Fifteen novel dimeric amide alkaloids possessing a cyclohexene ring, nigramides A−O (1−15), as well as four novel dimeric amide alkaloids possessing a cyclobutane ring, nigramides P−S (17−20), have been isolated from the roots of Piper nigrum. Their structures were elucidated on the basis of their spectroscopic data. The biosynthestic hypothesis of nigramides A−O (1−15) was proposed by an intermolecular Diels−Alder reaction from the corresponding monomeric amides. On the basis of this biosynthetic hypothesis, the first study of the thermal and Lewis acid mediated Diels−Alder reactions of piperine in different organic solvents and under solventless conditions is also described.