The antihistamines operate by blocking histamine receptors (see Section
10.1 for an explanation of receptors). Peripherally, this has the effect of
reducing the symptoms of histamine activity (stuffy and runny nose, itchy
eyes, hives, rashes, etc.) associated with infections and allergies. In the
brain, histamine is partially responsible for wakefulness, and
antihistamines that cross the blood-brain barrier will cause sleepiness. In
fact, most OTC “sleeping pills” in the USA are really just antihistamines
(although melatonin is making inroads as an alternative). There are
antihistamines that do not cross the blood-brain barrier (e.g., SeldaneTM)
but these are prescription in the USA.

High doses of antihistamines can result in dizziness, impairment of
concentration, extreme sedation (or, paradoxically, insomnia), headache,
heart palpitations, dry mouth, gastric discomfort, delusions, and
abnormally high blood pressure. Doses of 30-60mg/kg have been fatal in very
young children; most adults, however, are very unlikely to overdose on
antihistamines. Death, when it does occur, is from cardiovascular collapse
or respiratory arrest (8). High doses of prescription antihistamines are
much more dangerous; do not mix DXM with prescription antihistamines!

The danger of an antihistamine overdose is very low when using a
DXM-containing product recreationally. However, you will most likely
experience some unpleasant symptoms, such as sleepiness, dry mouth, heart
palpitations, etc. These side effects increase as the dosage increases. A
very small amount of antihistamines might be useful in preventing
DXM-induced histamine release.

Conclusion: Traditional antihistamines may be suitable for first and second
plateau dosage levels, but should not be used at the upper plateaus. NEVER
use DXM with prescription, non-drowsy antihistamines!

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