To summarize and systematically review the efficacy and safety of high frequency repetitive transcranial magnetic stimulation (HF-rTMS) for depression in stroke patients.
Date: March 11, 2019
Source: University of North Carolina Health Care
Summary: With a weak alternating electrical current sent through electrodes attached to the scalp, researchers successfully targeted a naturally occurring electrical pattern in a specific part of the brain and markedly improved depression symptoms in about 70 percent of participants in a clinical study.
The research, published in Translational Psychiatry, lays the groundwork for larger research studies to use a specific kind of electrical brain stimulation called transcranial alternating current stimulation (tACS) to treat people diagnosed with major depression.
“We conducted a small study of 32 people because this sort of approach had never been done before,” said senior author Flavio Frohlich, PhD, associate professor of psychiatry and director of the Carolina Center for Neurostimulation. “Now that we’ve documented how this kind of tACS can reduce depression symptoms, we can fine tune our approach to help many people in a relatively inexpensive, noninvasive way.”
Frohlich, who joined the UNC School of Medicine in 2011, is a leading pioneer in this field who also published the first clinical trials of tACS in schizophrenia and chronic pain.
His tACS approach is unlike the more common brain stimulation technique called transcranial direct stimulation (tDCS), which sends a steady stream of weak electricity through electrodes attached to various parts of the brain. That approach has had mixed results in treating various conditions, including depression. Frohlich’s tACS paradigm is newer and has not been investigated as thoroughly as tDCS. Frohlich’s approach focuses on each individual’s specific alpha oscillations, which appear as waves between 8 and 12 Hertz on an electroencephalogram (EEG). The waves in this range rise in predominance when we close our eyes and daydream, meditate, or conjure ideas — essentially when our brains shut out sensory stimuli, such as what we see, feel, and hear.
Previous research showed that people with depression featured imbalanced alpha oscillations; the waves were overactive in the left frontal cortex. Frohlich thought his team could target these oscillations to bring them back in synch with the alpha oscillations in the right frontal cortex. And if Frohlich’s team could achieve that, then maybe depression symptoms would be decreased.
His lab recruited 32 people diagnosed with depression and surveyed each participant before the study, according to the Montgomery-Åsberg Depression Rating Scale (MADRS), a standard measure of depression.
The participants were then separated into three groups. One group received the sham placebo stimulation — a brief electrical stimulus to mimic the sensation at the beginning of a tACS session. A control group received a 40-Hertz tACS intervention, well outside the range that the researchers thought would affect alpha oscillations. A third group received the treatment intervention — a 10-Hertz tACS electrical current that targeted each individual’s naturally occurring alpha waves. Each person underwent their invention for 40 minutes on five consecutive days. None of the participants knew which group they were in, and neither did the researchers, making this a randomized double-blinded clinical study — the gold standard in biomedical research. Each participant took the MADRS immediately following the five-day regimen, at two weeks, and again at four weeks.
Prior to the study, Frohlich set the primary outcome at four weeks, meaning that the main goal of the study was to assess whether tACS could bring each individual’s alpha waves back into balance and decrease symptoms of depression four weeks after the five-day intervention. He set this primary outcome because scientific literature on the study of tDCS also used the four-week mark.
Frohlich’s team found that participants in the 10-Hertz tACS group featured a decrease in alpha oscillations in the left frontal cortex; they were brought back in synch with the right side of the frontal cortex. But the researchers did not find a statistically significant decrease in depression symptoms in the 10-Hertz tACS group, as opposed to the sham or control groups at four weeks.
But when Frohlich’s team looked at data from two weeks after treatment, they found that 70 percent of people in the treatment group reported at least a 50 percent reduction of depression symptoms, according to their MADRS scores. This response rate was significantly higher than the one for the two other control groups. A few of the participants had such dramatic decreases that Frohlich’s team is currently writing case-studies on them. Participants in the placebo and control groups experienced no such reduction in symptoms.
“It’s important to note that this is a first-of-its kind study,” Frohlich said. “When we started this research with computer simulations and preclinical studies, it was unclear if we would see an effect in people days after tACS treatment — let alone if tACS could become a treatment for psychiatric illnesses. It was unclear what would happen if we treated people several days in a row or what effect we might see weeks later. So, the fact that we’ve seen such positive results from this study gives me confidence our approach could help many people with depression.”
Frohlich’s lab is currently recruiting for two similar follow-up studies.
Other authors of the Translational Psychiatry paper are co-first authors Morgan Alexander, study coordinator and graduate student, and Sankaraleengam Alagapan, PhD, a postdoctoral fellow, both in the department of psychiatry at UNC-Chapel Hill; David Rubinow, MD, the Assad Meymandi Distinguished Professor and Chair of Psychiatry at the UNC School of Medicine; former UNC postdoctoral fellow Caroline Lustenberger, PhD; and Courtney Lugo and Juliann Mellin, both study coordinators at the UNC School of Medicine.
This research was funded through grants from the Brain Behavior Research Foundation, National Institutes of Health, the BRAIN Initiative, and the Foundation of Hope.
Frohlich holds joint appointments at UNC-Chapel Hill in the department of cell biology and physiology and the Joint UNC-NC State Department of Biomedical Engineering. He is also a member of the UNC Neuroscience Center.
To summarize and systematically review the efficacy and safety of high frequency repetitive transcranial magnetic stimulation (HF-rTMS) for depression in stroke patients.
Six databases (Wanfang, CNKI, PubMed, Embase, Cochrane Library, and Web of Science) were searched from inception until November 15, 2018.
Seventeen randomized controlled trials were included for meta-analysis.
Two independent reviewers selected potentially relevant studies based on the inclusion criteria, extracted data, and evaluated the methodological quality of the eligible trials using the Physiotherapy Evidence Database (PEDro).
We calculated the combined effect size (standardized mean difference [SMD] and odds ratio [OR]) for the corresponding effects models. Physiotherapy Evidence Database scores ranged from 7 to 8 points (mean = 7.35). The study results indicated that HF-rTMS had significantly positive effects on depression in stroke patients. The effect sizes of the SMD ranged from small to large (SMD = −1.01; 95% confidence interval [95% CI], −1.36 to −0.66; P < .001; I2 = 85%; n = 1053), and the effect sizes of the OR were large (response rates: 58.43% VS 33.59%; OR = 3.31; 95% CI, 2.25 to 4.88; P < .001; I2 = 0%; n = 529; remission rates: 26.59% VS 12.60%; OR = 2.72; 95% CI, 1.69 to 4.38; P < .001; I2 = 0%; n = 529). In terms of treatment side-effects, the HF-rTMS group was more prone to headache than the control group (OR = 3.53; 95% CI, 1.85 to 8.55; P < .001; I2 = 0%; n = 496).
HF-rTMS is an effective intervention for post-stroke depression, although treatment safety should be further verified via large sample multi-center trials.
via Efficacy and Safety of High-frequency Repetitive Transcranial Magnetic Stimulation for Post-Stroke Depression:A Systematic Review and Meta-Analysis – Archives of Physical Medicine and Rehabilitation
Current treatments for depression and PTSD only suppress symptoms, if they work at all. What if we could prevent these diseases from developing altogether? Neuroscientist and TED Fellow Rebecca Brachman shares the story of her team’s accidental discovery of a new class of drug that, for the first time ever, could prevent the negative effects of stress — and boost a person’s ability to recover and grow. Learn how these resilience-enhancing drugs could change the way we treat mental illness.
This talk was presented at an official TED conference, and was featured by our editors on the home page.
Some of these people have treatment-resistant depression, which means common prescription drugs do not alleviate the symptoms.
Recent studies have pointed to alternative treatment methods for major depression, such as non-invasive brain stimulation techniques.
For instance, a study that appeared at the end of last year showed that using small electric currents to stimulate a brain area called the orbitofrontal cortex significantly improves the mood of people who did not benefit from conventional antidepressants.
An even more recent trial of a form of brain stimulation called “transcranial alternating current stimulation” (tACS) found that the technique halved depression symptoms in almost 80 percent of the study participants.
Despite such promising results, doctors do not use these techniques widely, as there is not enough data available on their efficacy.
So, a team of researchers led by Julian Mutz at the Institute of Psychiatry, Psychology & Neuroscience at King’s College London, United Kingdom, set out to review some clinical trials that have examined the benefits of non-invasive brain stimulation techniques for people living with depression.
Specifically, Mutz and team examined the results of 113 clinical trials. Overall, these trials included 6,750 participants who were 48 years old, on average, and were living with major depressive disorder or bipolar depression.
The original clinical trials involved randomly assigning these participants to 18 treatment interventions or “sham” therapies. The reviewers focussed on the response, or “efficacy” of the treatment, as well as the “discontinuation of treatment for any reason” — or “acceptability” of the therapies. Mutz and colleagues also rated the trials’ risk of bias.
The therapies included in the review were “electroconvulsive therapy (ECT), transcranial magnetic stimulation (repetitive (rTMS), accelerated, priming, deep, and synchronized), theta burst stimulation, magnetic seizure therapy, transcranial direct current stimulation (tDCS), or sham therapy.”
Of these, the treatments that the researchers in the original trial examined most often were high frequency left rTMS and tDCS, which they tested against sham therapy. On the other hand, not many trials covered more recent forms of brain stimulation, such as magnetic seizure therapy and bilateral theta burst stimulation, the review found.
Kutz and his team deemed 34 percent of the trials they reviewed as having a low risk of bias. They considered half of the trials to have an “unclear” risk of bias, and finally, 17 percent to have a high risk of bias. The newer the treatments, the higher was the uncertainty of the trials’ results.
The review found that bitemporal ECT, high dose right unilateral ECT, high frequency left rTMS and tDCS were all significantly more effective than sham therapy both in terms of efficacy and acceptability.
When considering “discontinuation of treatment for any reason,” the researchers found that the participants were not any likelier to discontinue brain stimulation treatments than they were sham therapy. Mutz and colleagues conclude:
“These findings provide evidence for the consideration of non-surgical brain stimulation techniques as alternative or add-on treatments for adults with major depressive episodes.”
“These findings also highlight important research priorities in the specialty of brain stimulation, such as the need for further well-designed randomized controlled trials comparing novel treatments, and sham-controlled trials investigating magnetic seizure therapy,” the authors add.
Finally, the researchers also note that their results have clinical implications, “in that they will inform clinicians, patients, and healthcare providers on the relative merits of multiple non-surgical brain stimulation techniques.”
Like seismic sensors planted in quiet ground, hundreds of tiny electrodes rested in the outer layer of the 44-year-old woman’s brain. These sensors, each slightly larger than a sesame seed, had been implanted under her skull to listen for the first rumblings of epileptic seizures.
The electrodes gave researchers unprecedented access to the patient’s brain. With the woman’s permission, scientists at the University of California, San Francisco began using those electrodes to do more than listen; they kicked off tiny electrical earthquakes at different spots in her brain.
Most of the electrical pulses went completely unnoticed by the patient. But researchers finally got the effect they were hunting for by targeting the brain area just behind her eyes. Asked how she felt, the woman answered: “Calmer in my nerves.”
Zapping the same spot in other participants’ brains evoked similar responses: “I feel positive, relaxed,” said a 53-year-old woman. A 60-year-old man described “starting to feel a little more alive, a little more energy.” With stimulation to that one part of the brain, “participants would sit up a little straighter and seem a little bit more alert,” says UCSF neuroscientist Kristin Sellers.
Such positive mood changes in response to light neural jolts, described in the Dec. 17 Current Biology, bring researchers closer to an audacious goal: a device implanted into the brains of severely depressed people to detect a looming crisis coming on and zap the brain out of it.
It sounds farfetched, and it is. The project is “fundamental, pioneering, discovery neuroscience,” says Mark George, a psychiatrist and neurologist at the Medical University of South Carolina in Charleston. George has been studying depression for 30 years. “It’s like sending a spacecraft to the moon.”
|This video shows the location of brain regions involved in emotion processing: the orbitofrontal cortex (green), cingulate (red), insula (purple), hippocampus (yellow) and amygdala (blue). The dots show where electrodes were placed to monitor seizures in patients with epilepsy.|
Still, in the last several years, teams of scientists have made startling amounts of progress, both in their ability to spot the neural signatures that come with a low mood and to change a person’s feelings.
With powerful computational methods, scientists have recently zeroed in on some key features of depressed brains. Those hallmarks include certain types of brain waves in specific locations, like the one just behind and slightly above the eyes. Other researchers are focused on how to correct the faulty brain activity that underlies depression.
A small, implantable device capable of both learning the brain’s language and then tweaking the script when the story gets dark would be an immensely important clinical tool. Of the 16.2 million U.S. adults with severe depression, about a third don’t respond to conventional treatments. “That’s a huge number of people with a very disabling and probably underdiagnosed and underappreciated illness,” says neurologist Vikram Rao, who is working on the UCSF project with Sellers.
When George began studying depression decades ago, the field was still haunted by Sigmund Freud, who blamed the disorder on bad parenting and repressed anger. Soon after came the chemical imbalance concept, which held that the brain just needs a dash of the right chemical signal to fix itself. “It was the ‘brain is soup’ model,” George says. Toss in more of the crucial ingredient — serotonin, for instance — and the recipe would sing.
“We have a very different view now,” George says. Thanks to advances in brain imaging, scientists see depression as a disorder of neural circuits — altered connections between important brain regions can tip a person into a depressed state. “We’ve started to define the road map of depression,” George says.
Depression is a disorder, but one that’s tightly linked to emotion. It turns out that emotions span much of the brain. “Emotions are more widespread than we thought,” says cognitive neuroscientist Kevin LaBar. With his colleagues at Duke University, LaBar has used functional MRI scans to find signatures of certain emotions throughout the brain as people are feeling those emotions. He found the wide neural reach of sorrow, for instance, by prompting the emotion with gloomy songs and films.
Functional MRI allows scientists to see the entire scope of a working brain, but that wide view comes with the trade-off of lower resolution. And resolution is what’s needed to precisely and quickly sense — and change — brain activity. Implanting electrodes, like those used in the UCSF project, gives a more nuanced look into select brain areas. Those detailed recordings, taken from people undergoing epilepsy treatment, are what allowed neural engineer Maryam Shanechi to decode the brain’s emotions with precision.
As seven patients spent time in the hospital with electrodes monitoring brain activity, their emotions naturally changed. Every so often, the participants would answer mood-related questions on a tablet computer so that researchers could measure when the patients shifted between emotions. Then Shanechi, of the University of Southern California in Los Angeles, and her colleagues matched the brain activity data to the moods.
The task wasn’t simple. The implanted electrodes recorded an enormous pile of data, much of it irrelevant to mood. Shanechi and her team developed an algorithm to distill all that data into a few key predictive brain regions for each person. The resulting decoder could tell what mood a person was in based on brain activity alone, the team reported in the October Nature Biotechnology. “In every single individual, we can show how their mood changes in real time,” Shanechi says.[…]
Depression is a multifaceted and insidious disorder, nearly as complex as the brain itself. As research continues to suggest, the onset of depression can be attributed to an interplay of the many elements that make us human—namely, our genetics, the structure and chemistry of our brains, and our lived experience. Second only, perhaps, to the confounding mechanics of anesthesia, depression is the ultimate mind-body problem; understanding how it works could unlock the mysteries of human consciousness.
Emma Allen, a visual artist, and Dr. Daisy Thompson-Lake, a clinical neuroscientist, are fascinated by the physical processes that underlie mental health conditions. Together, they created Adam, a stop-motion animation composed of nearly 1,500 photographs. The short film illuminates the neuroscience of depression while also conveying its emotive experience.
“It was challenging translating the complicated science into an emotional visual story with scenes that would flow smoothly into each other,” Allen told The Atlantic.
“One of the most complex issues we had to deal with,” added Thompson-Lake, “is that there no single neuroscientific explanation for depression…While scientists agree that there are biological and chemical changes within the brain, the actual brain chemistry is very unique to the individual—although, of course, we can see patterns when studying large numbers of patients.” As a result, Allen and Thompson-Lake attempted a visual interpretation of depression that does not rely too heavily on any one explanation.
The film’s first sequence depicts the brain’s vast network of neuronal connections. Neurons communicate via synapses, across which electrical and chemical signals are exchanged. In a depressed patient’s brain, some of these processes are inefficient or dysfunctional, as the animation illustrates. Next, we see a positron emission tomography (PET) scan of a depressed brain, demarcated by darkened areas. Finally, the animation shows activity in the hippocampus and the frontal lobe. Abnormalities in the activity of both of these areas of the brain have been implicated in depression by recent research.
For Allen, one of the main objectives in creating Adam was to help dispel the notion that depression is a character flaw. “A common misconception is that the person is at fault for feeling this way, and that to ask for help is a weakness or embarrassing,” Allen said. “But depression has a physical component that needs treating.”
“The shame surrounding mental health still exists,” Allen continued. “In fact, in the case of Kate Spade, it was reported that she was concerned about the stigma her brand might face if this were made public.”
And who, exactly, is Adam? “Daisy lost a friend to suicide,” said Allen, “so the film is named in his memory.”
“Adam” was directed by animator Emma Allen and neuroscientist Daisy Thompson-Lake. It is part of The Atlantic Selects, an online showcase of short films from independent creators, curated by The Atlantic.
Vagal nerve stimulation is gaining recognition as an important therapeutic approach especially for non-communicable diseases such as cardiovascular disease (CVD), Depression, Fibromyalgia, Arthritis, Type 2 Diabetes, Alzheimer, and certain types of cancer. In turn, decreased vagal tone its implicated in the prognosis of a wide range of diseases. Afferent vagal stimulation seems to have the key to reset certain pathophysiological states of the body leading to health improvement by reshaping neural networks.
via Non electrical and non pharmacological ways of vagus nerve stimulation: Overview, pathways and clinical implications – Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation
New research from the Centre for Addiction and Mental Health (CAMH) in Toronto has revealed something remarkable about mental illness: years of persistent depression-caused inflammation permanently and physically alter the brain. This may dramatically affect how we understand mental illness and how it progresses over time.
In a study published in The Lancet Psychiatry, researchers found that those who had untreated depression for over a decade had significantly more inflammation in their brains, when compared to those with untreated clinical depression for less than a decade. This work jumps off of senior author Jeff Meyer’s previous work, in which he found the first concrete evidence that those with clinical depression experience inflammation of the brain.
This study went even further, proving for the first time that long-term depression can cause extensive and permanent changes in the brain. Dr. Meyer thinks that this study could be used to create treatments for different stages in depression. This is important because now it is clear that treating depression immediately after diagnosis should be significantly different than treatment after 10 years with the illness.
Once a doctor and patient find a treatments for depression that works for the patient, treatment typically remains static throughout the course of the patient’s life. Taking this new study into account, this might not be the most effective method.
This study examined a total of 25 patients who have had depression for over a decade, 25 who had the illness for less time, and 30 people without clinical depression as a control group. The researchers measured depression-caused inflammation using positron emission tomography (PET), which can pick out the protein markers, called TSPO, that the brain immune cells produce due to inflammation. Those with long-lasting depression had about 30 percent higher levels of TSPO when compared to those with shorter periods of depression, as well as higher levels than the control group.
Many misunderstand mental illness to be entirely separate from physical symptoms, but this study shows just how severe those symptoms can be. These findings could spark similar studies with other mental illnesses.
It is even possible that depression might now be treated as a degenerative disease, as it affects the brain progressively over time: “Greater inflammation in the brain is a common response with degenerative brain diseases as they progress, such as with Alzheimer’s disease and Parkinson’s disease,” Meyer said in a press release.
A significant proportion of people who are living with major depression do not get any relief from existing treatments.
In fact, up to 30 percent of those affected by depression have an intractable form of the condition.
Recently, deep brain stimulation (DBS) has emerged as a potential therapy that may succeed where other treatments have failed.
In DBS, specialists surgically implant stimulating electrodes in the brain to send electrical currents to targeted areas.
In the new study, Dr. Eddie Chang and his colleagues used DBS in 25 people who had symptoms of depression. They report their findings in the journal Current Biology.
Dr. Chang is also a professor of neurosurgery at the University of California San Francisco (UCSF).
Dr. Chang explains what made the researchers focus on the orbitofrontal cortex in this study. The area “has been called one of the least understood regions in the brain,” he reports, “but it is richly connected to various brain structures linked to mood, depression, and decision-making, making it very well positioned to coordinate activity between emotion and cognition.”
The team had access to a clinic that specializes in epilepsy. People with epilepsy have electrodes surgically implanted in their brains as part of routine preparation for surgery.
For this study, Dr. Chang and team recruited 25 participants with epilepsy who also had mild to severe depression.
With the electrodes already in place, the participants reported how they were feeling a few times per day using an app. This enabled the researchers to link changes in brain activity with different moods, focusing on the brain area that was most involved in depression and also accessible with DBS.
The scientists also used mild electrical stimulation on different brain regions and asked participants to say how it affected their mood using specific keywords.
Afterward, they — with the help of a specific piece of software — quantified and analyzed the words that the volunteers had used.
The study revealed that, while stimulating most brain areas had no effect on the participants’ mood, 3 minutes of stimulating the lateral orbitofrontal cortex led to significant improvements.
The successful results were only seen among those with moderate to severe depression; there was no effect in people with mild depression symptoms.
Study co-author Kristin Sellers, Ph.D. — who is a postdoctoral researcher in Dr. Chang’s laboratory — reports on the results. “Patients said things like ‘Wow, I feel better,’ ‘I feel less anxious,’ ‘I feel calm, cool, and collected.'”
“And just anecdotally, you could see the improvements in patients’ body language. They smiled, they sat up straighter, they started to speak more quickly and naturally.”
The patterns of brain activity also supported these noticeable improvements in mood. The authors note that the participants’ brain activity after the stimulation resembled the brain activity that occurred when the volunteers reported feeling naturally good.
“These […] observations suggest that stimulation was helping patients with serious depression experience something like a naturally positive mood state, rather than artificially boosting mood in everyone.”
Dr. Vikram Rao
“This is in line with previous observations,” he adds, “that [orbitofrontal cortex] activity is elevated in patients with severe depression and suggests electrical stimulation may affect the brain in a way that removes an impediment to positive mood that occurs in people with depression.”
The researchers note, however, that more studies will be needed before they can conclude that stimulating the orbitofrontal cortex improves mood in the long-term.
“The more we understand about depression at this level of brain circuitry, the more options we may have for offering patients effective treatments with a low risk of side effects,” says study co-author Heather Dawes, Ph.D.
“Perhaps by understanding how these emotion circuits go wrong in the first place, we can even one day help the brain ‘unlearn’ depression.”
Now, thanks to some serious investment from high-profile institutions like Johns Hopkins University, and thanks to changing government attitudes toward psychoactive drugs, it may be possible for psilocybin, the active ingredient in “magic mushrooms,” to get legal approval for therapy in a clinical setting by 2021. “For the first time in U.S. history,” Shelby Hartman reports at Rolling Stone, “a psychedelic drug is on the fast track to getting approved for treating depression by the federal government.”
As Michael Pollan has detailed in his latest book, How to Change Your Mind, the possibilities for psilocybin and other such drugs are vast. “But before the Food and Drug Administration can be petitioned to reclassify it,” Brittany Shoot notes at Fortune, the drug “first has to clear phase III clinical trials. The entire process is expected to take about five years.” In the TEDMED video above, you can see Roland R. Griffiths, Professor of Psychiatry and Behavioral Sciences at Johns Hopkins, discuss the ways in which psilocybin, “under supported conditions, can occasion mystical-type experiences associated with enduring positive changes in attitudes and behavior.”
The implications of this research span the fields of ethics and medicine, psychology and religion, and it’s fitting that Dr. Griffiths leads off with a statement about the compatibility of spirituality and science, supported by a quote from Einstein, who said “the most beautiful and profound emotion we can experience is the sensation of the mystical. It’s the source of all true science.” But the work Griffiths and others have been engaged in is primarily practical in nature—though it does not at all exclude the mystical—like finding effective means to treat depression in cancer patients, for example.
“Sixteen million Americans suffer from depression and approximately one-third of them are treatment resistant,” Hartman writes. “Depression is also an epidemic worldwide, affecting 300 million people around the world.” Psychotropic drugs like psilocybin, LSD, and MDMA (which is not classified as a psychedelic), have been shown for a long time to work for many people suffering from severe mental illness and addictions.
Although such drugs present some potential for abuse, they are not highly addictive, especially relative to the flood of opioids on the legal market that are currently devastating whole communities as people use them to self-medicate. It seems that what has most prevented psychedelics from being researched and prescribed has as much or more to do with long-standing prejudice and fear as it does with a genuine concern for public health. (And that’s not even to mention the financial interests who exert tremendous pressure on drug policy.)
But now, Hartman writes, “it appears [researchers] have come too far to go back—and the federal government is finally recognizing it, too.” Find out why this research matters in Dr. Griffiths’ talk, Pollan’s book, the Multidisciplinary Association for Psychedelic Studies, and some of the posts we’ve linked to below.