Cough syrup can cause intoxication, though the resulting state is chemically distinct from being “drunk” on alcohol. This effect occurs when over-the-counter cold and cough products are consumed in doses far exceeding therapeutic recommendations. Misusing these medications for their psychoactive properties has become a serious public health concern, particularly among adolescents due to product accessibility. This intoxication is characterized by a dissociative experience rather than the sedative effects typically associated with ethanol.
The Role of Dextromethorphan (DXM)
The primary agent responsible for the intoxicating effects of many over-the-counter cough syrups is Dextromethorphan (DXM), a cough suppressant. At standard therapeutic doses, DXM acts centrally on the brain to elevate the threshold for coughing, effectively interrupting the cough reflex. It is widely available in various formulations, including liquids, gel capsules, and lozenges, contributing to its accessibility for misuse. The effects of DXM are not solely due to the parent drug, but also its active metabolite, dextrorphan.
Once ingested, DXM is rapidly absorbed from the gastrointestinal tract and processed by the liver. A specific liver enzyme, cytochrome P450 2D6 (CYP2D6), converts DXM into the psychoactive compound dextrorphan. The speed and efficiency of this metabolic conversion vary significantly among individuals due to genetic polymorphisms of the CYP2D6 gene.
Individuals are categorized as “extensive metabolizers” or “poor metabolizers” based on their CYP2D6 activity. Extensive metabolizers process DXM quickly, leading to a shorter duration of effect. Poor metabolizers break down the drug much slower, extending the half-life of DXM from a few hours to over a day. This variability means the same dose can produce widely different levels of intoxication and toxicity, making recreational dosing highly unpredictable and dangerous.
DXM’s Mechanism of Action in the Brain
At recreational doses, DXM transitions from a simple cough suppressant to a psychoactive substance with multiple targets in the central nervous system. The primary mechanism underlying its intoxicating and hallucinogenic effects is its action as a non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor. The NMDA receptor is a subtype of glutamate receptor, which plays a role in regulating synaptic plasticity, memory function, and consciousness.
By blocking the NMDA receptor, DXM and its metabolite dextrorphan disrupt the normal flow of excitatory signals in the brain, leading to the subjective feeling of detachment from reality. DXM is classified as a dissociative anesthetic, sharing pharmacological similarities with substances like ketamine and phencyclidine (PCP). The interruption of sensory and cognitive processing results in altered perceptions of time, space, and body awareness.
Beyond its primary action at the NMDA receptor, DXM also exhibits other significant pharmacological properties. It acts as a sigma-1 receptor agonist, which contributes to its overall psychological effects. Furthermore, DXM functions as a serotonin and norepinephrine reuptake inhibitor (SNRI), meaning it increases the concentration of these neurotransmitters in the synaptic cleft. This additional mechanism of action heightens the risk of developing Serotonin Syndrome, particularly if DXM is combined with other serotonergic drugs.
The Dissociative Experience and Dosage Levels
The experience of DXM intoxication is highly dose-dependent, often described in terms of distinct “plateaus” representing increasing levels of dissociation.
- First plateau (100 to 200 mg): Characterized by mild stimulation and an uplift in mood. Users may feel more talkative and experience mild euphoria.
- Second plateau (200 to 400 mg): Introduces a state similar to severe alcohol intoxication combined with minor hallucinogenic effects. Effects include euphoria, mild visual or auditory hallucinations, slurred speech, and impaired mobility.
- Third plateau (400 to 600 mg): Involves a profound shift toward dissociation. Users report feeling disconnected from their bodies and reality, similar to the effects of ketamine, alongside intense hallucinations and significant loss of motor coordination.
- Fourth plateau (Exceeding 500 mg): Characterized by extreme sedation, delirium, and a complete break from reality. This level can induce out-of-body experiences and a near-total reduction of pain perception, carrying a severe risk of accidental injury and overdose.
Hidden Dangers in Combination Formulas
A major and often lethal danger of misusing cough syrup comes not from the DXM itself, but from the other active ingredients commonly included in multi-symptom cold and flu formulas. These combination products are intended to treat multiple symptoms simultaneously, but they pose a significant threat when consumed in large quantities. The most common and dangerous additive is Acetaminophen (Paracetamol), included for its pain-relieving and fever-reducing properties.
Ingesting massive doses of acetaminophen in pursuit of a DXM high can quickly lead to acute liver failure. The liver-toxic dose of acetaminophen is easily reached when consuming the large volumes of cough syrup necessary to achieve a recreational DXM effect. This liver damage is often irreversible and can be fatal, making it the most common cause of death associated with cough medicine misuse.
Other combination ingredients also present serious health hazards. Many cold formulas contain sedating antihistamines, such as Diphenhydramine, which amplify the central nervous system depression caused by DXM. Furthermore, decongestants like Pseudoephedrine or Phenylephrine, which act as stimulants, can cause dangerously elevated blood pressure, heart palpitations, and cardiac arrhythmia.