Beyond the bright colors and hallucinogenic imagery of psychedelic artthe visuals of Ram Dass's 1971 book Be Here Now has never left public consciousness there has long been a crusade to clinically research substances such as LSD, psilocybin, MDMA, DMT, and ibogaine. We've been informed, again and again and again, about the various ways that current pharmaceutical treatments in our for-profit mental health system is not only not working, but doing more damage than healing. Discussion over health care inevitably defaults to mechanisms for paying for a broken model, rarely touching upon the root causes of why so many people are depressed, sick, anxious, and suicidal in the first place.

We. Need. Better. Solutions.

In regard to psychedelics, an entire herd of elephants remain locked in a room. Thanks to the questionable (and admittedly racist) wars launched by the Nixon and Reagan administrations (first dreamed up during the Anslinger crusades), we've been denied access to these potentially therapeutic substances. Fortunately, a renaissance is occurring in psychedelics research, with ketamine being the first to be legally prescribed psychedelic for treatment-resistant depression and both psilocybin and MDMA being fast-tracked by the FDA after being labelled breakthrough therapies.

One challenge psychedelics advocates will have to face is how these drugs are treated moving through the current medical model. Regardless of personal feelings on the subject, these substances have to contend with a system that requires expensive clinical trials and will be sold in a capitalist marketplace. There will inevitably be patent issues and territorial fights. Unlike cannabis, which is a relatively mild substance with few documented consequences, psychedelics need to be rigorously evaluated and tested. While some label everyone working in medicine as minions of Big Pharma, we need to separate researchers and scientists from the shady dealings of shareholders and profiteers.

Michael Ehlers is an industry figure that has long taken an interest in psychedelics, predominantly from an outsider perspective. Now the former executive vice president for research and development at Biogen is accepting an advisory role with Field Trip Health, the psychedelics-focused organization that recently opened the world's first psilocybin research center. (You can listen to my talk with Field Trip co-founder, Ronan Levy, here.)

I chatted with Ehlers, he is also the former chief scientific officer for neuroscience at Pfizer, about his interest in psychedelics, their potential efficacy, their historical usage in ritual, and how the current model will deal with their vetting and potential applications. With every question, he was informed and honest, offering what he knows and being truthful about what he does not. There is a lot of work ahead in pharmaceuticals, yet it is undeniable the mental health industry needs a reboot, in the same way psychedelics are said to reboot the neural circuitry of the brain, making this class of substances an ideal medicine for study.

Part of my conversation with Ehlers is below; you can read the full transcript here.

Photo courtesy of Michael Ehlers

Derek: You have an accomplished career in the pharmaceutical industry. Now you've taken on an advisory role with a company specializing in psychedelics. I would love to know when you first became interested in psychedelics as a potential therapeutic tool.

Michael: I've followed this area for quite some time. I've been intensely involved in different aspects of drug discovery and development, particularly, although not exclusively, within CNS or neuroscience drug discovery, including neuropsychiatric disease. I've followed more peripherally some of the efforts both in standard pharmacology and then some of the emerging work, whether it was more acute, high-dose psychedelics or microdosing psychedelics in neuropsychiatric disease.

At the same time, I was following a lot of the work on some of the core receptor biology and neurobiology, which was really advancing in systems neuroscience. Following this field and some of the early indications of potential clinical efficacy were some of the things that really got me quite excited. I was particularly close with aspects of what's been done over the past 10 years with ketamine, which is a very different agent but also in the class, initially leading from small trials on ketamine for acute, anti-depressive actions, now to Janssen and J&J using a variation of this, esketamine, to get full-on FDA approval for the first new mechanism in depression in 20 years. The combination of these things indicated to me that there could be a new paradigm change or highly-active psychopharmacology to potentially treat some of these otherwise fairly intractable types of neuropsychiatric disorders.

There are some other things that were also on the horizon. The history of CNS drug development, particularly in neuropsychiatric disease, has been one where the empirical observations in human patients have really guided efficacious therapeutics by and large. Even though I know we like to talk a lot about rational drug discovery and development, at least in the field of neuropsychiatry, because there's still so much that is not known that we've had to rely a lot more on empirical observations in humans.

There's probably no more profound CNS pharmacology out there than that with psychedelics like psilocybin or LSD or ketamine. I've actually long thought it was just a matter of figuring out what a treatment paradigm could look likehow maybe when you dose it could you alter aspects of its dose exposure and distribution and then in what exact disease or syndrome.

Derek: You have a history of working with rare diseases. Field Trip is going to tackle a wide range of studies, but the ones that are really on everyone's mind (in terms of what psychedelics could potentially help) ranges from PTSD to treatment-resistant depression and anxiety. These are much more common diseases. Do you have any background in those diseases and, in the advisory role, what will you be doing for them?

Michael: I've got a lot of background in that. I worked for nine years in large biopharma, six years at Pfizer. I started in neuroscience and pain, but ultimately ran several divisions of Pfizer R & D, that did include rare disease, but included a bunch of other things. Then I ran R & D advising for three-and-a-half years. I've done clinical trials in depression, schizophrenia, PTSD, generalized anxiety disorder, Alzheimer's disease, and Parkinson's disease. I've done both rare diseases and a lot of common disorders: hemophilia, genetic disease, and some of the rare diseases as well. I've done stroke trials. I've had experience across a range.

One thing I like is about what Field Trip is doing and the prospect of these diseases is that they're incredibly common. Roughly 25 percent of people will have some experience with major depression in their lives. One percent of the world has schizophrenia. These are serious and significant disorders. I really love the fact that this fieldand Field Trip is really part of that in a leadership roleis looking to take some of these on.

Although the lore has been that there hasn't been that much innovation, I actually think that's not true. I think we're just at the beginning of a whole new era of advances in neuropsychiatric disease. I can point to several things that indicate that. I have a feeling that if we really understand that the best way to dose and conduct trials with psychedelics like psilocybin and be able to segment patients who are the most likely to benefit, this can become quite important.

Derek: You mentioned that pharma companies stepping away from neuropsychiatric disease. There is obviously a problem with SSRIs over the long-term. Efficacy rates tend to be high in the short-term, but over the long-term prove problematic. When you're stepping into substances that potentially could help treatment-resistant mental health diseases in one dose (or just a couple of doses), how do you think that companies are going to be able to monetize this, especially given the incredible amounts of money that have to go into R & D and clinical trials?

Michael: It's a very good question. I think we haven't solved that problem yet. There are a lot of open questions. Will some of these therapies really be single dose or short regiments and you're done? Will it have to be that there's some degree of maintenance where there's some regularity in the need for therapy? Will it really be like antibiotics or gene therapy? We don't know.

A lot of these neuropsychiatric diseases, although they're complex, have genetic features that are polygenetic but they're related. Whether you're talking about, schizophrenia, autism, bipolar disorder, ADHD, there's a complex genetic architecture that has shared features across all of those. The risk of relapse and occurrences will be there in a given population. I tend to think the likelihood of things like ketamine or psychedelic treatments for depression will be one of periodic needs.

The question you raised is an excellent one, which is what ultimately is the commercial model for that? Certainly, the hope is that it doesn't go down the road of antibiotics for which the commercial incentivization for real R & D and drug development has been catastrophic. I don't see that in this space. I just don't think it's going to be quite as simple as "one and done." The prevalence alone will be a strong incentive for investment when there's real efficacy potential.

Derek: Please correct me if I'm wrong; I'm fascinated by neuroscience, but not having an academic background my knowledge is limited. That's why I love talking to people about this. From my understanding, SSRIs work in a much different manner in terms of the serotonin release then psychedelics. Do you see any potential benefits or dangers in the ways that psychedelics deal with the serotonergic system?

Michael: It is quite different. From a simple pharmacology point of view, SSRIs are, as their name indicates, selective serotonin reuptake inhibitors: they block serotonin transporters that would normally release serotonin back up into nerve cells so that it increases serotonergic tone. Once released, it stays released in the extracellular space for longer, acting on all the different receptors in the places that it does.

The psychedelics typically act directly on serotonin receptors within serotonin transporters, but their action at different receptors has different potency. It's not a clean pharmacology. People will talk about 5-HT-2A receptors and they're clearly important, and there's been a lot of study on that, but we also know that if you just give a pure 5-HT-2A receptor an agonist you do not reproduce the effects of psilocybin or LSD.

The pharmacology is complex; it's clearly different than SSRIs. Obviously, the behavioral and therapeutic groups are very different. It just highlights that we really need to understand it better. It's going to reveal I think very important things about psychiatric disease and fundamental neuroscience.

A shaman gathers the raw materials to make ayahuasca in the jungle outside of Iquitos.

Photo by Andrew Lichtenstein/Corbis via Getty Images

Derek: One of the criticisms of the way that the industry is right now is that, why would a doctor spend an hour talking to a patient when you can see six patients in an hour and write a script? Efficacy rates are different for different people, dealing with the microbiome, for example, and the way that their gut processes drugs. It's a very complex issue. One thing I believe is going to be important is that psychotherapy is going to be tethered with psychedelics, especially if people have never done them before. Will that coupling provide a sustainable model?

Michael: Here's an aspect of what's important to understand: the field has understandably taken a cautious approach, which I think is warranted in this whole guided therapy concept and that will probably be required for certain dosing regimens. I would personally like to see this converted into what is a very standard thing in a lot of drug administration in practice or trials, which is more about medical monitoring. Change it from the notion of it's guided therapy to monitoring like you would for a lot of things. People go to IV infusion centers to get their IV drug. It's different, but there's nothing that unusual about the notion of having a monitored pharmaceutical or pharmacological drug intervention even in standard practice. This will likely be part of that.

If you're a neurologist treating MS and you've got MS patients on Alemtuzumab or Natalizumab as your IV drugs. They come in, you've got your IV clinic. They come in regularly, every month or every quarter depending on the drug, and they get their IV infusion. They get monitored while it happens because they can have an immune response. I see a future for some of these psychoactive therapeutics where you have something similar.

Now the question will be to what extent does the guided as opposed to monitoring aspect of that influence the degree of efficacy? That's something which really would need to be studied. To the extent it really requires some special type of guided activity that will be a little bit more of a limitation. To the extent that it can be ultimately the design in a more monitoring approach with education, the more widespread this can become.

Does that analogy make sense to you? There's a lot of precedence for this in other areas. The way this has gotten utilized now is still a remnant of causing people to have profound hallucinations and behavioral stuff and paranoia. Some people get afraid of that, so we need to have some monitoring.

We need to understand doses. We need to know the extent to which those experiences are part and parcel to a therapeutic response or not associated with a therapeutic response.

Derek: How much do you think anecdote is going to matter? One main issue I have with the whole cannabis legalization process is the extraction of CBD being sold for every possible ailment out there when the actual evidence is almost nothing at this point, besides epilepsy. At the same time, dealing with mental health disorders, how much are we going to rely on anecdote? If people think they're getting better, there's placebo, and it actually helps them get better.

Michael: I hope we moved beyond anecdotes, and I think that you're right about CBD, but it's interesting the way you put that because of the fact that rigorous trials have been done in rare epilepsies, like Dravet and Lennox-Gastaut syndrome, nobody disputes that. Patients in need can get insurance companies or health systems in other countries to reimburse for that. That's what I mean by saying real location impact is going to require that component of it too. You'd like to be able to generate the evidence because nothing comes without safety concerns. The nice thing about putting this all through the lens of drug discovery and development is that it allows the communityand here I mean the medical community, policymakers, others to have a much clearer view of the benefit-risk, and where the benefit-risk is positive, in which case that's usually a required element for real access for patients.

Of course, you could argue and say, "well, if it's just out there, people can try it, we'll see and that's fine," but this doesn't allow us from a clinical scientific vantage point to really know when and where we are going to provide benefits. That's what we really need to work toward. There's enough anecdotal evidence out there to justify rigorous evaluation.

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Stay in touch with Derek on Twitter and Facebook. His next book is Hero's Dose: The Case For Psychedelics in Ritual and Therapy.

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The 2020s: The decade of psychedelic breakthroughs? - Big Think

2019 was nuts for neuroscience. I said this last year too, but thats the nature of accelerating technologies: the advances just keep coming.

Therere the theoretical showdowns: a mano a mano battle of where consciousness arises in the brain, wildly creative theories of why our brains are so powerful, and the first complete brain wiring diagram of any species. This year also saw the the birth of hybrid brain atlases that seek to interrogate brain function from multiple levelsgenetic, molecular, and wiring, synthesizing individual maps into multiple comprehensive layers.

Brain organoids also had a wild year. These lab-grown nuggets of brain tissue, not much larger than a lentil, sparked with activity similar to preterm babies, made isolated muscles twitch, and can now be cloned into armies of near-identical siblings for experimentationprompting a new round of debate on whether theyll ever gain consciousness.

Then of course, theres the boom in neurotech. Fostered by insight into how neurons and circuits communicate with each other through a complex neural code, weve gotten ever closer to decoding the brain. Mind-controlled prosthetics are old news; the frontier now is engineering robotic limbs that can truly feel. Insight into our sensory cortices are inspiring light-based nervous systems that give robots multitudes of sensations. Elon Musks Neuralink finally came out after years of speculation, and a Wild West of brain-computer interfaces have sprung up, with the hope of one day restoring broken brain circuits without the need for surgery.

Thats already achievement-a-plenty. But as we wrap up the year, there are four mind-bending stories that still stick with meby asking about the nature of death, the promise of mind-reading, and new paths that may finally help us beat Alzheimers. These are the ones Ill leave you with.

The brain is a powerful but ultra-sensitive organ thats prone to injury. Once deprived of oxygen and nutrients, cells can begin to die within the hour. Thats why, zombie lore aside, scientists once thought its near impossible to resuscitate a brain to any sort of function hours after death.

Not true. In April, a team at Yale University reported that they successfully detected electrical activity in pig brains four hours after death. The results were a surprise: the team originally set out to develop a system that helps the brain maintain its integrity after removal for experimental purposes. How well it worked went beyond the teams expectations. Its impossible to say if the brains were conscious; that is, whether they were aware of being revived, though its highly (and I mean highly) unlikely. When the team saw signs of widespread, coordinated electrical activitywhich underlies consciousnessin their initial experiments, they anesthetized future experimental brains to block this sort of united firing, drastically reducing the chance consciousness could emerge in these brains.

Nevertheless, the study suggests that the brain is much more resilient to injuries such as stroke or trauma than previously thought. In the long term, it asks whether we might one day have a sort of CPR for the brain. And if so, how long can brains maintain their health after being separated from the body? We might have just taken the first step into the uncharted territories of death.

A few years ago, Dr. Miguel Nicolelis linked up animals brains into an internet that allowed each member to work collaboratively on a common problem. When connected to each other through implanted electrodes, the animals synced up their brains electrical activity in a way reminiscent of a single hive brain.

Nicolelis has now done the same experiment in humans, minus surgery. In a feat of neural engineering, the team used non-invasive electroencephalographs (EEGs) to read brain waves from two individuals and sent these signals to a third person by zapping their brain with magnetic pulsesa technology called transcranial magnetic stimulation, or TMS. Together, five triad groups solved a Tetris-like game using their brain waves alone, with an accuracy of over 80 percent, even when the researchers introduced noise.

One caveat: the system was rigged so that the neurotech wasnt detecting thought, for example, rotate the block or dont rotate. That decision was encoded as the presence or absence of light flashes, which are much easier for the EEG to read and for the TMS to deliver to the visual cortex. But its still a powerful proof-of-concept, in that even with our rudimentary brain reading and writing tech, its possible to link up human minds into a hive mind to solve problems. Nicolelis imagines a biological supercomputer made from networked human brains, which could conceivably cross language barriers and even enhance cognitive performance. The question is, if we open the sanctuary of our minds to others for gains in computing power, what do we stand to lose in privacy and autonomy?

Playing a collaborative game of Tetris isnt the only way scientists advanced mind reading technology. In January, one team combined deep learning with speech synthesis technology to translate what a person is hearing into reconstructed speech. The system captured electrical signals from the auditory cortex while a person listened to recordings of people speaking. These activity patterns were then decoded by an AI-based speech synthesizer and produced intelligible, if somewhat robotic, speech. Unfortunately, the system couldnt decode someones own internal thoughts.

But that changed three months later.

Another team engineered a neural decoder that decodes electrical signals measured from the cortex, the outermost layer of the brain. Rather than containing information about semantics, these signals represent movement of the lips, tongue, larynx, and jaw. Different movement patterns are associated with different sounds, which the decoder can identify and synthesize into actual comprehensible sentences. For the first time, its possible to know what someone is trying to say by reading their brain activity alone, and the tech was further validated in a Q&A conversation. Earlier this month, yet another team found its possible to decode words and syllables based on recordings from the brains motor cortexthe part usually responsible for hand and arm movements. This opens another avenue of reading speech directly from the brain.

Not to be outdone, a team at Russian firm Neurobotics found they could use AI to decode what video clips people are watching based on their brainwaves alone. In contrast to the speech-decoding studies, which use implanted electrodes, here non-invasive EEG was sufficient to reconstruct nature scenes, sports, and human faces.

For now, our private thoughts are still private, and the tech mainly helps those who cant speak reconnect with the world. But think about this: if someday a tech giant offers you the ability to text or post using your mind only, would (and should) you go for it?

Dementia is one of the most frustrating neurological disorders of our time. Despite decades of research, nearly every single Alzheimers drug that targets toxic protein clumpscalled beta-amyloidthought responsible for the disease has failed. Generally, these drugs are proteins that break up clumps or neutralize their toxic effects.

This year saw an explosion in alternative potential treatments and theories.

One that especially gained steam suggests flashing lights and clicking sound could potentially break up toxic protein clumps and improve brain function, at least in mice. The treatment, cheap, non-invasive, and dramatically effective, offers new hope to the long-struggling field. Others suggest that mutations to DNA in brain cells scrambles certain genes and could be a root cause. Yet others are taking a gene therapy approach to the Alzheimers dilemma, adding in a dose of a protective gene variant in high-risk individuals.

Although its impossible to say if any of these new routes will lead anywhere, one thing is clear: the more scientific treatment ideas we have, the higher the chance well finally tame Alzheimers in the near future.

Image Credit: Gerd Altman / Pixabay

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This Year's 4 Most Mind-Boggling Stories About the Brain - Singularity Hub

Before she became a sous-chef at McMurdo research station in Antarctica, Rose McAdoo was a pastry chef in New York City. But even on the other side of the world, surrounded by polar research staff, she couldnt stop thinking about cake.

During the summer season, more than a thousand people work at McMurdo. Theyre not all scientists. The majority of residents at the station are there in support roles, to keep the place running like a little village. But the research is never far away, and while working in the 24-hour kitchen, McAdoo learned about the scientific studies happening around her.

Everything I learned, my brain instantly processes into cake format, says McAdoo. Ascending and descending data sets or systems become different sized stacked tiers. The ever-changing ice break patterns that I watched morph every day looked like massive sheets of fondant. I saw NASA Operation IceBridge data as future time-lapsed cake decor videos.

Four of the science-themed cakes that pastry chef Rose McAdoo created after spending several months ... [+] working at McMurdo research station in Antarctica. From left to right, the cakes represent a paleontological dig in Antarcticas Dry Valleys, a polar icebreaker clearing the way for a resupply ship to reach the research station, LIDAR laser research studying the Earth's atmosphere from the 24-hour darkness of Antarctic winters, and Dr. Shawn Devlin collecting sediment samples under the ice of Lake Fryxell.

There was no opportunity to put these elaborate cake ideas into practice right away, but as soon as she left Antarctica during the off-season, McAdoo started work on the cakes. She stayed in touch with some of the researchers she met, who provided feedback and resources to help her get the science just right.

McAdoos creations demonstrate the wide variety of research that takes place at McMurdo: Ice core samples that hold the key to historic environmental conditions, sea spiders living in freezing cold water, astronomical observations, paleontological digs. One glimpse at the cakes immediately tells you that Antarctic research is about much more than penguins.

Unmolding of an ice core sample created out of isomalt. This project was a collaboration between ... [+] Rose McAdoo and Chelsea Burgess.

But you dont have to be an experienced pastry chef to make a science cake. Several scientists are making their own research or that of their colleagues deliciously edible.

Last year, physicist Katharine Leney made a cake to celebrate a successful year for the ATLAS experiment she was involved with at CERN. ATLAS is a detector at the Large Hadron Collider that measures a range of different signals. It was one of the detectors that spotted the Higgs Boson a few years ago, for example. Leneys cake features edible replicas of some of the graphs describing the results of ATLASs work throughout 2018. This year, a similar cake even included a replica muon detector.

Katharine Leney created this cake to mark the end of run 2 of the ATLAS experiment at CERN, in late ... [+] 2018.

These are not the only cakes Leney has made at CERN. Together with colleague Katy Grimm she has turned cake making into a way to introduce people to new scientific concepts. Their outreach project Physics Cakes shares many of the cakes on Twitter.

Biologist Lusa Jabbur makes science cakes for the birthdays of her coworkers. This summer, she created this tiered cake with a phylogenetic tree a diagram that shows how closely related different species are to each other. On Jabburs cake, the tree almost resembles a real tree, with the birds sitting on the branches.

Lusa Jabbur's bird phylogeny cake shows how different bird species are related to each other.

Five years ago, ecologists Carly Ziter and Rose Graves baked a forest fire cake to celebrate the successful PhD defence of forest ecologist Brian J Harvey at the University of Wisconsin Madison. The most striking feature of the cake are the large flames made of melted hard candies, which engulf a wafer roll forest.

Carly Ziter and Rose graves baked this forest fire cake several years ago, to mark the PhD defence ... [+] of forest ecologist Brian Harvey.

Cookies are another popular medium for science bakers. Crystal Lantz (@BoozyBrain on Twitter) even designed and 3D-printed her own neuroscience-themed cookie cutters to make it easier to create cookies in the shape of neurons, mouse brains or fruit flies (which are often studied in neuroscience labs).

Crystal Lantz created these neuroscience-themed cookies with custom cookie cutters she designed and ... [+] 3D-printed.

And what about a gingerbread lab bench? A few years ago, microbiologist and science communicator Anne A. Madden (@AnneAMadden) deviated from the traditional gingerbread house blueprint and created a lab bench with edible lab equipment. This year, she built a new bench to help lab supply company Thermo Fisher run a gingerbread lab bench competition, in which even more scientists were encouraged to get creative and scientific in their kitchen.

Anne A. Madden created this lab bench out of gingerbread, complete with confectionary lab equipment.

The challenge of making science cake or cookies is to get the core concept of the research across in a medium that doesnt lend itself to a lot of details. Usually, scientific information comes with a lot of caveats and footnotes, graphs, figures, and subtle explanations. On a cake or cookie, youre limited by what fits on a cake, and by what you can express in icing and decorations.

At the moment, Rose McAdoo is back in Antarctica. Shes working as sous-chef for NASA's long-duration balloon atmospheric research camp, but she has also found some time for her next science baking project.

I'm currently building a large sugar art piece for the McMurdo Alternative Arts Gallery (taking place in our fuels barn on December 30), which will be a 3D replica of a galaxy star-origin thermal map from a NASA-funded research team here.

McAdoos shares her scientific and tasty creations on her Instagram account @WhiskMeAwayCakes

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Have Your Science And Eat It: Scientific Research As Cakes - Forbes