Evaluating the effects of Caffiene Withdrawl with Placebo

Project Proposal

Introduction

Placebo effect is the relief that people get from the anticipation of treatment, even if the treatment turns out to be nothing more than a sugar pill. Alternatively, the changes in the brain and the body that can occur as a result of a change in perception about a situation.

Placebo Effect is a term frequently used in clinical trials, when the group, which has been taking placebo instead of the actual drug, shows signs of improvement. It has also been observed that people sometimes say that they are feeling better after taking an aspirin, even before it had time to act.

In fMRI experiments done by Wager et.al. ¹, it was found that the placebo analgesia was related to decreased brain activity in pain-sensitive brain regions including the thalamus, and was associated with increased activity during the anticipation of pain in the prefrontal cortex, providing evidence that placebos alter the experience of pain.

Placebo effects also have also bee recorded in diseases like Parkinson's due to the release of dopamine in the striatum. It has been proposed that the placebo effect might be related to reward mechanisms. The expectation of reward (i.e. clinical benefit) seems to be particularly relevant ². It has been recorded that the effect of placebo effect in Parkinson's disease is powerful and mediated through activation of the damaged nigrostriatal dopamine system ³.

The effect of Placebos is also being used in day-to-day patient care and marketting of goods. It has been shown that high price increases consumers' expectations and enhances behavorial performance. ⁴

Previous Work

Caffeine is a CNS stimulant which is widely consumed around the world. Acute administration of caffeine increases alertness, simulates attention and restores performances degraded by factors such as fatigue and boredom (Weiss and Lates, 1962). But it has a wide variation of effects on high level consumption.

A series of experiments done by Bruce et. al. in 1986 focussed on assessing the caffeine consumption of habitual caffeine users. On each day, there were given either 250mg or 500 mg of anhydrous caffeine or a placebo in matching capsules. They were tested on three occasions, atleast 1 week apart. The experiments included Blood and Urine Samples, Skin Conduction Tests, Pulse rate and Blood Pressure and various Psychological Measures llike Tapping rate, Reaction time etc. The participants were also asked to rate themselves on mood, bodily symptoms and anxiety. ⁵

The main drawback was that the psychological effcts didn't show much effects, even after these tests had known sensitivity to the depressant effects of a wide range of psychotropic drugs. This may be because normal subjects are usually well-motivated and are performing the tests at their maximum capability, leaving no room for drug induced improvement.

In a recent experiment, Peter Rogers et.al. studied the effects of caffeine and caffeine withdrawl symptons. Their experiments included various tasks for testing alertness, reaction times and memory in low/high caffeine consumers. ⁶

Proposed Methodology

The idea of the project was to analyze the effect of caffeine abstinence with placebo by using caffeinated coffee and placebo coffee (decaffeinated coffee). This requires dividing the subjects into 4 groups, A, B, C and D. All the participants in the experiments would include high caffeine consumers. A group will be the control group and include high caffeine consumers (coffee/tea) adicts, who would be given placebo coffee in accordance with their daily intake. The group B would include high caffeine consumers which would totally abstrain from any caffeinated products during the course of experiements. The group C would include high caffeine comsumers which would continue their normal intake of caffeine. The details that whether a person is in the control group would not be disclosed, i.e, they won't be told if they are given placebo coffee. Group D would consist of people who would record the readings (This group is necessary so as to ensure that the experiments are double blinded and the readings are not biased because the experimentar expects to see the difference because of their knowledge of which person was administered real coffee and which was administered placebo (decaffeinated) coffee).

The tests would include include various reaction time testing and memory testing experiments.

1. Reaction Timing tests:

1. http://sciencenetlinks.com/interactives/zap.html - Here you have to zap the fly as soon as you see it on the screen or you hear the buzzing sound. This tests both the audio and visual reaction times.
2. http://www.exploratorium.edu/baseball/reactiontime.html - In this the reaction time is measured based on how quickly you hit the ball.
3. http://faculty.washington.edu/chudler/java/dottime.html - This is similar to "whack-a-mole" game. As the dot moves around the grid, the person has to hit it as many times as possible within 30 secs.
4. http://www.bbc.co.uk/science/humanbody/sleep/sheep/ - Tranquilize the sheep as they try to escape.
5. Fastest Finger First Quiz - This is similar to the traditional quizzing rounds in which the participants have to press the button as soon as soon as possible. The difference would be to replace the guiding action from knowing the answer to a question to that of a picture being shown or a music being played.

2. Memory Testing Experiments:

1. http://faculty.washington.edu/chudler/stm0.html - Remember the groups of letters as they flash on the screen.
2. http://faculty.washington.edu/chudler/stm0.html - Remember the groups in which a given face appears
3. http://www.oddtodd.com/concentration/memory.htm - Pick two cards until they match in pairs.

We can also include accuracy tests like calculating the heart beat or pulse rate counting. To remove the differences in the varied heart beats or pulse rates of different people, we can use a video of a recorded heartbeat etc. eg. This video is of the microscopically recorded heartbeats of the Daphnia flea (these fleas are used in many experiments to check the effect of various substances on heartbeat).

The experiment would aim to differentiate the results of caffeine taking group with non caffeine taking group and the control group, and comparison of the same.

To test the physiological effects on the body, tests like change in breathing rate, heart beat, etc could be included if possible.

These tests would be done on the participants 3 times spread over a week. During this period, they should totally abstrian from any kind of caffeine products except from the coffee/tea provided.

The expected results are that there would not be much difference from people of group A and those of Group C and would vary highly from those who were totally abstrained from any kind of coffee (caffeinated and placebo).