Benadryl as a local anaesthetic

Last updated on 15 May 2025

What

I know right.

I just saw this on reddit that apparently you can use it as a local anaesthetic and had to know more, so here it is with a bit more evidence behind it.

Remind me about Benadryl

Sedating antihistamine used for allergies and insomnia
H1 Histamine antagonist that crosses blood brain barrier and has central effects
Anticholinergic as well, can cause anticholinergic syndrome at high doses
Also used to treat akathisia and parkinsonism caused by antipsychotics
40–60% bioavailability
98% protein bound
Metabolised by CYP2D6 (same as codeine) in the liver
Excreted in urine 94% and faeces 6%
Peak effect at around two hours, lasts around seven
Also has local anaesthetic properties, and can be used in patients who cannot have amine or ester anaesthetics

Side effects

Dry mouth
Tachycardia
Pupil dilatation
Urinary retention
Constipation
Delirium and hallucination if you take loads*

*Hence the ridiculous 'Benadryl challenge' on TikTok

So it's a local anaesthetic too?

Yeah apparently it blocks sodium channels much like it's -caine counterparts, and it's been used since 1939 in dental clinics and emergency departments around the world to good effect in patients who are or claim to be allergic to local anaesthetics.

Injecting 1% apparently diphenhydramine stings a bit more than lidocaine but then produces decent local anaesthesia within a few minutes for superficial dermatological procedures, and lasts up to three hours apparently.

Plus they won't get itchy...

Some have tried 5% solution but this caused significant tissue irritation for a few days afterwards, and a couple of times even resulted in tissue necrosis, so probably best to stick to 1% for now.

How to do it

Take 5% diphenhydramine
Dilute down to 1% (put 1ml in 4ml saline)
Inject subcut as much as you would lidocaine
That's it

Whether you decide to suddenly start using it is up to you - everything here is just for interest and information only - but it might be a useful option to consider if you're presented with a very high GA risk patient who says they're deadly allergic to lidocaine.

Another cool thing I learned

So apparently if you inject saline under the skin and create a visible wheal or bleb, then this has rather impressive local anaesthetic properties for small incisions.

The four ways subcut saline might work

Mechanical

The bleb compresses small nerve endings of unmyelinated C and Aδ fibres, and also pushes them away from the site of slicing
This dulls their sensation, causing mild mechanical hypoaesthesia

Washout

Injecting saline might wash away some of the pro-inflammatory pain mediators like histamine and bradykinin

Gate control theory

Like rubbing your knee when you hurt it, injecting saline might just stimulate all the other sensors in the area and distract you from the pain

Placebo

It's weird how powerful this effect is

It is theorised that this is why lidocaine appears to work immediately, when in reality its pharmacological data says you should wait a little before stabbing and slicing the poor patient.

I inject local anaesthetic before I draw up my spinal anaesthetic, to give it a chance to properly work

Also apparently normal saline inexplicably produces anaesthetic effects when used intrathecally, proving once again that this job his half science and half magic.