Oct. 5, 2001 -- Could a drug similar to the active ingredient in marijuana protect your brain?
Research at the Hebrew University in Israel, reported in the journal Nature, shows that a cannabinoid, similar to the active ingredient found in marijuana and produced in the brains of many animals, protects mice from brain injury.
Mice that sustained brain injuries were discovered to have elevated levels of a compound known as 2-Arachodonoyl glycerol, or 2-AG. Theorizing that this cannabinoid was produced to prevent damage, the researchers administered more of the compound to injured mice and found it protected the brain.
Currently, there is no effective drug for the treatment of traumatic brain injury. In the U.S., there are nearly 52,000 deaths and roughly 80,000 cases of severe disability related to traumatic brain injury every year.
There are more than 5.3 million people in the U.S. living with disabilities related to traumatic brain injury — numbers far greater than those for multiple sclerosis, Parkinson's disease and Alzheimer's disease.
"Brain injury is not a one-shot deal. The primary injury occurs from the initial hit. Neurochemical injuries can cause secondary damage," said Dr. Ken Strauss of Temple University.
The secondary effects of brain injuries, such as swelling and the release of toxic chemicals, can be more damaging than the initial blow, said Dr. Esther Shohami, lead author of the study.
The cannabinoid, 2-AG, is believed to work in three ways. First, it reduces the levels of glutamate, a toxic molecule, released after injury. Second, it decreases the amount of free radicals and TNF (a chemical that induces inflammation) after injury. Third, it increases the blood supply to the brain. All three mechanisms are essential for limiting the damage done after the primary injury.
"The dose has to be very carefully controlled," Dr. Shohami said — noting that requirement is one of a number of reasons why marijuana, which can vary in potency, would likely be an unreliable treatment for head injuries.
She added that 2-AG must be administered within a four- to six-hour window after the injury to be effective.
Use in Humans
Although 2-AG has only been tested on animals, Dr. Shohami said she didn't "see any problems with using a drug from this family to treat patients." Other cannabinoids have been approved for use in humans, such as synthetic forms of THC used to stimulate appetite.
In fact, one pharmaceutical company is trying to develop a similar drug for humans. With the help of researchers at the Hebrew University, Pharmos is set to begin the final stage of clinical trials of Dexanabinol — a drug that is essentially the mirror image of THC, the active ingredient in marijuana. Because it is not exactly like THC, it does not bind to the same part of the brain, and therefore does not have the unwanted side effects.
However, the drug appears to exert effects similar to other cannabinoids on the brain after injury — that is, a decrease in toxic chemicals and swelling. The first two phases of clinical trials were completed in Israel to test for safety. The third and final phase of the trials is set to begin in Europe in January, followed closely by trials in the U.S.
"Helmets are for preventing primary injury, and hopefully this work can protect people from the secondary effects," Dr. Strauss said.