CB1 antagonist seems to contribute to depression

I didn’t notice this before, but in a study of about 4000 subjects, people who took Rimonabant (marketed as Acomplia), a selective antagonist of the cannabinoid type 1 receptor (CB1), apparently had a 3.2% incidence of depressive disorders where placebo-takers apparently had a 1.6% incidence. Also, irritability went from .6% to 1.9%, parasomnia from .2% to 1.5%, nervousness from .2% to 1.2%, sleep disorders from .4% to 1.0%, memory loss from .9% to 1.6%, hypoesthesia from .6% to 1.6%, and sciatica from .4% to 1.0%. Psychiatric adverse events were dose-dependent.

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If dopamine fails, try glutamate

Happy Labor Day (US)! Topping the NYT most popular articles list right now is an interesting article about a new schizophrenia treatment that targets certain glutamate receptors unlike previous dopaminergic drugs. The drug, which is being developed by Eli Lilly, is partially due to this interesting observation:

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.

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Review on TMS for therapy

There’s a nice NRN review on the many recent papers on therapeutic use of transcranial magnetic stimulation.

Is there a future for therapeutic use of transcranial magnetic stimulation?

The past year has seen the publication of a remarkable number of papers about the potential therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) in conditions ranging from cocaine addiction to stroke and depression. Are we witnessing the discovery of a miraculous cure-all or will this bubble burst like the magnetotherapies of the Victorian era1? We argue below that there is good evidence that rTMS can produce after-effects on the brain, and that these translate into effects on simple behaviours. However, the rationale for applying the same methods to treat disease is in many cases unclear.

Human 2.0: New Minds, New Bodies, New Identites

The MIT Media Lab is holding a conference on May 9th, “Human 2.0: New Minds, New Bodies, New Identites” which will launch a number of new initiatives centered around the goal of inventing a better future via direct engineering of the human. Amongst these things will be the initiation of the MIT Center for Human Augmentation, and the launch of a number of novel applied Neurotechnology Projects.

Guest speakers on May 9th will include MIT professors (Roz Picard, Hugh Herr, myself, etc.) and many acclaimed speakers such as Oliver Sacks and John Donoghue. Registration may be close to being full, but it will be webcast.

More information at:

— posted by Ed

Brain stimulation and depression?

Brain stimulation and depression has been one of the hot topics of the last decade. Now, a Washington Post story suggests that at least some of this may be overrated, at least for the NeuroStar Transcranial Magnetic Stimulation (TMS) device from Neuronetics:
A novel machine designed to treat depression by zapping the brain with magnetic pulses shows no clear evidence of working, federal health advisers concluded Friday.

The device is called the Neurostar TMS, or transcranial magnetic stimulation, system. It uses magnetic energy to induce electrical currents in the region of the brain associated with mood…

A clinical trial of the device provided results that, in one analysis, suggested it’s no better than sham treatment, according to FDA documents.”

Going to be a long slog. TMS *has* been approved for treating depression in Canada and Israel, for the company NeoPulse.

OpenStim: The Open Noninvasive Brain Stimulator

Transcranial magnetic stimulation (TMS) is a popular technology for stimulating human cortical neurons, due to its safety, noninvasiveness, and efficacy. A TMS device is just a little coil of wire, through which 10,000 Amps of current is cranked during a period of only a few hundred microseconds; the resultant rapidly-changing magnetic field induces eddy currents in the brain. Depending on the protocol used, TMS can drive/inhibit a region of cortex corresponding to roughly a cubic centimeter or two, and is being explored for the treatment of depression, the reduction of auditory hallucinations during schizophrenia, and the alleviation of tinnitus and migraines. Thousands of papers on medicine and psychology have been written using this tool.

Yet the device itself is expensive and rare — they can run from $20,000 to $50,000 or even more, despite the fact that they are, in essence, a coil, a switch, a bank of capacitors, and a power supply. Much of the art lies in making the devices safe and fail-proof. Is it possible to hack/engineer a system that is safe, fault-tolerant, efficacious, and inexpensive? And furthermore, can we facilitate a community that will devise such devices, and share information about protocols and approaches to brain hacking?

This past August at Foo Camp, a hackers’ conference in Northern California, a group of people got together and set out to do just that. We are designing a safe, noninvasive, modular, and “open source” brain stimulator that will open up the field of circuit modulation to a wider audience. Members of the group include therapists and mental health professionals, engineers, programmers, and others interested in either the development of such devices, or the sharing of information on this front. Key to the design is safety — we want to make sure that the devices we create are as safe as devices on the market. Also, all the information is released under the Creative Commons “Attribution and Sharealike” license. This is a new model for “open source” medical device development — which may move it beyond the domain of simply creating “cool toys,” and to creating real devices.

You can find out more information, or contribute to the project, or learn from the project, at


Overexpression of Rab1 prevents Parkinson-like cell death

{alpha}-Synuclein Blocks ER-Golgi Traffic and Rab1 Rescues Neuron Loss in Parkinson’s Models — Cooper et al., Science

Fascinating evidence pointing toward a treatment for parkinson’s. Basically, Lindquist’s group finds that overexpression of a trafficking protein Rab1 that moves folded proteins from the ER to the Golgi can prevent alpha-synuclein accumulation-triggered death of rat neurons.

Of course, in vitro is not in vivo. And, for all we know, Parkinson’s could be a complex, multi-mechanism disease. But this looks promising!


Alpha-synuclein misfolding is associated with several devastating neurodegenerative disorders including Parkinson’s Disease (PD). In yeast cells and in neurons {alpha}Syn accumulation is cytotoxic, but little is known about its normal function or pathobiology. The earliest defect following {alpha}Syn expression in yeast was a block in endoplasmic reticulum (ER) to Golgi vesicular trafficking. In a genome-wide screen, the largest class of toxicity modifiers were proteins functioning at this same step, including the Rab GTPase Ypt1p, which associated with cytoplasmic {alpha}Syn inclusions. Elevated expression of Rab1, the mammalian YPT1 homolog, protected against {alpha}Syn-induced dopaminergic neuron loss in animal models of PD. Thus synucleinopathies may result from disruptions in basic cellular functions that interface with the unique biology of particular neurons to make them especially vulnerable.