Dextromethorphan (DXM) is a common active ingredient in many over-the-counter cough suppressants, used for managing non-productive coughing. At therapeutic doses, DXM acts primarily on the cough center in the brainstem. However, when ingested at doses significantly exceeding medical guidelines, the effects change dramatically, leading to a psychoactive experience. At high levels, DXM is classified primarily as a dissociative anesthetic and hallucinogen. This article will explain the pharmacological context that establishes DXM’s place within the dissociative class, distinguishing it from deliriant compounds.
The Pharmacological Classification of DXM
Dissociative agents are psychoactive substances defined by their ability to induce feelings of detachment from one’s body or environment. These compounds distort perceptions of sight, sound, and the sense of self, often resulting in experiences described as out-of-body or unreal. Well-known members of this group include ketamine and phencyclidine (PCP); DXM is grouped alongside them when consumed in high quantities. At recreational doses, DXM acts as a non-competitive antagonist, binding to and blocking specific receptors. This action interferes with normal brain signaling, leading to characteristic sensory and cognitive disruptions.
The Biology Behind Dissociation
The mechanism defining DXM as a dissociative involves its interaction with the N-methyl-D-aspartate (NMDA) receptor. This receptor is a component in the brain’s communication network, mediating excitatory signals transmitted by the neurotransmitter glutamate. When DXM or its active metabolite, dextrorphan (DXO), enters the brain, they block the ion channel associated with the NMDA receptor. By acting as an antagonist, DXM prevents the glutamate signal from passing through the channel, dampening excitatory signaling in the central nervous system. This interruption of normal sensory input causes the profound detachment and altered reality associated with dissociation. DXM also has secondary activity as an agonist at the Sigma-1 receptor, which contributes to its unique range of effects.
Clarifying the Difference: Deliriants vs. Dissociatives
The distinction between a deliriant and a dissociative rests on their mechanism of action and the resulting subjective experience. Deliriants, such as those found in certain antihistamines or nightshade plants, work primarily through anticholinergic action, blocking acetylcholine at muscarinic receptors. Blocking acetylcholine leads to true delirium, characterized by severe confusion, memory loss, and realistic hallucinations that the user cannot distinguish from reality. Dissociatives, conversely, create a feeling of separation from the self, with hallucinations often being abstract or dreamlike, and users typically retain some insight that the experience is drug-induced. While DXM possesses minor affinity for muscarinic acetylcholine receptors, its effects are dominated by NMDA receptor antagonism, solidifying its classification as a dissociative.
The Spectrum of DXM’s Dose-Dependent Effects
The effects of DXM are highly dependent on the amount consumed, often described using a system of “plateaus.” At low doses (the first and second plateaus), effects are mild, involving slight inebriation, mild euphoria, and enhanced appreciation for music, sometimes compared to alcohol intoxication. As the dose increases to the third and fourth plateaus, more intense dissociative states occur. Users experience significant alterations in consciousness, visual and auditory distortions, and impaired motor control. The highest doses can result in complete mind and body dissociation, described as an “out-of-body” experience, which is definitive evidence of its function as a dissociative agent.