Inhale or Don't?

(Marijuana is not the ‘soft drug’ people like to think it is)

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Clinton didn’t inhale, Obama did—and maybe Reagan should have. New research suggests that THC, the chemical that gives marijuana its mind-bending properties, kills developing neurons, yet oddly, the same chemical saves neurons in adults with Alzheimer’s disease.

“Marijuana is not the ‘soft drug’ people like to think it is,” says neuro pharmacologist Veronica Campbell of Trinity College in Dublin, whose latest study uncovered the harmful effects of THC on young neurons. When Campbell and her co-workers treated brain cells from newborn or adolescent rats with THC, the neurons died, but THC did not have such deadly effects on neurons taken from adult rats. In fact, work from other labs shows that THC benefits adult neurons. “We don’t know why,” Campbell says. Several possi bilities are being investigated for this “Jekyll and Hyde” effect.

Marijuana, like tobacco and opium, has powerful effects on the brain because certain compounds in the plant happen to have a chemical resemblance to naturally occurring substances in the body. Called endocannabinoids, these natural chemicals regulate important brain functions by controlling synapses in neural circuits that process thought and perception. According to several recent studies, these chemicals have many other functions in the brain and immune system, too—including regulating development and aiding survival of young neurons, as well as controlling the wiring of neurons into circuits for learning and memory. Smoking marijuana during the period of life when the brain is still developing obscures these critical chemical signals, Campbell suspects.

The slaughter of young neurons by THC could explain the developmental cognitive impairment seen in children born to women who smoked marijuana during pregnancy. In addition, some research on adolescent marijuana abusers shows brain damage in neural circuits that are still developing at that age.

In older brains, however, THC seems to have a protective effect. Campbell’s findings indicate that the biochemistry of neurons changes as the cells mature. The role of endocannabi noids shifts to regulate different functions—most important, assisting in the survival of aged neurons. In patients with Alzheimer’s disease, THC protects neurons from death in several ways. THC boosts depleted levels of the neurotransmitter acetylcholine, which, when diminished, contributes to the weakened mental function in Alzheimer’s patients. THC also suppresses the toxic effects of the so-called a-beta protein that may kill neurons in Alzheimer’s disease. It stimulates secretion of neuron growth by promoting substances such as brain-derived neurotrophic factor, and it dampens release of the excitatory neurotransmitter glutamate, which kills neurons by overstimulation. THC and other cannabinoids also have powerful anti-inflammatory and antioxidant actions that protect neurons from immune system attack.

Despite these benefits, THC and other compounds in marijuana also have many undesirable side effects on the brain. The trick for scientists will be to isolate the active ingredients in marijuana that are beneficial and develop drugs that can be applied in the proper dose for the specific age of the patient. Campbell finds that the beneficial effects of THC are seen in much lower concen trations of the chemical than are found in the plants people use to get high. “It’s a matter of trying to balance that low concentration within a nice safety margin,” she explains. Synthetic THC-like drugs are already available, as is a naturally derived drug called Sativex that contains THC and other cannabinoids, approved in Canada for treating pain from multiple sclerosis and cancer.

In contrast to these well-controlled drugs, the weed itself is a complex witches’ brew of many brain-altering chemicals. The cannabis plant contains about 60 different cannabinoids, so the challenge lies in trying to tease out which are the important ones for protecting neurons, Campbell explains, echoing the views of other marijuana researchers. “Depending on how the plant is cultivated, the relative proportion of the different types of cannabinoids changes,” she says. “The ‘joints’ that are available now are much stronger in terms of their THC content than those that would have been around when people were thinking of cannabis as being quite a soft drug.” ...Neurobiol Aging. 2009 Sep 21

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