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.
A newly discovered brain cell may lead to better treatments for cognitive disorders
Swiss researchers have discovered a third type of brain cell that appears to be a hybrid of the two other primary types — and it could lead to new treatments for many brain disorders.
The challenge: Most of the cells in the brain are either neurons or glial cells. While neurons use electrical and chemical signals to send messages to one another across small gaps called synapses, glial cells exist to support and protect neurons.
Astrocytes are a type of glial cell found near synapses. This close proximity to the place where brain signals are sent and received has led researchers to suspect that astrocytes might play an active role in the transmission of information inside the brain — a.k.a. “neurotransmission” — but no one has been able to prove the theory.
A new brain cell: Researchers at the Wyss Center for Bio and Neuroengineering and the University of Lausanne believe they’ve definitively proven that some astrocytes do actively participate in neurotransmission, making them a sort of hybrid of neurons and glial cells.
According to the researchers, this third type of brain cell, which they call a “glutamatergic astrocyte,” could offer a way to treat Alzheimer’s, Parkinson’s, and other disorders of the nervous system.
“Its discovery opens up immense research prospects,” said study co-director Andrea Volterra.
The study: Neurotransmission starts with a neuron releasing a chemical called a neurotransmitter, so the first thing the researchers did in their study was look at whether astrocytes can release the main neurotransmitter used by neurons: glutamate.
By analyzing astrocytes taken from the brains of mice, they discovered that certain astrocytes in the brain’s hippocampus did include the “molecular machinery” needed to excrete glutamate. They found evidence of the same machinery when they looked at datasets of human glial cells.
Finally, to demonstrate that these hybrid cells are actually playing a role in brain signaling, the researchers suppressed their ability to secrete glutamate in the brains of mice. This caused the rodents to experience memory problems.
“Our next studies will explore the potential protective role of this type of cell against memory impairment in Alzheimer’s disease, as well as its role in other regions and pathologies than those explored here,” said Andrea Volterra, University of Lausanne.
But why? The researchers aren’t sure why the brain needs glutamatergic astrocytes when it already has neurons, but Volterra suspects the hybrid brain cells may help with the distribution of signals — a single astrocyte can be in contact with thousands of synapses.
“Often, we have neuronal information that needs to spread to larger ensembles, and neurons are not very good for the coordination of this,” researcher Ludovic Telley told New Scientist.
Looking ahead: More research is needed to see how the new brain cell functions in people, but the discovery that it plays a role in memory in mice suggests it might be a worthwhile target for Alzheimer’s disease treatments.
The researchers also found evidence during their study that the cell might play a role in brain circuits linked to seizures and voluntary movements, meaning it’s also a new lead in the hunt for better epilepsy and Parkinson’s treatments.
“Our next studies will explore the potential protective role of this type of cell against memory impairment in Alzheimer’s disease, as well as its role in other regions and pathologies than those explored here,” said Volterra.
Researchers claimed they built a breakthrough superconductor. Social media shot it down almost instantly.
Harsh Mathur was a graduate physics student at Yale University in late 1989 when faculty announced they had failed to replicate claims made by scientists at the University of Utah and the University of Wolverhampton in England.
Such work is routine. Replicating or attempting to replicate the contraptions, calculations and conclusions crafted by colleagues is foundational to the scientific method. But in this instance, Yale’s findings were reported globally.
“I had a ringside view, and it was crazy,” recalls Mathur, now a professor of physics at Case Western Reserve University in Ohio.
Yale’s findings drew so much attention because initial experiments by Stanley Pons of Utah and Martin Fleischmann of Wolverhampton led to a startling claim: They were able to fuse atoms at room temperature – a scientific El Dorado known as “cold fusion.”
Nuclear fusion powers the stars in the universe. However, star cores must be at least 23.4 million degrees Fahrenheit and under extraordinary pressure to achieve fusion. Pons and Fleischmann claimed they had created an almost limitless source of power achievable at any temperature.
Like fusion, superconductivity can only be achieved in mostly impractical circumstances.
But about six months after they made their startling announcement, the pair’s findings were discredited by researchers at Yale and the California Institute of Technology. It was one of the first instances of a major scientific debunking covered by mass media.
Some scholars say the media attention for cold fusion stemmed partly from a dazzling announcement made three years prior in 1986: Scientists had created the first “superconductor” – material that could transmit electrical current with little or no resistance. It drew global headlines – and whetted the public’s appetite for announcements of scientific breakthroughs that could cause economic transformations.
But like fusion, superconductivity can only be achieved in mostly impractical circumstances: It must operate either at temperatures of at least negative 100 degrees Fahrenheit, or under pressures of around 150,000 pounds per square inch. Superconductivity that functions in closer to a normal environment would cut energy costs dramatically while also opening infinite possibilities for computing, space travel and other applications.
In July, a group of South Korean scientists posted material claiming they had created an iron crystalline substance called LK-99 that could achieve superconductivity at slightly above room temperature and at ambient pressure. The group partners with the Quantum Energy Research Centre, a privately-held enterprise in Seoul, and their claims drew global headlines.
Their work was also debunked. But in the age of internet and social media, the process was compressed from half-a-year into days. And it did not require researchers at world-class universities.
One of the most compelling critiques came from Derrick VanGennep. Although he works in finance, he holds a Ph.D. in physics and held a postdoctoral position at Harvard. The South Korean researchers had posted a video of a nugget of LK-99 in what they claimed was the throes of the Meissner effect – an expulsion of the substance’s magnetic field that would cause it to levitate above a magnet. Unless Hollywood magic is involved, only superconducting material can hover in this manner.
That claim made VanGennep skeptical, particularly since LK-99’s levitation appeared unenthusiastic at best. In fact, a corner of the material still adhered to the magnet near its center. He thought the video demonstrated ferromagnetism – two magnets repulsing one another. He mixed powdered graphite with super glue, stuck iron filings to its surface and mimicked the behavior of LK-99 in his own video, which was posted alongside the researchers’ video.
VanGennep believes the boldness of the South Korean claim was what led to him and others in the scientific community questioning it so quickly.
“The swift replication attempts stemmed from the combination of the extreme claim, the fact that the synthesis for this material is very straightforward and fast, and the amount of attention that this story was getting on social media,” he says.
But practicing scientists were suspicious of the data as well. Michael Norman, director of the Argonne Quantum Institute at the Argonne National Laboratory just outside of Chicago, had doubts immediately.
Will this saga hurt or even affect the careers of the South Korean researchers? Possibly not, if the previous fusion example is any indication.
“It wasn’t a very polished paper,” Norman says of the Korean scientists’ work. That opinion was reinforced, he adds, when it turned out the paper had been posted online by one of the researchers prior to seeking publication in a peer-reviewed journal. Although Norman and Mathur say that is routine with scientific research these days, Norman notes it was posted by one of the junior researchers over the doubts of two more senior scientists on the project.
Norman also raises doubts about the data reported. Among other issues, he observes that the samples created by the South Korean researchers contained traces of copper sulfide that could inadvertently amplify findings of conductivity.
The lack of the Meissner effect also caught Mathur’s attention. “Ferromagnets tend to be unstable when they levitate,” he says, adding that the video “just made me feel unconvinced. And it made me feel like they hadn't made a very good case for themselves.”
Will this saga hurt or even affect the careers of the South Korean researchers? Possibly not, if the previous fusion example is any indication. Despite being debunked, cold fusion claimants Pons and Fleischmann didn’t disappear. They moved their research to automaker Toyota’s IMRA laboratory in France, which along with the Japanese government spent tens of millions of dollars on their work before finally pulling the plug in 1998.
Fusion has since been created in laboratories, but being unable to reproduce the density of a star’s core would require excruciatingly high temperatures to achieve – about 160 million degrees Fahrenheit. A recently released Government Accountability Office report concludes practical fusion likely remains at least decades away.
However, like Pons and Fleischman, the South Korean researchers are not going anywhere. They claim that LK-99’s Meissner effect is being obscured by the fact the substance is both ferromagnetic and diamagnetic. They have filed for a patent in their country. But for now, those claims remain chimerical.
In the meantime, the consensus as to when a room temperature superconductor will be achieved is mixed. VenGennep – who studied the issue during his graduate and postgraduate work – puts the chance of creating such a superconductor by 2050 at perhaps 50-50. Mathur believes it could happen sooner, but adds that research on the topic has been going on for nearly a century, and that it has seen many plateaus.
“There's always this possibility that there's going to be something out there that we're going to discover unexpectedly,” Norman notes. The only certainty in this age of social media is that it will be put through the rigors of replication instantly.