Derek Lowe explains from personal experience that innovation in drug development isn't easy:

"And it's not like there aren't plenty of highs and lows in what we're pleased to call "normal" drug discovery. It should be enough.

But it isn't, not always. These roll-the-dice ideas keep occuring to me, and some of them just seem to have to be tried out. It's hard dealing with the results, which (so far) have been relentlessly negative. That goes for this current idea, which is a little over a year old, and for the ones I've had in past years. None of the really good ones have worked, not one. And that bothers me, as it would bother anyone. But I think, eventually, it would bother me more if I never tried. Here goes, again.

From all of us who will eventually benefit from your years of hard work, I'd like to say thank you and make a toast to you as a future famous man.

Halloween turns millions of kids (and some adults) into candy-loving monsters with more than ample supply of candy to satisfy their "sweet tooth." Now, HHMI researchers have moved closer to understanding why some people cannot resist the impulses brought on by sweets.

The findings, reported in today's issue of the journal Cell details how the researchers created mice with the same sweet-tooth preferences as humans by inserting the gene that codes for a human sweet-taste receptor protein into the animals. They also inserted an entirely different receptor gene into the taste cells of mice, thereby producing animals that perceive a previously tasteless molecule as sweet.

This research is a wonderful step in the development of flavorceuticals, a type of sensoceutical focused on our sense of taste. Now just imagine if we can get them to figure out how to make all those yucky foods taste sweet.

Happy Halloween! Casey and I are going together as Sydney Bristow and Michael Vaughn from Alias.

Derek Lowe recently posted a very good explanation of the presumed mode of action of the new Alzheimer’s drug memantine.

Memantine has some affinity for a wide range of receptors in the brain, but at the doses that are seen therapeutically, the relevant interactions seems to be with the NMDA receptor....The weird thing is, memantine is an antagonist; it blocks NMDA signaling. So at high doses, it actually interferes with memory....At clinical doses, the compound does play against type and seem to improve memory. The best guess for how this works is through a mechanism for neuronal injury in Alzheimer's. Too frequent (and too prolonged) firing of excitatory pathways like NMDA have long been associated with cellular damage in the brain, and this seems to be going on in AD as well...

There is some evidence that neurons with NMDA receptors are lost in AD, but it’s hard to explain the improvement in cognitive performance of some patients if you are merely stopping or slowing damage. Also memantine has been shown to have a short term effect on memory and memory related cellular plasticity. Why not consider this evidence that memantine is working through a more subtle mechanism than preventing excitotoxicity?

NMDA is believed to function in learning by giving a neuron “memory” of previous activity. Since we have to be picky about which memories are stored and which can be forgotten, NMDA is thought to be a sort of memory “bouncer” determining whether the stimulus is strong enough to be laid down permanently, or whether you really don’t need to remember where you left your keys.

So a reasonable theory would be that in Alzheimer’s, NMDA is underactive and is not letting in any new memories. But the efficacy (though slight) of memantine suggests that maybe NMDA is overactive, letting in any memory at all and promoting the cellular changes that allow memories to be stored at random. Without any barrier for memory formation, perhaps a neuron can’t distinguish between important and unimportant events, so it appears that nothing is stored, when really “everything” is stored and each event instantly erases the last event. Memantine can reduce the activity of NMDA and restore its selectivity for the right memories.

Complicated explanations may not suit a pharmaceutical company, but understanding the true therapeutic nature of current pharmaceuticals will be an important part of future neuroceutical development. For example, SSRI's like Prozac take several weeks to be effective, but for years pharma claimed that the anitdepressant effect was due to a short term reduction in serotonin reuptake. The fact is we still don't know why SSRI's have the effect they do.

Thanks Casey.

Neuroceuticals are tools. They hold the promise and peril of any new set of tools.

Tools like the oxen plow, railroads, electricity, automobiles, planes, cell phones, and the web, have all in one way or another been used for good and evil purposes.

By providing new tools for people to manage their behavior and empathize with others, neurotechnology represents potential breakthroughs in human productivity, political stability and ecological balance. In the wrong hands, this technology also could be used for mind control, coercive truth detection or as neuroweapons that have the potential to erase the memories or feelings of entire populations.

Neuroceuticals, although perhaps daunting and perhaps a bit scary because they have the capacity to influence our moods and perceptions, are being developed rapidly. My purpose is to help begin a broad and thoughtful public discussion of the social implications of neuroceuticals before they arrive. My intention is not to promote them but to highlight the fact that they will emerge no matter what stringent standards may be adopted by most of the world's governments.

My thinking is that neuroceutical adoption for competitive advantage will likely begin outside the jurisdiction of western governments, as the regulatory process will be slow to adapt. It is in the smaller countries or regions that initial adoption will occur where the political process can be persuaded quickly.

Moreover, when people within large multinational companies begin to experience the advantages these new tools bring, the pressure to accept and legalize them will grow quickly. Governments and regions that don’t won’t be able to compete. It would be as if a region didn’t allow telephone service.

Neuroceuticals will one day be considered very ordinary and disappear into people’s daily lives like all successful technologies do. Just like irrigation is an invention we don't think about much anymore, neurotechnology will in time seamlessly become part of our lives.

As I alluded to in Forecasting Happiness, neuroceuticals will play a prominent role in accelerating productivity across all economic sectors during the neurotechnology wave.  One pervasive process that will be affected is the social process of innovation.  Innovation is a key determinant of organizational success wherein cognitive assessment and emotional compassion combine to accelerate the creation of new knowledge. 

Over the past several decades access to a growing global information web has improved innovation cycle times across every industry.  Over the next decade this trend will continue as social networks (opinions, thoughts and concerns) become embedded across this information sea, creating a knowledge web that is vastly more reliable. 

By improving cognitive clarity and emotional stability , neuroceuticals will make possible new behavioral repertoires that most of us cannot consistently attain today.  For example, enhancing an individual's working memory with cogniceuticals will play a role in extending individual creativity, a critical component of the innovation process.

As different aspects of mental health are better understood, more parts of the innovative process will be impacted such as accelerating learning via cogniceuticals to enhancing interpersonal communication with emoticeuticals. As neuroceutical usage spreads across industries it will create a new economic “playing field” wherein individuals who use neuroceuticals will achieve a higher level of productivity than those who don’t. 

The resulting competitive gap will be substantial. To put this in historical perspective, imagine the competitive advantage that a team living in the year 2003 with the Internet as their information source has over a group living in 1953 that must rely on the local library.

by Tom Ray

The goal of mapping "receptor space" is to chart the relationships between complex alterations in chemical signaling, and resulting changes in mental states. These data are expected to provide an empirical basis for the development of an understanding of the chemistry of mind. To do this we need to understand what mental states are associated with various regions of the receptor space. We need to understand what kinds of interactions between transmitter systems and neural pathways result from chemical perturbations into various regions of receptors space.

This knowledge can help us to build a theoretical foundation for the rational design of drugs for the treatment of mental illness. In a loose sense, mental illnesses are also a kind of perturbation in receptor space. We need to determine what regions of receptor space are associated with these illnesses, and develop a pharmacology for these regions.

We do not yet understand why different individual members of this family (e.g., clozapine, risperidone, olanzapine, quetiapine, ziprasidone) are more effective in treating different individual patients. It is plausible that these differences in efficacy derive from the interactions of the different receptor binding profiles of the different antipsychotic drugs, with the specific characteristics of the disorders manifested by individual patients.

If we can develop a detailed knowledge of the relationship between chemical balance and mental state, methods for treating mental illness can be greatly improved. The atypical antipsychotics are some of the most effective drugs in treating the most difficult cases of schizophrenia. These drugs bind to a very large number of receptors, and therefore cause complex perturbations in "receptor space".

The understanding of the chemistry of consciousness is the ultimate goal of my research. By mapping receptor space we will be able to create a more rational basis for developing effective treatments of mental disorders. Please feel free to email me directly if you are interested in learning more about my research.

by Tom Ray

Let's consider a brain-centered reference frame, in which the origin is based on some arbitrary absolute levels of activity at each receptor population. The origin could be the time-averaged activity at each receptor, or no activity at each receptor, it doesn't matter much. In this reference frame, the state of the brain is constantly on the move, regardless of medication. We can think of it as a complex dynamical system, in which the trajectory likely does not traverse the entire receptor space, but rather follows certain high-dimensional orbits, and switches among many "attractors", where the attractors represent the major emotional states and moods, and whatever other mental phenomena the chemical systems are mediating. Mental illnesses can be thought of as pathological attractors.

In this more dynamic reference frame, the notion of drugs perturbing the brain along a vector of binding affinities in receptor space seems simplistic. It is more likely that drugs will create a perturbation along the binding vector, thereby pushing the system into a new attractor.

As pharmacologists, we want to understand how patterns of activity at receptor populations associate with mental phenomena. We want to get to know the pharmacology of the attractors. It seems unlikely that the attractors will be on-axis, resulting from changes in the activity of single receptor populations.

We have our hands on the receptors and we are enchanted by them. We have come to think of selectivity in terms of receptors, and in the process we have lost sight of the mind that we wish to understand. There are other approaches to thinking about pharmacological selectivity. Selectivity can be defined in terms of different or distinct behavioral or subjective mental effects produced by drugs.

The conventional approach to pharmacology is to find a drug that is receptor selective, and then observe its behavioral effect. An alternative approach is to find a drug that produces a distinctive behavior, and then observe its receptor binding profile. I believe that it is this alternative approach that holds the greatest promise for understanding the pharmacology of the attractors, and thus the major mental states mediated by receptors. The two approaches are complementary, and we need both to provide the most comprehensive understanding. The new approach is only now becoming possible, as it requires the full post-genome pharmacology provided by PDSP.

by Tom Ray

I would like to share a metaphor, or image, that I use when thinking about the new pharmacology: receptor space.

Imagine a coordinate system based on receptors, one axis for each receptor ("receptor space"). This notion of "receptor space" is in the reference frame of the unmedicated brain. Drugs perturb the system from its pharmacological origin by altering the activity of transmitter and receptor systems, through increasing or decreasing transmission or transmitter levels, or up or down regulating receptor populations.

From a pharmacological point of view, the origin of the receptor space represents the state of an individual brain at any moment, without the application of any drug. When a drug is applied that binds to receptors, it shifts the balance of activity of the brain away from the origin, by a vector representing displacement along the axes corresponding to the receptors where the drug binds (and perhaps others due to secondary interactions).

The distance of the shift represents the affinity of the drug for the receptor, or the degree to which the drug activates the receptor. Negative axes could correspond to blocking or deactivation of the receptor. For convenience, I would like to refer to molecules with a non-zero value on only one axis as "on-axis", and molecules with a non-zero value on more than one axis as "off-axis".

These kinds of changes occur spontaneously and constantly in the unmedicated brain. Thus our pharmacological reference frame, of the unmedicated brain at the origin, is a very dynamic one.

by Tom Ray

The completion of the human genome has revealed the tremendous complexity of the chemical signaling pathways in our bodies. There appear to be over three hundred different kinds of receptors expressed in the brain.

To understand how variations in the activities of these chemical signaling pathways can combine to produce mental states and mental disorders, we need to develop an empirical understanding of the influence of these systems on mental states. This understanding must include interactions between different chemical signaling systems, as well as the role of individual systems. The cloning and development of receptor binding and functional assays for a large number of receptors is opening a new "post-genome" era of pharmacology, which permits us to look at the global effects of drugs on the brain and body.

The National Institute of Mental Health set up a Psychoactive Drug Screening Program (PDSP) using this new post-genome approach. PDSP is the "supercomputer" of pharmacology. It is a facility, still under development, that allows us to screen drugs against the entire human "receptome" (all receptors in the human body).

It is a facility like a supercomputer, that is so massive and expensive, that in this case, only one can exist. Therefore NIMH has set up one such facility, and makes its screening services available to researchers, like the supercomputers at the National Center for Supercomputing Applications (NCSA).

A few years ago, it was a very difficult task to screen a drug against a single receptor, to deterine if the drug binds to the receptor, and if so, what it does there (blocks, activates or de-activates). In the past, pharmacologists were like the blind men and the elephant only able to look at one or a few parts of the chemical system. Now for the first time it is becoming possible to look at the whole system.

by Tom Ray

1. Why are there so many different neurotransmitter receptors in the brain?
   
2. What is the functional role of each, and how are they organized in the brain?
   
3. How are the activities of these transmitter systems and their interactions associated with mental states?

In short, what is the chemical architecture of the brain and the mind that emerges from it? The answers to these questions should ultimately provide a firmer basis for understanding mental illness and developing treatments.

The pharmacological approach to these questions is to develop compounds that bind selectively at receptors, and activate or block them, and use them as probes to receptor function. When the molecular mechanisms of action of a drug are known, they can be correlated with the behavioral effects in animals or the subjective reports of humans, to understand the mental correlates of their underlying biological effects. When used in this way, pharmacology is a means of exploring the chemical organization of the brain and mind.

Peter Kramer's book "Listening to Prozac" introduced the pharmacological approach to the general public. The title "Listening to Prozac" means that we learned something new about the nature of the human mind by observing the effects of prozac.

Prozac was developed to treat depression, but when it was prescribed to large numbers of people, it was discovered that it also changed personality (from timid to self-confident). Before this unplanned experiment, it was not known that such aspects of personality were under chemical influence. By listening to prozac, we learned something about the chemical organization of the human mind.

Although pharmacology is generally thought of as a branch of medicine that uses chemicals to treat illness, pharmacology can also be used as a method of probing living systems to understand how they are organized and how they function.

by Tom Ray

Understanding the chemistry of the brain and the mind that emerges from it is one of the remaining great frontiers of science. Developing a fundamental understanding of the chemistry of the mind will provide us with a deeper understanding of ourselves and a theoretical basis for a more rational system for treating mental disorders. Without an *understanding* of the chemistry of the mind, pharmacology remains a trial-and-error "science".

The brain is a chemical organ and our mental states are dramatically altered by chemical shifts. Chemical shifts can be caused by drugs but they also occur naturally. Moods and emotions are likely to have chemical foundations, and even without the influences of drugs, much of our mental life is a chemical dance. Features of the human personality, such as the spectrum between timidity and social confidence, can be influenced by chemistry. A wide variety of serious mental disorders, from depression to schizophrenia, have yielded to effective chemical treatments, suggesting that chemical imbalances may underlie some of these disorders.

Different disorders (see DSM-IV, 2000) yield to different chemical treatments, indicating that each disorder is associated with a specific chemical imbalance. Yet there is currently no rational way to predict which antidepressant is more likely to work than another in a depressed patient or which antipsychotic will work in a specific schizophrenic patient. Furthermore, no single abnormality in any neurotransmitter or in any of its enzymes or receptors has been shown to cause any common psychiatric disorder. It is currently believed that the major mental disorders are the result of an accumulation of factors that together cause the disorder.

Next week Tom Ray, tropical ecologist, artificial life expert, and now neuro-mapping pioneer will share his thoughts on accelerating our understanding of the neurochemistry of consciousness by mapping what he calls "receptor space."

Tom is a true complexity expert -- an evolutionary ecologist of both the biological and digital worlds.  Tom's rich research agenda and advice have inspired me over the past 15 years.  His ecological research and conservation efforts in Costa Rica stimulated my work on disturbance behaviors in Atta cephalotes (leaf cutter ants) at Finca La Selva.  His work at the Santa Fe Institute on Tierra, a distributed digital artificial life reserve, pushed the science of complexity to new levels.

Hundreds of articles have been written about Tom's previous research.  I'm confident his approach to mapping the potential mental states that the human mind can experience will prove to be his most important work to date.  Few people have first-hand experience with multiple complex evolutionary systems.  It is this deep perspective that should allow him to contribute significantly to our understanding of the human mind.

Tom Ray is currently a Professor of Zoology at the University of Oklahoma and an Invited Researcher at ATR Human Information Sciences Laboratories, Kyoto, Japan.

As Paul Allen mentioned earlier this week, understanding the brain and how the mind emerges from it remains one of great frontiers of science.  I'm honored to have Tom Ray, for the first time, share his new research direction with us on Brain Waves.  Expect great thoughts!

Randall Parker blogs on an interesting development in our understanding of how pharmacological agents can inhibit and enhance human sensory system performance.  Citing the researchers:

"We are at the beginning of an era where we can interact with the brain. We can apply what we know about brain plasticity to train it to alter behavior. People are always trying to find ways to improve learning. What we tested is unconscious skill learning. How far could this carry to cognitive learning?…that remains to be seen," said Dinse.

Published in Science, the research showed that stimulation combined with methamphetamines could improve tactile sensitivity of people's fingertips.  It is research like this that focuses on the basic neuroscience of sensory system learning that will lead to sensoceutical breakthroughs in the coming years.

Daily, weekly, monthly and annually great thoughts of produced.  Here are a few of the recent best:

• Will Starbucks Carry It?: Yes. Better tasting decaffeinated GM coffee beans.
  
• The Pharmaceutical's Dilemma: Pharma is due for a shake up (my take)

Weekly: Science Magazine

• Excited by Glutamate: Glutamate receptors are the new dopamine
  
• Stability at the Brain and Synapse Level: Evidence of neural plasticity continues to increase

Monthly: Seed Magazine (June/July print version)

• The Strange Case of Dr. Sell, Drugging the Accused: Important Supreme Court decision
  
• The Neuroscience of Proust: Brilliant artists are many times ahead of science

Annual (books):

• Law and the Mind -- Biological Origins of Human Behavior by Margaret Gruter:  Margaret's insight into how evolutionary biology can inform our legal system is still as relevant today as it was when it was first published 20 years ago.
  
• MWO-It was an honor to be the fourth reviewer of a manuscript written by someone most of us know.  Unfortunately, I'm unable to share the enticing personal perspective of neurotechnology developed within...at least not yet...867-5309.

The transfer of information between nerve cells occurs when chemicals called neurotransmitters are released into the synapse, the junction between neurons. Electrical impulses in the neuron cause tiny vesicles (graphic) loaded with neurotransmitters to be released into the synapse.

Today's Nature reports on a new technique that researchers have created to image the movement of individual vesicles after they have released their neurotransmitter cargo. The new technique helps answer questions like the rate at which synaptic vesicles are recycled which helps illuminate how much information nerve cells can transmit.

There are three distinct ways that a "used vesicle" can be recycled from the surface of the nerve cell once it has released its cargo:

• "Kiss-and-Run" mode is the fastest, less than a second
  
• “Compensatory” mode is slower, up to 21 seconds
  
• “Stranded” mode leaves the vesicle stuck at the surface until the next nerve impulse triggers its retrieval

"The optical recording technique devised by Stevens and Gandhi involves genetically modifying a gene for one type of vesicle protein to incorporate a special form of green fluorescent protein. This modified fluorescent protein, developed by other researchers, does not fluoresce under acidic conditions normally present in vesicles fully loaded with neurotransmitter. However, when the vesicle releases its payload, the interior becomes less acidic and the vesicle glows a bright green."

Synesthesia, which means "joined sensation,” is a condition wherein information obtained through one sense creates sensations in another sense. For example, when a synesthete hears a bell they would also see colors.  Many brilliant people have had synesthesia, including:

• Physicist Richard Feynman who saw colors in his physics equations
  
• Abstract painter David Hockney who visualized the colors for his paintings when hearing music
  
• Composer Franz Liszt who pictured colors upon hearing musical notes.

The phenomenon is involuntary, consistent over a lifetime, hereditary, and fairly common. In fact, some form of synesthesia affects 1 in 200 people.  In its own particular way, synesthesia points to yet another way that the wiring of the brain can create different ways to experience life. 

Yesterday I uncovered a recent 17 minute film made last year by Carrie Shultz that tracks the experiences of three women living with synesthesia.  She is sending me a copy.  I'll let you know how it is. 

As the brain imaging bottleneck is overcome allowing live neuron-specific resolution of our brains, this information will be combined with data from the ‘whole biochip', making possible a new sets of tools that I am calling, neuroceuticals.  

Neuroceuticals act to reduce the severity of a mental disorder or enhance an aspect of mental health.  They can be broadly categorized into three classes:

• Cogniceuticals focus on thinking, decision-making, learning, attention, and memory
  
• Emoticeuticals focus on feelings, moods, drive, and awareness
  
• Sensoceuticals focus on seeing, smelling, moving, tasting, hearing and touching

Obviously this categorization is simplified, as our senses, cognition and emotions are inextricably interconnected.  However, by introducing these terms, it should make discussions of their interdependency clearer over time.

How will complex mixtures of neuroceuticals that simultaneously influence multiple aspects of human behavior impact social relations? How will a person who is slightly less depressed, slightly less anxious, slightly more aware, and with slightly better recall behave? 

By influencing multiple characteristics along varying gradients, behaviors will emerge that will culminate into a substantially different behavior repertoire than people currently encounter.  In effect, a different “playing field” will arise wherein people will act perceptually different than if one were to just enable people to be happier.

It is important to view neuroceuticals not as drugs that unnaturally change the human condition.  Rather neuroceuticals are tools that humanity is developing to help each of us better control our mental health, allowing us to organize more effectively in an ever-complex world. 

The breakthrough required to develop true neuroceuticals are still 10-15 years off.  However, as they emerge individuals and organizations will adopt these new tools just as information technology, motorized transportations systems, electricity, steam engines, and canals have been leverage to increase humanity's overall control and effectiveness of physical and information assets.

An important conversation between Richard, a biotech pro, and Derek a pharma veteran, highlights the pathetic state of the current drug discovery and development process. 

Both point out how Pharma's current top down development process is tedious, disconnected and in many cases just don't work.  Although Richard's prescription seems logical on paper, the reality of industrial reorganization coming from the inside is a long shot.

Industries evolve in a similar manner as ecological systems, via punctuated equilibrium. Industries progress slowly and then suddenly a new organism/organization that has been evolving along the fringe emerges to replace the parent species by taking advantage of a new adaptation/technology.

The history of economic geography is full of examples of how industries evolve between being vertically integrated structures to vertical disintegrated ecosystems, driven primarily by the disruptive effects of a new organizational species.

The current pharmaceutical industry is highly vertically integrated.  Although attempts are being made to extend their expertise through alliances and acquisition, the history of life proves time and time that most powerful driver of change is the emergence of an organization that leverages a specific adaptation to out fight, out wit and out compete the current dominant species.

With gene chips just beginning to fulfill their promise, I believe that the organizational form that will dominate the future of drug development will be the one who cracks the proteomics bottleneck and leverages this new information to dominate its ecology.  On that note, I'd give the upper hand to a biotech company that is most likely not even on today's industrial landscape.

Research into the neurobiology of drug addiction is progressing rapidly, leading prominent researchers to claim that within the decade there will be effective treatments for drug addiction. 

But will these new treatments actually stop people from seeking pleasure inducing drugs? Only time will tell.

A warm welcome to Derek Lowe who has joined Corante's blogging team to share his knowlege and insight into the complex world of drug development.  

In The Pipeline: Drug Discovery will cover: "recent developments in drug discovery and medicine and the IP issues and financial implications they have, along with general thoughts about research. Also likely to make an appearance: occasional digressions into useful topics like which lab reagents smell the worst." I highly recommend taking a look at the three months of blogs already in his archives.

The future of neurotechnology and the drug development process are intimately related as my blogs on emotions, sensoceuticals and barriers to drug delivery have previously pointed out.  Derek's daily focus on the drug development process along with Richard Gayle's "Living Code" blog on biotechnology will be excellent sources of inspiration and information as I try to untangle our emerging posthuman society.

Substantial variation in taste sensitivity exists in humans. Understanding taste's relationship to diet and other behaviors like smoking will have important implications for human health.

Taste plays a crucial role in food choice, allowing people to identify beneficial foods those with high caloric value (typically sweet) from foods likely to be toxic (usually bitter).  Breakthroughs in taste research began in 1931 when Science published the finding that many individuals are unable to taste the compound, phenylthiocarbamide (PTC), a relatively bitter compound. It turns out that one-fourth Americans cannot taste PTC.

Companies like IFF (International Flavor and Fragrances) have been focused on developing "better" tasting food for years while start-ups like Senomyx are working on products that block bitter tastes in coffee, make low-sodium snacks taste salty, and block unpleasant odors. 

Although these don't come close to the new experiences that are on the horizon, but continued research by sensory scientists should lead to the development of new taste specific sensoceuticals in the coming years.  At the very least this might mean better tasting MREs.

This month's Scientific American describes many of problems faced in getting pharmaceuticals to their intended targets throughout our bodies. Delivering neuropsychopharmaceuticals to our brain remains even more of a problem.

Drug delivery to our brain can occur through several methods: orally (pills), gaseous/inhaled, intramuscularly (skin patch), intravenously, and neural injection.  The method used greatly influences the amount of the drug that is required for the same effect to be observed.  For example, a single dose of an amphetamine creates the same effect but requires hugely different volumes depending on the method of delivery:

• 1000 micrograms if ingested orally
  
• 100 micrograms if injected or inhaled
  
• 10 micrograms if injected in the cerebral spinal fluid
  
• 1 microgram if injected onto the neuron

The primary delivery limiters are the digestive system and the blood brain barrier.  Many effective treatments for mental illnesses have been kept off the market due to the inability to safely deliver therapeutic chemicals whose large molecular sizes makes it impossible for them to pass the blood brain barrier. 

Neural chips may play a role in effectively delivery, but the cultural "acceptability barrier" of implanting chips into our brains will likely remain the largest obstacle to adoption on wide scale for some time to come.  It is one thing if you are deaf and get a cochlear implant, it is another to be willing to go through a surgical procedure if you are a bit anxious or occasionally depressed.  The likely pathway will depend on the pay-off for the patient.  One thing is for sure, more effective drug delivery systems will require new partnerships and new techniques to make precise delivery possible.

To date, media attention across the emerging field of neurotechnology has primarily focused on neural prosthetics that are electro-mechanical in nature.

For example, to help the hearing impaired, cochlear implants have been developed that translate sound waves collected via a tiny microphone into electrical impulses. Most people with profound deafness have lost the ability to translate the acoustic energy of sound into the electrical signals carried to the brain by the 30,000 fibers of the auditory nerve.  Cochlear implants bypass the external and middle ears by using electrical stimulation of electrodes implanted in the cochlea to reintroduce the signals carried by auditory nerve fibers to the brain.

As exciting and important as electro-mechanical advances like this are, they represent just one type of neurotechnology that will be developed in the coming years to restore and enhance human sensory systems, such as hearing. 

Sensoceuticals, sensory-specific biopharmaceuticals, use a different approach to restore and enhance human sensory systems.  Sensoceuticals leverage the natural regenerative capacity of our genes, proteins, and neurons to re-grow damaged sensory tissues and extend sensation capacity.

For example, sensoceuticals for hearing will be able to prevent and restore hearing loss. Current research indicates that the inner ear can be protected from the irreversible effects of noise damage using sensoceuticals. This will be an important breakthrough for soldiers who, due to the complexity of the today’s battlefield, can’t wear earplugs to protect their ears.

For those people who already have substantial hearing loss, researchers are also optimizing compounds that antagonize specific cell cycle proteins resulting in new cell division or proliferation. Most exciting is that these newly dividing cells have the capacity to become replacement auditory hair cells, restoring hearing loss for the deaf or partially deaf.

As the field of neurotechnology evolves it will be interesting to see how the developments occurring “from the inside” begin to mingle and compete for funding resources with advances coming “from the outside.”