The following is an excerpt from Aldous Huxley's Hands: His Quest for Perception and the Origin and Return of Psychedelic Science, by Allene Symons (Prometheus Books, 2015).
A certain phrase often mentioned in any gathering where the topic is psychedelic science comes from Huxley’s final novel, Island. Ever the wordsmith, he borrowed one component from Indian philosophy (moksha, referring to emancipation or freedom from the cycle of birth and death) and added medicine, so that moksha-medicine becomes a balm for treating afflictions both physical and spiritual. A mushroom-based hallucinogen, this elixir is not consumed with casual disregard on Huxley’s fictional island. I recently reread the novel and was surprised to see how Huxley gives us a prescient glimpse of moksha-medicine at work today.
Eager to snag a good seat, I arrived early in Pasadena to hear a talk about “Psychedelic Science: From ’60s Counterculture to Modern Medicine,” a forum sponsored by Southern California Public Radio station KPCC on a warm September night in 2014.
I would soon sense, by catching the number of knowing expressions, that most audience members had experienced these substances firsthand. They, or rather we, knew about distortions in time and perception, how these drugs gave rise to visions, how they often induced profound feelings of interconnectedness.
Clearly, generational change is bringing a more accepting attitude toward substances banned for forty years, and the proof is that officially sanctioned human research is back. I had been following news reports and Google alerts, but unlike the ’60s, with its troika of mescalin, LSD, and psilocybin, the information streaming in needed translation, a guide for the psychedelically perplexed. I had questions. What about the dizzying roster of substances currently called psychedelic drugs—how did they fit the picture? How did a therapeutic session relate to neurological research, tell the imaging story of powerful substances acting on the brain?
Having done explanatory journalism in a former life, I aimed for immersion. This seemed about to begin when I stepped inside the theater-like ambiance of the “Psychedelic Science” forum, where blue lights evoked the dreamlike feeling that I was about to dive into an indigo pool. The setting made sense, with its moody tint and a soundtrack from before mind-altering substances were banned, like Jackie Wilson’s 1967 pop hit “(Your Love Takes Me) Higher and Higher.”
Wilson’s song hit the charts three years before psychedelic research went into full hibernation. That happened after LSD, psilocybin, and other drugs were banned under the sweeping prohibition of the Comprehensive Drug Abuse Prevention and Control Act of 1970. An amendment to the law established five categories or schedules, capped by Schedule I for drugs deemed to have no medical purpose, unsafe even under supervision, and with a high potential for abuse.
This designation partly explains why the operative phrase on this night was “modern medicine.” This panel was not mainly about psychedelics for expanding creativity (though the Beckley Foundation in England is funding a pilot study on creativity with University of California, Berkeley), nor about inducing mystical experience (though a three-part psilocybin study was conducted from 2001–2006 under the auspices of the Johns Hopkins School of Medicine). Nor did talk turn to recreational use, because the first matter of business in order to utilize a Schedule I drug is to demonstrate medicinal value.
Or, prove it once again. Before such prohibitions went into effect, circa 1970, mental health professionals had published an estimated one thousand clinical papers involving tens of thousands of participants. Such research often fell below today’s methodological standards, being mainly anecdotal accounts rather than double blind, randomized, and placebo-controlled studies with results tracked using specific questionnaires or psychological measures called inventories.
Despite design flaws, early studies showed good outcomes for patients suffering from afflictions ranging from depression and anxiety to alcohol addiction. Treatment with psychedelics was beneficial for improving the mental state of subjects suffering from deep trauma, as well as patients facing terminal illness. The two most recent studies, described in current terminology, examine psychedelics as a treatment for anxiety in advanced-stage cancer patients and look at psychedelic-assisted psychotherapy for posttraumatic stress disorder (PTSD), and these two studies now lead the way in the rebirth of psychedelic science research in the United States.
LSD was formerly the preferred drug for such investigations. Holdover baggage from the ’60s means LSD is currently less likely to win research approval from US government agencies, though a LSD-assisted psychotherapy study with advanced cancer patients in Switzerland was recently completed, as was a pilot study in the United Kingdom.
Enter the lower-profile alternative, psilocybin, the active compound in magic mushrooms and a substance used in several categories of psychedelic research today. Another relative newcomer increasingly in favor is MDMA (3,4-methylenedioxy-N-methylamphetamine), which may seem an unlikely choice considering its dance-club reputation as Ecstasy. When I attended an event not long ago I overheard one difference described this way: “With LSD once you take it, you’re on your way. MDMA is gentler and easier to control.”
Similar in effect to marijuana, MDMA is structurally akin to mescalin but without its perception-altering qualities. MDMA, under the name Adam, became available in the mid-1970s and was found to induce an empathetic response beneficial in the therapist-patient dynamic. Consequently, it was prescribed to patients and clients by mental health professionals and, prior to restriction as a Schedule I drug in 1985, showed promise in psychotherapy for conditions ranging from phobias to depression.
The two compounds moving the field of psychedelic medicine forward are MDMA and psilocybin, according to Charles S. Grob, MD, chief of Child Psychiatry and professor of Psychiatry and Biobehavioral Sciences at UCLA’s David Geffen School of Medicine. Grob was the first researcher in decades to lead an approved study with MDMA. That pilot study was conducted in the mid-1990s, though much of his subsequent work has been with psilocybin. Grob is also co-founder of the New Mexico–based nonprofit Heffter Research Institute, which supports research of classical hallucinogens and related compounds.
If MDMA and psilocybin are the most promising drugs in this rapidly expanding field of research, then the type of study farthest along in the approval process turns out to be psilocybin-assisted therapy with advanced cancer patients. This study originated with Grob’s team at UCLA, and where it stands today gives an idea of how the process works.
“After our study began, two other research groups began studies at New York University and Johns Hopkins,” Grob told me in a telephone interview a few weeks before the Pasadena event. “They have just finished the treatment phase, and now we have to wait for a sixmonth follow up.” That would take it into 2015. “Then there will be analysis of their data, a pooling of data from our studies, and we will submit a proposal for a multisite grant.” Results involving a larger population of patients is likely to bring psilocybin closer to FDA approval as a treatment.
Such approval would not make psilocybin a prescription for the masses like Prozac nor sanction a last trip like Huxley’s (nor a dreamstate exit like the Edward G. Robinson character’s parting in the 1973 film Soylent Green). The application would be specifically for assisted psychotherapy in a medical setting during the period between diagnosis and the last months of life.
A reference to end-of-life and psychedelics naturally brings up the Huxley connection, because he left his mark in both literature and biography. “Huxley described it before any studies were done,” Grob told me, noting that the pioneering study by Eric Kast of the Chicago Medical School came after Huxley’s last book, adding to Huxley’s reputation as a futurist. “Huxley wrote about this in Island,” Grob said. “He walked the walk when it was his time.”
Whether applied to improve the last months of life or interrupt the grip of addiction, this field of old-is-new medicine is not about downing a pill and feeling better. Psychotherapy is an essential component in the process. In psychedelic-assisted therapy the drug opens the mind, which increases the chance of bringing about behavioral change. The hoped-for outcome may be smoking cessation, breaking free of horrific recurring memories of rape or a firefight in combat, or escaping an obsession or deep depression. On the procedural level, a course of treatment might involve several three-hour preparatory sessions before drugs are administered, subsequent psychotherapy sessions, and longer-term follow-up.
Terminology referring to substances in this field can be confusing. The word psychedelic remains the popular, eyeball-drawing, often-preferred-by-the-media term, though usually the preferred medical term is hallucinogen. Another term often used in psychospiritual studies with hallucinogens is entheogen, meaning god- or spirit-facilitating. Pinning down terminology for mind-altering substances dates back at least to German pharmacologist Louis Lewin’s five categories of psychoactive plants and drugs set down over a century ago, when his list consisted of euphoriant, inebriantia, exitantia, hypnotica, and phantastica. Lewin had hallucinogens pegged under the last category.
In more recent times, categories and usage have been in flux since the mid-1950s, and even today debates arise over how to categorize MDMA, which has been variously called an empathogen, for its effect of creating an empathetic state of mind, or an entactogen, for its ability to assist in recovering repressed memories. One such debate surfaced in 1956, of course, when Huxley and Osmond exchanged letters about needing an umbrella term for a burgeoning number of psychoactive drugs. Today, many opponents of these drugs call them psychotogens because in the medically predisposed wrong hands they can trigger prolonged psychosis.
Whether you call them psychedelics or hallucinogens (or psychotogens), because these are Schedule I drugs the key to reopening a legal door is through the process of federally and locally approved clinical studies. Even gaining approval for a pilot study would have been out of the question until just over a decade ago. “As time goes on,” noted Grob, “I am hearing less controversy, more resonance.”
Generational change has contributed to a shift at the Food and Drug Administration and the Drug Enforcement Agency. As personnel who experienced the 1960s are promoted to higher positions, their approach to policy is likely to differ from those under the sway of the 1970s War on Drugs.
Rising healthcare costs provide another opportunity for change associated with two large subgroups: aging baby boomers facing endof-life care and thousands of returning veterans diagnosed with longterm posttraumatic stress disorder, or PTSD.
PTSD is a centerpiece of clinical studies funded by the Santa Cruz, California-based Multidisciplinary Association of Psychedelic Studies (MAPS), whose founder and director, Rick Doblin, has a doctorate from Harvard in public policy. MAPS was established around the time MDMA became illegal in the mid-1980s, with the mission of supporting psychedelic research and promoting changes in drug policy. It is the only organization specifically funding research leading to clinical trials of MDMA-assisted psychotherapy, though it funds studies with other psychoactive drugs as well. The nonprofit organization’s stated priority is to make MDMA a prescription drug by the year 2021.
Among the MAPS accomplishments so far is a study of MDMAassisted therapy for posttraumatic stress disorder with US veterans in South Carolina, and similar studies are underway in Vancouver and Israel. One of the latest MDMA studies, approved in November 2014 and funded by MAPS, is a study of MDMA-assisted psychotherapy for anxiety associated with life-threatening illness, to be conducted with eighteen subjects in Northern California.
MAPS also had a presence at the “Psychedelic Science” event in September of 2014, when a video sponsored by MAPS showed interviews with several PTSD patients who had undergone MDMA-assisted psychotherapy. One was a young mother named Rachel, who had been a victim of childhood sexual assault. She recounted how she unsuccessfully sought help for her PTSD until MDMA-assisted psychotherapy enabled her to dredge up painful memories and recast them in a new light.
A dramatic narrative such as Rachel’s adds a human face and a persuasive power to the story of psychedelic research, especially in an era of sharing via Facebook, Twitter, and YouTube. Less alluring is the practical side of research, the data essential for a clinical study, involving inventories or questionnaires that can be statistically quantified. A personal account, which may have the effect of a testimonial, conveys the message that psychedelic therapy deserves a second look, even though one could say that an anecdote speaks for a single subject. By contrast, data based on larger numbers of participants is essential to advance a clinical trial.
I was drawn in, actually taken up short, by one such personal story. I first read about it in an article in Discover magazine in which journalist Linda Marsa quoted a woman named Annie who had been a participant in Charles Grob’s 2004–2008 study with terminal cancer patients.12 I learned that Annie’s ovarian cancer, which had gone into remission, had returned; I read how, through the process of psilocybin-assisted therapy, she had somehow unclenched, let go of her fear, and opened up to experiencing greater joy with loved ones in the time she had left. Then I found a video of Annie’s interview on the Heffter Research Institute’s website, and I heard her say, “It connected me with the universe.”
Annie’s story hit home because I am an ovarian cancer survivor. At the time of this writing it has been a dozen years since my surgery, but when I read how Annie’s cancer had “come roaring back” then I saw the sensitive interview, well, it gave me a queasy taste of my own mortality. I know that when my time comes near I would want this consolation, though it is not legally available yet. I guess that makes me an advocate with a dog in the fight.
This brings up another reason why the attitude toward psychedelics is changing. Your mind can be changed when you personally know, or have heard about, someone who has been helped through psychedelic therapy. This seems to be a persuasive factor in the states where voters have approved medical marijuana.
The current reevaluation of psychoactive substances comes after a forty-year period of dormancy, depending on how you look at the calendar. Some people say it has been four decades since a new study was approved. Or, viewed another way, there were twenty years between the Controlled Substances Act of 1970 and the next legal psychedelic study, which began in 1990. That was when psychiatrist Rick Strassman at the University of New Mexico School of Medicine designed an experiment with the hallucinogen DMT (N,N-dimethyltryptamine). DMT is an active compound found in ayahuasca, an Amazonian psychedelic tea attracting both scientific and popular attention today.
Strassman, who conducted his research with sixty volunteers, was not looking for a therapeutic benefit but was more interested in how DMT induces a psychospiritual, or mystical, experience. His study ended after five years without advancing further, apparently due to various factors at the sponsoring institution.
Taking up a similar research question in 1993, Charles Grob conducted a private study in Brazil of ayahuasca in the UDV church (Centro EspÃrita Beneficente UnÃ£o do Vegetal), for which drinking the psychedelic tea is part of a sacramental ritual.
Since then, and especially since 2000, a number of clinical studies have been conducted in the United States, many spanning several years and continuing today. Some reprise work interrupted decades ago. An example is the previously noted Harvard–Marsh Chapel Experiment in the early 1960s, examining psilocybin as a catalyst for psychospiritual or mystical effects, a study conducted by Walter Pahnke and Timothy Leary. A legacy from that project is a measurement used today called the Pahnke-Richards Mystical Experience Questionnaire. The MEQ, a self-report tool, assesses seven areas of mystical experience, such as transcendence of time and space, and a sense of the unity of all things. Volunteer responses are rated on a 6-point scale.
A subsequent 2001–2006 version with psilocybin was the one conducted at Johns Hopkins University School of Medicine, headed by Roland Griffiths. In both cases many of the participants reported profound spiritual experiences. In the first round of the modern study, which was more carefully managed than its predecessor, an analysis of responses from the thirty-six volunteers tracked fourteen months later showed that 58 percent rated it as among the five most personally meaningful experiences of their lives.
Another once-promising study looked at psychedelic-assisted therapy for psychosocial distress in terminal cancer patients. The first study, under Eric Kast of the University of Chicago in the mid-1960s, was an outgrowth of an investigation of LSD as an analgesic for patients with advanced cancer, but Kast discovered that his subjects were experiencing a transformation in how they viewed the end of life. The last LSD-assisted terminal-cancer study took place in the early 1970s at the Maryland Psychiatric Research Center, led by psychiatrist Stanislav Grof, whose results informed the design of the Charles Grob–led psilocybin end-of-life study conducted from 2004–2008.
Psychedelic-assisted treatment for alcohol addiction was one of the first therapeutic applications in the 1950s, led by Humphry Osmond and Abram Hoffer in Canada. Currently, a study investigating the therapeutic potential of psilocybin in alcohol dependence is underway at the University of New Mexico; another addiction study, this one for smoking, is being carried out at Johns Hopkins in Baltimore, and positive results could improve support for studies of hallucinogen-assisted therapy for other addictions.
Among outpatient psychiatric disorders, one of the most common is obsessive-compulsive disorder. The Heffter Institute has sponsored an initial psilocybin-assisted study at the University of Arizona, looking at obsessive-compulsive disorder, Though results seem to warrant further investigation, no more studies are underway as yet.19 A recently-launched study in Los Angeles is investigating MDMAassisted therapy for social anxiety in patients with adult autism, the latter a study funded by MAPS and led by Grob and his team at Harbor-UCLA in conjunction with Stanford University.
Without funding, however, such studies of the healing and other potential benefits of psychedelics would not take place. Clinical and preclinical research is expensive, with little in the way of federal or state grants available for work with Schedule I drugs (exceptions include some addiction research). Medical marijuana appears to be paving the way, however. MAPS received an unprecedented $2 million grant in December 2014 from the state of Colorado for a pilot study of marijuana-assisted therapy for symptoms of PTSD in US veterans. This looks like an opening for more than medical marijuana, or as Doblin of MAPS recently said, announcing the study, “The Veterans Administration is willing to collaborate with MAPS on PTSD-MDMA research.”
Charles Grob also believes that psychedelic medicine will eventually go mainstream, or as he said at the Pasadena forum on psychedelic science, “I think in ten to fifteen years it will be an accepted part of psychiatry and medicine, and there will not be a problem with funding. I am optimistic.”
Major foundations largely stay clear of supporting projects involving these substances, as Huxley and Osmond found out in the 1950s when they sought grants from the Ford and Rockefeller Foundations in support of their own psychedelic project. But the current funding story has an upbeat though poignant sequel. It concerns the Rockefeller Brothers Fund and Richard Rockefeller, a great-grandson of John D. Rockefeller Sr. Long a generous donor to MAPS and a physician himself, Richard Rockefeller was interested in sponsoring psychedelic-assisted therapy for trauma survivors. Though he unfortunately perished in a private plane crash in June of 2014, Rockefeller made provisions for support of the work of MAPS to continue after his death.
Along with MAPS, of course, another major organization, in terms of seeking and granting funding for psychedelic research, is the Santa Fe, New Mexico–based Heffter Research Institute, cofounded by Charles Grob and David E. Nichols of Purdue University. The Institute was named for German pharmacologist Dr. Arthur Heffter, who in 1889 showed that mescalin was responsible for the psychoactive properties of peyote. Both MAPS and Heffter work across borders, as does the Beckley Foundation, based in Oxford in the United Kingdom. Under its founder and director, Amanda Feilding, the Beckley Foundation supports collaborative research with European as well as American university medical centers, including UC Berkeley, UC San Francisco, and Johns Hopkins University.
One of the Beckley Foundation’s special interests is gaining a greater understanding of the effects of psychedelics by means of brain-imaging technology, which involves tracking cerebral blood flow of subjects who have been given a psychoactive drug.24 It turns out that two of the leading experts disagree on what they see. Their debate brings to mind a pet theory of Aldous Huxley's.
Classic hallucinogens work on the brain, at the level of single neurons, by stimulating serotonin 2A receptors, as Robin CarhartHarris and his colleagues recently explained in a special issue of the British journal The Psychologist. 25 Carhart-Harris notes that most of us picture neuroscience at the system level, in which a proxy for brain activity is seen in blood flow to particular areas of the brain. What we might see pictured in the media in a graphic (such as illustrated in red and blue) are three-dimensional volume pixels, called voxels, that have been visually translated into an activation map.
On the system level, how hallucinogens work on the brain is not understood, but one theory from the 1950s still has a kind of historical credence. In Huxley’s view, as expressed in The Doors of Perception, the everyday brain acts like a filtering mechanism to reduce or organize input in a way useful for everyday decisions. In this view, substances like mescalin, LSD, or psilocybin override the filter, giving rise to what Huxley called Mind-at-Large. If this is the case, then in terms of magnetic imaging a mind-manifesting substance should produce an abundance of brain activity.
This happens to fit one neuroscientist’s theory, though at first it sounds like the opposite. Robin Carhart-Harris and his colleagues saw in their subjects decreased brain activity in structures important for “integration and routing in the brain” meaning managerial function. If those practical hubs (thalamus, posterior cingulate cortex, and medial prefrontal cortex) register a decrease in activity then this more or less Huxlean filter-override could account for “an unconstrained mode of brain function.”
On the other hand, Franz Vollenweider, a neuropsychopharmacologist at the University of Zurich who also sits on the Heffter board, sees it another way. Vollenweider saw not a decrease but an increase in activity in those same management-oriented areas of the brain, though the difference between the two experiments could have been caused by a variance in dosage or how dosage was delivered, orally in one case and by injection in the other.26 For the time being, lacking agreement over how classic hallucinogens work on the brain, we do not know if Huxley (or philosopher Henri Bergson, who originated the idea of brain as a filter) was right all along.
The practical question is what happens if psychedelic-assisted psychotherapy, whether near the end of life or for treating PTSD, reaches the FDA approval stage and becomes a prescription drug? Or as one audience member in Pasadena during the Q&A session phrased it, “What would a treatment model look like?”
"It would not be just any health provider,” Grob replied. “There would be rigorous training, supervision, and oversight. Otherwise there would be a risk of it spinning out of control.”