A Long, Strange Trip

As medical marijuana gains acceptance across the country, one scientist thinks LSD should be next.

Long before he was a scientist, long before he wrote more than 100 journal articles, held six patents, or became an investigator for the NIH's Alzheimer's Disease Research center, Juan Sanchez-Ramos was an acid-dropping street artist. He had come to Paris in 1967 from Venezuela, intent on soaking up all the jazz and culture the city had to offer. His father, his two uncles, and his older brother were all doctors, and Sanchez-Ramos was expected to follow the family blueprint. Instead, he chose art. When student riots in Paris shut down his school and his father cut off his funds, a defiant Sanchez-Ramos decided to stay, hawking tourist portraits across Europe for pocket money and immersing himself in the psychedelic counterculture of the era. That's when he took his first hit of LSD.

For Sanchez-Ramos, dropping acid was an intensely intellectual experience. He was fascinated by the vivid Technicolor hallucinations, warped perception of time and space, and the temporary dismantling of the ego. "You see the relationship between time and matter, body and soul," he recalls. But what intrigued him most was his brain's chemistry. "I was extremely curious about how the brain generated consciousness, how images occur in [the visual system of] the brain," he says.

Since casual experimentation wouldn't answer his questions, he grasped for the science. As others of his generation "turned on, tuned in, and dropped out," Sanchez-Ramos's mind-altered state inspired him to drop into graduate school in pharmacology, landing him right back on the academic track his parents had wished for him.

Today, Sanchez-Ramos is a clinical neurologist who's been studying neurodegenerative disorders for more than 30 years. Slim and youthful, his dark hair streaked with gray, you can still see hints of the Latin playboy he once was. He delights in regaling visitors with tales of his youthful adventures. And he brings the same exuberance to his work.

Although research on psychedelics still hovers on the fringe of social acceptance, Sanchez-Ramos has never yielded to popular sentiment. Instead, the artist-turned-scientist has aggressively pushed for the study of illegal drugs, hopping to force regulatory agencies to acknowledge the the million suffering from neurodegenerative diseases deserve every chance at a cure. "Our whole drug policy is fundamentally mistaken in that it tries to ascribe good or bad qualities to the drugs themselves and ignores the relationship people have with these drugs," says Rick Doblin, one of Sanchez-Ramos's colleagues and the founder of the Multidisciplinary Association for Psychedelic Studies. It's not the drug that matters -it's how it's used.

BORN IN A LAB IN 1938, LSD was first prescribed in the 1950s to treat psychiatric disorders. Doctors became interested in LSD because of its chemical similarity to serotonin, one of the neurotransmitters linked to anxiety and depression. Serotonin molecules work by pairing with receptors in the brain to regulate mood. But when LSD bonds to those same receptors, it disrupts the tightly-controlled communications system.

"LSD is like a chemical microscope that allows you to amplify signals that don't  normally come into everyday consciousness," Sanchez-Ramos explains. Initially, doctors and academics were incredibly optimistic about LSD's clinical value. Between 1950 and 1965, more than 1,000 research papers were published on the therapeutic benefits of LSD. A California radiologist named Herman Hartman teamed up with psychiatrist Arthur Chandler to set up the Psychiatric Institute of Beverly Hills, charging $100 a pop for acid-augmented sessions. At its peak, treatment rooms were crowded with Hollywood luminaries like Cary Grant and Esther Williams. Canadian scientists were equally enamored with the drug. In the late 1950s, researchers gave LSD to World War II veterans who were chronic alcoholics; when they followed up one year later, they found that a staggering 55 percent were still sober.

But as people began experimenting outside the lab and LSD entered the mainstream, a culture war ignited. Stories of horrific trips, temporary psychosis, and flashbacks became commonplace. Hysteria was further stoked by the antics of Timothy Leary, a Harvard psychology professor who was fired in 1963 for his experiments with psychedelics. As the government clamped down, the lingering stigma associated with LSD would hamper its scientific study for the next 40 years.

Today, it isn't just LSD that Sanchez-Ramos is interested in. He believe its siblings-  3,4-methylenedioxymethamphetamine (ecstasy); psilocybin (magic mushrooms); mescaline (peyote); and dimethyltryptamine (ayahuasca) -hold untapped medical benefits. As he told the New York Times, "You have to take this out of the realm of mythology. A drug that is taboo may be extremely useful. But if it's taboo, you'll never find out."

Currently, most psychedelics are illegal, classified by the U.S. Drug Enforcement Agency as Schedule I substances with "no medicinal value." This makes getting federal funding and the drugs needed for trial studies virtually impossible. But through the efforts of a handful of scientists -including Sanchez-Ramos- research into psychedelics is experiencing a budding renaissance. Today, a growing number of labs all over the world are exploring the use of such drugs to treat tough-to-combat diseases like cluster headaches, alcoholism, post traumatic stress disorder, depression, and anxiety. But Sanchez-Ramos is primarily concerned with a different pathology.

WHEN SANCHEZ-RAMOS began his graduate studies in neuropharmacology at the University of Chicago, opportunities to analyze LSD's effects on the brain in a scientific setting were few and far between. Instead, he focused his attentions on opiates and addiction.

In 1982, there were several cases of drug addicts who had injected a street drug called China White, a contaminated homemade form of the high-dosage pain medication Demerol. The addicts showed signs of early-onset Parkinson's disease. This fascinated Sanchez-Ramos. The culprit, it seems, was a chemical compound in the concoction that destroys dopamine neurons in the brain -just like Parkinson's. In fact, Parkinson's patients' characteristic muscle tremors stem from a drop in dopamine, a neurotransmitter that's necessary for muscle function. As Sanchez-Ramos dug further into the research, he realized that roughly 25 percent of Parkinson's patients experience hallucinations as a side effect of their medication. Was there a connection between psychedelics and the kinds of drugs used to treat Parkinson's?

Intrigued, he decided to leave pharmacology for clinical neurology. In 1990 he stumbled upon the decades-old work of a German pharmacologist Named Louis Lewin, who had become fascinated by the South American ceremonial brew ayahuasca in the 1920s. In the spirit of scientific study, Lewin had ingested the drug and found that he didn't experience the usual hallucinations or altered states of perception, because the psychoactive compound (DMT) was absent. Rather, he felt strong and vigorous, with an increased appetite and improved motor control. Lewin concluded that a compound he called banisterine, found in ayahuasca, might be an excellent treatment for Parkinson's.

What piqued Sanchez-Ramos's interest was the fact that in the 1950s, years after Lewin's studies, banisterine was found to be a monoamine oxidase (MAO) [inhibitor]. MAO [inhibitors] are a class of drugs used widely to stave off the most debilitating effects of Parkinson's by boosting dopamine levels. But their effectiveness decreases over time. In 2000, Sanchez-Ramos and several other scientists conducted their own rigorously controlled study on banisterine as a potential treatment. Because of legal restrictions in the United States, they set up shop in Ecuador. Like Lewin, they found the drug improved motor function in those suffering from Parkinson's, even after a single dose. (There were also some nasty side effects -namely, nausea and vomiting. At ayahuasca ceremonies, participants are often advised to bring a bucket.)

But regulatory roadblocks stalled the research, and Sanchez-Ramos soon found himself looking for Parkinson's treatments in other forms. He began collaborating on a clinical study led by Deborah Mash at the University of Miami for the use of a lesser-known psychoactive, ibogaine, to treat drug addiction. Derived from the root bark of the African shrub called Tabernathe iboga, ibogaine had been popular in 19th century Paris as a diet drug. In 1962, a 19-year-old junkie named Howard Lotsof scored some ibogaine and noticed an unusual effect: He no longer craved his usual bit of heroin, nor did he experience any withdrawal symptoms. He became a powerful advocate, convincing the National Institute on Drug Abuse to undertake an ibogaine research project. A number of studies have since borne out Lotsof's experience: Ibogaine blocks cravings and alleviates withdrawal symptoms for many drugs, especially opiates.

When the FDA killed the Miami study after another research group found that ibogaine destroyed neurons in rats brains, Mash set up a clinic to treat addicts and alcoholic in St. Kitts, where the drug is legal. Today, her clinical trials are on pace for eventual FDA approval. There is also preliminary evidence from other studies that ibogaine, as Sanchez-Ramos hoped, might actually improve the function of the remaining dopamine neurons in Parkinson's patients. In the end, ibogaine could turn out to be the magic bullet -the psychedelic treatment for Parkinson's that Sanchez-Ramos had spent his career hunting.

DESPITE HIS FORAYS into psychedelics, Sanchez-Ramos's best-known contribution to medicine is the development of a method for repairing damaged neurons. His process uses bone marrow cells rather than the more controversial embryonic stem cells. And while it isn't yet possible to harvest the bone marrow cells in sufficiently large quantities for practical treatment, Sanchez-Ramos's discoveries remain promising. With a half-million plus Americans already affected by parkinson's and baby boomers hitting the average onset age of 60, Sanchez-Ramos expects his studies will help lay the groundwork for future solutions. Now approaching 67, he's scheduled to retire next year. At least, technically. The scientist still plans to keep his hand in psychedelic research, hoping to study how psilocybin impacts cognition and the regenerative neurons of the brain. He attended Burning Man this past year, as part of a medical team organized to treat revelers experiencing bad trips. He's working on a picaresque novel based in part on his own globe-trotting adventures. And his most recent contribution to the fight against his longtime nemesis? A series of limited-edition prints called "Neon Neurons." The artworks, which were inspired by the branching patterns of neurons and their dendrites, were featured at a recent exhibit to benefit the Parkinson's Research Foundation. If science can't defeat Parkinson's on its own, Sanchez-Ramos is happy to have his art share the load.

Note: Dr. Sanchez-Ramos responded with some corrections and clarifications to this article in the comments.

(Artworks by Zeno Sanchez-Ramos)

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This article by Jennifer Ouellette is reprinted with permission from the January-February 2013 issue of mental_floss magazine.

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