Various molecules, including LSD, can bind with serotonin receptors.

Recent research indicates that the serotonin 2A receptor is like “a lock into which both hallucinogenic and nonhallucinogenic keys fit. While LSD may turn this lock to the right, kicking off one set of responses, lisuride turns the tumbler to the left, an action that only causes a subset of those responses.”

Since the 1980s researchers in this field have agreed that LSD, which was first synthesized by Swiss scientists in 1938, likely affects serotonin 2A receptors in the brain (serotonin is a neurotransmitter suspected to play a role in the communication of mood and consciousness). These receptors show up in many places in the brain, including several areas in the cortex (known for sensory perception), and the thalamus (an interior region known for relaying messages to the cortex as well as regulating arousal and awareness).

The current research was performed by creating a mouse model that enabled scientists to observe behavioral and cell-signaling responses to hallucinogenic drugs by comparing them with those triggered by lisuride, an anti-Parkinson’s disease drug chemically similar to LSD that does not have hallucinogenic effects. After determining that mice given psychedelic drugs consistently experience head twitching, the team bred mice with the serotonin 2A receptor knocked out to determine whether the hallucinogens still caused head twitching.

After testing many candidate regions, the researchers localized the effects of hallucinogens to the pyramidal neurons in layer V of the somatosensory cortex, a relatively high-level region known to modulate the activity of other sections in the cortex and subcortical areas. Using what he calls an “imperfect but usual analogy,” Stuart Sealfon, a neurologist at Mount Sinai Hospital in New York City likens the receptors to a lock into which both hallucinogenic and nonhallucinogenic keys fit. While LSD may turn this lock to the right, kicking off one set of responses, lisuride turns the tumbler to the left, an action that only causes a subset of those responses. “Both the hallucinogens and the nonhallucinogens activate what we would call the classical signaling cascade downstream of this receptor in these cells,” Sealfon says. “But, the hallucinogens, we show, are activating an additional signaling cascade and we believe the sum of both of them together is probably what causes the effect we see.”

… While Roth concedes that cortical serotonin 2A receptors are likely part of the mechanism of hallucinogenic drugs, Dave Nichols, a molecular pharmacologist at Purdue University, believes the thalamus must be involved in some manner. “The thalamus is the major relay station for sensory information that is sent to the cortex, and there are serotonin 2A receptors localized in the thalamus and the reticular nucleus of the thalamus, which controls the flow of information through the thalamus,” he argues. “For the authors to say that a unique mechanism has been identified that does not involve the thalamus, I therefore think cannot be correct.”

[Scientific American]

Speaking of mice and men and LSD …

Alfred Matthew Hubbard: the original acid prophet —

In 1951, reading The Hibberd Journal, a scientific paper of the time, Hubbard stumbled across an article about the behavior of rats given LSD. “He knew that was it,” says Harman. Hubbard went and found the person conduction the experiment, and came back with some LSD for himself. After his very first acid experience, he became a True Believer.

“Hubbard discovered psychedelics as a boon and a sacrament,” recalls [Timothy] Leary.

… Hubbard’s secret connections allowed him to expose over 6,000 people to LSD before it was effectively banned in ‘66. He shared the sacrament with a prominent Monsignor of the Catholic Church in North America, explored the roots of alcoholism with AA founder Bill Wilson, and stormed the pearly gates with Aldous Huxley (in a session that resulted in the psychedelic tome Heaven and Hell), as well as supplying most of the Beverly Hills psychiatrists, who, in turn, turned on actors Cary Grant, James Coburn, Jack Nicholson, novelist Anais Nin, and filmmaker Stanley Kubrick.

[Rense.com]