Like many other first generation antihistamines, is also a potent anticholinergic agent. This leads to profound drowsiness as a very common side-effect, along with the possibilities of motor impairment (ataxia) and tardive dyskinesia, dry mouth and throat, flushed skin, rapid or irregular heartbeat (tachycardia), blurred vision at nearpoint due to lack of accommodation (cycloplegia), abnormal sensitivity to bright light (photophobia), pupil dilatation (mydriasis), urinary retention (ischuria), constipation, difficulty concentrating, short-term memory loss, visual disturbances, hallucinations, confusion, erectile dysfunction, and delirium. Diphenhydramine also has local anesthetic properties, and has been used for patients allergic to common local anesthetics like lidocaine. [2]
It is known that diphenhydramine contains sedative properties. Many new antihistamines have been introduced without the side effect of sedation. The drug is also used as a sleep aid and is an ingredient in many sleep aids, such as Unisom gelcaps, and most notably Tylenol PM where it is combined with Acetaminophen (Paracetamol), and Sominex which has diphenhydramine as its only active ingredient.
Those who use diphenhydramine recreationally take a higher dose than recommended dose (usually between 100mg and 450mg) for its deliriant effects. The mental effects are described by many as "dreaming while awake" involving visual and auditory hallucinations which, unlike those experienced with most psychedelic drugs, often cannot be readily distinguished from reality. People who consume a high recreational dose can possibly find themselves in a hallucination which places them in a familiar situation with people and friends and rooms they know, while in reality being in a totally different setting. Inexperienced users of hallucinogens are liable to panic. Many users report a side effect profile consistent with tropane glycoalkaloidal poisoning. This is due to antagonism of muscarinic acetylcholine receptors in both the central and autonomic nervous system, inhibiting various signal transduction pathways. In the CNS, diphenhydramine readily crosses the blood-brain barrier, exerting effects within the visual and auditory cortex, accounting for reported visual and auditory disturbances.
Other CNS effects occur within the limbic system and hippocampus, causing confusion and temporary amnesia. Toxicology also manifests in the autonomic nervous system, primarily at the neuromuscular junction, resulting in ataxia and extrapyramidal side-effects, and at sympathetic post-ganglionic junctions, causing urinary retention, pupil dilation, tachycardia, irregular urination, and dry skin and mucous membranes. Considerable overdosage can lead to myocardial infarction (heart attack), serious ventricular dysrhythmias, coma and death. Such a side-effect profile is thought to give ethanolamine-class antihistamines a relatively low abuse liability. The specific antidote for diphenhydramine poisoning is physostigmine, usually given by IV in hospital.