rate and chest tightness (0.30±0.46; vs 0.92±0.28, P<0.01). Conclusion. Polyherbal supplementation such as HyperBalance could benefit old adults with prehypertension/hypertension and improve treatment-related symptoms. Further studies are needed to validate the current findings.


Pharmacology ◽  
2019 ◽  
Vol 104 (1-2) ◽  
pp. 1-6
Author(s):  
Alfredo Costa ◽  
Daniele Bosone ◽  
Matteo Cotta Ramusino ◽  
Giulia Perini ◽  
Natascia Ghiotto ◽  
...  

Aim: To assess the effects of chronic evening oral administration of bromazepam alone or in combination with propranolol on ambulatory blood pressure (BP) and heart rate (HR) in mild hypertensive subjects. Methods: Thirty-seven mild hypertensive patients after a 2-week placebo period were randomized to bromazepam 3 mg, propranolol 40 mg, bromazepam 3 mg plus propranolol 40 mg or placebo for 2 weeks according to a double-blind, double dummy, cross-over design. After each treatment period, 24-h BP and HR ambulatory monitoring was performed by using a non-invasive device. Results: Ambulatory monitoring showed that during night-time SBP and DBP values were unaffected by bromazepam as compared to placebo, whereas SBP was significantly reduced by propranolol both when taken alone and in combination with bromazepam. HR nocturnal values were significantly reduced by propranolol, whereas they were significantly increased by bromazepan both when taken alone (+11.5%, p < 0.05 vs. placebo) and in combination with propranolol (+12.8%, p < 0.05 vs. propranolol). No significant difference in day-time values of SBP, DBP and HR was observed among the 4 treatment groups. Conclusions: In mild hypertensive patients, evening consumption of bromazepam for a 2-week period did not affect BP, while it increased nocturnal HR. Such an increase was observed both when bromazepam was taken alone and in combination with propranolol, which suggests that it depends on a bromazepam mediated decrease in vagal tone. Whatever the mechanism, the HR nocturnal increase might be of clinical relevance, due to the role of high HR as cardiovascular risk factor, particularly in already at risk hypertensive subjects.


1981 ◽  
Vol 139 (6) ◽  
pp. 545-549 ◽  
Author(s):  
Elizabeth A. Taylor ◽  
Paul Turner ◽  
Jean Harrison

SummaryThe influence of beta-adrenoceptor antagonism on the effects of a simple experimental stress was investigated in 12 healthy volunteers, using a double-blind protocol. A single oral dose of 80 mg propranolol reduced the stress-induced increase in heart rate and systolic blood pressure to 49.9 per cent and 8.3 per cent respectively compared to 61.0 per cent and 17.4 per cent with placebo. The rise in diastolic blood pressure was small and unaffected by beta-adrenoceptor blockade. The rise in temperature of the skin of the trunk was significantly reduced by propranolol. The self-rating of anxiety, alertness and concentration by the subjects was unaffected by propranolol.


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