"Blocking cannabinoid receptors could thwart this developmental process, the researchers said."

Anti-obesity drugs that work by blocking brain molecules similar to those in marijuana could also interfere with neural development in young children, according to a new study from MIT’s Picower Institute for Learning and Memory. Marijuana is known to be an appetite stimulant, and a new class of anti-obesity drugs—such as rimonabant (trade name Acomplia) developed by Sanofi-Aventis and awaiting approval for use in the United States—work by blocking brain receptors that bind to marijuana and other cannabinoids.

Marijuana, derived from the plant Cannabis sativa, contains special active compounds that are referred to collectively as cannabinoids. But other cannabinoids (endocannabinoids) are generated naturally inside the body.

The MIT study, which was done in mice, found that blocking cannabinoid receptors could also suppress the adaptive rewiring of the brain necessary for neural development in children. The work is reported in the May 8 issue of Neuron.

“Our finding of a profound disruption of cortical plasticity in juvenile mice suggests caution is advised in the use of such compounds in children,” wrote lead author Mark F. Bear, director of the Picower Institute and Picower Professor of Neuroscience.

The researchers investigated plasticity—the brain’s ability to change in response to experience—by temporarily depriving newborn mice of vision in one eye soon after birth. This well-known experiment induces a long-lasting loss of synapses that causes blindness in the covered eye, while synapses shift to the uncovered eye. How and where this synaptic shift occurs in the primary visual cortex has remained controversial.

Understanding the mechanism behind this phenomenon is key because the same brain mechanisms are used for normal development and may go awry in conditions that cause developmental delays in humans, and may reappear in old age and contribute to synaptic loss during Alzheimer's disease, Bear said.

In mice, the MIT researchers found, even one day of deprivation from one eye starts the shift to dominance of the uncovered eye. But injecting the mice with a cannabinoid receptor blocker halted the shift in certain brain regions, indicating that cannabinoids play a key role in early synaptic development.

Blocking cannabinoids receptors could thwart this developmental process, the researchers said.

"There is some evidence of a long-term effect," Dr John Zajicek, who heads the trial, confirmed to the BA Festival of Science at Exeter University.

He also said the data so far "were consistent" with the idea the drugs could arrest nerve death in sufferers.

He was presenting results that update a study published in The Lancet last year.

There was evidence of an effect on spasticity and on disability Dr John Zajicek

But an analysis of the data suggested there was little reduction in spasticity among the research subjects - one of the key tests used to assess the drugs.

Spasticity refers to feelings of stiffness and a wide range of involuntary muscle spasms or sudden movements.

Speaking at the annual British Association meeting, Dr Zajicek, from the Peninsula Medical School in Devon, said this assessment might have been premature.

Longer-term monitoring, he said, had now shown patients experiencing significant improvement in this area.

Continued support

In MS, the protective sheath that surrounds nerves (myelin) wastes away, leaving scar tissue known as a sclerosis. Sometimes the nerve fibre itself is damaged.

This disrupts the ability of the nerves to conduct electrical impulses to and from the brain, producing the various symptoms of MS. These include pain, deadening fatigue, problems with sight, mobility and coordination.

"We have generated some very interesting results which suggest there may be a potential long-term benefit from these drugs," Dr Zaijcek told journalists.

"There was evidence of an effect on spasticity and on disability."

Asked whether cannabis might work by arresting the death of nerve cells in MS sufferers, Dr Zajicek answered: "Our results are certainly consistent with that hypothesis."

Patients were given up to 25mg per day of either whole cannabis extract in pill form, a tetrahydrocannabinol (THC) pill, or a placebo. The first trial, with 667 volunteers, lasted 15 weeks and was published in The Lancet in November.

These subjects were then asked if they wanted to participate in a further 52-week trial. About two-thirds of the original participants signed up for this long-term study.

A strong beneficial effect on symptoms of the disease was reported by patients throughout the 15-week trial and the one-year study. But this did not by itself demonstrate an underlying physical basis for this effect, Dr Zajicek admitted.

"What we've been trying to do is to have some objective, independent evidence of that," said Dr Zajicek.

Test of safety

Asked whether he thought cannabis should be approved as a medicine, Dr Zajicek answered: "I think the licensing agencies need to assess all the evidence and we need further, long-term studies before we make that decision."

"This comes with lots of caveats. The experiment was only designed for a 15-week trial. We followed the subjects up expecting to find out only whether cannabis was safe in the longer term.

"But some of the experimental data emerged over the course of our study."

In the last 15 years, scientists have discovered a variety of cannabis-like chemicals (or cannabinoids) in the brain.

They reduce the amount of neurotransmitters that mediate communication between nerve cells.

Certain cannabinoids may have more of an effect than others, Dr Zajicek said.

These cannabis-like chemicals have been used as treatments for increasing appetite associated with cancer and Aids, as well as various movement disorders.

Article Published 2004

By Paul Rincon
BBC News Online science staff, at the BA festival

Source: BBC News