The Economist covered the research work of the Turin based Italian neuroscientist, Dr Fabrizio Benedetti, with the teasing title: “How to cheat without cheating.”The work describes the power of suggestion, expectation and placebo. Four sets of volunteers were recruited to do an athletic exercise that would cause pain if done beyond a point. Benedetti’s paper appears in the October 31, 2007 issue of the Journal of Neurosciences.
The teams
Team A was given no special treatment in either the three practice sessions or on the day of the competition. Team B was treated likewise but on the event day, were told that they have been given morphine in order to kill the pain and do better. In actuality they were given just a shot of saline water. Team C was given nothing in the first two sessions, but morphine in the third, and was shot with the same placebo on the competition day as Team B, but told that they too have been morphined.
Team D was treated just as C was, but on the event day, was given placebo plus the drug called naloxone. They too were told that they had been given the pain-killing performance-enhancing morphine, but not about naloxone, which cancels the effects of morphine.
We thus have a good comparison set. Team A is the control. If Team B does better than A in the event, it would reflect the effect of the placebo. Team C had actually experienced the performance enhancing effect of morphine in a trial session, and thinks the same would happen to them in the competition.
Their performance would again reflect placebo effect. The performance of Team D should in principle be worse than that of C.
The results
What were the results of the exercise competition? Team A tolerated pain up to 15 seconds in practice sessions and at the event. Team B did a bit better at the event, clocking 17 seconds.
The suggestion about morphine injection seems to have made them do better! The drug-in-practice Team C maintained its usual 21-22 second tolerance time even on the placebo-given event day. Team D dropped from its usual 23 seconds to about 15 seconds on that day.
Morphine is a performance-booster and is not allowed by the World Anti-Doping Agency (WADA) during sports competitions. However, it differs from drugs like steroids in an important way. Its action is temporary, lasting but a few hours. Steroids, on the other hand, build muscles and thus give much longer lasting effects. They are completely banned for sportsmen by WADA, but morphine is banned on competition days alone.
Benedetti asks: my volunteers did not use morphine on the competition day, yet their performance was better. Is placebo response then doping?
Are placebo responses ethically acceptable in sports competitions or should they be considered a doping procedure in all respects?
Placebo (literally meaning ‘I shall please, I shall be useful’) is a chemically inert substance given in place of a drug. The act of taking it, and the suggestion or expectation that it would help seems to be sufficient to produce the effect — not totally but in large measure. It generates a powerful psychological response. As they say, it acts on the mind, and thus on the body. Dr. Aaron Vallance has a comprehensive, readable review of placebo effects in his recent paper: ‘Something out of nothing: the placebo effect’ in Advances in Psychiatric Treatment, 2006; 12: 287- 296 (downloadable for free).
Placebo responses, being on the mind, do not affect the actual course of the disease. It is the hope, the expectation that the treatment is useful that makes us tolerate pain, the awful taste and the other ‘baddies.’
Half the battle
The reassuring attitude of the doctor or caregiver and their bedside manner wins half the battle. Dr. Beecher, who first researched on placebo in 1955, showed that about 30 per cent of the effect of any drug is in reality a placebo phenomenon!
He showed that saline injections instead of morphine (when supplies dwindled) actually helped sailors feel better; this is what Benedetti finds fifty years later. Placebo responses are not for ever; they produce short-term effects.
It is not clear whether all illnesses would be helped by a placebo. Any painful, invasive or uncomfortable treatment tends to invoke or enhance it. This is perhaps why placebo effects are more often prevalent in cancer treatment.
Placebos tend to relieve anxiety and work on expectation. Some doctors have even said that larger pills, and coloured pills produce better effects.
Sensitive patients
Some patients, obviously a bit too sensitive (and perhaps a bit hypochondriac?), also feel what they consider to be side effects from placebos, because they have been led to believe that it might occur with the real drug!
This ‘negative effect’ is referred to as Nocebo (in opposition to placebo, meaning ‘I shall harm’). And some others, including The Economist, suggest that homeopathy acts largely as a placebo phenomenon. I shall just mention this and let it go!
The biology behind placebo effects is becoming clearer. Dr. Tor D. Wager and associates of Columbia University, New York, have shown (PNAS USA 2007; 104: 11056-11061) that placebo administration actually releases pain-reducing chemicals called opioids from certain parts of the brain. (The name is derived from opium, the pain-killing drug.)
Also called endorphins (meaning innately present morphine-like molecules), they reduce the sensation of pain. Compounds like naloxone go to inhibit their biological effects, and are thus pain-killer-killers.
Placebos are another indication of how a thought in the mind can influence the effects we feel, or not feel. The power of positive thinking cannot be ignored.
Many have rephrased Descartes’ saying “Cogito ergo sum”, or “I think therefore I am” into “I think therefore I can.”
D. BALASUBRAMANIAN
dbala@lvpei.org
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