Poison Puffer Placates Pain
by Dr. Byron Law-Yone, M.D.
Dr. Law-Yone is a Scientific Advisory Board member for WEX Technologies,
Medical Science Searches for the Perfect Pain Reliever
A major challenge medical science faces is the search for more
effective drugs to control pain. Neuroscientists continue to study
the complex molecular mechanisms involved in the production, transmission
and recognition of pain and map intricate pathways that conduct
impulses to the brain where specific receptor sites are responsible
for triggering pain . A drug can influence pain where it originates,
along the pain pathways or the myriad of pain receptor sites in
In America, the annual cost of over the counter analgesics alone
is $3 billion a year. These drugs however, do little to alleviate
more severe pain that often becomes chronic and unremitting. This
is the type of pain commonly experienced by the 6 million cancer
patients in America and typically, adequate control of this pain
requires treatment with opioids such as morphine, oxycodone and
Physicians are often accused of either under treating or over
treating pain and they readily attest to the difficulty of providing
adequate pain relief for chronic malignant pain without producing
side effects in a population already receiving a plethora of potent
drugs. These opioids do not always prove adequate pain relief
and can act in unpredictable ways, causing unwanted side effects
such as nausea, vomiting, dizziness, constipation, drowsiness
and respiratory depression. There are also risks of addiction
and painful withdrawal symptoms.
Puffer Fish Poison for Pain Relief?
A new approach to combat pain avoids the use of opioids completely
and relies instead on a poison found in puffer fish. Tetrodotoxin
(TTX), a neurotoxin present mainly in the liver and gonads of
puffer fish is so powerful that a single milligram - an amount
that could be placed on the head of a pin, could kill an adult.
TTX modifies pain perception by blocking the sodium channel on
the nerve axon, thereby preventing the propagation of nerve impulses.
The puffer fish, known as "Fugu" in Japan, has to be
prepared by specially trained and licensed chefs that can separate
the fish from the toxin, rendering it safe for consumption by
adventurous Japanese who pay hundreds of dollars to play gastronomic
Russian roulette. In Japan, fugu may be a popular dish for the
well heeled, but for the emperor and his family, this is the only
delicacy they are never served.
Puffer fish have fascinated observers around the world for centuries.
Symbols of the fish have been identified on Egyptian tombs dated
2700 BC. The ancient Chinese and Japanese were aware of the toxin
contained in puffer fish and used the non-poisonous parts of the
fish as a general health tonic.
Chinese scientists have studied extensively TTX and its analgesic
properties, and recent clinical trials in China have led to some
remarkable findings. The intractable malignant pain of cancer
patients was controlled within minutes of microgram doses of TTX
and pain relief lasted 2 to 3 weeks. Another important finding
was the usefulness of TTX in managing the painful withdrawal symptoms
of heroin addicts. It appears that TTX acts quickly, offers a
long duration of action and is safe given in very small doses.
There is also no evidence of any addiction or risk of withdrawal
International Wex Technologies, a Canadian neuro-bioscience
company based in Vancouver has developed Tectinâ, a purified
form of TTX now undergoing Phase II trials in Canada with test
sites in hospitals in Edmonton, Montreal, Toronto, London, Saskatoon
and Calgary. Each site will carefully screen and select 6 patients
with cancer pain refractory to traditional pain medication.
Though the Phase II trials have not been completed, preliminary
results have generated considerable interest and positive responses
from the investigators involved. Dr. Edward Sellers, the chief
investigator, was also responsible for the successful completion
of Phase I trials where the drug was tested on 127 healthy volunteers.
He states, "
small doses can have very, very powerful
. it's a very interesting drug and it offers probably
huge potential advantages".
Another physician, Dr. Oneschuk confirms the findings that a
common side effect is usually a numbness or tingling around the
mouth, but otherwise deems it well tolerated. She remarks, "It
is something a little different. It's quite exciting. It may be
a breakthrough in pain medication". She has reported a 50%
response rate, even with the use of tiny amounts of the drug.
A more robust response is likely as higher doses are employed.
As we approach the final stages of these clinical trials, we
may be witnessing the achievement of a major milestone in medical
science, one that may forever change the quality of our lives.
Dr. Byron Law-Yone, M.D.
is Medical Director, Addiction Medicine, Baylor Richardson Medical
Center, Richardson, Texas. Dr. Law-Yone became a Member of the
Royal College of Psychiatrists of London, England in 1971 and
in 1978 became a Diplomate at the American Board of Psychiatry
and Neurology. In 1988, he was certified by the American Society
of Addiction Medicine and, in 1993, he obtained his certification
as a Diplomat with added qualification in Addiction Psychiatry
from the American Board of Psychiatry and Neurology.