Volunteers placebo responses

We found quite early that our volunteers were not placebo responders. This was apparent when we used very low doses of active drag and found no significant deviation from baseline responses. To give placebos routinely would have doubled the workload and exposed volunteers to many more hours of testing with little benefit, since the lowest doses had already been found to have little or no effect and the differences between responses to increasing doses were obvious. 

In 1999, TA-CD was tested on human subjects. Volunteers were injected with the cocaine vaccine once a week for four weeks and, according to researchers, antibody responses lasted almost three months without any adverse affects. In October of 2003, Xenova began testing TA-CD in a randomized, placebo-controlled clinical trial involving 132 human subjects. They expect to complete this study in 2005 and move into Phase III studies. ... 

HO-DMT is a minor metabolite of DMT in man, and it was studied for the same reasons. Could this compound play a role in explaining the activity of the parent dialkylamine It was explored in a series of subjects who had responded spectacularly to DMT. The five volunteers in this study were former opium addicts who were serving sentences for violation of United States narcotics laws. They were administered 6-HO-DMT at either 0.75 mg/Kg (one subject) or 1.0 mg/Kg (four subjects) and reported no differences from the inactive placebo control. The objective measures (blood pressure, respiration and heart rate, pupillary dilation) confirmed this absence of activity at this level. The active control drug was DMT itself, and it showed the expected responses in all regards. 

Naylor et al. (50) also reported beneficial effects of methylphenidate in female volunteers who received 5-, 10-, or 20-mg doses. Like Peloquin and Klorman (42), they found no significant changes in the P-300 component of the evoked response, but RT on an information-processing task was improved compared to placebo. For a task in which the target was easy to identify, the 10-mg dose significantly decreased RT (the 20-mg dose tended to have the same effect). For a task in which target selection was more difficult, both the 5- and 20-mg doses enhanced RT, but the 10-mg dose had no effect. 

The interaction of the dopamine antagonist haloperidol 5 mg orally with subanesthetic doses of ketamine has been studied in a placebo-controlled study in 20 healthy volunteers over 4 days (53). Haloperidol pretreatment reduced impairment of executive cognitive functions produced by ketamine and reduced the anxiogenic effects of ketamine. However, it failed to block the ability of ketamine to produce psychosis, perceptual changes, negative symptoms, or euphoria, and it increased the sedative and prolactin responses to ketamine. These results imply that ketamine may impair executive cognitive functions via dopamine receptor activation in the frontal cortex, but that the psychoactive effects of ketamine are not mediated via dopamine receptors, but rather via NMDA receptor antagonism. 

Cranberries have been used traditionally for the treatment and prevention of urinary tract infections. Their effectiveness was demonstrated by a randomized, double-blind placebo-controlled trial (Avom et ah, 1994). Escherichia coli are the principal bacterial species responsible for urinary tract infection. The consumption of cranberry juice reduced the adherence of E. coli to the uroepithelial bladder cells in healthy human volunteers (Di Martino et ah, 2006). A-type procyanidin dimers and trimers that were isolated from cranberries were found to inhibit the adherence of uropathogenic E. Coli, whereas (—)-epicatechin and a B-type dimer were not effective (Foo et ah, 2000). 

To avoid false conclusions. The use of placebos is valuable in Phase I healthy volunteer studies of novel drugs to help determine whether minor but frequently reported adverse events are drug-related or not. Placebos are also helpful to distinguish between real and imaginary responses in short-term trials with new analgesic agents. 

In another study, different doses of flunisolide hydrofluoroalkane were tested in 21 healthy adult volunteers for 4.5 days (170, 340, and 680 pg) there was a dose-related response after both single- and multiple-dose administration (22). There was no accumulation of flunisolide with repeated dosing, suggesting that the systemic availability of flunisolide hydrofluoroalkane is low. A randomized, double-blind, placebo-controlled study with daily doses of 80 and 160 pg over 12 weeks in 353 asthmatic children gave similar results (23). 

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