Psychedelic therapy shows great promise. More states should legalise it
Oregon’s trailblazing sets a fine example
Jan 29th, 2022 ECONOMIST
Picture yourself in a boat on a river, with tangerine trees, marmalade skies—and licensed professionals who may finally be able to help you overcome your treatment-resistant depression. The first half of that sentence reflects the Beatles-era view of psychedelic drugs. The second is a new policy being pioneered in Oregon, which could herald a welcome shift in America more broadly.
The view in the 1960s was that psychedelic drugs put users into an indolent, blissed-out state that encouraged them, in the words of an early booster, the one-time Harvard psychologist, Timothy Leary, to “turn on, tune in, drop out”. Unfortunately, the moral panic that this stirred up in the United States shut down research into the therapeutic possibilities of psychedelics and led the federal government to declare that they have “a high potential for abuse and serve no legitimate medical purpose”.
That assessment was wrong, and the era of American moral panic over the drugs appears, at last, to be waning. Early next year, following the passage of a ballot measure in 2020 and under conditions currently being carefully worked out, Oregonians will be able to avail themselves of therapy using psilocybin, the psychoactive compound in “magic mushrooms”. Several other states, including conservative ones such as Texas, have approved medical research into psychedelics. America’s drugs regulator may approve MDMA, better known as Ecstasy, for treating post-traumatic stress disorder as early as next year, and has hailed psilocybin as a “breakthrough therapy” in treating severe depression. The European Medicines Agency is conducting large-scale trials of psilocybin to treat otherwise intractable depression.
The conditions that psychedelics seem to ameliorate include depression, addiction, and post-traumatic stress disorder. Precisely how they work is unclear, which is one reason more research is required. Users report an increased sense of connectedness, a decrease in anxiety (particularly for terminally ill patients nearing the end), and a reduction in depressive symptoms. It seems that these benefits persist. In one study, 14 months after taking psilocybin users reported a heightened sense of well-being and a belief that taking the drug was among the most meaningful experiences of their lives.
It is true that the reported experiences are subjective, and some feelings may be suggested by people’s expectations of how this sort of drug will affect them. But a number of things about psychedelics can be said with confidence. They are not addictive; consuming too much of them may be unpleasant but is not fatal; and any harm they cause is limited to the person taking them. At the very least—as a comfortable majority of Oregon’s voters realised in 2020 when, alongside legalising psychedelics, they decriminalised possessing small amounts of all drugs—nobody should be imprisoned for using them.
They certainly show enough promise to justify Oregon’s experimental policy. Psilocybin will be available only in a licensed setting with a trained facilitator, after screening for contraindicative conditions such as schizophrenia or heart trouble. This reduces risk, and will foster networks of professionals who can learn from each other. It will also let people choose a setting that best suits them. Some may feel most comfortable in a surgery; others may prefer to be at a retreat in nature. Psilocybin is not intended to replace conventional therapies, but to sit alongside them; reaping the full benefits requires users to build the experience into their lives.
You answer quite slowly
Some may find psilocybin does not bring them all they hoped for. The drug is not a cure-all; and Oregon’s policies may need to be tweaked. But the state’s voters deserve praise for their clear-headed sense of proportion, too long absent from American drug policy. More states should follow Oregon’s lead of cautious experimentation. Psychedelic drugs show tremendous promise. Initiatives like Oregon’s are essential if they are to realise their potential to help those who today must bear their suffering
One way to heal a brain injury? Let LSD open your mind—literally.
Psychedelic drugs such as DMT and Ecstasy may offer a unique treatment pathway for various brain injuries and diseases because of their potency, helping patients learn lost and new skills.
Most brain-injury research so far—conducted in test tubes and lab animals, with only a few small studies in people—points to the psychedelics’ potential to limit brain damage after injury, stimulate the birth of new neurons to replace impaired ones, and open the learning windows that let the brain acquire new skills. One recent study, published in the journal Nature, found lab animals taking psychedelics adopted skills as adults that were previously limited to childhood.
“My lab got really lucky when we discovered that psychedelics are the master keys for reopening critical periods that scientists have been looking for so long,” says Gül Dölen, an associate professor of neuroscience at the Johns Hopkins School of Medicine in Baltimore, who coauthored the Nature article.
These drugs could prove especially valuable because brain-injury conditions generally lack effective therapies, says Sunil Aggarwal, an integrative rehabilitation medicine physician in Seattle who coauthored a review of research on psychedelics for brain injuries in the medical journal Frontiers in Neurology. “It’s still early on, but this is a very exciting time. There’s a lot of interesting research that suggests this will be a really helpful treatment for these patients.”
Expanding an injured brain’s ability to learn
Human brains develop in a way that specific skills are most easily learned during targeted developmental stages, known as critical periods. People who attempt to learn a new language in adulthood tend to understand this concept, because the critical period for language closes after the teenage years.
Yet this summer, the Johns Hopkins scientists reported that adult rodents given a psychedelic learned certain socialization skills that are typically acquired only as juveniles.
Such an ability has implications for treating strokes and TBIs. When a person suffers these injuries, many neurons in the brain are damaged. Fortunately, a critical learning period for speech and motor skills reopens naturally following the event, enabling the person to regain some lost abilities. But it generally closes within six months, hindering improvement after that time.
In the study, adult mice lacking certain social skills were trained to associate a specific environment with solitude and another with communal interaction. After they were given a single dose of LSD, psilocybin, or other psychedelic, they could choose to spend time in either environment. The majority preferred the social location.
All the drugs had this effect, but those that produce the longest psychedelic experience in humans reopened the rodents’ critical period for the longest duration afterwards. With LSD, for example, whose psychedelic effects last around 10 hours, the mice keep learning the value of socialization for months afterwards, compared to weeks for psychedelics producing shorter hallucinations.
“That tells us the same mechanism is probably at work,” Dölen says. After autopsying the animals’ brains, Dölen discovered that the psychedelics seem to work by dissolving components around neurons that stabilize the memory encoded there—a slurry of proteins, sugars, and other compounds known as the extracullar matrix. Dölen likens this matrix to the grout between floor tiles, because when it is removed tiles can freely move about. In the brain, with the matrix weakened, the neurons are open to new learning.
This likely happens because having psychedelics like LSD sit in their receptors so long overwhelms the neurons and causes them to hit a sort of reset button, like a hard reset after a computer freezes. The resulting cascade of cellular events reboots the brain back to an earlier developmental stage, Dölen says.
The reopening of learning windows seems to explain why psychedelic studies for mood disorders emphasize the importance of post-drug psychotherapy known as integration. As the brain is open to new ideas during integration it can approach its mental illness in novel ways, Dölen says. [Read more in Psychedelic Medicine Is Coming—But Who’s Going to Guide Your Trip.]
Enhancing socialization for autism spectrum disorder
Reopening learning windows may also help people who don’t have injuries but whose brains are wired differently, such as those with autism spectrum disorder, a neurological and developmental condition that, among other things, affects how people interact with others. Research has shown that the brains of people with autism bear some distinctions from those without the condition, especially in the frontal cortex that regulates emotions and relationships.
In one study, eight adults with autism spectrum disorder experienced a marked decline in social anxiety after taking two doses of the psychedelic MDMA, each of which was followed by three psychotherapy sessions. The benefits of the therapy persisted through the six-month follow up, the University of California, Los Angeles study found.
MDMA could be a particularly valuable psychedelic for autism because it facilitates the desire for socialization, a skill many on the spectrum find challenging, says Robert Malenka, a professor of psychiatry and behavioral sciences at Stanford University who has performed animal research using the drug. “Under the influence of MDMA, one has this profound … sense of wanting to interact with other people in a non-aggressive, prosocial and empathic way,” he says.
Andrew Amick, a 34-year-old Los Angeles office administrator training to become a psychotherapist, participated in the UCLA research. Before the study, contemplating even casual social situations like riding in an elevator with coworkers or passing them in the hall made him so anxious he took steps to avoid them.
He remembers during the MDMA sessions focusing on the peaceful nature of the room, the soothing music, and his relaxed body. Afterwards, he realized that he could tap into these same sensations when interacting with people. “It’s easier for me to choose to be peaceful in social situations,” even six years later, Amick says. When he finds himself in his office elevator with colleagues, not only does he not feel compelled to run, but he can also comfortably start a conversation.
Helping the brain help itself
Other ways that psychedelics seem to impact the brain include reducing inflammation, a key perpetrator of the damage following a brain injury. While this swelling is a useful biological response to injured tissue because it accompanies immune cells and other healing chemicals that flood the area, too much is a serious problem.
“The body needs to turn on the inflammation, but it also needs to turn it off,” Aggarwal says. When it doesn’t do the latter in a timely matter, neurons that escaped the initial injury can subsequently be damaged. One way that psychedelics decrease inflammation is by binding to serotonin receptors called 5-HT2A—which are responsible for producing the hallucinogenic sensations and also regulate inflammation. Psychedelics additionally stimulate a brain protein called glial cell-derived neurotrophic factor (GDNF) that is responsible for the growth and recovery of injured neurons.
Several labs are evaluating the psychedelic DMT as a possible medication to boost recovery after stroke. DMT works by stimulating another class of receptors called sigma-1 (S1R), which seem to be important for protecting cells from the injury that occurs when blood reflows to the brain following a stroke.
Rats slowly infused with low doses of DMT after a stroke had fewer damaged tissues and more extensive recovery; brain levels of anti-inflammatory compounds and sigma-1 proteins were abundant in the treated animals.
“The body has many intrinsic defense mechanisms, but in a stroke these systems get overwhelmed,” says Christopher Bryan, vice president of research and operations for the Canadian company Algernon. His company is currently testing whether DMT could reduce this process in people.
Algernon first studied healthy individuals to evaluate whether it is safe to infuse low doses of DMT over six hours. Results are unpublished, but Bryan says this delivery proved safe, enabling the company to soon begin clinical trials in hospitalized stroke patients. By slowly infusing the drug, Bryan says that patients get a therapeutic dose without triggering DMT’s psychedelic effects, which could be jarring to someone recovering from a brain injury.
Treating the most challenging brain injuries
Traumatic brain injuries, which result from a violent blow to the head such as from a car accident or wartime explosive, are especially difficult to treat because multiple parts of the brain can be damaged. Nolan Williams, director of the Brain Stimulation Lab at Stanford University in California, was intrigued by ibogaine’s potential after hearing stories of veterans with TBI going overseas to take the drug and returning with their memory and neurological functions dramatically improved. [Read more in These Pioneering Therapies Are Treating Hard to Heal Wounds As Never Before.]
Williams recently conducted a clinical trial in which 30 veterans were administered ibogaine. Results have not been published, but mental processing skills improved for many of the vets, Williams told attendees at a recent Psychedelic Science conference in Denver. Moreover, brain scans found that blood flow to parts of the brain involved in rehabilitation increased.
It may turn out that novel psychedelics engineered to remove the altered consciousness could prove particularly effective for brain injuries. That prospect was enhanced following recent research that found in addition to 5-HT2A serotonin receptors, psychedelics also bind to a receptor called TrkB (pronounced track B), which helps nerve cells communicate with one another. Antidepressants similarly activate this receptor, but psychedelics were found to be a thousand times more potent, says Eero Castrén, a neuroscientist at the University of Helsinki in Finland who coauthored the study.
TrkB does not cause hallucinogenic effects, meaning drugs engineered to bind to these receptors without activating 5HT2A might produce similar healing. Although some people believe the psychedelic high is an important aspect in mood-disorder treatment, it may be less necessary for brain injuries, Castrén says. [Read more in Scientists Want to Create Psychedelics that Give Better Trips.]
Many physicians and researchers say that the advantage of psychedelic therapies is that they are so potent only one or a few doses are generally required, so they could offer a unique treatment pathway.
“A lot of the drugs we currently use for brain injuries must be taken daily,” Aggarwal says. Using psychedelic drugs “is a different paradigm, which relies a lot more on the body’s innate healing capabilities and stimulating that process to occur more robustly.”
Psychedelic medicine is coming—but who’s going to guide your trip?
The U.S. may approve therapies using MDMA and psilocybin—aka ecstasy and magic mushrooms. The medical community is preparing for the deluge of demand.
“It was incredibly scary. I was really afraid it wasn’t going to come back,” the 51-year-old San Diego attorney recalls. The nurse attending her session quickly called in the psychiatrist, who verbally reassured St.Clair and squeezed her hand to make her feel safe. His soothing presence kept her calm during the 40 minutes until the hallucination passed and the drug was out of her system.
The importance of having well-trained professionals administer powerful psychedelic drugs is becoming urgent now. Not only will Oregon soon allow mental-health treatments with psilocybin—the active ingredient in magic mushrooms—but the United States Food and Drug Administration is expected to evaluate its first true psychedelic, methylenedioxy-methamphetamine (MDMA, aka ecstasy), for treating post-traumatic stress disorder later this year.
It was the realization that psychedelics might one day be integrated into mainstream medical care that spurred the California Institute of Integral Studies in San Francisco to become the first in the U.S. to offer a psychedelic-assisted therapy training program seven years ago, says Janis Phelps, director of the school’s Center for Psychedelic Therapies and Research.
A dose of psilocybin rests in a ceremonial chalice. Psilocybin and MDMA are poised to be the hottest new therapeutics since Prozac.
In recent years, a growing number of institutions have followed. Psychotherapists, nurses, doctors, clergy, and others primarily in the mental health or spiritual professions are learning the chemistry of psychedelic molecules, safety concerns, historical Indigenous use, and, most importantly, the unique mental states unleashed by these drugs, whose effects last for six hours or more. But because psychedelics are currently illegal, no program enables participants to personally experience their effects.
Demand for these courses is booming, experts say, in large part due to a better understanding of the drugs’ potential mental health benefits. But national standards do not exist, leading to fears some graduates may have inadequate abilities as each institution create its own curriculum.
Inspired by promising clinical trials
Why are medical providers looking to MDMA as a potentially useful PTSD treatment? The powerful drug is thought to enable the brain to confront traumatic memories without triggering emotions like shame and rage, which can overwhelm and impede healing.
Preliminary results from the Multidisciplinary Association for Psychedelic Studies’ (MAPS) most recent large clinical trial confirm that two or three doses of MDMA reduced or eliminated PTSD. Most notable was that the effects persisted for six to 12 months. (These findings were released in April on MAPS’ website but have not been published in a medical journal.)
Positive results were also noted in MAPS’ first phase three clinical trial published in Nature Medicine in 2021, which showed that after three sessions of between 80 and 180 milligram doses of MDMA, three preparatory therapy sessions, and nine sessions post-medication, two-thirds of study participants no longer had PTSD.
Institutions around the world are revealing psychedelics’ promise for a range of mental-health disorders, including depression, anxiety, addiction, and reducing the fear of being diagnosed with a terminal disease.
Results like these inspired Anthony Back, a doctor at the University of Washington School of Medicine, to take the California Institute training in 2020. The 60-year-old Back says growing up in the 1980s around prominent antidrug ads kept him from experimenting in his youth. But the scientific research convinced him “there’s something really important here.”
In Back’s work as a palliative care physician, his primary goal is to reduce pain for patients with cancer. But “we haven’t had good ways of dealing with the terror” of learning your life is likely ending, he says.
How to administer a psychedelic drug
Institutions offering training programs vary greatly. Oregon has authorized nearly two dozen groups to conduct training for its statewide program, ranging from small facilities like the Earth Medicine Center to established universities including the University of California, Berkeley. Around the country, programs generally last six months to a year and cost thousands of dollars.
Most programs emphasize the importance of conducting multiple sessions before a drug is administered to discuss what patients hope to gain from the experience and what they might expect. Students also learn how to oversee the one or more sessions where the drug is administered. “The psychedelic experience is largely an internal one,” Phelps says, so therapists are taught not to interject themselves unless required to restore a sense of safety.
Administering psychedelic-assisted therapy is vastly different for professionals used to conventional mental-health treatments, says Bit Yaden, a psychiatrist at Johns Hopkins Medicine, who is working on a pilot curriculum for Hopkins, Yale, and New York University psychiatry students. “When I prescribe Lexapro, my patient picks up the prescription and I hear in a month how it’s going,” she says. But with psychedelics, the actual dispensing of the medicine along with subsequent talk therapy are required, she says. During the many hours of a psychedelic session, one or more therapists must remain in the room.
Trainees are also taught how to help with a process known as integration, where patients incorporate insights and emotions from their psychedelic trip into their everyday lives. Here too, conventional therapists can find themselves in novel territory. “In psilocybin trials, there are reports of people having mystical experiences. Talking about those experiences may not have traditionally fit in a psychotherapeutic framework,” Yaden says.
Some programs have adopted the belief that therapists are best positioned to help others process powerful insights only after they have dealt with their own mental-health issues. That’s why Vancouver Island University in Canada offers a year-long training with numerous personal-development exercises and discussions to foster the personal and emotional growth of the therapist. “Using psychedelics is a way of remembering who you are,” says Geraldine Manson, a member of Canada’s Snuneymuxw First Nation who teaches in the program.
Training without psychedelics
Because psychedelics remain illegal, most programs are unable to have students facilitate an actual session with a psychedelic, an unfortunate limitation to their training, Phelps says. (Vancouver Island’s students, however, can do so because of government waivers allowing some mental-health patients to legally use the drugs.)
For the same reason, many students haven’t had personal experience with the drugs either. “It is clear when someone has never used a psychedelic. The types of questions they ask shows they have no idea what experience they’ll be providing to their patient,” says Pam Kryskow, medical chair of the Vancouver Island program.
Some encourage students to try ketamine under supervision to understand the extreme vulnerability of a being under the influence. Others attempt to simulate the state with a breathing practice known as Holotropic breathwork, which employs fast respiration to yield temporarily altered consciousness.
Some trainees seek out their own psychedelic experience with an underground guide or through by traveling to countries where Indigenous populations have long used the drugs. Palliative-care physician Back used a guide several years ago, an experience that prompted his desire to take the training. During the experience, as he later wrote in a medical journal, “my familiar sense of ‘me’—my preferences, my body, my history—dropped away, all at once, and what became palpable was an oceanic sensation of being unified with everything….There was a sense of being complete belonging…of having access to an energy in the universe that normally was hidden. It was exhilarating.”
Back believes such a framework would be helpful for his terminal patients. “I realized the process of dying was much more spiritual than I knew,” he now says, and he is eager for these drugs to be legalized.
Other medical professionals apparently feel similarly. In the California Institute’s first class of 42 students, several doctors and nurses insisted their participation be kept quiet to avoid potential harm to their professional reputations. But this year, some 800 people competed for the school’s 400 slots.
Despite the growth, experts worry there won’t be enough trained therapists to meet the expected demand after FDA approval of MDMA and possibly psilocybin, when thousands of professionals will be needed. In Oregon, not a single facilitator has so far met all criteria to be granted a license for psilocybin therapy.
“No training program is keeping up with the demand,” Phelps laments. Her university is developing a licensing program so other colleges can obtain the school’s training materials and videos, with some 25 already expressing interest, she says.
The only way psychedelics can succeed as a mental-health remedy is by ensuring enough professionals receive high-quality training, Back says. “This is a different kind of treatment than most others. Those are about the technology or the drug. Here, you have to have the therapy and the medicine together.”
