Are there any long term effects associated with the daily use of 50mg diphenhydramine?

Short term use is ok: Long term use of drugs, even over-the-counter ones, should be under a doctor's supervision. Benadryl (diphenhydramine) 50mg a day is ok for a few weeks in an average adult. It can lose its effectiveness when used long term. In older folks, it can lead to slower thinking, dizziness, and perhaps blood pressure changes. Since Benadryl has sedating effects, alcohol & other sedatives should be avoided.

Maybe: Diphenhydramine has been around for a long time and is very safe. However, you should be aware of a few things. First, driving with it in your system is a DUI in many states. Second, chronic use at night can reduce your sleep quality even though it makes you drowsy. Third, even if you do not feel it is making you sleepy, it can slow your thinking and reflexes.