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)

___________________________

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

Be sure to visit mental_floss' entertaining website and blog for more fun stuff!


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And I should mention that I never said LSD should be "next" to be allowed to be used legally as a medication. I agree that it should be re-evaluated as an aid to psycho-therapy or treatment of drug dependence. I also opined that it could be a useful tool for exploring "inner space", or as Roland Fisher noted---for the cartography of inner space, a dimension that remains largely misunderstood and mysterious. The editors of the original profile in Mental Floss wrote: "As medical marijuana gains acceptance across the country, one scientist thinks LSD should be next" as a header to suck readers into the article.
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For the record:
There are major and minor errors in the story.
1. "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). "

The important word ----inhibitor was dropped----Banisterine is an MAO inhiibitor. MAO is an enzyme (a protein) that metabolizes monoamines such as serotonin, dopamine as well as DMT. So the combination of an MAO inhibitor and DMT results in free passage of the DMT from gut to blood to brain without oxidaton and elmination. Hence, ayahuasca can be taken orally. Many indigeous people use DMT containing snuffs that are snorted and in this formulation, DMT will quickly enter brain and produce rapid, intense effects. DMT taken orally will not reach brain to produce altered states of consciousness, unless an inhibitor of MAO is taken to protect the DMT in its passage from gut to blood to brain. The signiicance of MAO inhibitors in the realm of Parkinson's disease is that this type of agent is in use to provide "neuroprotection" of dopamine neurons and hence slow progression of disease. MAO-I drugs also enhance the actions of dopamine, another useful application. The diferece between banisterine which was studied in the late 1920s and the new generation MAO inhibitors used now (selegiline and rasagiline) is their selectively for brain MAO (ie the MAO subtype . Hence there are less likely to be adverse effects (and drug interactions) when using the newer generation of MAO-B inhibotors.

2. "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.)"

In fact, I met an Ecuadorean neurologist in Rio de Janeiro at a scientific symposium on Hoasca, sponsored by the UDV---Unioa do Vegetal (the state approved church of the 'two plants'.)
My talk discussed the use of banisterine for PD and lamented the fact that replication of Lewin's studies in Germany could not be done in the US. Dr. Serrano of Ecuador approached me later and commented that many of the elderly in his town regularly drank tea made only of the vine (banisteriopsis) and they were remarkable vigorous. So he decided with my help in the research design, to conduct a clinical trial of the tea made from the banisteriopsis vine. We in the states (my lab) ran the analysis of the tea's components but the entire clinical study was performed in Dr. Serrano's clinic with Ecuadorean PD patients. Results were published in Scientific Rev of Alt Med. The biggest side effect was worse kinetic tremor but there was not the nausea and vomiting typical of ingesting ayahuasca (hoasca in Brazil).

Serrano-Duenas M, F. Cardozo-Pelaez, J. Sanchez-Ramos. Effects of Banisteriopsis Extracts on De Novo Parkinson’s Disease Patients. Scientific Rev of Alternative Medicine 3:127-132, 2001

3. "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."

Rick Doblin pointed out the following:

FDA didn't kill the study. NIDA refused to fund it. The article makes FDA out to be seriously concerned about claims of ibogaine neurotoxicity with questionable clinical relevance. Actually, FDA is fine with ibogaine research in humans and puts science and risk/benefit analysis before politics.

Mash has no clinical trials underway with ibogaine, as far as I know. Ibogaine is side-tracked and is not making any progress toward becoming an FDA-approved prescription medicine. MAPS' long-term observational outcome study of ibogaine in opiate addicts shows it has benefits but is not a miracle cure with many people relapsing shortly after treatment or within the first year (there needs to be aftercare). Mash is interested in noribogaine, the non-psychedelic long-lasting metabolite that she identified and thinks is involved in the reduction of craving.

Also, Ibogaine is initially mentioned in the context of French diet drug in the 19th century Paris. Ibogaine's centuries of historical roots in the Bwiti religion in Gabon, Africa were not mentioned at all and it wasn't actually a French diet drug in the 19th century Paris. It was a low dose stimulant in 20th century France.

Brief text below about ibogaine's history as a prescription drug in France, for the curious:

After the isolation of ibogaine from Tabernanthe iboga in 1901 by Dybowsky and Landrin, there was very little research done on the effects of ibogaine other than by a few French pharmacologists including Phisalix, Lambert, Heckel, Pouchet, Chevalier and Closmonil. For approximately the next forty years, little interest was shown in ibogaine and it was regarded as an obscure cardiac stimulant.

Renewed interest in ibogaine occurred in 1939 when Wurman published his Doctorate of Medicine thesis in Paris entitled,"Contribution a l`etude experimentale et therapeutique d`un extrait de Tabernanthe manii d`origine gabonaise," (Contribution to the experimental and therapeutic study of an extract of T. manii from Gabon). This led to the dry extract of the roots of Tabernanthe manii being prepared in tablet form and given the tradename Lambarene(TM) in honor of Dr. Schweitzer.

Lambarene(TM) was produced in France, and contained about 200mg of extract or 8mg of ibogaine per tablet. The package label described it as: "a neuromuscular stimulant, promoting cell combustions and getting rid of fatigue, indicated in cases of depression, asthenia, in convalescence, infectious diseases, greater than normal physical or mental efforts by healthy individuals. 2-4 tablets daily. Rapid and prolonged action not followed by depression. May be administered to hypertensives."

Lambarene(TM) was of particular interest to post-World War II athletes and French mountaineers because of its antifatigue properties, and continued to be marketed in France until 1966 when ibogaine was prohibited in France. Since 1989, ibogaine has also been banned by the International Olympic Committee, the International Union of Cyclists and the French State Secretariat for Youth and Sports (Gouteral, 1992).

Finally, there are a few minor errors:
"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..."

1. I indeed was an investigator in an NIH-funded AD Research Center at University of South Florida. There are many NIH-funded AD research centers throughout the US. I was not at NIH! I've published over 300 scientific articles and 157 were full-length peer-reviewed papers based on basic and clinical research. From an academic perspective, holding an Endowed Chair (the Helen Ellis Endowed Chair) is more prestigious than being an investigator funded by NIH. The endowed chair provide funds to be used to protect my research time (ie so I won't be forced to become a full time clinician and can focus a significant amount of time on research).

2. I didn't arrive in Paris from Venezuela. I arrived in NYC from Venezuela at age 5 and after finishing college at University of Chicago in 1967, I travelled to Paris...

Reason I'm sending these corrections is that my academic peers are starting to see the article and I want that info to be correct. Also important is that when I had these experiences with LSD it was legal and in fact my LSD was produced by Sandoz!!

---Juan (Zeno) Sanchez-Ramos, PhD, MD
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