Rehabilitating psychedelic drugs: Another key to treating severe mental health disorders
Lori Tipton's life was a cascade of trauma that even a soap opera would not dare inflict upon a character: a mentally unstable family; a brother who died of a drug overdose; the shocking discovery of the bodies of two persons her mother had killed before turning the gun on herself; the devastation of Hurricane Katrina that savaged her hometown of New Orleans; being raped by someone she trusted; and having an abortion. She suffered from severe PTSD.
“My life was filled with anxiety and hypervigilance,” she says. “I was constantly afraid and had mood swings, panic attacks, insomnia, intrusive thoughts and suicidal ideation. I tried to take my life more than once.” She was fortunate to be able to access multiple mental health services, “And while at times some of these modalities would relieve the symptoms, nothing really lasted and nothing really address the core trauma.”
Then in 2018 Tipton enrolled in a clinical trial that combined intense sessions of psychotherapy with limited use of Methylenedioxymethamphetamine, or MDMA, a drug classified as a psychedelic and commonly known as ecstasy or Molly. The regimen was arduous; 1-2 hour preparation sessions, three sessions where MDMA was used, which lasted 6-8 hours, and lengthy sessions afterward to process and integrate the experiences. Two therapists were with her every moment of the three-month program that totaled more than 40 hours.
“It was clear to me that [the therapists] weren't going to heal me, that I was going to have to do the work for myself, but that they were there to completely support my process,” she says. “But the effects of MDMA were really undeniable for me. I felt embodied in a way that I hadn't in years. PTSD had robbed me of the ability to feel safe in my own body.”
Tipton doesn’t think the therapy completely cured her PTSD. “But when I completed the trial in 2018, I no longer qualified for the diagnosis, and I still don't qualify for the diagnosis today,” she told an April workshop on psychedelics as mental health treatment by the National Academies of Sciences, Engineering and Medicine, or NASEM.
A Champion
Rick Doblin has been a catalyst behind much of the contemporary research into psychedelics. Prior to the DEA clamp down, the Boston psychotherapist had seen that MDMA and other psychedelics could benefit some of his patients where other measures had failed. He immediately organized efforts to question the drug rescheduling but to little avail. In 1986, he created the nonprofit Multidisciplinary Association for Psychedelic Studies (MAPS), which slowly laid the scientific foundation for clinical trials, including the one that Tipton joined, using psychedelics to treat mental health conditions.
Now, only slowly, have researchers been able to explore the power of these drugs to treat a broad spectrum of severely debilitating mental health conditions, including trauma, depression, and PTSD, where other available treatments proved inadequate.
“Psychedelic psychotherapy is an attempt to go after the root causes of the problems with just a relatively few administrations, as contrasted to most of the psychiatric drugs used today that are mostly just reducing symptoms and are meant to be taken on a daily basis,” Doblin said in a 2019 TED Talk. Most of these drugs can have broad effect but “some are probably more effective than others for certain conditions,” he added in a recent interview with Leaps.org. Comparative head-to-head studies of psychedelic therapies simply have not been conducted.
Their mechanisms of action are poorly understood and can vary between drugs, but it is generally believed that psychedelics change the activity of neurons so that the brain processes information differently, says Katrin Preller, a neuropsychologist at the University of Zurich. A recent important study in Nature Medicine by Richard Daws and colleagues used functional magnetic resonance imaging (fMRI) of the brain and found that “functional networks became more functionally interconnected and flexible after psilocybin treatment…implying that psilocybin's antidepressant action may depend on a global increase in brain network integration.”
Rosalind Watts, a clinical investigator at the Imperial College in London, believes there is “an overestimation of the importance of the drug and an underestimation of the importance of the [therapeutic] context” in psychedelic research. “It is unethical to provide the drug without the other,” she says. Doblin notes that “psychotherapy outcomes research demonstrates that the therapeutic alliance between the therapist and the patients is the single most predictive factor of outcomes. [It is] trust and the sense of safety, the willingness to go into difficult spaces” that makes clinical breakthroughs possible with the drug.
Excitement and Challenges
Recurrent themes expressed at the NASEM workshop were exciting glimpses of the potential for psychedelics to treat mental health conditions combined with the challenges of realizing those potentials. A recent review paper found evidence that using psychedelics can help with treating a variety of common mental illnesses, but the paper could identify only 14 clinical trials of classic psychedelics published since 1991. Much of the reason is that the drugs are not patentable and so the pharmaceutical industry has no interest in investing in expensive clinical trials to bring them to market. MAPS has raised about $135 million over its 36-year history to conduct such research, says Doblin, the vast majority of it from individual donors and none from foundations.
The workshop participants’ views also were colored by the history of drug crackdowns and a fear that research might easily be shut down in the future. There was great concern that use of psychedelics should be confined to clinical trials with high safety and ethical standards, instead of doctors and patients experimenting on their own. “We need to get it right this time,” says Charles Grob, a psychiatrist at the UCLA School of Medicine. But restricting access to psychedelics will become even more difficult now that Oregon and several cities have acted to decriminalize possession and use of many of these drugs.
The experience with ketamine also troubled Grob. He is hoping to “mitigate the rush of rapid commercialization” that occurred with that drug. Ketamine technically is not a psychedelic though it does share some of their potentially euphoric properties. In 2019, soon after the FDA approved a form of ketamine with a limited label indication to treat depression, for profit clinics sprang up promoting off label use of the drug for psychiatric conditions where there was little clinical evidence of efficacy. He fears the same thing will happen when true psychedelics are made available.
If these therapies are approved, access to them is likely to be a problem. The drugs themselves are cheap but the accompanying therapy is not, and there is a shortage of trained psychotherapists. Mental health services often are not adequately covered by health insurance, while the poor and people of color suffer additional burdens of inadequate access. Doblin is committed to health care equity by training additional providers and by investigating whether some of the preparatory and integration sessions might be handled in a group setting. He says it is important that the legal aspects of psychedelics also be addressed so that patients “don't have to go underground” in order to receive this care.
These doctors have a heart for recycling
This is part 3 of a three part series on a new generation of doctors leading the charge to make the health care industry more sustainable - for the benefit of their patients and the planet. Read part 1 here and part 2 here.
One could say that over 400 people owe their life to the fact that Carsten Israel fell in love. Twenty years ago, as a young doctor in Frankfurt, Germany, he began to court an au pair from Kenya, Elisabeth, his now-wife of 13 years with whom he has three children. When the couple started visiting her parents in Kenya, Israel wanted to check out the local hospitals, “just out of professional curiosity,“ says the cardiologist, who is currently the head doctor at the Clinic for Interior Medicine in Bielefeld. “I was completely shocked.“
Often he observed there were no doctors in the E.R.s, and hte nurses could render only basic first aid. “When somebody fell into a coma, they fell into a coma,“ Israel remembers. “There weren’t even any defibrillators to restart a patient’s heart,” while defibrillators are standard equipment in most clinics in the U.S. and Europe as lifesaving devices. When Israel finally visited the largest and most modern hospital in Nairobi, he found it better equipped but he learned that its services were only available to patients who could afford them. The cardiologist there had a drawer full of petitions from patients with heart ailments who couldn’t afford lifesaving surgery. Even two decades ago, a pacemaker cost $5,000 in Kenya, which made it unaffordable for most Kenyans who earn an average of $600 per month.
Since 2003, Israel and a team of two doctors and two nurses visit Kenya and Zambia once or twice a year to implant German pacemakers for free. Notably, the pacemakers and defibrillators Israel exports to Africa would end up in the landfill in Germany. Clinics have to pay for specialized services to dispose of this medical equipment. “In Germany, I could go to jail if I used a defibrillator that is one day past its expiration date,“ Israel says, “but in Kenya, people don’t have the money for the cheapest model. What nonsense to throw this precious medical equipment away while people in poorer countries die because they desperately need it.“
Israel works at the breakpoint between the laws in a wealthy country like Germany and the reality in the global South. The U.S. and most European countries have strict laws that ban the reuse of medical implants and enforce strict expiration dates for medical equipment. “But if a pacemaker is a few days past its expiration date, it still works perfectly fine,“ Israel says. “And it also happens that we implant a pacemaker and five months later it turns out that the patient needs a different kind. Then we replace it and we’d have to trash the first one in Germany, though it could easily run another 12 years.“
“If we get this right, we have lots of devices we can implant, hips and knees, etcetera. Where this will lead is limitless," says Eva Kline Rogers, the program coordinator for My Heart, Your Heart.
Israel has been collecting donations of pacemakers and defibrillators from manufacturers but also from other doctors and from funeral homes for his nonprofit Pacemakers for East Africa since 2003. Most funeral homes in the U.S. and Europe are legally obliged to remove pacemakers from the dead before cremation. “Most pacemakers survive their owners,“ says Israel. He sterilizes the pacemakers and finds them a new life in East Africa. Studies show that reused pacemakers carry no greater risk for the patients than new ones.
In the U.S., University of Michigan professor Thomas Crawford heads up a similar initiative, My Heart, Your Heart. “Each year 1 to 2 million individuals worldwide die due to a lack of access to pacemakers and defibrillators,” the organization notes on its website. The nonprofit was founded in 2009, but it took four years for the doctors to get permission from the FDA to export pacemakers. Since receiving permission, the organization has sent dozens of devices to the Philippines, Haiti, Venezuela, Kenya, Sierra Leone and Ukraine. “We were the first doctors ever to implant a pacemaker in Sierra Leone in 2018,” says Crawford, who has traveled extensively to most of the recipient countries.
Even individuals can donate their pacemakers; the organization offers a prepaid envelope. “My mother recently passed and she donated her device,” says Tina Alexandris-Souphis, one of the doctors at University of Michigan who collaborates on My Heart, Your Heart. The organization works with World Medical Relief and the U.K. based charity Pace4Life to maintain a registry of the most urgent patients and send devices to where they are needed the most.
My Heart, Your Heart is also conducting a randomized controlled trial to provide further evidence that reused pacemakers pose no additional risk. “Our vision is that we establish this is safe and create a blueprint for organizations around the world to safely reuse these devices instead of them being thrown in the trash,” says Eva Kline Rogers, the program’s coordinator. “If we get this right, we have lots of devices we can implant, hips and knees, etc. Where this will lead is limitless.” She points out that in addition to receiving the donated devices, the doctors in the global South also benefit from the expertise of renowned cardiologists, such as Crawford, who sometimes advise them in complex cases.
And Adrian Baranchuk, a Canadian doctor at the Kingston General Hospital at the Queen’s University, regularly travels through South America with his “cardiology van” to help villagers in remote areas with heart problems.
Israel says that he’s been accused of racism, in thinking that these pacemakers are suitable for those in the global South - many of whom are people of color - even though officials in wealthier countries consider them to be trash. The cardiologist counters such criticism with stories about desperate need of his patients. At his first medical visit to Nairobi that he organized with a local cardiologist, six patients were waiting for him. “In Germany, they would all be considered emergencies,” Israel says. One eighty-year old grandmother had a heartrate of 18. “I’ve never before seen anything like this,” Israel exclaims. “At first I thought I couldn’t find her pulse before I realized that her heart was only beating once every three seconds.” After the surgery, she got up, dressed herself and hurriedly packed her bag, explaining she had a ton of work to accomplish. Her family was in disbelief, Israel says. “They told me she had been bedridden for five years because as soon as she tried to get up she would faint.”
Israel has been accused of racism, in thinking that these pacemakers are suitable for those in the global South even though they're considered to be trash by officials in wealthier countries. The cardiologist counters such criticism with stories about desperate need of his patients.
Carsten Israel
The hospital in Nairobi where Israel conducts the surgeries, charges patients $200 for the use of its facilities. If patients can’t afford that sum, Israel will pay it from the funds of his nonprofit. For some people, $200 far exceeds their resources. Once, a family from the extremely poor Northern region of Kenya told him they couldn’t afford the $3 for the bus ride to Nairobi. Israel suspected this was a pretense because they were afraid of the surgery and agreed to reimburse the $3, “but when they came, they were wearing rags and were so rail-thin, I understood that they really needed every cent they had for food.”
Israel is a renowned cardiologists in Germany. And yet, he considers his work in East Africa to be particularly meaningful. “Generally, most patients in Germany will get the treatment they need,” he says, “and I never before experienced that people have an illness that is easily curable but simply won’t be treated.” He also feels a heavy responsibility. Many patients have his personal cell phone and call him when they have problems or good news about how they’re doing.
Some of those progress reports come much faster than in Israel’s home country. Before he implanted a pacemaker in a tall Massai in Kenya, the man had been picked on by his family because he wouldn’t help much with the hard work on the family peanut farm. “When I examined him, he had a pulse of 40,” Israel says. “It’s a miracle he was even standing upright, let alone hauling heavy bags.” After the surgery, Israel advised his patient to stay the night for observation, but the patient couldn’t wait to leave. Two hours later, he returned, covered in sweat. He’d been running sprints with his brothers to test the new device. Israel shakes his head. In Germany, it would be unthinkable for a patient to engage in athletics immediately after surgery. But the patient was exuberant: “I was the fastest!”
The success stories are notable partly because the challenges remain so steep. In Zambia, for instance, there is a single cardiologist; she determined to become one after losing her younger sister to an easily curable heart disease. Often, the hospitals not only lack pacemakers but also sterile surgery equipment, antibiotics and other essential material. Therefore, Israel and his team import everything they need for the surgeries, including medication. If necessary, they improvise. “I’ve done surgery with a desk lamp hanging from the ceiling by threads,” Israel says. He already knows that he will need to return to Kenya in six months to replace the pacemaker of one of his patients and replace the batteries in others. If he doesn’t travel, lives are at risk.These technologies may help more animals and plants survive climate change
This article originally appeared in One Health/One Planet, a single-issue magazine that explores how climate change and other environmental shifts are making us more vulnerable to infectious diseases by land and by sea - and how scientists are working on solutions.
Along the west coast of South Florida and the Keys, Florida Bay is a nursery for young Caribbean spiny lobsters, a favorite local delicacy. Growing up in small shallow basins, they are especially vulnerable to warmer, more saline water. Climate change has brought tidal floods, bleached coral reefs and toxic algal blooms to the state, and since the 1990s, the population of the Caribbean spiny lobster has dropped some 20 percent, diminishing an important food for snapper, grouper, and herons, as well as people. In 1999, marine ecologist Donald Behringer discovered the first known virus among lobsters, Panulirus argus virus—about a quarter of juveniles die from it before they mature.
“When the water is warm PaV1 progresses much more quickly,” says Behringer, who is based at the Emerging Pathogens Institute at the University of Florida in Gainesville.
Caribbean spiny lobsters are only one example of many species that are struggling in the era of climate change, both at sea and on land. As the oceans heat up, absorbing greenhouse gases and growing more acidic, marine diseases are emerging at an accelerated rate. Marine creatures are migrating to new places, and carrying pathogens with them. The latest grim report in the journal Science, states that if global warming continues at the current rate, the extinction of marine species will rival the Permian–Triassic extinction, sometimes called the “Great Dying,” when volcanoes poisoned the air and wiped out as much as 90 percent of all marine life 252 million years ago.
Similarly, on land, climate change has exposed wildlife, trees and crops to new or more virulent pathogens. Warming environments allow fungi, bacteria, viruses and infectious worms to proliferate in new species and locations or become more virulent. One paper modeling records of nearly 1,400 wildlife species projects that parasites will double by 2070 in the far north and in high-altitude places. Right now, we are seeing the effects most clearly on the fringes—along the coasts, up north and high in the mountains—but as the climate continues changing, the ripples will reach everywhere.
Few species are spared
On the Hawaiian Islands, mosquitoes are killing more songbirds. The dusky gray akikiki of Kauai and the chartreuse-yellow kiwikiu of Maui could vanish in two years, under assault from mosquitoes bearing avian malaria, according to a University of Hawaiʻi 2022 report. Previously, the birds could escape infection by roosting high in the cold mountains, where the pests couldn’t thrive, but climate change expanded the range of the mosquito and narrowed theirs.
Likewise, as more midge larvae survive over warm winters and breed better during drier summers, they bite more white-tailed deer, spreading often-fatal epizootic hemorrhagic disease. Especially in northern regions of the globe, climate change brings the threat of midges carrying blue tongue disease, a virus, to sheep and other animals. Tick-borne diseases like encephalitis and Lyme disease may become a greater threat to animals and perhaps humans.
"If you put all your eggs in one basket and then a pest comes a long, then you are more vulnerable to those risks," says Mehroad Ehsani, managing director of the food initiative in Africa for the Rockefeller Foundation. "Research is needed on resilient, climate smart, regenerative agriculture."
In the “thermal mismatch” theory of wildlife disease, cold-adapted species are at greater risk when their habitats warm, and warm-adapted species suffer when their habitats cool. Mammals can adjust their body temperature to adapt to some extent. Amphibians, fish and insects that cannot regulate body temperatures may be at greater risk. Many scientists see amphibians, especially, as canaries in the coalmine, signaling toxicity.
Early melting ice can foster disease. Climate models predict that the spring thaw will come ever-earlier in the lakes of the French Pyrenees, for instance, which traditionally stayed frozen for up to half the year. The tadpoles of the midwife toad live under the ice, where they are often infected with amphibian chytrid fungus. When a seven-year study tracked the virus in three species of amphibians in Pyrenees’s Lac Arlet, the research team found that, the earlier the spring thaw arrived, the more infection rates rose in common toads— , while remaining high among the midwife toads. But the team made another sad discovery: with early thaws, the common frog, which was thought to be free of the disease in Europe, also became infected with the fungus and died in large numbers.
Changing habitats affect animal behavior. Normally, spiny lobsters rely on chemical cues to avoid predators and sick lobsters. New conditions may be hampering their ability to “social distance”—which may help PaV1 spread, Behringer’s research suggests. Migration brings other risks. In April 2022, an international team led by scientists at Georgetown University announced the first comprehensive overview, published in the journal Nature, of how wild mammals under pressure from a changing climate may mingle with new populations and species—giving viruses a deadly opportunity to jump between hosts. Droughts, for example, will push animals to congregate at the few places where water remains.
Plants face threats also. At the timberline of the cold, windy, snowy mountains of the U.S. west, whitebark pine forests are facing a double threat, from white pine blister rust, a fungal disease, and multiplying pine beetles. “If we do nothing, we will lose the species,” says Robert Keane, a research ecologist for the U.S. Forest Service, based in Missoula, Montana. That would be a huge shift, he explains: “It’s a keystone species. There are over 110 animals that depend on it, many insects, and hundreds of plants.” In the past, beetle larvae would take two years to complete their lifecycle, and many died in frost. “With climate change, we're seeing more and more beetles survive, and sometimes the beetle can complete its lifecycle in one year,” he says.
Quintessential crops are under threat too
As some pathogens move north and new ones develop, they pose novel threats to the crops humans depend upon. This is already happening to wheat, coffee, bananas and maize.
Breeding against wheat stem rust, a fungus long linked to famine, was a key success in the mid-20th century Green Revolution, which brought higher yields around the world. In 2013, wheat stem rust reemerged in Germany after decades of absence. It ravaged both bread and durum wheat in Sicily in 2016 and has spread as far as England and Ireland. Wheat blast disease, caused by a different fungus, appeared in Bangladesh in 2016, and spread to India, the world’s second largest producer of wheat.
Insects, moths, worms, and coffee leaf rust—a fungus now found in all coffee-growing countries—threaten the livelihoods of millions of people who grow coffee, as well as everybody’s cup of joe. More heat, more intense rain, and higher humidity have allowed coffee leaf rust to cycle more rapidly. It has grown exponentially, overcoming the agricultural chemicals that once kept it under control.
To identify new diseases and fine-tune crops for resistance, scientists are increasingly relying on genomic tools.
Tar spot, a fungus native to Latin America that can cut corn production in half, has emerged in highland areas of Central Mexico and parts of the U.S.. Meanwhile, maize lethal necrosis disease has spread to multiple countries in Africa, notes Mehrdad Ehsani, Managing Director for the Food Initiative in Africa of the Rockefeller Foundation. The Cavendish banana, which most people eat today, was bred to be resistant to the fungus Panama 1. Now a new fungus, Panama 4, has emerged on every continent–including areas of Latin America that rely on the Cavendish for their income, reported a recent story in the Guardian. New threats are poised to emerge. Potato growers in the Andes Mountains have been shielded from disease because of colder weather at high altitude, but temperature fluxes and warming weather are expected to make this crop vulnerable to potato blight, found plant pathologist Erica Goss, at the Emerging Pathogens Institute.
Science seeks solutions
To protect food supplies in the era of climate change, scientists are calling for integrated global surveillance systems for crop disease outbreaks. “You can imagine that a new crop variety that is drought-tolerant could be susceptible to a pathogen that previous varieties had some resistance against,” Goss says. “Or a country suffers from a calamitous weather event, has to import seed from another country, and that seed is contaminated with a new pathogen or more virulent strain of an existing pathogen.” Researchers at the John Innes Center in Norwich and Aarhus University in Denmark have established ways to monitor wheat rust, for example.
Better data is essential, for both plants and animals. Historically, models of climate change predicted effects on plant pathogens based on mean temperatures, and scientists tracked plant responses to constant temperatures, explains Goss. “There is a need for more realistic tests of the effects of changing temperatures, particularly changes in daily high and low temperatures on pathogens,” she says.
To identify new diseases and fine-tune crops for resistance, scientists are increasingly relying on genomic tools. Goss suggests factoring the impact of climate change into those tools. Genomic efforts to select soft red winter wheat that is resistant to Fusarium head blight (FHB), a fungus that plagues farmers in the Southeastern U.S., have had early success. But temperature changes introduce a new factor.
A fundamental solution would be to bring back diversification in farming, says Ehsani. Thousands of plant species are edible, yet we rely on a handful. Wild relatives of domesticated crops are a store of possibly useful genes that may confer resistance to disease. The same is true for livestock. “If you put all your eggs in one basket and then a pest comes along, then you are more vulnerable to those risks. Research is needed on resilient, climate smart, regenerative agriculture,” Ehsani says.
Jonathan Sleeman, director of the U.S. Geological Survey National Wildlife Health Center, has called for data on wildlife health to be systematically collected and integrated with climate and other variables because more comprehensive data will result in better preventive action. “We have focused on detecting diseases,” he says, but a more holistic strategy would apply human public health concepts to assuring animal wellbeing. (For example, one study asked experts to draw a diagram of relationships of all the factors affecting the health of a particular group of caribou.) We must not take the health of plants and animals for granted, because their vulnerability inevitably affects us too, Sleeman says. “We need to improve the resilience of wildlife populations so they can withstand the impact of climate change.”