Researchers Are Experimenting With Magic Mushrooms' Fascinating Ability to Improve Mental Health Disorders
Mental illness is a dark undercurrent in the lives of tens of millions of Americans. According to the World Health Organization, about 450 million people worldwide have a mental health disorder, which cut across all demographics, cultures, and socioeconomic classes.
One area of research seems to herald the first major breakthrough in decades — hallucinogen-assisted psychotherapy.
The U.S. National Institute on Mental Health estimates that severely debilitating mental health disorders cost the U.S. more than $300 billion per year, and that's not even counting the human toll of broken lives, devastated families, and a health care system stretched to the limit.
However, one area of research seems to herald the first major breakthrough in decades — hallucinogen-assisted psychotherapy. Drugs like psilocybin (obtained from "magic mushrooms"), LSD, and MDMA (known as the club drug, ecstasy) are being tested in combination with talk therapy for a variety of mental illnesses. These drugs, administered by a psychotherapist in a safe and controlled environment, are showing extraordinary results that other conventional treatments would take years to accomplish.
But the therapy will likely continue to face an uphill legal battle before it achieves FDA approval. It is up against not only current drug laws (all psychedelics remain illegal on the federal level) and strict FDA regulations, but a powerful status quo that has institutionalized fear of any drug used for recreational purposes.
How We Got Here
According to researchers Sean Belouin and Jack Henningfield, the use of psychedelic drugs has a long and winding history. It's believed that hallucinogenic substances have been used in healing ceremonies and religious rituals for thousands of years. Indigenous people in the U.S., Mexico, and Central and South America still use distillations from the peyote cactus and other hallucinogens in their religious ceremonies. And psilocybin mushrooms, also capable of causing hallucinations, grow throughout the world and are thought to have been used for millennia.
But psychedelic drugs didn't receive much research until 1943, when LSD's psychoactive effects were discovered by chemist Albert Hoffman. Hoffman tested the compound he had discovered years earlier on himself and found that the drug had profound mind-altering effects. He made the drug available to psychiatrists who were interested in testing it out as an adjunct to talk therapy. There were no truly effective drugs at the time for mental illnesses, and psychiatrists early on saw the possibility of psychedelics providing a kind of emotional catharsis that might represent therapeutic breakthroughs for many mental conditions.
During the 1950s and early 1960s, psychedelic drugs saw an increase in use within psychology, according to a 2018 article in Neuropharmacology. During this time, research on LSD and other hallucinogens was the subject of over 1,000 scientific papers, six international conferences, and several dozen books. LSD was widely prescribed to psychiatric patients, and by 1958, Hoffman had identified psilocybin as the hallucinogenic in "magic mushrooms," which was also administered. By 1965 some type of hallucinogenic had been given to more than 40,000 patients.
Then came a sea change. Psychedelic drugs caught the public's attention and there was widespread experimentation. The association with Hippie counterculture alarmed many and led to a legal and cultural backlash that stigmatized psychedelics for decades to come. In the mid-1960s, psychedelics were designated Schedule 1 drugs in the U.S., meaning they were seen as having "no accepted medical use and a high potential of abuse." Schedule 1 also implied that the drugs were more dangerous than cocaine, methamphetamine, Vicodin, and oxycodone, a perception that was far from proven but became an institutionalized part of drug enforcement. Medical use ceased and research dwindled down to close to zero.
For years, research into hallucinogenic-assisted therapy was basically dormant, until the 1990s when interest started to revive. In the 2000s, the first modern clinical trials of psilocybin were done by Francisco Moreno at the University of Arizona and Matthew Johnson at Johns Hopkins. Scientists in the 2010s, including Robin Carhart-Harris, started studying the use of psychedelics in the treatment of major depressive disorder (MDD).
In small trials with these patients, results showed significant and long-term improvement (for at least six months) after only two episodes of psilocybin-assisted therapy. In several studies, the guided experience of administering one of the psychedelic drugs along with psychotherapy seemed to result in marked improvement in a variety of disorders, including depression, anxiety, PTSD, and addiction.
The drugs allowed patients to experience a radical reframing of reality, helping them to become "unstuck" from the anxious and negative tape loops that played in their heads. According to Michael Pollan, an American author and professor of journalism who wrote the book, "How to Change Your Mind: What the New Science of Psychedelics Teaches Us About Consciousness, Dying, Addiction, Depression and Transcendence," psychedelics allow patients to see their lives through a kind of wide angle, where boundaries vanish and they're able to experience "consciousness without self." This perspective is usually accompanied by profound feelings of oneness with the universe.
Pollan likens the effect to a fresh blanketing of snow over the deep ruts of unproductive thinking, which characterize depression and other mental disorders. Once the new snow has fallen, the ruts disappear and a new path can be chosen. Relief from symptoms comes immediately, and in numerous studies, is sustained for months.
In spite of growing evidence for the safety and efficacy of psychedelic-assisted psychotherapy, the practice has major hurdles to cross on its quest for FDA approval.
Some of the most influential studies have focused on testing the use of psilocybin to treat end-of-life anxiety in patients diagnosed with a terminal illness. In 2016, Stephen Ross and colleagues tested a single dose of psilocybin on 29 subjects with end-of-life anxiety due to a terminal cancer diagnosis. A control group received a niacin pill. The researchers reported that of the 29 receiving psilocybin, all of the patients had "immediate, substantial, and sustained clinical benefits," even after six months.
In spite of growing evidence for the safety and efficacy of psychedelic-assisted psychotherapy, the practice has major hurdles to cross on its quest for FDA approval. The National Institutes of Health is not currently supporting any clinical trials and the research relies on private sources of funding, often with small research organizations that cannot afford the high cost of clinical trials.
Given the controversial nature of the drugs, researchers in psychedelic-assisted therapies may be cautious about publicity. Leapsmag reached out to several leaders in the field but none agreed to an interview.
Still, interest is building in the combination of psychedelic drugs and psychotherapy for treatment-resistant mental illnesses. Two months ago, Johns Hopkins University launched a new psychedelic research center with an infusion of $17 million from private investors. The center will focus on psychedelic-assisted therapies for opioid addiction, Alzheimer's disease, PTSD and major depression, to name just a few. Currently, of 51 cancer patients enrolled in a Hopkins study, more than half reported a decrease in depression and anxiety after receiving therapy with psilocybin. Two thirds even claimed that the experience was one of the most meaningful of their lives.
It is not unheard of for Schedule 1 drugs to make their way into medical use if they're shown to provide a bonafide improvement in a medical condition through well-designed clinical trials. MDMA, for example, has been designated a Breakthrough Therapy by the FDA as part of an Investigational New Drug Application. The FDA has agreed to a special protocol assessment that could speed up phase three clinical trials. The next step is for the data to be submitted to the FDA for an in-depth regulatory review. If the FDA agrees, MDMA-assisted therapy could be legalized.
Will the positive buzz around psychedelics persuade the NIH to provide the millions of dollars needed to push the field forward?
Robin Carhart-Harris believes the first drug that will receive FDA clearance is psilocybin, which he speculates could become legal in the next five to ten years. However, the field of psychedelic-assisted therapy needs more and larger clinical trials, preferably with the support of the NIH.
As Rucker and colleagues noted, the scientific literature bends toward the theme that the drugs are not necessarily therapeutic in and of themselves. It's the use of hallucinogens within a "psychologically supportive context" with a trained expert that's helpful. It's currently unknown how many users of recreational drugs are self-medicating for depression, anxiety, or other mental illnesses. But without the guidance of a knowledgeable psychotherapist, those who are self-medicating may not be helping themselves at all.
Will the positive buzz around psychedelics persuade the NIH to provide the millions of dollars needed to push the field forward? Given the changing climate in public opinion around these drugs and the need for breakthroughs in mental health therapies, it's possible that in the foreseeable future, this bold new therapy will become part of the mental health arsenal.
In December 1958, on a vacation with his wife in Kenya, a 28-year-old British tea broker named Robin Cavendish became suddenly ill. Neither he nor his wife Diana knew it at the time, but Robin's illness would change the course of medical history forever.
Robin was rushed to a nearby hospital in Kenya where the medical staff delivered the crushing news: Robin had contracted polio, and the paralysis creeping up his body was almost certainly permanent. The doctors placed Robin on a ventilator through a tracheotomy in his neck, as the paralysis from his polio infection had rendered him unable to breathe on his own – and going off the average life expectancy at the time, they gave him only three months to live. Robin and Diana (who was pregnant at the time with their first child, Jonathan) flew back to England so he could be admitted to a hospital. They mentally prepared to wait out Robin's final days.
But Robin did something unexpected when he returned to the UK – just one of many things that would astonish doctors over the next several years: He survived. Diana gave birth to Jonathan in February 1959 and continued to visit Robin regularly in the hospital with the baby. Despite doctors warning that he would soon succumb to his illness, Robin kept living.
After a year in the hospital, Diana suggested something radical: She wanted Robin to leave the hospital and live at home in South Oxfordshire for as long as he possibly could, with her as his nurse. At the time, this suggestion was unheard of. People like Robin who depended on machinery to keep them breathing had only ever lived inside hospital walls, as the prevailing belief was that the machinery needed to keep them alive was too complicated for laypeople to operate. But Diana and Robin were up for the challenges – and the risks. Because his ventilator ran on electricity, if the house were to unexpectedly lose power, Diana would either need to restore power quickly or hand-pump air into his lungs to keep him alive.
Robin's wheelchair was not only the first of its kind; it became the model for the respiratory wheelchairs that people still use today.
In an interview as an adult, Jonathan Cavendish reflected on his parents' decision to live outside the hospital on a ventilator: "My father's mantra was quality of life," he explained. "He could have stayed in the hospital, but he didn't think that was as good of a life as he could manage. He would rather be two minutes away from death and living a full life."
After a few years of living at home, however, Robin became tired of being confined to his bed. He longed to sit outside, to visit friends, to travel – but had no way of doing so without his ventilator. So together with his friend Teddy Hall, a professor and engineer at Oxford University, the two collaborated in 1962 to create an entirely new invention: a battery-operated wheelchair prototype with a ventilator built in. With this, Robin could now venture outside the house – and soon the Cavendish family became famous for taking vacations. It was something that, by all accounts, had never been done before by someone who was ventilator-dependent. Robin and Hall also designed a van so that the wheelchair could be plugged in and powered during travel. Jonathan Cavendish later recalled a particular family vacation that nearly ended in disaster when the van broke down outside of Barcelona, Spain:
"My poor old uncle [plugged] my father's chair into the wrong socket," Cavendish later recalled, causing the electricity to short. "There was fire and smoke, and both the van and the chair ground to a halt." Johnathan, who was eight or nine at the time, his mother, and his uncle took turns hand-pumping Robin's ventilator by the roadside for the next thirty-six hours, waiting for Professor Hall to arrive in town and repair the van. Rather than being panicked, the Cavendishes managed to turn the vigil into a party. Townspeople came to greet them, bringing food and music, and a local priest even stopped by to give his blessing.
Robin had become a pioneer, showing the world that a person with severe disabilities could still have mobility, access, and a fuller quality of life than anyone had imagined. His mission, along with Hall's, then became gifting this independence to others like himself. Robin and Hall raised money – first from the Ernest Kleinwort Charitable Trust, and then from the British Department of Health – to fund more ventilator chairs, which were then manufactured by Hall's company, Littlemore Scientific Engineering, and given to fellow patients who wanted to live full lives at home. Robin and Hall used themselves as guinea pigs, testing out different models of the chairs and collaborating with scientists to create other devices for those with disabilities. One invention, called the Possum, allowed paraplegics to control things like the telephone and television set with just a nod of the head. Robin's wheelchair was not only the first of its kind; it became the model for the respiratory wheelchairs that people still use today.
Robin went on to enjoy a long and happy life with his family at their house in South Oxfordshire, surrounded by friends who would later attest to his "down-to-earth" personality, his sense of humor, and his "irresistible" charm. When he died peacefully at his home in 1994 at age 64, he was considered the world's oldest-living person who used a ventilator outside the hospital – breaking yet another barrier for what medical science thought was possible.
Sarah Watts is a health and science writer based in Chicago. Follow her on Twitter at @swattswrites.
In June 2012, Kirstie Ennis was six months into her second deployment to Afghanistan and recently promoted to sergeant. The helicopter gunner and seven others were three hours into a routine mission of combat resupplies and troop transport when their CH-53D helicopter went down hard.
Miraculously, all eight people onboard survived, but Ennis' injuries were many and severe. She had a torn rotator cuff, torn labrum, crushed cervical discs, facial fractures, deep lacerations and traumatic brain injury. Despite a severely fractured ankle, doctors managed to save her foot, for a while at least.
In November 2015, after three years of constant pain and too many surgeries to count, Ennis relented. She elected to undergo a lower leg amputation but only after she completed the 1,000-mile, 72-day Walking with the Wounded journey across the UK.
On Veteran's Day of that year, on the other side of the country, orthopedic surgeon Cato Laurencin announced a moonshot challenge he was setting out to achieve on behalf of wounded warriors like Ennis: the Hartford Engineering A Limb (HEAL) Project.
Laurencin, who is a University of Connecticut professor of chemical, materials and biomedical engineering, teamed up with experts in tissue bioengineering and regenerative medicine from Harvard, Columbia, UC Irvine and SASTRA University in India. Laurencin and his colleagues at the Connecticut Convergence Institute for Translation in Regenerative Engineering made a bold commitment to regenerate an entire limb within 15 years – by the year 2030.
Dr. Cato Laurencin pictured in his office at UConn.
Photo Credit: UConn
Regenerative Engineering -- A Whole New Field
Limb regeneration in humans has been a medical and scientific fascination for decades, with little to show for the effort. However, Laurencin believes that if we are to reach the next level of 21st century medical advances, this puzzle must be solved.
An estimated 185,000 people undergo upper or lower limb amputation every year. Despite the significant advances in electromechanical prosthetics, these individuals still lack the ability to perform complex functions such as sensation for tactile input, normal gait and movement feedback. As far as Laurencin is concerned, the only clinical answer that makes sense is to regenerate a whole functional limb.
Laurencin feels other regeneration efforts were hampered by their siloed research methods with chemists, surgeons, engineers all working separately. Success, he argues, requires a paradigm shift to a trans-disciplinary approach that brings together cutting-edge technologies from disparate fields such as biology, material sciences, physical, chemical and engineering sciences.
As the only surgeon ever inducted into the academies of Science, Medicine and Innovation, Laurencin is uniquely suited for the challenge. He is regarded as the founder of Regenerative Engineering, defined as the convergence of advanced materials sciences, stem cell sciences, physics, developmental biology and clinical translation for the regeneration of complex tissues and organ systems.
But none of this is achievable without early clinician participation across scientific fields to develop new technologies and a deeper understanding of how to harness the body's innate regenerative capabilities. "When I perform a surgical procedure or something is torn or needs to be repaired, I count on the body being involved in regenerating tissue," he says. "So, understanding how the body works to regenerate itself and harnessing that ability is an important factor for the regeneration process."
The Birth of the Vision
Laurencin's passion for regeneration began when he was a sports medicine fellow at Cornell University Medical Center in the early 1990s. There he saw a significant number of injuries to the anterior cruciate ligament (ACL), the major ligament that stabilizes the knee. He believed he could develop a better way to address those injuries using biomaterials to regenerate the ligament. He sketched out a preliminary drawing on a napkin one night over dinner. He has spent the next 30 years regenerating tissues, including the patented L-C ligament.
As chair of Orthopaedic Surgery at the University of Virginia during the peak of the wars in Iraq and Afghanistan, Laurencin treated military personnel who survived because of improved helmets, body armor and battlefield medicine but were left with more devastating injuries, including traumatic brain injuries and limb loss.
"I was so honored to care for them and I so admired their steadfast courage that I became determined to do something big for them," says Laurencin.
When he tells people about his plans to regrow a limb, he gets a lot of eye rolls, which he finds amusing but not discouraging. Growing bone cells was relatively new when he was first focused on regenerating bone in 1987 at MIT; in 2007 he was well on his way to regenerating ligaments at UVA when many still doubted that ligaments could even be reconstructed. He and his team have already regenerated torn rotator cuff tendons and ACL ligaments using a nano-textured fabric seeded with stem cells.
Even as a finalist for the $4 million NIH Pioneer Award for high-risk/high-reward research, he faced a skeptical scientific audience in 2014. "They said, 'Well what do you plan to do?' I said 'I plan to regenerate a whole limb in people.' There was a lot of incredulousness. They stared at me and asked a lot of questions. About three days later, I received probably the best score I've ever gotten on an NIH grant."
In the Thick of the Science
Humans are born with regenerative abilities--two-year-olds have regrown fingertips--but lose that ability with age. Salamanders are the only vertebrates that can regenerate lost body parts as adults; axolotl, the rare Mexican salamander, can grow extra limbs.
The axolotl is important as a model organism because it is a four-footed vertebrate with a similar body plan to humans. Mapping the axolotl genome in 2018 enhanced scientists' genetic understanding of their evolution, development, and regeneration. Being easy to breed in captivity allowed the HEAL team to closely study these amphibians and discover a new cell type they believe may shed light on how to mimic the process in humans.
"Whenever limb regeneration takes place in the salamander, there is a huge amount of something called heparan sulfate around that area," explains Laurencin. "We thought, 'What if this heparan sulfate is the key ingredient to allowing regeneration to take place?' We found these groups of cells that were interspersed in tissues during the time of regeneration that seemed to have connections to each other that expressed this heparan sulfate."
Called GRID (Groups that are Regenerative, Interspersed and Dendritic), these cells were also recently discovered in mice. While GRID cells don't regenerate as well in mice as in salamanders, finding them in mammals was significant.
"If they're found in mice. we might be able to find these in humans in some form," Laurencin says. "We think maybe it will help us figure out regeneration or we can create cells that mimic what grid cells do and create an artificial grid cell."
What Comes Next?
Laurencin and his team have individually engineered and made every single tissue in the lower limb, including bone, cartilage, ligament, skin, nerve, blood vessels. Regenerating joints and joint tissue is the next big mile marker, which Laurencin sees as essential to regenerating a limb that functions and performs in the way he envisions.
"Using stem cells and amnion tissue, we can regenerate joints that are damaged, and have severe arthritis," he says. "We're making progress on all fronts, and making discoveries we believe are going to be helping people along the way."
That focus and advancement is vital to Ennis. After laboring over the decision to have her leg amputated below the knee, she contracted MRSA two weeks post-surgery. In less than a month, she went from a below-the-knee-amputee to a through-the-knee amputee to an above-the-knee amputee.
"A below-the-knee amputation is night-and-day from above-the-knee," she said. "You have to relearn everything. You're basically a toddler."
Kirstie Ennis pictured in July 2020.
Photo Credit: Ennis' Instagram
The clock is ticking on the timeline Laurencin set for himself. Nine years might seem like forever if you're doing time but it might appear fleeting when you're trying to create something that's never been done before. But Laurencin isn't worried. He's convinced time is on his side.
"Every week, I receive an email or a call from someone, maybe a mother whose child has lost a finger or I'm in communication with a disabled American veteran who wants to know how the progress is going. That energizes me to continue to work hard to try to create these sorts of solutions because we're talking about people and their lives."
He devotes about 60 hours a week to the project and the roughly 100 students, faculty and staff who make up the HEAL team at the Convergence Institute seem acutely aware of what's at stake and appear equally dedicated.
"We're in the thick of the science in terms of making this happen," says Laurencin. "We've moved from making the impossible possible to making the possible a reality. That's what science is all about."