Rehabilitating psychedelic drugs: Another key to treating severe mental health disorders
A recent review paper found evidence that using psychedelics such as MDMA can help with treating a variety of common mental illnesses, but experts fear that research might easily be shut down in the future.
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.
Urinary tract infections account for more than 8 million trips to the doctor each year.
Few things are more painful than a urinary tract infection (UTI). Common in men and women, these infections account for more than 8 million trips to the doctor each year and can cause an array of uncomfortable symptoms, from a burning feeling during urination to fever, vomiting, and chills. For an unlucky few, UTIs can be chronic—meaning that, despite treatment, they just keep coming back.
But new research, presented at the European Association of Urology (EAU) Congress in Paris this week, brings some hope to people who suffer from UTIs.
Clinicians from the Royal Berkshire Hospital presented the results of a long-term, nine-year clinical trial where 89 men and women who suffered from recurrent UTIs were given an oral vaccine called MV140, designed to prevent the infections. Every day for three months, the participants were given two sprays of the vaccine (flavored to taste like pineapple) and then followed over the course of nine years. Clinicians analyzed medical records and asked the study participants about symptoms to check whether any experienced UTIs or had any adverse reactions from taking the vaccine.
The results showed that across nine years, 48 of the participants (about 54%) remained completely infection-free. On average, the study participants remained infection free for 54.7 months—four and a half years.
“While we need to be pragmatic, this vaccine is a potential breakthrough in preventing UTIs and could offer a safe and effective alternative to conventional treatments,” said Gernot Bonita, Professor of Urology at the Alta Bro Medical Centre for Urology in Switzerland, who is also the EAU Chairman of Guidelines on Urological Infections.
The news comes as a relief not only for people who suffer chronic UTIs, but also to doctors who have seen an uptick in antibiotic-resistant UTIs in the past several years. Because UTIs usually require antibiotics, patients run the risk of developing a resistance to the antibiotics, making infections more difficult to treat. A preventative vaccine could mean less infections, less antibiotics, and less drug resistance overall.
“Many of our participants told us that having the vaccine restored their quality of life,” said Dr. Bob Yang, Consultant Urologist at the Royal Berkshire NHS Foundation Trust, who helped lead the research. “While we’re yet to look at the effect of this vaccine in different patient groups, this follow-up data suggests it could be a game-changer for UTI prevention if it’s offered widely, reducing the need for antibiotic treatments.”
MILESTONE: Doctors have transplanted a pig organ into a human for the first time in history
A surgeon at Massachusetts General Hospital prepares a pig organ for transplant.
Surgeons at Massachusetts General Hospital made history last week when they successfully transplanted a pig kidney into a human patient for the first time ever.
The recipient was a 62-year-old man named Richard Slayman who had been living with end-stage kidney disease caused by diabetes. While Slayman had received a kidney transplant in 2018 from a human donor, his diabetes ultimately caused the kidney to fail less than five years after the transplant. Slayman had undergone dialysis ever since—a procedure that uses an artificial kidney to remove waste products from a person’s blood when the kidneys are unable to—but the dialysis frequently caused blood clots and other complications that landed him in the hospital multiple times.
As a last resort, Slayman’s kidney specialist suggested a transplant using a pig kidney provided by eGenesis, a pharmaceutical company based in Cambridge, Mass. The highly experimental surgery was made possible with the Food and Drug Administration’s “compassionate use” initiative, which allows patients with life-threatening medical conditions access to experimental treatments.
The new frontier of organ donation
Like Slayman, more than 100,000 people are currently on the national organ transplant waiting list, and roughly 17 people die every day waiting for an available organ. To make up for the shortage of human organs, scientists have been experimenting for the past several decades with using organs from animals such as pigs—a new field of medicine known as xenotransplantation. But putting an animal organ into a human body is much more complicated than it might appear, experts say.
“The human immune system reacts incredibly violently to a pig organ, much more so than a human organ,” said Dr. Joren Madsen, director of the Mass General Transplant Center. Even with immunosuppressant drugs that suppress the body’s ability to reject the transplant organ, Madsen said, a human body would reject an animal organ “within minutes.”
So scientists have had to use gene-editing technology to change the animal organs so that they would work inside a human body. The pig kidney in Slayman’s surgery, for instance, had been genetically altered using CRISPR-Cas9 technology to remove harmful pig genes and add human ones. The kidney was also edited to remove pig viruses that could potentially infect a human after transplant.
With CRISPR technology, scientists have been able to prove that interspecies organ transplants are not only possible, but may be able to successfully work long term, too. In the past several years, scientists were able to transplant a pig kidney into a monkey and have the monkey survive for more than two years. More recently, doctors have transplanted pig hearts into human beings—though each recipient of a pig heart only managed to live a couple of months after the transplant. In one of the patients, researchers noted evidence of a pig virus in the man’s heart that had not been identified before the surgery and could be a possible explanation for his heart failure.
So far, so good
Slayman and his medical team ultimately decided to pursue the surgery—and the risk paid off. When the pig organ started producing urine at the end of the four-hour surgery, the entire operating room erupted in applause.
Slayman is currently receiving an infusion of immunosuppressant drugs to prevent the kidney from being rejected, while his doctors monitor the kidney’s function with frequent ultrasounds. Slayman is reported to be “recovering well” at Massachusetts General Hospital and is expected to be discharged within the next several days.