When Shakespeare wrote about a "noted weed" he may have been referring to cannabis.
A study has shown clay pipes from Stratford-upon-Avon at the time contain traces of the drug.
There is no evidence Shakespeare took it but the discovery may explain the phrase, which appeared in his Sonnet 76.
South African researchers also found evidence of other hallucinogenic drugs and even cocaine.
Dr Francis Thackeray of the Transvaal Museum in Pretoria said: "We do not claim that any of the pipes belong to Shakespeare."