Keep Your Brain From Going to Pot
The active chemical in marijuana can do more for your head than give you a high -- it could protect your brain in emergency situations.
An altered version of cannabis could be the first drug ever to shield the brain from the cascade of injury that follows head trauma.
When the brain is injured in a fall or car accident, the damage does not stop after the impact. When cells in the brain die, they send signals to nearby cells to die also, causing continued, uncontrollable injury. Researchers have been trying to find a way to stop this domino effect for decades, but nothing has worked well yet.
Researchers at Pharmos, a pharmaceutical company in Iselin, New Jersey, are seeing promising results with their injectable synthetic cannabis drug. While pharmaceutical giants like Pfizer and Bayer have failed at developing emergency treatments for head trauma, Pharmos scientists say theirs will be the one to succeed.
The drug, called Dexanabinol, is a synthetic version of the active chemical in cannabis, tetrahydrocannabinol, known commonly as THC. The researchers flip its molecules around to form a mirror image of THC. In this form it doesn't cause some of the potential negative effects of hashish or marijuana, such as low blood pressure or impairment of motor function.
"If you ask me 'Is hashish good for health?' well, maybe, but the results are very controversial," said Gad Riesenfeld, president and COO of Pharmos. "We have selected Dexanabinol because of its mechanism of action and efficacy in animal models, and the way it worked in the phase 2 study." It's now in phase 3 of testing; drugs must undergo three phases of trials to be considered for approval by the FDA.
He added that THC at this dosage would cause serious low blood pressure, which can be particularly problematic when coupled with a brain injury.
Other attempts have focused on just one aspect of brain trauma, such as inflammation. But three basic processes contribute to damaging the brain when injury occurs, and the cannabis-derived drug acts on all of them: inflammation, neuron death and the breakdown of communication between neurons called "excitotoxicity."
In Pharmos' phase 2 study of 100 patients with severe traumatic brain trauma, about 30 percent were completely recovered or had just moderate disability six months after their injury when treated with the drug -- compared with 15 percent of those who received a placebo.
"We think the FDA will give approval to a drug that has even 10 percent more patients achieving good outcomes on the Glasgow scale," Riesenfeld said.
Pharmos' phase 3 study will include 900 severe traumatic brain injury patients at 80 clinics around the world. Fifteen of the clinics are in the United States, and 750 patients have been recruited so far.
Performing the trial is complicated by the fact that emergency workers must inject Dexanabinol no more than six hours after the injury. While that seems like a good chunk of time, it can fly by in a triage situation, especially when doctors must get informed-consent documents signed before using an experimental drug, one doctor said.
"Six hours seems long, but when you're doing 'ABC' (a routine check of airway, breathing and circulation), then you begin finding the next of kin -- since many will be unconscious -- the time slips away quickly," said David Bonovich, fellowship program director in neurocritical care at the University of California at San Francisco.
Still, Bonovich said it's a reasonable window of time in which to administer a drug -- it might not do any good if administered later.
About 1.5 million people suffer traumatic brain injuries in the United States every year, according to the Centers for Disease Control. Riesenfeld said about 150,000 of those could be candidates for the drug. That's not a huge market, but each treatment would cost between $4,000 and $7,000, he said.
Researchers previously hoped that inducing hypothermia might slow the progress of brain injury, because lowering body temperature slows all of the body's processes. They had high hopes for a large study called the National Acute Brain Injury Study using Hypothermia, known as the NABISH trial, sponsored by the National Institute of Neurological Disorders and Stroke.
But the treatment ultimately failed to show a significant improvement. However, researchers saw some evidence that the treatment could benefit patients who already have a low temperature when they receive hypothermia treatment, so researchers are continuing with a NABISH 2 trial focusing on only those patients.
Pharmos researchers think they have a good chance to do better. They say they have taken great care to learn from past failed trials, to identify the patients who are most likely to benefit from the drug, and to find the proper dosage and time frame in which to administer it. They hope to have approval of the drug in late 2004, and to put it on the market in early 2005.
The researchers are also testing the drug to prevent brain damage that can occur after cardiac surgery, said Robert Cook, chief executive officer of Pharmos. Surgeons would give the injection prophylactically.