Editor’s Note: This post was written by Lucas Richert and Erika Dyck, and was originally published on The 2×2 Project, an online journal from Columbia University’s Department of Epidemiology.

In February 2014, Scientific American surprised readers with an editorial that called for an end to the ban on psychedelic drug research and criticized drug regulators for limiting access to such psychedelic drugs as LSD (Lysergic acid-diethylamide), ecstasy (MDMA), and psilocybin.

A few months later, Science further described how scientists are rediscovering these drugs as legitimate treatments as well as tools of investigation. “More and more researchers are turning back to psychedelics” to treat depression, obsessive-compulsive disorder, various addictions, and other categories of mental illness.

Historians of medicine and drugs have long held a view that psychoactive substances conform to cyclical patterns involving intense periods of enthusiasm, therapeutic optimism, critical appraisals, and finally limited use. The duration of this cycle has varied, but this historical model suggests psychedelics are due for a comeback tour. It was just a matter of time.

A PROBLEM CHILD

While treating patients with psychedelic drugs may seem bizarre, in the 1950s and 1960s expectations were “high” (ho ho, apologies). Dr. Albert Hofmann’s discovery of LSD in 1943 drew attention from multiple fields, including psychiatry and psychotherapy Ultimately, “doctors and scientists embraced LSD,” writes Science correspondent Kai Kupferschmidt. By the mid-1960s, the biomedical community had published over 1,000 academic papers on the subject, and researchers reported positive results, if not major breakthroughs, in treating anxiety, depression, and obsessive compulsive behavior.

But just as this was happening, LSD and other psychoactive substances took on a public image as the drug of counter-cultural and anti-authority ideas, associated with the visceral images of the Charles Manson murders and hedonism of the late 1960s. Recreational abuse, in short, helped scuttle research. In 1968, amid widespread disagreement within the scientific and research community over the potential therapeutic applications of LSD, the U.S. government regulated it out of legal territory altogether.

Dr. Hofmann could only shake his head. In his 1980 book, LSD My Problem Child: Reflections on Sacred Drugs, Mysticism, and Science, he captured the mixture of initial excitement of discovery and the gut-wrenching disappointment of seeing his “child’s” potential wasted.

(Dr. Albert Hofmann, who discovered LSD)

THE RETURN

Before Dr. Hofmann passed away at the age of 102 in 2008, he expressed some pleasure that doctors were studying his so-called problem child again. His native Switzerland, had, a year earlier approved the first LSD investigation in nearly four decades. The next year, the U.S. Food and Drug Administration joined the Swiss regulators in accepting protocols to study whether LSD could be used to treat anxiety.

According to Dr. Peter Gasser, head of the Swiss Medical Society for Psycholytic Therapy, Dr. Hofmann’s final wish had come to pass with this development. He presented his findings (as yet unpublished) in April 2013 at the Mind and Medicine Psychedelic Conference in Oakland, California. He called the paper, which was warmly received, “LSD-Assisted Psychotherapy in the Treatment of Anxiety Secondary to Life Threatening Illness.”

Dr. Gasser’s research—and, indeed, LSD’s resurgence—has various causes. Such organizations as the Multidisciplinary Association for Psychedelic Studies and the Heffter Research Institute have formed partnerships with labs based in the U.S. as well as Switzerland; thus psychoactive drugs have stronger institutional champions. The subsequent advance of the psychedelic research agenda can also be partially explained by a change in personnel at the FDA to a newer generation of regulators, according to Dr. David Nichols an emeritus professor of pharmacology at Purdue University and a cofounder of the Heffter Research Institute.. “The psychedelic revival” as Andrew Brown, writing in The Spectator calls it, has become far removed from the “wackier end of the pro-LSD lobby.”

A FULL-BLOWN COMEBACK?

Yet, for all the progress that LSD has made in the past decade, there have been no major scientific breakthroughs and no marketable prescription drugs. Meanwhile the scientific community and regulatory authorities are still divided over bringing LSD back as a therapeutic tool.

A segment of the press and scientific community have even challenged the “comeback” narrative. Gains have been slow and LSD is still considered by many researchers to be a dirty drug–that is, imprecise compared to other psychedelics. Similarly, in a very recent study based in the Czech Republic, even for those researchers who support the drug there was lack of agreement about whether it was possible to totally eliminate potential harm to a patient during the LSD experience.

Still, researchers are now examining LSD as a treatment for alcoholism, post-traumatic stress disorder, cluster headaches, and as a supplement to palliative care. In the field of neuroscience, researchers have initiated brain studies that explore how LSD “modulates neural circuits that have been implicated in mood affective disorders, and can reduce clinical symptoms of these disorders. Even more intriguing, a couple of neuropsychopharmacology researchers at the University of Zurich speculate in a Nature Reviews Neuroscience article that a drug-induced transcendent peak (or mystical experience) and its integration in the psychotherapeutic process might be the “crucial mechanism that enables neuroplasticity and behavioral changes.”

Dr. Hofmann’s problem child, then, has come back and, while the study of LSD remains somewhat contentious, it ought to be considered in a new context. As turbulent teen? Perhaps in mid-life crisis? If nothing else, according to Nicolas Langlitz in his book Neuropsychedelia: The Revival of Hallucinogen Research since the Decade of the Brain, LSD has matured, and has moved “from wonder and shame to inquiry.”