Table 1.

Drug classification and main characteristics of misuse of the selected OTC drugs.

Drug/drug classification	Administration path	Mechanism of action	Effects	Does it cause dependence?	Street names and brand names
Chlorpheniramine (antihistamine)	Oral	• Chlorpheniramine acts primarily as a potent H1 antihistamine drug • Moderate anticholinergic activity • Chlorpheniramine has been found to act as a serotonin reuptake inhibitor	• ACUTE EFFECTS: psychiatric effects: (i) sedating and anxiolytic properties; (ii) its abuse has been related to pleasurable feelings such as euphoria and stimulating effects; (iii) it may be associated with psychotic symptoms in predisposed individuals (e.g., people with mental illnesses or individuals concomitantly abusing other drugs) • CHRONIC EFFECTS: dependence	• Drug dependence is recorded after long-term use • Withdrawal symptoms, including excessive irritability, anger outbursts, insomnia, sweating, and craving	“Triple c” refers to Coricidin® cough and cold tablets; the combination of codeine, methyl ephedrine chlorpheniramine, and caffeine is marketed as Bron® Panadol® is a combination of chlorpheniramine, paracetamol and pseudoephedrine; Advil® includes ibuprofen, chlorpheniramine and phenylephrine; other brand names: Polaramine®, Chlortrimeton®
Codeine (opioid)	Oral, IV	• It is a selective agonist of the mu-opioid receptor; it is a natural isomer of methylated morphine, requiring metabolic activation by O-demethylation to morphine by CYP2D6	• ACUTE EFFECTS: psychiatric effects: euphoria, elation, analgesia, calmness; physical effects: respiratory depression, extreme somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, and sometimes bradycardia and hypotension. The triad of coma, pinpoint pupils, and respiratory depression is strongly suggestive of opiate poisoning. In severe overdosage, death may occur • CHRONIC EFFECTS: dependence	• Codeine has an identified abuse liability potential, given its effect and development of tolerance within a short timeframe on regular or excessive use • Codeine-dependence was here recorded, and associated with daily use of codeine	Street names: “Captain Cody,” “Cody,” “Little C,” “Schoolboy,” “Doors & Fours.” Common brand names for codeine and codeine containing combinations: Aspalgin® for aspirin and codeine; Nurofen Plus® for ibuprofen and codeine; Panadeine Forte® for paracetamol and codeine
Dextromethorphan (DXM) (non-competitive NMDA receptor antagonist and sigma 1 agonist antitussive)	Oral; IV and IN use also recorded in misuse cases	• At high doses, acting as a NMDA receptor antagonist, DXM and its potent metabolite dextrorphan inhibit the excitatory amino acid and neurotransmitter glutamate, causing hallucinogenic and dissociative states • DXM also exhibits binding activity at serotonergic receptors	• Neurobehavioural effects begin within 30–60 min of ingestion and persist for approximately 6 h • They are dose-related, starting from a mild to moderate stimulation with restlessness and euphoria (100–200 mg), to a state characterized by hallucinations, paranoia, perceptual distortions, delusional beliefs, ataxia, and out-of-body experiences (>1,000 mg) • ACUTE EFFECTS: (i) psychiatric effects: euphoria, altered mental status, mania, mood lability, irritability, dysphoria, insomnia; (ii) physical effects: tachycardia, hypertension, vomiting, mydriasis, diaphoresis, nystagmus, dystonia, loss of motor coordination; • CHRONIC EFFECTS: (i) toxic psychosis and cognitive deterioration; (ii) folate deficiency and neuropathy; (iii) since DXM is produced as the crystalline hydrobromide salt, bromism is a rare consequence that has been identified in heavy chronic abusers of DXM (neurotoxic effects, resulting in somnolence, psychosis, seizures, and delirium	• Although DXM is not thought to have addictive properties, its chronic use might determine addiction due to GABAergic/antiglutamatergic mechanisms, including substance-taking compulsive behaviors, tolerance, and autonomic withdrawal symptoms • EMCDDA: regarded as NPS	Street names: “Bromage,” “Brome,” “Candy,” “Dex,” “Dextro,” “DM,” “Drex,” “DXM,” “Red Devils,” “Robo,” “Rojo,” “Skittles,” “Triple C,” “Tussin,” “Velvet,” and “Vitamin D,” “Poor Man's Ecstasy”; the practice of using large amounts of DXM to achieve psychoactive effects is known as “robotrippin.” Common brand names are: Balminil DM®, Benylin DM®, Bronchophan®, Buckleys D®, Calylin #1, Delsym®, Koffex DM®, Novahistex DM®, Robitussin®
Diphenhydramine (DPH) (antihistamine moiety of dimenhydrinate/DH)	Oral; IV and IN use also recorded in misuse cases	• It is a first generation H1-antihistamine • Diphenhydramine also acts as a potent anticholinergic agent • It can acutely block the cell membrane pump mechanism of central 5-hydroxytryptophane and peripheral noradrenaline neurons	• ACUTE EFFECTS: (i) psychiatric effects: euphoria, altered mental status, hallucinations, and/or psychosis; (ii) physical effects: tachycardia, xerostomia, mydriasis, blurred vision, ileus, urinary retention, CNS depression, agitation, and hyperactivity • CHRONIC EFFECTS: dependence	• Reported cases of DPH dependence have resulted from usage of large doses (often over 1,000 mg per day) over periods of months or years. Withdrawal symptoms include craving, worsening of insomnia, rhinorrhoea, nausea, irritability, restlessness, abdominal cramps, sweating, and diarrhea. Gradual tapering has been the only described detoxification treatment plan	Different brand names, including Benadryl®, Dimedrol®, Daedalon®, Sominex®, Unisom® and Nytol®
Promethazine (antihistamine)	Oral	• It is a phenothiazine derivative and a H1 receptor antagonist; It also acts as a direct antagonist at muscarinic (M1) and dopamine (D2) receptors. It is classified as a first-generation antihistamine molecule which easily penetrates the blood-brain barrier and is associated with adverse effects such as sedation	• ACUTE EFFECTS: from mild sedation and CNS depression to profound hypotension, respiratory depression, unconsciousness, and sudden death; overdosage might determine an antimuscarinic delirium, agitation and neuroleptic malignant syndrome • it can be used to enhance effects of other co-ingested substances, e.g., opioids • CHRONIC EFFECTS: NR	• EMCDDA: regarded as NPS • Dependence might develop after long-term use of promethazine cough mixtures (containing opioids)	Promethazine mixed with a soft drink and/or alcohol is known as “purple drank,” “lean,” “syzzurp,” “Texas tea”; Phenergan® and Phenadoz® are common brand names
Pseudoephedrine (decongestant)	Oral; IV use also recorded in misuse cases	• Sympathomimetic properties, exerting a stimulating action on alpha, beta1-, and beta2-adrenergic receptors	• ACUTE EFFECTS: stimulant effects, e.g., euphoria, insomnia, diminished sense of fatigue, anorexia, and accelerated thinking; psychotic symptoms with auditory and visual hallucinations, persecutory delusions, fear, disorganized behavior might develop after high-dose consumption • CHRONIC EFFECTS: dependence	• Dependence might be developed after long-term use • Withdrawal symptoms include: dysphoria, restlessness, abnormal perceptions • Due to the possibility to be used to manufacture the class A controlled drug methylamphetamine, restrictions have been in place in the UK to manage the risk of products containing pseudoephedrine and ephedrine; in the US, a prescription is not needed in most States, and in remaining States there are limits on how much an adult subject can buy each month	“Chalk,” “Crank,” “Meth,” “Speed”; ‘Russian Cocktail' includes pseudoephedrine consumed together with potassium permanganate and acetylsalicylic acid diluted in water; common brand names: Sudafed®, Nexafed®, Zephrex-D® Claritin® includes pseudoephedrine and loratadine

CNS, central nervous system; DH, Dimenhydrinate; DPH, Diphenhydramine; EMCDDA, European Monitoring Centre for Drugs and Drug Addiction; GABA, Gamma-Amino-Butyric Acid; H, Histamine; IN, Intranasal; IV, Intravenous; NMDA, N-Methyl-D-Aspartate; NPS, New Psychoactive Substance; OTC, Over-The-Counter; 5-HT, Serotonin.