Psychedelics are back! As readers of Scientific American know, scientists have recently reported that psychedelics show promise for treating disorders such as depression, post-traumatic stress disorder, and anxiety in terminal cancer patients. This weekend, researchers and other enthusiasts are gathering in New York City for a two-day celebration, "Horizons: Perspectives on Psychedelics," sponsored by the Multidisciplinary Association for Psychedelic Studies, or MAPS, along with other groups.

Overall, I'm thrilled by the psychedelic revival. I've had good trips, which gave me first-hand evidence of the drugs' therapeutic potential. But like many other people I've also had bad trips, which left me feeling alienated from, rather than blissfully connected to, the world. In fact, it's worth recalling that the godfather of psychedelic research—the chemist Albert Hofmann, whom I interviewed before his death in 2008—occasionally harbored doubts about these potent drugs.

In 1943, when war wracked the world, Hofmann was in Basel, Switzerland, working for the pharmaceutical company Sandoz. On April 16, he was investigating a compound related to ergot, a toxic extract of a fungus that infects grain-producing plants. Hofmann hoped that the ergot compound, which he had originally synthesized five years earlier, might have potential for stimulating blood circulation.

During his experiments, Hofmann was overcome by what he recalled later as "remarkable restlessness, combined with a slight dizziness." He guessed that he had absorbed the ergot compound through his skin. Three days later, to test his theory, he dissolved what he thought would be an extremely small dose of the chemical—250 millionths of a gram, or micrograms—in a glass of water and drank it. Within 40 minutes Hofmann felt so disoriented that he rode his bicycle home.

When he arrived at his house he spotted a female neighbor, who looked like a "malevolent, insidious witch with a colored mask." Inside his house "furniture assumed grotesque, threatening forms." Hofmann feared he was losing his mind or even dying. He was tormented by the thought that his wife and three children would never understand "that I had not experimented thoughtlessly, irresponsibly, but rather with the utmost caution."

Gradually, "the horror softened and gave way to a feeling of good fortune and gratitude." This sense of well-being persisted through the following morning. When Hofmann walked out into his garden after a rainfall, "everything glistened and sparkled in a fresh new light. The world was as if newly created."

Thus did Hofmann discover the psychotropic properties of lysergic acid diethylamide, LSD. Hofmann's psychedelic research continued. In the late 1950s he showed that psilocybin and psilocin are the primary active ingredients of Psilocybe cubensis, a "magic" mushroom consumed as a sacrament by Indians in Central and South America.

I met Hofmann in 1999 in Basel at a conference on altered states of consciousness—including drug-induced states—at which Hofmann received a prize. We spoke in a lounge of the ultramodern conference center as speakers and guests milled around us. Then 93, Hofmann was a stooped, white-haired man, in coat and tie. He spoke in halting, thickly accented English, but he energetically defended his legacy.

Hofmann blamed Timothy Leary, the renegade Harvard psychologist turned psychedelic guru, for the backlash against LSD and other psychedelics in the 1960s. "You should not tell everybody, even the children, 'Take LSD! Take LSD!'" Hofmann said. Young people "are still in growth, and it is a very dangerous stage."

LSD is "very, very potent," Hofmann acknowledged, "and everything that is potent is dangerous." If used improperly, LSD "can hurt you, it can disturb you, it can make you crazy." But Hofmann believed that scientists and psychiatrists should be allowed to investigate LSD's effects and prescribe it in a safe, controlled fashion. "I don't want to promote absolute freedom," Hofmann said, "but the medical professions should have access to it."

Although it can harm people by provoking reckless or suicidal behavior, LSD is neither toxic nor addictive, Hofmann said; it has never killed anyone by overdose. Used with respect, it has enormous potential as a tool for investigating human consciousness and as an adjunct for psychotherapy. Psychedelics can also stimulate the "inborn faculty of visionary experience" that we all possess as children but lose as we mature. Hofmann hoped that in the future people would be able to take psychedelic drugs in "meditation centers" to awaken their religious awe.

Although Hofmann was not conventionally religious, he believed in God. "I am absolutely convinced," he said, "by feeling and by knowledge—my knowledge as a natural scientist—that there must be a creative spirit, an intelligence, which is the reason for what we have." Everything that exists, Hofmann said, pounding the table between us with his fist, is a manifestation of this plan. "It is impossible to have this without a plan," he insisted. "Otherwise you have only material, material, material!"

Hofmann had had frightening psychedelic experiences, including the early stages of his first LSD trip in 1943, but they usually yielded to more positive emotions. Hofmann's worst trip occurred on a psilocybin trip, when he hallucinated that he was wandering all alone deep inside Earth. "I had the feeling of absolute loneliness," he said. "A terrible feeling!" When he emerged from this nightmare and found himself with his companions again, he felt ecstatic. "I had feeling of being reborn! To see now again! And see what wonderful life we have here!"

Yet in his memoir LSD: My Problem Child (McGraw-Hill, 1980), Hofmann acknowledged that some of the young drug-users who had appeared at his doorstep over the years seemed terribly disturbed. He confessed that he sometimes had misgivings about having brought LSD into the world and helping to popularize psilocybin. He compared his discoveries with that of nuclear fission; just as fission threatens our fundamental physical integrity, so do psychedelics "attack the spiritual center of the personality, the self." Psychedelics, he feared, might "represent a forbidden transgression of limits."

Hofmann also worried about psychedelics' metaphysical implications. The fact that minute amounts of a chemical such as LSD can have such profound effects on our perceptions, thoughts and beliefs suggests that free will, which supposedly gives us the power to shape our destiny, might be an illusion; moreover, our deepest spiritual convictions may be nothing more than fluctuations in brain chemistry. To emphasize this point, Hofmann quoted from an essay that stated: "God is a substance, a drug!"

In other words, psychedelics can undermine as well as promote spiritual faith, and they can shatter as well as heal our psyches. We should keep these risks in mind as the psychedelic renaissance continues.

Uncredited photograph of Albert Hofmann from GEARFUSE