At doses much higher than medically recommended, dextromethorphan and its major metabolite, dextrorphan, acts as an NMDA receptor antagonist, which produces dissociative hallucinogenic states somewhat similar to ketamine and phencyclidine.It may produce distortions of the visual field – feelings of dissociation, distorted bodily perception, excitement, and a loss of sense of time. Some users report stimulant-like euphoria, particularly in response to music. Dextromethorphan usually provides its recreational effects in a non-linear fashion, so that they are experienced in significantly varied stages. These stages are commonly referred to as "plateaus". These plateaus are numbered from one to four, with the first having the mildest effects to fourth being the most intense. Each plateau is said to come with different related effects and experiences.The first plateau is said to induce music euphoria and mild stimulation, likened to that of MDMA. The second plateau is likened to the state of being drunk and high at the same time, featuring euphoria, sedation and minor hallucinations. The third plateau induces a significant dissociative state which can often cause anxiety in users. Reaching the fourth plateau is said to cause extreme sedation and a significant hallucinatory state as well as complete dissociation from reality. Teens tend to have a higher likelihood to use dextromethorphan-related drugs as they are easier to access, and an easier way to cope with psychiatric disorders.
Pharmacology
Pharmacodynamics
Dextromethorphan has been found to possess the following actions (<1 μM) using rat tissues:
Uncompetitive antagonist of the NMDA receptor via the MK-801/PCP site
SERT and NET blocker (cf. serotonin–norepinephrine reuptake inhibitor)
Sigma σ1 receptor agonist
Negative allosteric modulator of nicotinic acetylcholine receptors
Ligand of the serotonin 5-HT1B/1D, histamine H1, α2-adrenergic, and muscarinic acetylcholine receptorsDextromethorphan is a prodrug of dextrorphan, which is the actual mediator of most of its dissociative effects through acting as a more potent NMDA receptor antagonist than dextromethorphan itself. What role, if any, (+)-3-methoxymorphinan, dextromethorphans other major metabolite, plays in its effects is not entirely clear. Pharmacokinetics
Following oral administration, dextromethorphan is rapidly absorbed from the gastrointestinal tract, where it enters the bloodstream and crosses the blood–brain barrier.At therapeutic doses, dextromethorphan acts centrally (meaning that it acts on the brain) as opposed to locally (on the respiratory tract). It elevates the threshold for coughing, without inhibiting ciliary activity. Dextromethorphan is rapidly absorbed from the gastrointestinal tract and converted into the active metabolite dextrorphan in the liver by the cytochrome P450 enzyme CYP2D6. The average dose necessary for effective antitussive therapy is between 10 and 45 mg, depending on the individual. The International Society for the Study of Cough recommends "an adequate first dose of medication is 60 mg in the adult and repeat dosing should be infrequent rather than qds recommended. "Dextromethorphan has an elimination half-life of approximately 4 hours in individuals with an extensive metabolizer phenotype; this is increased to approximately 13 hours when dextromethorphan is given in combination with quinidine.