Dextromethorphan (DXM) is a common ingredient in many over-the-counter cough and cold suppressants. While effective at therapeutic doses for relieving coughs, higher doses can lead to psychoactive effects. This article explores how DXM interacts with brain chemistry, its immediate effects, and the potential long-term health implications of prolonged misuse.
How DXM Works in the Brain
DXM primarily acts as an N-methyl-D-aspartate (NMDA) receptor antagonist. NMDA receptors, a type of glutamate receptor, are crucial for excitatory neurotransmission. They play a role in brain functions such as learning, memory formation, and synaptic plasticity, the brain’s ability to adapt. DXM blocks these receptors, altering normal brain signaling and leading to dissociative effects.
Beyond this, DXM affects other receptor systems, contributing to its complex effects. It acts as a nonselective serotonin reuptake inhibitor, increasing serotonin levels. This carries a risk of serotonin syndrome, especially when combined with other serotonergic drugs. DXM also acts as a sigma-1 receptor agonist and has minor activity at opioid receptors, though it doesn’t cause typical opioid side effects like respiratory depression at therapeutic concentrations. Its active metabolite, dextrorphan, is a more potent NMDA receptor antagonist, mediating many of its dissociative effects.
Immediate Brain Effects and Perception
At doses exceeding medical recommendations, DXM produces psychoactive effects by disrupting normal brain communication, particularly via NMDA receptor antagonism. Users may experience dissociative effects, such as feeling detached from their body or reality, manifesting as an “out-of-body” sensation.
Perception of time and space can alter, and individuals may experience visual or auditory hallucinations. Other effects include euphoria, confusion, impaired motor coordination and balance, slurred speech, and poor muscle control. Mood changes are also common, ranging from elevated mood to paranoia and anxiety. These experiences result from DXM’s interference with the brain’s normal processing of sensory information and cognitive functions.
Long-Term Brain Adaptations and Health
Prolonged misuse of DXM can lead to long-term health concerns. Tolerance may develop, requiring higher doses for the same effects. This can progress to psychological dependence, a compulsive urge to use DXM despite negative consequences. Cessation of use can trigger withdrawal symptoms, including anxiety, restlessness, insomnia, depression, and cravings.
Chronic high-dose DXM use may result in persistent cognitive deficits, including impaired memory, learning difficulties, and attention problems. Studies suggest the prefrontal cortex (decision-making, impulse control) and hippocampus (memory, learning) can be particularly affected. The controversial “Olney’s lesions” refer to brain damage in animal models exposed to high quantities of NMDA receptor antagonists. While it’s not definitively clear if long-term high-dose DXM use causes these specific lesions in humans, concerns about potential brain damage persist. Prolonged misuse also increases the risk of developing or exacerbating mental health conditions like psychosis, depression, or anxiety disorders; some users experience persistent psychotic symptoms. The full extent of these long-term effects remains an active area of investigation.