with eyes open. More specifically, one does not hallucinate nonexistent objects; rather, one comes to see external reality in a new and more enhanced way. It is for these reasons that the term
It is believed that psilocybin works by mimicking the neurotransmitter serotonin (known as 5-HT), one of the most important and widespread of the brain’s synaptic messengers. The mimicking occurs because psilocin (the active metabolite of psilocybin that is formed in the body) possesses a molecular structure almost identical to serotonin. Psilocin’s shape is so similar to serotonin that it is able to infiltrate parts of the brain that process information using serotonergic synapses.
Serotonin is employed in a number of brain structures that control functions like sleep, mood, and general arousal. One of these structures is the raphe system at the base of the brain, whose serotonergic neuronal axons project to all other major areas of the brain, notably the limbic system (which controls emotional responses) and areas of the visual system.
Research indicates that the serotonin-using raphe system has a homeostatic, or balancing, function in which two primary effects emerge. First, in the waking state the system acts to enhance the activity of motor neurons, which govern the control of muscular movement. Second, and more significant, during the waking state this same serotonergic system acts to suppress sensory systems, which relay information about the external world. This second effect appears to screen out, or filter out, distracting sensory information. Furthermore, it has been speculated that this filtering mechanism allows us to perceive reality in a steady way, almost as if the serotonergic raphe system were a balancing stick enabling us to walk the “tightrope” of normal perceptual awareness. If this serotonergic homeostatic balancing system is interfered with, then the perception of reality will be correspondingly altered, so much so that we may plunge off the tightrope into new dimensions of perceived reality. Chemically dismantling the raphe system’s screening effect would therefore admit the entry of latent information into consciousness. Is this how visionary agents like psilocybin work?
Most of the detailed physiological experimentation that was carried out with psychedelics in the 1960s concentrated on LSD and psilocybin and used rat brains, cat brains, and isolated rat neurons. Perhaps the most important finding was indeed that LSD and psilocybin depress the action of serotonin neurons in the raphe system (a neuronal system shared by rats, cats, and humans).
The usual activity of the particular serotonergic neurons that psilocin and LSD depress is inhibitory, which means that their normal firing serves to dampen or suppress activity in those parts of the brain with which they synapse. Thus it was believed that psilocybin and LSD’s dampening effect on serotonergic neurons facilitated an increase in neuronal firing in those areas of the brain in contact with the raphe system (like the aforementioned visual and limbic/emotion systems). It was this effect, this enhancement of neuronal activation, that was believed to correlate with the psychedelic experience itself.
It seemed like a nice, neat theory. However, the above scenario does not take into account the recently discovered neuropharmacological action of mescaline, another classic entheogen. With not a little irritation we find that, like psilocybin, mescaline induces the full spectrum of visionary phenomenology, but it is not known to significantly influence the raphe system. Therefore our raphe theory cannot be the whole story.
Research over the past decade has revealed that there are distinct kinds of serotonin receptors, or serotonin binding sites, within the brain. In other words, neurons that are modulated by the release of serotonin from other neurons with which they synapse are not tied down to just one kind of serotonin receptor. In typical fashion, Nature has made things more complex and intriguing than that. In fact, there are different kinds of serotonin receptor (classified by grouping them into subtype receptors), and it is believed that different psychedelic drugs have differential effects upon these receptors. One particular serotonin receptor, however—the so-called 5 -HT2A type—appears to represent a common site of action for both psilocybin and mescaline.
The 5-HT2A receptors are found throughout the cortex and also in abundance in the brain system known as the locus coeruleus, which, like the raphe, is situated at the base of the brain. The locus coeruleus processes so many sensory inputs (a flow of incoming data, if you like) that it is considered to function as a “novelty detector” and is able to influence one’s state of arousal. By monitoring the constant surge of “electrochemical traffic” passing through it, the locus coeruleus is able to detect changes in the flow of data and alert other parts of the brain. When something changes in the environment around us, the locus coeruleus alerts the rest of the brain to the change. Both psilocin and mescaline bind to these 5-HT2A sites in the locus coeruleus and thereby alter the functioning of this system, ultimately raising levels of arousal. In other words, it once again seems that psychedelics function by making more information available to the experiencer.
This explanation is still not the full story, however, as pharmacology expert professor David Nichols attests.
5-HT2A receptor sites are located in a number of other key areas of the brain. Importantly, they are located on neurons in the frontal cortex called pyramidal cells. The frontal cortex is often referred to as the area where executive decisions are made. It is there that we make sense of all the information that is arriving. It is a sort of conscious integrating center where the brain makes decisions about what to do about all the information that it is receiving. Laugh? Cry? Get up and go to the bathroom? Experiments… suggest that stimulation of 5-HT2A receptors makes these pyramidal cells fire more easily, thus enabling them to process more information.{28}
Professor Nichols also points out yet another area of the brain that might be involved in entheogenesis.
There is an area in the middle of the brain called the thalamus. The thalamus is a relay station through which all of the sensory information we receive (except for smell) is sent to the cortex. This part of the brain is sometimes called the “searchlight” of attention. It is wrapped in yet another layer of neurons called the reticular nucleus of the thalamus, and it is this layer that helps to control which sensory information actually gets through the thalamus and is sent on to the cortex. The 5-HT2A receptor is located on neurons in both of these two areas, so its activation has a direct effect on the control and flow of information that ultimately reaches the cortex. It is thought that psilocybin and LSD decrease the efficiency of this thalamic filter or gating mechanism, and allow much more information to be sent to the cortex.{29}
Despite introducing yet more areas of the brain, Professor Nichols appears to concur that the chief effect of psilocybin is
The Novel Orchestration of Information
We are now in a position to summarize the above findings in fairly straightforward terms: the net result of psilocybin’s combined effects upon the locus coeruleus, the raphe system, the thalamus, and cortical cells is an increase in neuronal firing in the cortex, a concurrent increase in consciousness (an expansion of perceived reality), and the emergence of often spectacular visions behind closed eyes.
Only the second of those claims is in any way contentious, for I suggest an increase in consciousness. Others might argue that the increase in neuronal firing in the brain is more of an unwelcome dysfunction than a constructive effect. However, a negative judgment like this misses the implications of the entheogenic state of mind. After all, Huxley claimed that psychedelics could, through an act of “gratuitous grace,” permit one access to perceptual information that was “out there,” but not normally needed because from an evolutionary standpoint we need only information regarding things like food and safety. Or at least those are the sorts of thing it has been essential to know in our evolutionary past. Of course for Huxley and other champions of the psychedelic experience, the knowledge made available through visionary plant and fungal alkaloids was suddenly very important in the light of contemporary Western culture. A transcendental reality appeared to be awaiting us, ready
