Detecting ancient ayahuasca, a traditional Amazonian hallucinogenic drink made from Banisteriopsis caapi liana and other plants, faces multiple challenges despite advanced analytical techniques. Harmine and harmaline found in Andean archaeological sites have led some to suggest Banisteriopsis was used as early as 500 CE. However, archaeological, ethnobotanical, biochemical, and analytical chemistry considerations make the true origins of these alkaloids in mummies and artifacts uncertain. The evidence does not convincingly prove ancient ayahuasca use.
Italy conducted the most clinical studies on psilocybin and lysergic acid amide (LSA) in the twentieth century, and humans first received a high dose of 500 mcg of lysergic acid diethylamide (LSD) there. The most successful Italian studies used psilocybin intravenously at 3 mg every second or third day, alternated with placebo, to treat depressive states. LSD and psilocybin also showed promise for treating neurosis. Italian psychiatrists contributed to theoretical debates on the psychotomimetic paradigm and the distinction between primary and secondary effects of psychedelics.