Mixing Codeine (lean) and Diphenhydramine (Benadryl)
Unsafe
Each makes the other stronger, raising the risk of memory loss, collapse and unconsciousness. Avoid this combination. Keep naloxone nearby.
Both substances are CNS depressants, potentiating each other strongly and unpredictably, raising the chances of memory loss, severe ataxia, and unconsciousness. The interaction will cause greater inhibition and risk of injury. DPH reduces histamine release by opioids, which reduces the itching side effect from opioids. DPH may reduce the nausea caused by opioids. DPH inhibits CYP2D6 activity which can lead to a reduction of effects in some opioids and potentiation of effects in others.
This combination carries bodily risk and can go badly psychologically. The headspace part often arrives first and makes the physical part harder to notice.
Headspace vs physical riskWhat to do
- Say what was taken and how much.Responders need it, and in most US states Good Samaritan laws protect both of you from drug possession charges when you call for an overdose.
- Unresponsive: put them on their side, tilt the head back, and stay until help arrives.Never leave someone alone to “sleep it off”.
- Give naloxone (Narcan) if you have it.It is sold over the counter in every US state and does no harm if opioids turn out not to be involved.
- Never Use Alone 1-800-484-3731Stays on the line and sends help if you stop responding.
- Full steps: what to do if it is already happeningOverdose signs, the recovery position, what to say on the call, and whether you can be charged for making it.
- Poison Control 1-800-222-1222Free and 24/7, for “is this bad?” before it becomes an emergency.
Can you mix Codeine (lean) and Diphenhydramine (Benadryl)?
MixSafe rates mixing Codeine and Diphenhydramine as "Unsafe" — risk of serious physical or psychological harm. Not recommended under any circumstances. No interaction specific to Codeine and Diphenhydramine is documented; this is the default for Opioids. Source: TripSit drug combination chart, retrieved 2026-08-20. Educational information, not medical advice.
This is a class-level answer, inherited from Opioids. Nothing specific to this exact pair is documented, so treat it as the default for the class rather than a measurement of these two drugs together.
- Codeine
- Weak, but metabolised unpredictably between people
- Codeine also called
- lean, purple drank, co-codamol, dihydrocodeine
- Diphenhydramine also called
- benadryl, dph, sleep aid, zzzquil, unisom, doxylamine
TripSit drug combination chart, retrieved 2026-08-20. View the dataset.
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Rated unsafe. Educational information only, not medical advice. Absence of a documented interaction is not evidence of safety.