Edward Jessup is a psychopathologist who, while studying schizophrenia, begins to think that "our other states of consciousness are as real as our waking states." Edward begins experimenting with sensory deprivation using a flotation tank, aided by two like-minded researchers, Arthur Rosenberg and Mason Parrish. At a faculty party, he meets fellow "whiz kid" and biological anthropologist Emily, and the two eventually marry.
Seven years later, Edward and Emily have two daughters, are on the brink of divorce, and reunite with the couple who first introduced them. When Edward hears of a Mexican tribe that experiences shared illusion states, he travels to Mexico to participate in what is apparently an Ayahuasca Ceremony. During the walk into the bush, his guide says that the indigenous tribe they are meeting works with Amanita muscaria, which they are collecting for next year's ceremonies. The tribe calls one of the ingredients of the mixture they use "First Flower." An indigenous elder is seen with Banisteriopsis caapi root in his hand before cutting Edward's hand, adding blood to the mixture he is preparing. Immediately after consuming the mixture, Edward experiences bizarre, intense hallucinations. He returns to the U.S. with a tincture and continues taking it to trigger altered states of consciousness.
When toxic concentrations of the substance make increased dosage dangerous, Edward returns to sensory deprivation, believing it will enhance the effects of the substance at his current dose. Repairing a disused tank in a medical school, Edward uses it to experience a series of increasingly drastic visions, including one of early Hominidae. Monitored by his colleagues, Edward insists that his visions have "externalized". Emerging from the tank, his mouth bloody, frantically writing notes because he is unable to speak, Edward insists on being X-rayed before he "reconstitutes." A radiologist inspecting the X-rays says they belong to a gorilla.
In later experiments, Edward experiences actual, physical biological devolution. At one stage he emerges from the isolation tank as a feral and curiously small-statured, light-skinned caveman, going on a rampage through some streets in town before returning to his natural form. Despite his colleagues' concern, Edward stubbornly continues.
In the final experiment, Edward experiences a more profound regression, transforming into an amorphous mass of conscious, primordial matter. An energy wave released from the experiment stuns Edward's colleagues and destroys his tank. Emily arrives to find a swirling maelstrom where the tank had been. She searches the vortex for Edward, finding him as he is on the brink of becoming a non-physical form of proto-consciousness and possibly disappearing from our version of reality altogether.
His friends bring Edward home, hoping that the transformations will end. Watched over by Emily, Edward begins to uncontrollably regress again, the transformations no longer requiring the intake of "first flower" or sensory deprivation. Urging Edward to fight the change, Emily grabs his hand, immediately being enveloped by the primordial energy emanating from Edward. The sight of his wife apparently being consumed by the energy stirs the human consciousness in Edward's devolving form. He fights the transformation and returns to his human form. In the final scene, Edward embraces Emily, and she returns to normal.
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