A hallucination is a sensory experience that feels completely real but is generated internally by the mind, rather than by any external stimulus. These perceptions can involve any of the five senses: sight, sound, touch, taste, or smell. Hallucinations are distinct from illusions, which are misinterpretations of actual external sensations. Various chemical compounds induce this state by temporarily altering the brain’s chemistry, creating experiences that range from enhanced perception to profound confusion.
Classic Psychedelics (Serotonin-Based Perception Alteration)
Classic psychedelics primarily affect the brain by stimulating the 5-HT2A serotonin receptor, which is found densely in the cerebral cortex. These compounds include psilocybin, mescaline, and synthetic lysergic acid diethylamide (LSD). They dramatically alter perception, heightening sensory input and reorganizing consciousness without causing a complete break from reality.
The visual distortions are often vivid and complex, featuring flowing geometric patterns, fractal imagery, and intensified colors. Users frequently report synesthesia, where senses cross over, such as “hearing” colors or “seeing” sounds. Even when the external environment is highly distorted, users usually retain some awareness that the experience is drug-induced.
These compounds disrupt communication between brain regions involved in mood, cognition, and perception. This temporary disruption of the brain’s information filtering mechanisms contributes to the altered state of consciousness.
Dissociative Hallucinogens (Detachment and Sensory Deprivation)
Dissociative hallucinogens interrupt signals between the conscious mind and other brain parts, causing a profound sense of detachment. This category includes phencyclidine (PCP), ketamine, and dextromethorphan (DXM). The altered state is defined by depersonalization (feeling disconnected from one’s body) and derealization (the environment seeming unreal or dream-like).
Dissociatives often induce experiences of floating or out-of-body sensations, rather than distorting external sensory input like psychedelics. Users may feel cut off from the environment, experiencing a form of sensory deprivation. The hallucinations are typically physical, relating to the body schema and the feeling of self, rather than visual.
These compounds primarily work by blocking glutamate, the brain’s main excitatory neurotransmitter, at the N-methyl-D-aspartate (NMDA) receptor. Glutamate is important for learning, memory, and pain perception, and its disruption leads to characteristic feelings of numbness and disconnection.
Deliriants and Atypical Inducers (Confusion and True Delirium)
Deliriants induce a state of true delirium, involving extreme confusion and a complete inability to distinguish reality from the hallucination. Unlike the relative lucidity of classic psychedelics, deliriants cause a profound loss of grounding in reality and often lead to memory loss during the experience. The resulting hallucinations are intensely realistic and frequently involve interactions with non-existent people or objects, similar to a waking nightmare.
A common hallucination associated with this group is tactile, where the user feels phantom sensations, such as insects crawling on the skin. Examples of deliriants include tropane alkaloids like atropine and scopolamine, found in plants such as Datura, and high doses of certain over-the-counter antihistamines like diphenhydramine.
These substances are classified as anticholinergics because they block the muscarinic acetylcholine receptors in the central nervous system. Acetylcholine is important for cognition, memory, and sensory processing. By inhibiting this function, deliriants severely disrupt the brain’s ability to process information coherently, resulting in confusion and realistic hallucinations.
The Neurochemical Basis of Hallucination
The three main categories of hallucinogens demonstrate that complex misperceptions arise from distinct neurochemical pathways.
Serotonin System
The altered perception caused by classic psychedelics is driven by the agonism of the serotonin 5-HT2A receptor in the cerebral cortex. This activation leads to a profound reorganization of sensory information processing.
Glutamate System
The detachment and depersonalization experienced with dissociative hallucinogens stem from the blockage of the NMDA receptor, which regulates glutamate activity. This antagonism disrupts the balance of excitation and inhibition in pathways involved in self-perception and memory. This mechanism is unique to dissociatives.
Acetylcholine System
The confusion and true delirium caused by deliriants result from the anticholinergic mechanism, which involves antagonism of the muscarinic acetylcholine receptors. Since acetylcholine is involved in attention and memory, its inhibition prevents the brain from properly filtering sensory data, causing hallucinations indistinguishable from reality.