Due to stigma, their illegal status and difficulty in finding control groups, research with psychedelics has been a challenge. But research increasingly shows that this class of drug has legitimate medicinal uses, and they may be just as good or even better than more traditional therapies.
Now, the Centre for Psychedelic Research at Imperial College London reports in the New England Journal of Medicine that when pitted against escitalopram (brand name: Lexapro), psilocybin was as effective as the popular SSRI (selective serotonin reuptake inhibitor) in treating moderate to severe depression. Perhaps most significantly, these results were obtained when comparing 6 weeks of daily doses of escitalopram to just two administrations of psilocybin.
Robin Carhart-Harris, head of the center who has published over 100 papers on psychedelics, is confident this study represents another step forward in applying psychedelics to mental health treatment protocols while also reducing fears a lot of citizens have around these substances. In a press release, he said:
"One of the most important aspects of this work is that people can clearly see the promise of properly delivered psilocybin therapy by viewing it compared with a more familiar, established treatment in the same study. Psilocybin performed very favorably in this head-to-head."
Credit: Robin Carhart-Harris et al, NEJM, 2021.
As depicted above, the phase 2 clinical trial included 59 volunteers. The escitalopram (control) group received six weeks of daily escitalopram in addition to two tiny (1-mg) doses of psilocybin — a dose so low that it is unlikely to produce hallucinogenic effects. The psilocybin (experimental) group received two 25-mg doses of psilocybin three weeks apart with placebo given on all the other days.
At the end of the study, both groups saw a decrease in depressive symptoms, though the results were not statistically significant. (That isn't necessarily bad because if the two drugs have similar effects, then they would not produce statistically significant results. Still, a larger study is needed to confirm that psilocybin is "just as good as" escitalopram.)
Additionally, several other outcomes favored psilocybin over escitalopram. For instance, 57 percent in the psilocybin group saw a remission of symptoms compared to 28 percent in the escitalopram group. This result was significant.
Psychedelics without tripping
As psychedelics become decriminalized and potentially legalized for therapeutic use, however, a large population of people might desire the antidepressant effects without the hallucinations. For example, the psychedelic ibogaine may be useful for treating addiction, so the company Mindmed is developing an analog that works without producing the unwanted hallucinogenic side effects.
A new research article, published in the journal PNAS, investigated the antidepressant effects of psilocybin on a group of chronically stressed mice. (Under immense stress, mice develop something resembling human depression.) As with humans, depressed mice lose a sense of joy, which can be assessed by determining their preference for sugar water over tap water. Normal mice prefer sugar water, but depressed mice simply don't care.
Once the mice were no longer juicing up on the sweetened water, the team dosed them with psilocybin alongside a drug called ketanserin, a 5-HT2A serotonin receptor antagonist that eliminates psychedelic effects. Within 24 hours of receiving the dose, the mice were rushing back to the sugar water, indicating that tripping is not necessary for psilocybin to work as an antidepressant.
While the team is excited about these results, they realize it needs to be replicated in a different population.
"The possibility of combining psychedelic compounds and a 5-HT2AR antagonist offers a potential means to increase their acceptance and clinical utility and should be studied in human depression."
Photo: Cannabis_Pic / Adobe Stock
The future of psychedelic therapy
Psychedelics such as psilocybin and LSD have a long track record of efficacy in clinical trials and anecdotal experiences. Almost all volunteers of the famous Marsh Chapel experiment claimed their experience on Good Friday in 1962 was one of the most significant events of their lives — and this was a quarter-century after the fact. A more recent, controlled study found that a single dose of psilocybin showed antidepressant effects six months later.
Proponents of macrodosing and ritualistic experiences sometimes argue that the full-blown mystical trip is the therapy, though this is anecdotal, not clinical research. As the Maryland team noted, a number of people are contraindicated for psychedelics, whether through a family history of schizophrenia or current antidepressant treatments.
Senior author Scott Thompson is excited for future research on this topic. As he said of his team's findings:
"The psychedelic experience is incredibly powerful and can be life-changing, but that could be too much for some people or not appropriate… These findings show that activation of the receptor causing the psychedelic effect isn't absolutely required for the antidepressant benefits, at least in mice."
Hopefully, with more research occurring in psychedelics than even in the 1950s (when studies predominantly relied on anecdotal evidence and little government support), the longstanding stigmatization of psychedelics is beginning to recede. This could open up new possibilities for both clinical research and, for those curious about the ritual effects, a continuation of introspective experiences.
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Stay in touch with Derek on Twitter and Facebook. His most recent book is "Hero's Dose: The Case For Psychedelics in Ritual and Therapy."
Neanderthals' image has undergone quite an upgrade in recent years. Where we once we thought of them as knuckle-dragging just-slightly-more-evolved apes, we now know that they were not so very unlike us. Evolutionarily more primitive, yes, but not by that much. They buried their dead, painted cave art, developed wooden tools, and even made string. We also know that their genetic traces remain in many modern humans. A new study from researchers at the University of Binghamton in New York State and Universidad de Alcalá in Spain pretty conclusively demonstrates they had the physical apparatus required for speaking and for understanding speech.
"This is one of the most important studies I have been involved in during my career," says co-author Ralph Quam. "The results are solid and clearly show the Neanderthals had the capacity to perceive and produce human speech. This is one of the very few current, ongoing research lines relying on fossil evidence to study the evolution of language, a notoriously tricky subject in anthropology."
The study is published in the journal Nature Ecology & Evolution.
Long-standing questions
Neanderthal reconstruction (right), 2014
Credit: Cesar Manso/Getty Images
"For decades, one of the central questions in human evolutionary studies has been whether the human form of communication, spoken language, was also present in any other species of human ancestor, especially the Neanderthals," says co-author Juan Luis Arsuaga.
The key to answering these questions, say the researchers, has to do first with Neanderthals' physical ability to hear in the frequency ranges typically involved in speech. In addition, while it's known that these ancient people had the physiological capacity for producing vowel sounds, the new research adds consonants to the Neanderthal repertoire, greatly expanding the possibilities for conveying a wide variety of meaning through the production of more types of sounds.
Neanderthal hearing
The authors made high-resolution CT scans of fossilized Neanderthal skulls—and skulls from some of their ancestors—found at UNESCO's archaeological site in northern Spain's Atapuerca Mountains. These scans served as the basis for virtual 3D models of the fossils' ear structures. Similar models of modern human ear structures were also created for comparison purposes.
Auditory bioengineering software assessed the hearing capabilities of the models. The software is capable of identifying sensitivity to frequencies up to 5 kHz, the midrange and low-midrange frequencies at which homo sapien speech primarily occurs. (We can hear much higher and lower frequencies, but that's where speech lies.)
Of particular importance is the "occupied bandwidth," the frequency region of greatest sensitivity, and therefore the spectrum most capable of accommodating enough different audio signals to represent a multitude of meanings. The occupied bandwidth is considered a critical requirement for speech since being able to produce and hear many different sounds—and understand their many different meanings—is the cornerstone of efficient communication.
Compared to their ancestors, the Neanderthal models turned out to have better hearing in the 4-5 kHz range, making their hearing more comparable to our own. In addition, the Neanderthals were found to have a wider occupied bandwidth than their predecessors, again more closely resembling modern humans.
Lead author of the study Mercedes Conde-Valverde says, "This really is the key. The presence of similar hearing abilities, particularly the bandwidth, demonstrates that the Neanderthals possessed a communication system that was as complex and efficient as modern human speech."
Consonants
Credit: sakura/Adobe Stock/Big Think
The study also suggests that Neanderthal vocalization were more advanced than previously thought. Says Quam: "Most previous studies of Neanderthal speech capacities focused on their ability to produce the main vowels in English spoken language."
However, he says, "One of the other interesting results from the study was the suggestion that Neanderthal speech likely included an increased use of consonants."
This is important, since "the use of consonants is a way to include more information in the vocal signal and it also separates human speech and language from the communication patterns in nearly all other primates. The fact that our study picked up on this is a really interesting aspect of the research and is a novel suggestion regarding the linguistic capacities in our fossil ancestors."
Bottom line
The study concludes that Neanderthals had the physiological hardware to produce a complex range of vocalizations, and the ability to understand them through ear structures not very unlike our own. This fits neatly with other recent insights as to the sophistication of the Neanderthals, a people who now seem to have been developing an expansive set of advanced capabilities simultaneously.
The authors of the study have been investigating the Neanderthals for almost 20 years, and others have been at it even longer. The work continues, and the study's publication marks a significant milestone in the much longer journey.
"These results are particularly gratifying," says co-author Ignacio Martinez. "We believe, after more than a century of research into this question, that we have provided a conclusive answer to the question of Neanderthal speech capacities."
When it comes to senses like ours, tiny single-celled organisms floating in the ocean don't have much going on. And yet, as Sacha Coesel, the lead author of a new study from University of Washington researchers, puts it: "If you look in the ocean environment, all these different organisms have this day-night cycle. They are very in tune with each other, even as they get moved around. How do they know when it's day? How do they know when it's night?"
The answer, according to Coesel and her colleagues, is four previously unknown groups of photoreceptors that may help these organisms detect day, night, and each other.
Light and dark are vital to these organisms. When the sun is up, they become energized and grow. Cell division occurs at night when the darkness' ultraviolet wavelengths are less damaging to their DNA.
"Daylight is important for ocean organisms," says senior author Virginia Armbrust, "we know that, we take it for granted. But to see the rhythm of genetic activity during these four days, and the beautiful synchronicity, you realize just how powerful light is."
Photoreceptors and optogenetics
Credit: ktsdesign/Adobe Stock
Aside from being fascinating in their own right, these little "light switches" are likely to be of great interest to people working in optogenetics, a transformative area of scientific research.
This combination of optical technologies and genetics is giving researchers new insights into the workings of the brain, allowing them to, for example, turn on and off single neurons as they explore the brain's myriad pathways and interactions. Optogenetics also holds promise for better management of pain, and has cast new light on brain motor decision-making.
These new-found, naturally occurring photoreceptors may substitute for, or complement, human-made photoreceptors currently used in optogenetics. It's hoped that these newcomers will prove more sensitive and better equipped to respond to particular light wavelengths. Possibly because water filters out red light—the reason the ocean looks blue—the new photoreceptors are sensitive to blue and green wavelengths of light.
"This work dramatically expanded the number of photoreceptors — the different kinds of those on-off switches — that we know of," offers Armbrust.
Finding the new photoreceptors
Credit: Dror Shitrit/Simons Collaboration on Ocean Processes and Ecology/University of Washington
The researchers identified the previously undiscovered groups of photoreceptors by analyzing RNA they'd filtered from seawater samples taken far from shore. The samples were collected every four hours over the course of four days from the Northern Pacific Ocean near Hawaii. One set of samples was collected from currents running about 15 meters beneath the surface. A second set sampled deeper down, gathering water from between 120 and 150 meters, in the "twilight zone" where organisms get by with little sunlight.
Filtering the samples produced protists—single-celled organisms with a nucleus—measuring from 200 nanometers to one tenth of a millimeter across. Among these were light-activated algae as well as simple plankton that derive their energy from the organisms they consume.
Under-appreciated, tiny drivers of sea health
The new photoreceptors help fill in at least one of the blanks in our knowledge of the countless floating communities of microscopic creatures in our seas, communities that have a far greater impact on our planet than many people realize.
Says Coesel, "Just like rainforests generate oxygen and take up carbon dioxide, ocean organisms do the same thing in the world's oceans. People probably don't realize this, but these unicellular organisms are about as important as rainforests for our planet's functioning."
