15 February 2007
Not so long ago, college students used to think that the way to understanding the mind more deeply was with the famous hallucinogenic drug LSD. And maybe they were right.
But
the trick to achieving such profound insight is not swallowing LSD and
turning your brain into a psychedelic light machine. Rather it is studying
what the LSD molecule does to other molecules in your brain.
Perception, thought processes and even mood are dramatically altered by LSD and other famous molecules, such as psilocybin, the stuff you get from magic mushrooms. All the resulting weirdness of taking these drugs has nothing to do with magic, though, or with transcending the psychological chains of worldly materialism (whatever that means). It has to do with the real-world chemistry underlying the brain's biology.
That biology is built on the interactions of molecules — some small, some enormously complex. Neurons — the brain cells that fire the electrical signals that direct thought and action — contain thousands of molecules. And each neuron's surface is studded with special molecules that act like antennas to detect the presence of other molecules in the neighborhood. One neuron communicates to another, in fact, by squirting out small "messenger molecules" to stimulate those antenna molecules (known technically as receptors).
Receptors are sort of like gloves, shaped to allow the entry of only
very specifically shaped hands. Messenger molecules (playing the part
of the hands) stimulate only those receptors where the fit is right. If
it doesn't fit, the molecule quits (and goes away). The brain possesses
many dozens of different messenger
molecules, allowing the complex orchestration of signaling necessary for
sophisticated mental function.
Dump some LSD in the brain, though, and you mess that signaling up. LSD molecules fit nicely into a receptor designed for the natural messenger molecule serotonin. Serotonin is important for normal perception and mood, which explains why stimulating its receptor with a rogue molecule disturbs those sorts of mental traits.
More than a dozen different subtypes of receptor molecules for serotonin are found in the brain; LSD attaches to one particular subtype, known as 2A. Mysteriously, though, other drugs also attach to the same serotonin receptor, on the same neurons, without inducing LSD's hallucinogenic effects. Figuring out why could help explain not only the actions of LSD, but would also provide new insight into how the brain works in general.
So researchers at the Mount Sinai School of Medicine in New York City, with collaborators from Columbia University, have been probing the chemistry of LSD in the brains of mice. The mice refuse to say what sorts of wild altered states they experience, but tests of known hallucinogenic drugs reveal that hallucinating mice twitch their heads (no doubt the way people would twitch their heads when hallucinating that they are the mouse).
Given LSD, the lab mice do, in fact, twitch their heads. But in some mice the scientists disable the gene for producing the serotonin 2A receptor. Mice without the receptor do not twitch in response to LSD, confirming that receptor's importance in generating hallucinations.
Studies of the chemistry within the neurons show that while other drugs can stimulate the 2A receptor, they don't elicit identical responses. One drug that acts on the 2A receptor is lisuride, used in some countries for treating Parkinson's disease. But mice given lisuride do not twitch their heads, even though it attaches to the same receptor used by LSD.
Further analysis suggests that lisuride initiates a chemical chain reaction that ultimately induces genes in the cell's nucleus to direct the production of certain proteins. LSD also elicits the production of those proteins, but in addition triggers another reaction chain, producing the chemicals apparently associated with hallucinations.
It's as if both lisuride and LSD fit the 2A glove, but LSD holds its fingers in a different position than lisuride does, and therefore causes some additional chemical effects.
Understanding the details of LSD's actions is good for more than explaining
why some people can't remember the 1960s. LSD's lessons may help sort
out other issues involving brain 
chemistry.
Medications for mental illness, for instance, often produce their benefits
in unknown ways. The same methods used for teasing out LSD's trickery
could illuminate the workings of therapeutic drugs, perhaps showing how
to make better ones.
"Our findings may advance the understanding of neuropsychiatric disorders that have specific pharmacological treatments whose mechanism of action are not fully understood," Javier Gonzalez-Maeso and collaborators write in their paper, published in the Feb. 1 issue of the journal Neuron.
More deeply, LSD teaches the lesson that the brain is a complicated chemical factory, easily sabotaged by malevolent molecular interlopers. Whether the interloper is admitted voluntarily as a recreational activity, or invades from a toxic environment, or is tailored internally by a traitorous gene, successful countermeasures depend on knowledge of its methods. Such knowledge comes not from altered states of consciousness, but from conscientious experiments — and an appreciation of the magic of molecules.
E-mail: tsiegfried@nasw.org
