In order to understand what it means to hallucinate, we first must gain an appreciation of what hallucinogens do inside the brain. One of the best studied hallucinogenic drugs is LSD. In the brain, LSD binds to a variety of different serotonin receptors; one of the first things that happen is that the activity of serotonin neurons slows to almost zero. The only other time this normally occurs is when we are asleep and start to dream. But that similarity is probably only a neat coincidence; given that the psychoactive effect of LSD far outlasts the slowing of serotonin neural activity, this slowed activity does not explain completely why we hallucinate on this drug and why the hallucinations are so like dreaming. Indeed, the effects of LSD on serotonin neurons may only be the initial trigger that sets in motion a cascade of complex processes throughout the brain that is experienced as a hallucination.

Psilocybin has a similar action upon serotonin neurons. Our ancestors probably discovered its source, Psilocybe Mexicana, (or any of the 75 different mushroom species that contain psilocybin), by accident when foraging for edible mushrooms. One can only imagine how unexpected the experience must have been for the first person who inadvertently prepared one of these mushrooms for consumption, bringing new meaning to the phrase "dinner and a show."

In truth, no one is currently certain how LSD or any of the hallucinogens actually works, or just how serotonin factors into their hallucinatory effects. Confounding this uncertainty is the fact that some hallucinogens have no apparent effect on serotonin at all. For example, Salvinorin A, from the Mexican plant Salvia divinorum, is a very potent naturally occurring hallucinogenic compound that is similar to morphine in its actions but has no identified action at serotonin receptors.

The complex sensory experience known as hallucinations can, however, occur under other circumstances, and this fact may shed some light on the nature of the hallucinatory experience, drug-induced or otherwise, and its connection to serotonin. Consider, for example, the following hypothetical scenario: 

Imagine yourself as a newborn lying in a crib. Your brain's serotonin neurons at this age, and during the first couple years of your life, are not working completely because the neurons and glia that support them have not fully developed. In addition, the profile of serotonin receptors has not yet converted to the adult balance of excitatory and inhibitory subtypes of receptors. Your sensory systems-visual, auditory, and olfactory abilities in particular-are working, but your serotonergic system is not adequately installed to assist them with the processing of the incoming sensory information to the brain. Suddenly, you sense something looming over your crib-a large green, distorted face with a screeching voice and reeking of a yellow odor-and you scream in fear. You have just had your first hallucination. You have also just experienced synesthesia, or the merging and mixing of sensory processes-for example, sights that produce sounds or smells that have color.

Now imagine yourself 20 years later, with your serotonergic system now fully developed. But take a hallucinogenic drug and you could have a temporary synesthesia experience similar to what you had in your crib as an infant. Why? The inhibited function of your serotonergic system that is induced by a hallucinogen may reproduce the condition of synesthesia that was simply "normal" when you were a newborn. As a newborn, you would find this condition to be frightening. But as an adult who has taken a hallucinogen, you might, in the right setting, come to believe that the condition is a transcendently mystical experience.

It's not mystical; it's a drug-induced duplication of the conditions that originally existed in your brain prior to the maturation of a small group of neurons that release serotonin. Fortunately, due to your "infant amnesia" you remember nothing of this bizarre experience. Keep this in mind next time you find yourself hovering over a crib!

© Gary L.Wenk, Ph.D. author of Your Brain on Food (Oxford, 2010);

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