Adam Halberstadt and Mark Geyer in Scientific American:
What would you see if you could look inside a hallucinating brain? Despite decades of scientific investigation, we still lack a clear understanding of how hallucinogenic drugs such as LSD (lysergic acid diethylamide), mescaline, and psilocybin (the main active ingredient in magic mushrooms) work in the brain. Modern science has demonstrated that hallucinogens activate receptors for serotonin, one of the brain’s key chemical messengers. Specifically, of the 15 different serotonin receptors, the 2A subtype (5-HT2A), seems to be the one that produces profound alterations of thought and perception. It is uncertain, however, why activation of the 5-HT2A receptor by hallucinogens produces psychedelic effects, but many scientists believe that the effects are linked to increases in brain activity. Although it is not known why this activation would lead to profound alterations of consciousness, one speculation is that an increase in the spontaneous firing of certain types of brain cells leads to altered sensory and perceptual processing, uncontrolled memory retrieval, and the projection of mental “noise” into the mind’s eye.
The English author Aldous Huxley believed that the brain acts as a “reducing valve” that constrains conscious awareness, with mescaline and other hallucinogens inducing psychedelic effects by inhibiting this filtering mechanism. Huxley based this explanation entirely on his personal experiences with mescaline, which was given to him by Humphrey Osmond, the psychiatrist who coined the term psychedelic. Even though Huxley proposed this idea in 1954, decades before the advent of modern brain science, it turns out that he may have been correct. Although the prevailing view has been that hallucinogens work by activating the brain, rather than by inhibiting it as Huxley proposed, the results of a recent imaging study are challenging these conventional explanations.