I’m a fan of it because it is an open-access journal featuring a “tiered system” and more.  From their website:

The Frontiers Journal Series is not just another journal. It is a new approach to scientific publishing. As service to scientists, it is driven by researchers for researchers but it also serves the interests of the general public. Frontiers disseminates research in a tiered system that begins with original articles submitted to Specialty Journals. It evaluates research truly democratically and objectively based on the reading activity of the scientific communities and the public. And it drives the most outstanding and relevant research up to the next tier journals, the Field Journals.

I’m a big fan of the variety of specialty journals they have:

• Aging Neuroscience
• Behavioral Neuroscience
• Cellular Neuroscience
• Computational Neuroscience
• Enteric Neuroscience
• Evolutionary Neuroscience
• Human Neuroscience
• Integrative Neuroscience
• Molecular Neuroscience
• Neural Circuits
• Neuroanatomy
• Neuroenergetics
• Neuroengineering
• Neurogenesis
• Neurogenomics
• Neuroinformatics
• Neuromethods
• Neuropharamacology
• Neuroprosthetics
• Neurorobotics
• Synaptic Neuroscience
• Systems Neuroscience

Readouts may be anything from classical enzymatic reactions, through FRET for changes in protein interaction, up to subcellular changes captured by automated high-content imaging. An investigator may send a group member to the Broad to take advantage of its resources or may entirely ‘outsource’ assay development to the chaperone. Assay development typically takes two to three months, sometimes up to a year. The assay is then used to screen one or more compound libraries, encompassing at present up to 400,000 substances and growing. (PsychHTS pays for screening a 50,000-compound subset.) ‘Hits’—compounds that affect the assay results in a way that indicates potential usefulness in a psychiatric research context—are automatically retested at several concentrations. The resulting collection of typically between 50 and 500 confirmed hits is then evaluated and prioritized according to criteria of scientific interest and potential drug promise, and thereby winnowed down to the top 10 or 20. The Broad Institute’s organic chemists then synthesize and retest these compounds plus a series of their chemical derivatives, with goals such as improved solubility and more specific binding to putative targets. The goal of the entire procedure is to deliver small-molecule probes that modulate a specific cellular function—essentially tools for subsequent research into the initial hypothesis regarding a psychiatric disease mechanism.

At this point, the new small-molecule probes will need to be tested in animal models of mental illness.

The most appealing aspect is that the Broad is opening up the process to anyone with good ideas for potential screens. The next application deadline is in September. Considering both PsychHTS and the Allen Brain Atlas, is neuroscience moving away from an individual lab model and more toward a “big science” model of projects with lots of collaboration?

“Varenicline is a partial agonist of the ?4?2 subtype of the nicotinic acetylcholine receptor.” — this is apparently the subtype that nicotine acts on in the CNS. Varenicline is also a partial or full agonist of some other nicotinic receptor subtypes.

The following article describes various disturbing psychedelic effects of long-term varenicline use. Excerpts after the break:

http://nymag.com/news/features/43892/

Note: from anecdotal evidence in other parts of the article, it seems like these sorts of effects don’t happen to everyone on the drug, in fact it sounds like they are uncommon.

”
The next night, I nodded off listening to Radiohead’s In Rainbows, feeling a little guilty that I’d paid zero dollars for it. I had a quick blip of a dream: A dark, inky fluid was jolting violently from the corners of my ceiling, zigzagging its way across the walls and wooden floor in jerky sync to the music.

It was only a dream, though it seemed more immediate and visceral than my usual fare, which I rarely remember after waking up. The following night, things got even stranger. I fell asleep with Bravo blaring on my TV and dreamed that a red-faced Tim Gunn was pushing me against the wall. “But I always thought you were so nice,” I said.

By night four, my dreams began to take on characteristics of a David Cronenberg movie. Every time I’d drift off, I’d dream that an invisible, malevolent entity was emanating from my air conditioner, which seemed to be rattling even more than usual. I’d nap for twenty minutes or so before bolting awake with an involuntary gasp. I had the uneasy sense that I wasn’t alone.

I smoked a cigarette, then tried going back to sleep. But each time I started napping, I’d dream that something increasingly ominous—carbon monoxide? Vampires?—was sucking vital essence out of me. Soon the clock on my desk read 3:20 a.m.

The most unsettling thing about sleeping on Chantix is that I never felt like I was truly asleep. Some part of me remained on guard. It was more like lucid dreaming, what I thought it might feel like to be hypnotized. And it didn’t entirely go away come morning. As I showered, shaved, and scrambled into clothes, I tried to shake a weird, paranoid sense that I’d just been psychically raped by a household appliance.

….

For me, self-destructive fantasies slowly began cropping up as cartoonish flights of fantasy—nagging, almost imperceptible chatter that became a little more concrete and domineering with every passing day.

A week into my Chantix usage, I started to feel as if the city landscape had imperceptibly shifted around me. Mundane details began to strike me as having deep, hidden significance. The neon arch above McDonald’s: The lights blinked on and off in some sort of pattern, and I needed to crack the code. One of my co-workers was messing with some papers: What is he trying to imply with all that damned crinkling? Sitting in the subway: A man hurries to get inside. His hand, holding a cup of coffee, gets stuck in the closing door. I watch the hand wriggle. The lid bursts open and steaming brown liquid hits the floor. Fingers twitch and splay. Coffee splashes in crisscrossing slats through the subway car. It was a sign—something bad was going to happen.

It felt as if the essential barrier between reality and my imagination had eroded. Was it because I wasn’t getting enough R.E.M. sleep, so my dream life was rebelling, pouring into daylight, insisting to be attended to, one way or another?

Meanwhile, smoking cigarettes had become an exercise in futility. At work, I’d put on my coat, head out, and light up—but there was no pleasure to be found, just a truly nasty taste.

One afternoon, I was typing away at advertising copy, and as I did so, I began to wonder how I had succeeded in fooling myself that my life had any sort of value at all. Writing? Sure, it was what I’d wanted to do since I was 6—but at the end of the day, who cared? Maybe I should just go downstairs and leap in front of a tour bus. Or launch my head through the computer screen. All this seemed logical, but also weirdly funny, even at the time: I could see how crazy these impulses were, I could recognize them as suicidal clichés. But I couldn’t make them go away.

A few minutes later, they did, and I thought, Who was the depressed seventh-grade goth girl who had just muscled into my brain? I hadn’t thought of suicide in any serious way since I was a teenager, and that had just been adolescent posturing. I had no interest in killing myself—that’s why I wanted to quit smoking in the first place.

After a few weeks on Chantix, I had managed to stop smoking altogether—but it didn’t feel like a triumphant turn of events. I’d become rather reclusive, avoiding calls from friends, and basically just shuttling back and forth between my office and my apartment. I began to dread six o’clock; it meant I had to walk through the streets again. The subway was now out of the question; it made me too nervous. I stopped going to the gym, too.

I wondered whether Chantix was zapping my brain’s pleasure-delivery system to such a degree that not only did I find no reward in cigarettes, but I also found no reward in socializing, exercising, writing, or any of my usual self-stimulating tricks. I’d pace the floor, sit on the bed, channel surf, pace some more, try to read, but the room had a stale, sinking feeling. Maybe I should go and grab a drink—then at least I might be able to get some rest.

There was no warning against drinking while on Chantix, and even if there had been, I can’t say with any honesty that I’d have adhered to it. (I wasn’t taking any other medication, though.) But while I’ve had my fair share of dark and drunken nights over the years, what I experienced on Chantix was something else altogether. One evening, I steeled myself to go on a date, but after a few drinks with the guy, I abruptly burst into tears mid-sentence. The crying jag lasted about 30 minutes, with the thought I can’t do this anymore looping through my head. This was happening a lot lately, as though someone had spliced other people’s thoughts into the tape whirl of my brain.

Another night, at an East Village bar, an older man in a trench coat caught my attention. I chatted him up for a while, until I realized I was actually trying to go home with the shadow cast by a potted plant. With alcohol in my system, I was somehow able to take this hallucination in stride: “The man who got away?…?” But that same evening ended with my taunting a skinhead who was improbably on the corner of Avenue A and 14th Street. “You must be lost,” I snapped. “Are you looking for 1993?” He ended up chasing me into a deli and saying he was going to murder me. (The guy at the register called the cops and the skinhead fled, so I’m fairly confident that he, at least, was real.)

I’ve blacked out a handful of times before, but now it wasn’t unusual to have five or six hours completely wiped out of my memory. I’d wake up with my clothes on, music blasting, and strange half-eaten sandwiches lying on the floor that I had no recollection of buying. One morning, I found an unopened container of dental floss in my coat, as well as a batch of business cards from people whom I couldn’t remember at all. Later that day I received a text message: “I had a great time meeting you … I could have talked to you for another two hours. ” I have no idea who that person was.

Why didn’t I just stop taking the drug? I did consider it. But there’s something particularly dispiriting about quitting a medicine that’s supposed to be helping you quit smoking. I kept thinking that my body was still getting used to being on Chantix and off cigarettes, that I should wait until everything readjusted itself.

A few nights later, a friend invited me to a party and I reluctantly agreed. I was still avoiding my closest friends for fear that they’d notice changes in my behavior. But maybe I’d feel better if I stopped keeping to myself, for just a night. At the party, I tried to impersonate myself as best I could, but I found myself staring and nodding blankly, actually having difficulty understanding what people were trying to say, and getting oddly touchy at offhand comments.

I was offered a piece of cake on a plate and a fork. For the life of me, I couldn’t figure out the puzzle. How the hell were these pieces supposed to fit together? Fork. Plate. Cake. What sort of maniac would present me with something like this at a party? I abandoned the cake for a vodka tonic, which I drank in silent rage.

I left without saying good-bye. In the cab, I watched the city slash past the windows and was tempted to just throw open the door. Running up the stairs to my apartment, I barely had the door open before the crying started again. I sat on the edge of the bed, doubled over, and I felt severely ill, as though some freakish primal despair had finally been loosened from my stomach. The sensation was more like vomiting than any sadness I’ve ever experienced, and the shrieking sobs were punctuated by sudden jags of rage. Like a spoiled teenager, I’d suddenly uproot drawers from the bureau, push all the belongings off shelves with a sudden swat of the arm, smash a glass against the wall, and then the crying would take over yet again. Meanwhile, the room seemed to be pulsing and reverberating around me, and my eye would keep zeroing in on objects—the television, the AC, a pair of shoes—and feel as though they were somehow buzzing with life and gleefully watching me endure the biggest meltdown I’d ever had. I had somehow ruined myself, and suicide seemed like a good way to avoid the embarrassment of this fact’s being exposed.

The next morning, I called in sick to work and started cleaning up the considerable mess I’d made. I had to throw out a bunch of broken CDs, smashed glasses, torn clothes, ripped photographs, and the remaining boxes of Chantix from my medicine cabinet.
”

“SPECT scans are not sufficiently sensitive or specific to be useful in the diagnosis of A.D.,” neurologist Michael Greicius , who runs the Stanford University memory clinic, and has a special interest in the use of functional brain imaging in the diagnosis of A.D., tells me. “The PBS airing of Amen’s program provides a stamp of scientific validity to work which has no scientific validity.”

Continued pontification on neuroethics issues after the jump.

Looking at Amen’s website, you can find all sorts of “neuro supplements” (many of them seem to be similar to basic multivitamins, probably not harmful but not really neuro treatments in any specific way) and more intriguing products like the $4.95 online Amen Brain System Test which “is a valuable tool to help determine if there are problems in the prefrontal cortex, anterior cingulate gyrus, basal ganglia, temporal lobes or deep limbic system.” Really? Anterior cingulate? Deep limbic system? Hmmm.

Although people are certainly getting duped by Amen who is out for a quick buck, he is likely indicative of a larger trend. Namely, cashing in on the public’s desire to apply modern neuro research to improving their own health. (After all, that is how/why a lot of neuroscience is funded.) Some of this type of stuff is legitimate and that’s fine, but a lot of it won’t be. How could Amen get promoted through many “respectable” media outlets? Didn’t anyone try to check out his claims? Amen’s response to the critical Salon article makes no headway in providing scientific support for his treatment. As Stephen Colbert might say, his response smacks of truthiness. Where are the neuroethicists and neuroscientists on this one? Shouldn’t they be complaining to the news outlets and reminding them of their duty to fact-check the reports made on their shows? And yes, I mean interviewed guests too. General popularity should not be conflated with scientific approval. People who make scientific claims need to be checked on!

This issue seems to be a pertinent one these days, as demonstrated by this front page NYT article (NYT, login) on the absurd use of ex-military as news analysts and their propagandistic use by the Pentagon. Truthiness seems to be all the rage right now. Let’s hope facts come back into the picture before bad neuroscience leaves a lasting bad impression.

On a more positive note, I’d be curious to hear any opinions on what kinds of products based on preliminary results from neuro research should be allowed and how the scientific community can become more active in approving what’s good and what’s not. I do think that we will soon have many neuroscience entrepreneurs and not all of them are going to have PhDs. What products can be trusted? Maybe we need a forum for reviewing and rating these products — even one based on feedback from users. Ideas?

Amazing. It looks like TTX (tetrodotoxin, a potent voltage-gated sodium channel blocker well-known to electrophysiologists) is not made by the pufferfish (which I had always assumed), rather it is from the bacteria/food consumed by the fish.

Decades earlier, another Japanese scientist had identified fugu’s poison as tetrodotoxin, a neurotoxin that leaves victims mentally aware while they suffer paralysis and, in the worst cases, die of heart failure or suffocation. There is no known antidote.

Researchers surmised that fugu probably got the toxin by eating other animals that carried tetrodotoxin-laden bacteria, developing immunity over time — though scientists then did not rule out the possibility that fugu produced the toxin on its own.

By this year, Mr. Noguchi had tested more than 7,000 fugu in seven prefectures in Japan that had been given only feed free of the tetrodotoxin-laden bacteria. Not one was poisonous.

“When it wasn’t known where fugu’s poison came from, the mystery made for better conversation,” Mr. Noguchi said. “So, in effect, we took the romance out of fugu.”

Aside from the interesting science, it appears there is also a small Japanese “industry” (de-ttx? detox?) seriously affected by TTX-free fugu. More after the jump

But what could be seen as potential good news for gourmands has instead been grounds for controversy: powerful interests in the fugu industry, playing on lingering safety fears, are fighting to keep the ban on fugu livers even from poison-free fish.

“We won’t approve it,” Hisashi Matsumura, the president of the Shimonoseki Fugu Association and vice president of the National Fugu Association, said of the legalization of fugu liver. He added, “We’re not engaging in this irrelevant discussion.”

Acting as a giant clearinghouse, this port city in southwestern Japan buys fugu from all over Japan and China, guts it and expertly removes its poison before shipping it throughout Japan and as far as New York. Though Shimonoseki’s share has fallen in recent years, it still controls about half of Japan’s fugu market.

There was a high rate of treatment discontinuation due to adverse events; 15.7% in the rimonabant 20mg group compared to 7.8% in the placebo group.

For more info, see page 33 of EMEA(Europe’s FDA)’s Scientific Discussion document.

This strengthens my earlier stance that patients should weigh the decision of whether to chronically consume a CB1 antagonist as carefully as if they were considering regularly taking a CB1 agonist (such as marijuana).

For decades, psychiatrists have known that users of PCP, a street drug sometimes called angel dust, have symptoms nearly identical to those of people with schizophrenia. By the 1980s, scientists had discovered that PCP blocked brain receptors that are triggered by an amino acid called glutamate. This led some companies and scientists to study ways to stimulate glutamate receptors as a treatment for schizophrenia.

But the brain has many different kinds of glutamate receptors, and figuring out how to stimulate or block them in medically beneficial ways has proved complicated. Instead of focusing on the receptors blocked by PCP, Dr. Schoepp concentrated on modulating the action of glutamate receptors in the brain’s prefrontal cortex, an area responsible for personality and learning.

The drug, “LY2140023″, is an mGlu2/3 agonist. It showed statistically significant results in a (mid-sized?) clinical trial. Here’s the paper:

Sandeep T Patil, Lu Zhang, Ferenc Martenyi, Stephen L Lowe, Kimberley A Jackson, Boris V Andreev, Alla S Avedisova, Leonid M Bardenstein, Issak Y Gurovich, Margarita A Morozova, Sergey N Mosolov, Nikolai G Neznanov, Alexander M Reznik, Anatoly B Smulevich, Vladimir A Tochilov, Bryan G Johnson, James A Monn & Darryle D Schoepp. Activation of mGlu2/3 receptors as a new approach to treat schizophrenia: a randomized Phase 2 clinical trial. Nature Medicine 13, 1102 – 1107 (2007).

Neurocritic also has a blog post about this.

It was the very last paragraph that caught my eye:

Ever since the atomic bomb, physicists have known that their work has potential military uses, and have spoken up about it. But on the morality of sending orders directly to the brain (of a soldier, employee, child, prisoner …), or of devices that read thoughts and intentions from afar, neuroscientists have been strangely silent. The time to speak up is before the genie is out of the bottle.

Whoa! To me, the physicists who spoke out early on against nuclear proliferation seemed (and still seem) both very courageous and prescient in their ideas. Are we neuroscientists dropping the ball? I would love to start a discussion on this subject and to hear your responses (both from neuro people and others) in the comments below.

I’ll start: I personally don’t think the arena of neural enhancement/intrusion (mind reading, mind control, cognitive enhancement, etc.) is comparable to the sheer destructive power of nuclear weapons. I do see in the near future the unfortunate potential for abuse of neurotechnology and violation of personal freedoms, but the threat does not seem as horrifying or deadly. Still, if neurotechnology allows governments greater control over their citizens, it seems reasonable that scientists who enable such technologies should intervene. Perhaps it is time for a neural bill of rights, which, similar to the freedoms granted by the US Bill of Rights, will clearly state what aspects of a person’s mental state or capacity cannot be infringed upon without permission from that person. Thoughts?

Lots of interesting stuff here on new treatments for addiction, including: A methadone (heroin-substitute) replacement called buprenorphine with less dependency and less of a high; an injectible version of alcoholism treatment naltrexone called Vivitrol, which is injectable and lasts one month; some medications that increase GABA production; and, perhaps most innovative is a vaccine against nicotine that allows antibodies to bind nicotine and prevent crossing through the blood-brain barrier.

Excerpts with some of the neat experiments involving dopamine receptors and environmental factors in addiction are after the jump.

On the role of D2 receptors in addiction:

In one experiment, Volkow increased the level of dopamine D2 receptors in rats that had low levels. After the increase, the rats significantly curtailed their intake of alcohol, which they had eagerly gulped down before. Unfortunately, we don’t yet know how to safely increase the number of dopamine D2 receptors in humans.

Also:

And remember the dopamine D2 receptors that some hypothesize may protect us from abusing drugs? There is evidence that our environment can affect those, too. In 2003, researchers at the Wake Forest School of Medicine measured the levels of dopamine D2 receptors of 20 macaque monkeys while they were housed in isolation. They then assigned the monkeys to social groups of four monkeys each, letting natural social hierarchies develop. Three months later, they tested the levels of D2 receptors again.

The dominant monkeys — who, the theory goes, were much less stressed and anxious than the subordinate ones — had 20 percent higher D2 receptor function, while the submissive ones were unchanged. The monkeys were then taught how to self-administer cocaine by pressing a lever, with researchers finding that the dominant monkeys took significantly less cocaine than the subordinate ones.

Interestingly, though, when the animals that seemed to be protected from addiction were given cocaine repeatedly, the number of their D2 receptors eventually went down, and they then became addicted. The moral of the monkey story, Volkow says, is that environment — if good or bad enough — can sometimes trump genetics and biology.

I found this idea of addiction prevention through an enriched environment fascinating:

[Bruce] Alexander [at Simon Fraser University] is among a vocal group of addiction researchers who argue that focusing on a pill to treat addicts fails to address the primary cause of becoming and staying hooked: our unhappy, disconnected lives. Beginning in the late 1970′s, Alexander and his team of researchers at Simon Fraser set out to study the role of our environment on addictive behavior. Until that point, most scientists studying addiction put rats in small, individual cages and watched as they eagerly guzzled drug-laced solutions and ignored water and food, sometimes dying in the process. This phenomenon was noted — first by researchers, then drug czars, then parents trying to keep their children off drugs — as proof of the inherently addictive quality of drugs and of the inevitable addiction of any human who used them. This was false, of course. Most people who use drugs don’t become addicted.

So what made all those lab rats lose their minds? Bruce Alexander and his research team had a rather simple hypothesis: The rats had awful lives. They were stressed, lonely, bored and looking to self-medicate. To prove it, Alexander created a lab-rat heaven he called Rat Park. The 200-square-foot residence featured bright balls and tin cans to play with, painted creeks and trees to look at and plenty of room for mating and socializing.

Alexander took 16 lucky rats and plopped them into Rat Park, where they were offered water or a sweet, morphine-based cocktail (rats love sweets). Alexander offered the same two drinks to the control group of rats he left isolated in cages. The results? The rat-parkers were apparently having too much fun to bother with artificial highs, because they hardly touched the morphine solution, no matter how sweet Alexander and his colleagues made it. The isolated and arguably depressed rats, on the other hand, eagerly got high, drinking more than a dozen times the amount of the morphine solution as the rats in paradise.