Chemical of the Week: Solid Oxygen

Last week, we had a look at dicyanoacetylene, a highly reactive chemical found in our very own solar system, in the atmosphere of Saturn's moon Titan. This week, we will look at the curious case of a synthetic chemical formed under crushing pressures right here on Earth.

Oxygen. We all know it, and for better or worse, love it. After all, oxygen makes up approximately 21% of our atmosphere. Aside from being a rather useful chemical, it gives us something to breathe other than that oh-so-common nitrogen that those nitrogen-fixing microorganisms and symbiotic plants allegedly rave about.

Clover. Thanks to the diazotrophic rhizobia in its root nodules, it now has a thing for nitrogen. 

In our common experience, oxygen is either a simple diatomic gas, or found cloistered away in minerals, oxides and the like. In terms of oxygen in its gaseous state, what happens when it is subjected to freezing temperatures? As with many other gases, oxygen will condense to form a liquid, and when cooled further, form a solid. In the case of oxygen, it has a melting point of -218.79°C, and a boiling point is at -182.95°C, so we rarely encounter diatomic oxygen in anything but its gaseous state.

Now, as I mentioned above oxygen freezes at -218.79°C to form solid oxygen, though this is only the beginning of our story. By changing the temperature of solid oxygen, and by subjecting it to different pressures, it undergoes phase transitions to form different phases of solid oxygen. That is to say, changing the temperatures and pressures solid oxygen to will generally still leave us with solid oxygen, but these disparate phases will have different physical properties.

In the article "Solid Oxygen", by Freiman and Jodi (2004), it is noted that "the existence of six solid-state phases is established unambiguously". Accordingly, these six different phases of solid oxygen are the:

• α phase
• β phase
• γ phase
• δ phase
• ε phase: "red oxygen", the phase we are interested in at the moment.
• ζ phase: a truly fascinating phase, where solid oxygen becomes metallic

Of these different phases, today we shall first focus on the ε phase, also known as "red oxygen". Why is it called "red oxygen"? Well, liquid oxygen and three of the phases of solid oxygen (α, β and γ phases) are various shades of blue in colour. In contrast, the ε (epsilon) phase of solid oxygen is dark red in colour, hence the name "red oxygen".

A sample of cryogenic liquid oxygen displays its charming blue colouration.
Maybe it's cold?

Unlike the α, β and γ phases of solid oxygen, the ε phase does not require freezing temperatures to form. Instead, it simply requires the application of pressure. Lots of pressure. In fact, to form the ε phase, you need to subject liquid or solid oxygen to more than 10 gigapascals (GPa) of pressure. In this phase, "red oxygen" is made up of four pairs of diatomic oxygen molecules in rhomboid cluster, forming an O₈ crystal structure. Previous theoretical work expected some manner of O₄ molecule to form, with no-one predicting the formation of an O₈ rhombohedral unit.

The mysterious crystal structure of solid oxygen in the ε phase.
Note the four O₂ molecules connected by the shorter bonds.

Depending on your point of reference and your knowledge of air pressure, and pressure in general, it may be hard to fathom the unbelievably crushing pressures needed to form the ε phase of solid oxygen. 

To put this into perspective, we need to define what a pascal is. In relation to atmospheric pressure, a pascal is a unit of measurement derived by the Système international d'unités, and one atmosphere is equivalent to  1.01325 ×10⁵ pascals. 

Taking this one step further, the pressure required to form the ε phase of solid oxygen is equivalent to a wee bit over 98,692 atmospheres.

Yikes.

Going back to the list of the phases of solid oxygen, the final, ζ (zeta) phase was given a very brief description of "where solid oxygen becomes metallic". I cannot simply leave it at that. The ζ phase forms when solid oxygen is subjected to more than 96 GPa of pressure whilst at room temperature. Once again putting this pressure into perspective, 96 GPa is equivalent to 947,446.34 atmospheres. We may well have thought that the ε phase exists under incredible conditions, but the ζ phase truly takes the cake (if one assumes solid oxygen is partial to cake).

To understand how the metallic phase of solid oxygen is formed, we need to look at the work of Akahama et. al. (1995). Here, liquid oxygen was placed in a diamond anvil cell, and whilst at room temperature, the sample of liquid oxygen was placed under increasing pressure, up to 116 GPa. The different phases of solid oxygen encountered were analysed by x-ray diffraction and synchrotron radiation. It was found that visual observation of the ζ phase yielded something rather fascinating:

"From visual observation under a metallurgical microscope, we saw that the appearance of the oxygen sample became as shiny as the metal gasket after the structural transition at 96 GPa"

In other words, not only can solid oxygen adopt a variety of colours, including blue, pink, orange and red, the ζ phase has a metallic lustre.

Pictured: The metal ζ phase of solid oxygen

The amazing properties of the ζ phase doesn't end here. In Letters to Nature, Shimizu et. al. (1998) report another remarkable piece of information with regards to metallic oxygen. When the metallic ζ phase is cooled to below 0.6 K (-272.55°C), the electrical resistance of solid oxygen rapidly drops, and in turn, the ζ phase exhibits superconductivity!

Superconductivity of the metallic ζ phase was confirmed at the above reported temperature, by subjecting the sample to a 0.0225 tesla magnetic field. The sample of metallic oxygen expelled the applied magnetic field, or alternately, the sample exhibited the Meissner effect, and thus its status as a superconducting material was proved.

In closing, it is amazing to see how a fairly common chemical can have so many amazing properties and phases.

Now off to contemplate how much a diamond anvil cell costs,
Nathan

A Musical Interlude: Bjӧrk - Mutual Core

A friend of mine recently forwarded this brilliant Icelandic songstress, Björk. Though only marginally related to my general topics of chemistry and toxicology, this song (and music video) is too good to pass up. It is ostensibly science-related, with its talk of plate tectonics, volcanism and the like.

So without any further delay, I present Björk, with her recent song, "Mutual Core".

Though a bit trippy, I hope you enjoyed it.

Until next time,
Nathan

On Drugs and Fish: Contamination of Aquatic Environments and Drug Detection

I happened across an interesting article in Nature the other morning, titled "Human drugs make fish flounder". It explores the effects of two drugs, the antidepressant fluoxetine, and a sex hormone, estradiol.

At first glance it may seem odd to be concerned about the effect of human medications on aquatic wildlife. After all, fish are not typically known for travelling down to the local pharmacy. Rather, this article highlights a significant issue relating to the impact of humans and their behaviours on local ecosystems. A veritable cornucopia of drugs and drug metabolites are excreted via our urine and faeces, and though wastewater and sewage is typically treated,  these compounds end up in local waterways, and the aquatic homes of a range of fauna. The end result of this type of chemical pollution is not good, to say the least.

I won't go into significant detail on this specific issue, as the article in Nature is rather informative in itself. In short, researchers at the University of Wisconsin-Milwaukee's Great Lakes Water Institute have studied the effects of fluoxetine on fathead minnows. By exposing this species of fish to different levels of fluoxetine, including concentrations that have been detected in wastewater, a series of significant effects were found.

Though females appear unaffected by the lowest concentration of fluoxetine tested, male fish were found to spend more time building their nests. Increasing the concentration of fluoxetine further, to 10 times the highest detected level in waterways, resulted in the male fish "[becoming] obsessive, to the point they're ignoring the females".

Depression in fish. Simultaneously adorable and so, so sad...
Image by Thezules

Further research was also done by Dan Rearick, an aquatic toxicologist from St Cloud State University in Minnesota. In this research, it was found that exposing the larvae of the fathead minnow to estradiol, an estrogenic sex hormone occasionally used in Hormone Replacement Therapy (HRT) had a negative effect on fish populations. Namely, larvae exposed to estradiol were ultimately less capable of escaping or eluding predators, as their reaction times to external stimulus had been significantly lessened.

Moving away from the effects of two specific drugs on a single species of fish, the fact that drugs and drug metabolites may be detected in the effluent from sewer systems may come as a surprise. So prevalent are these compounds in aquatic environments, they are considered emerging environmental contaminants. As a consequence, the detection of these compounds has some rather significant implications for humans.

How?

Well, as most drugs and metabolites end up in the sewer system, this provides an excellent opportunity for chemists and toxicologists to analyse this effluent. Detection of these compounds may, in turn, allow for the analysis of drug use in local populations serviced by a section of the sewer system. Indeed, it is entirely possible to detect and compare illicit drug use in local populations through the collection and analysis of sewage, with the technique known as sewage epidemiology. As many drugs are metabolised to more polar compounds prior to excretion, much of this work revolves around the detection of drug metabolites, and using both their presence and relative concentrations to calculate drug consumption.

Though the following list is by no means exhaustive, it may provide you with a reasonable idea of the different drugs and respective metabolites reportedly detected in both wastewater and groundwater:

• Amphetamine-type substances (amphetamine, methamphetamine, ecstasy)
• Benzodiazepines (alprazolam, diazepam, lorazepam)
• Cannabis
• Cocaine
• LSD
• Opiates (heroin, morphine, methadone)

To date, a range of different populations and their apparent drug use/abuse has been studied. A quick read through peer-reviewed literature on this subject revealed the following areas that have been subjected to analysis via sewage epidemiology:

• Barcelona, Spain (Jurado et. al., 2012)
• Brussels, Belgium (van Nuijs, et. al., 2011)
• Correctional facility/prison, Catalonia, Spain (Postigo et. al., 2011)
• Ebro River basin, Spain (Postigo et. al., 2010)
• Paris, France (Karolak et. al., 2010)
• North-Eastern Spain (Huerta-Fontela, et. al., 2009)
• Three unnamed cities, Canada (Metcalfe et. al., 2010)

In addition to the above, a fascinating piece of research and collaboration, entitled "Comparing illicit drug use in 19 European cities through sewage analysis", sought to compare illicit drug abuse in a number of European cities. The range and number of cities selected in this study was rather impressive, and specifically sought to compare the usage rates of cannabis, cocaine and three amphetamine-type substances (amphetamine, methamphetamine, ecstasy). Perhaps the most incredible aspect of this manner of toxicological and chemical analysis is that this study allowed for the quantitative, non-intrusive and objective analysis of illicit drug use of approximately 15 million individuals, all over a one-week period.

An impressive feat, all things considered.
Image by Ssolbergj.

The general trends discovered in this work were quite fascinating. It would appear that cocaine use is more prevalent in more urbanised towns or cities within a set country. In terms of cannabis use, the data apparently indicated that the highest use was, unsurprisingly, in the Netherlands. In addition, the *ahem* highest reading recorded for cannabis use was in Amsterdam. Outside of the Netherlands, other high levels of cannabis use were detected in the Czech Republic, Spain, Italy and France. 

Moving on to the amphetamine-type substances, and in particular apparent methamphetamine use, it would appear that Finland, Norway and the Czech Republic collectively hold the dubious honour of having the highest methamphetamine usage rates in the cities studied. Meanwhile, for amphetamine, high apparent use rates were found in Northern Belgium and in the Netherlands. Ecstasy use, on the other had, was allegedly quite high in Eindhoven, Amsterdam and Utrecht (the Netherlands), and also in London (England). 

This method of assessing intra- and inter-community drug use may be considered rather contentious. On one hand, it allows for a non-intrusive method of assessing drug use, which may be of use for providing adequate health services and allow for the effective development of government policy. However, such techniques may also be construed as invasive. Indeed, some may well view with suspicion the position posed in an article by van Nuijs et. al., (2011), where the following point was made with respect to estimating drug consumption based on analysis of wastewater:

"The consumption of illicit drugs causes indisputable societal and economic damage. Therefore it is necessary to know their usage levels and trends for undertaking targeted actions to reduce their use... [and] could be used in routine drug monitoring campaigns"

That being said, Frost, Griffiths and Fanelli (2008), provide a fascinating editorial concerning detection of drugs of abuse in wastewater, and the ethical and political concerns therein. 

All in all, it is clear that the contamination of waterways with drugs and their respective metabolites may have a significant impact on aquatic wildlife. Though perhaps the fish are getting their own back, with it now possible to examine sewage and wastewater to monitor both licit and illicit drug use.

Until next time, 

Nathan

The Wandering Rover: Big News From Mars?

A short piece to bring to your attention some interesting news from NASA. It appears that the most recent robotic wanderer on Mars, the Curiosity Rover, may have found something whilst analysing the chemical composition of Martian soil.

What did they find?

Well, at the moment the team over at NASA, and the Mars Science Laboratory, are only hinting at something potentially significant. A very recent article from NPR indicates that one of the instruments present on the rover, the Sample Analysis at Mars (SAM), has picked up some soil from the Martian surface, and may have detected something of note. To use the words of John Grotzinger, the principal investigator for the rover mission:

"This data is gonna be one for the history books. It's looking really good..."

Despite hinting at a potential groundbreaking discovery on Mars, no specific details have been released as yet. Though I'm sure those in the know at NASA may well be bursting at the seams to let us know what they have found, they are also being understandably cautious. As is so often the case with science, one needs to be sure of what they have, or have not, found. Indeed, it will apparently take several weeks until any findings, if there are any, are released.

A self-shot of the Curiosity Rover. No duck-face in sight, thankfully.
(Image courtesy of NASA)

Too often we can become excited by some breath-taking discovery, only to find that there is a simpler, more mundane, explanation available. It brings to mind the scientists over at CERN, where a a skeptical team working on the OPERA project were left scratching their heads after supposedly detecting subatomic particles, neutrinos, travelling slightly faster than the "universal speed-limit", the speed of light. As opposed to rushing to the media to capitalise on a truly remarkable discovery, they announced that they were understandably skeptical. As a consequence of this healthy skepticism, they attempted to verify the results whilst simultaneously asking other scientists to identify any potential flaws in their experimental design that may have given rise to an erroneous result.

Ultimately, it was found that the neutrinos detected by OPERA were not travelling faster than the speed of light, and were behaving as good neutrinos do. Instead of being embarrassed by rushing to let everyone know about something incredible, these scientists followed good practice and double-checked their data and, though not confirming any upheavals in the laws of physics, they set a fantastic example for all scientists.

Going back to the Curiosity Rover, and this recent hint of something newsworthy, it is nice to hear that NASA isn't overtly rushing to tell us what they allegedly have found. That being said, they are certainly building up an appreciable amount of hype over something they are currently looking into.

A few friends asked me what they may have found, and though I am no expert on the composition and chemistry of Martian soil, I gladly offered this comment:

"We won't know for sure until NASA issues an official press release, though it is fun to ponder. Evidence of past life? Complex molecules? Oil? A fat-free fudge cake that doesn't let you down in the flavor department like so many others? Only time will tell..."

Until next time,
Nathan

Chemical of the Week: Dicyanoacetylene

Welcome to the first Chemical of the Week! This week, we shall have a brief look at compound composed entirely of carbon and nitrogen: dicyanoacetylene.

Dicyanoacetylene, or carbon subnitride, is a fairly interesting compound. Structurally, it is completely linear, thanks to its alternating triple bonds. Ciganek and Krespan (1968) report that dicyanoacetylene was first synthesised by the scientists Moureu and Bongrand in 1909 and was achieved by dehydrating the bisamide of acetylenedicarboxylic acid, also known as 2-butynediamide. Graupner and Saunders (2008) report that dicyanoacetylene can be produced by heating 2-butynediamide with phosphorous pentoxide under vacuum.

At the time, this compound has been noted for its high reactivity, an aspect which is not surprising when one considers the presence of two electron-withdrawing groups (EWG's) at the terminal ends of this molecule (specifically, two cyano groups). Due to the presence of these electron-withdrawing groups and their attachment to an acetylene backbone, dicyanoacetylene is a potent dienophile, and of particular use in the Diels-Alder reaction. Indeed, it is so reactive that it is capable of reacting with dienes that are considered, due to low reactivity, poor candidates for the Diels-Alder reaction.

Ah, the things chemists find fascinating... 

Aside from the work of Moureu and Bongrand, there have been numerous methods proposed for the synthesis of dicyanoacetylene, with five proposed by Ciganek and Krespan back in 1968. Two reactions of note were found capable of producing dicyanoacetylene: the heating of nitrogen gas at 2500°C over graphite; and the gas-phase pyrolysis of a chemical with a rather cool structure (below), 4,5-dicyano-1,3-dithiol-2-one.

Told you it was a cool structure!

Though I'm sure I could happily go on a tangent regarding 4,5-dicyano-1,3-dithiol-2-one, dicyanoacetylene has a few more fascinating bits of information up its sleeve. Due to the presence of three triple covalent bonds in its structure, dicyanoacetylene is thermodynamically unstable, and under the right conditions will explode to form carbon powder and nitrogen gas. As such, when exploring the heat of combustion of dicyanoacetylene, Armstrong and Marantz (1960) analysed the results of earlier experiments and proposed that dicyanoacetylene will burn in an oxygen atmosphere and produce a flame with a temperature in excess of 5000K (4726.85°C).

Let me repeat that.

In theory, dicyanoacetylene will burn in an oxygen atmosphere and produce a flame with a temperature greater than 4700°C.

In reality dicyanoacetylene doesn't disappoint. In an oxygen atmosphere, it burns with an intense blue-white flame with a temperature of 5260K (4986°C)!. That is a truly incredible temperature.

Even more remarkable was that the work of Kirshenbaum and Grosse (1956), who used the experimentally determined heat of combustion of dicyanoacetylene in oxygen, in combination with the enthalpy data for carbon monoxide and molecular nitrogen, to discover that burning dicyanoacetylene in an atmosphere of ozone will increase the heat of combustion. Indeed, burning dicyanoacetylene in an atmosphere of ozone (at standard atmospheric pressure) will produce a flame with a temperature of 5516K (5242.85°C).

At this point I am tempted to make a joke about dicyanoacetylene being hot stuff, but I fear I would be burned in the process...

Continuing on, this fascinating molecule has also been found in the atmosphere of Titan, the largest moon of Saturn. Yung (1987), proposed new chemical schemes for the formation of both cyanogen and dicyanoacetylene in order to explain data obtained by the infrared spectra obtained by the Voyager 1 spacecraft. Detection of dicyanoacetylene, and other compounds, is of importance as it gives important information regarding the atmospheric chemistry of Titan.

Titan: Known hideout for dicyanoacetylene.
(Photo courtesy of NASA)

Of particular note is that the abundance of dicyanoacetylene in Titan's atmosphere varies based on the season. According to Samuelson et. al. (1997), in the spring of the northern hemisphere, the stratosphere cools, allowing dicyanoacetylene vapour to condense out of the atmosphere into lower, cooler regions that will be protected by the shadow of the cloud layers above. In the upper stratosphere, the progression of the season means increasing levels of sunlight, which breaks down dicyanoacetylene in a photolytic process. All in all, these variations in the concentration of dicyanoacetylene in Titan's atmosphere gives us a remarkable means of studying the weather on Titan.

So there you have it. A fascinating molecule that burns at an incredible temperature, and is also found in the far-flung reaches of our very own solar system.

Until next time,
Nathan

Further ponderings: legalisation of recreational marijuana in Colorado and Washington

One of my posts from a few days ago was in relation to the recent passing of two key amendments in Colorado and Washington, in relation to recreational marijuana use. At the time, I noted that I was curious to see the implications of the passing of these amendments, and the potential problem this may pose to Federal authorities in the United States. 

The reason that this may be problematic for Federal authorities is that since marijuana is classified as a Schedule 1 drug in the Comprehensive Drug Abuse Prevention and Control Act of 1970, it is illegal to possess, use, buy, sell, and/or cultivate marijuana. This stance, combined with failed attempts at rescheduling marijuana, does put Washington and Colorado at odds with the Federal government, and puts lawmakers in these two states into a tricky situation until the ramifications of these votes develop.

Map of current United States cannabis laws
Light Green: State with legal medical cannabis
Olive Green: State with decriminalized cannabis possession laws
Dark Green: State with both medical and decriminalization laws
Purple: State with legalized cannabis
(Map courtesy of Wikipedia)

It was brought to my attention that in March of 2009, Eric H. Holder Jr, current Attorney General of the United States, indicated that the Justice Department has no intentions to prosecute medical marijuana dispensaries in California and other states. In this regard, use of medical marijuana may seem to be on a sure footing in Colorado, Washington, and in any other states that have passed laws pertaining to this matter. What is not sure sure is whether this "tolerance" of the Justice Department and U.S. Government will extent to recent attempts to legalise the recreational use of cannabis. 

Indeed, this concept was the focus of an article by professor and former Federal prosecutor Mark Olser, published on the CNN website. Professor Olser expresses his view in a rather succinct, and perhaps even poetic, manner: 

"The residents of Colorado and Washington state have voted to legalize the recreational use of marijuana, and all hell is about to break loose -- at least ideologically"

Without delving into the conflict between State's rights and appeals from ethics and morality within an ideologically diverse nation such as the United States, it will be curious to see the broader implications of this vote. Already, four leaders from Latin American countries (Mexico, Belize, Honduras and Costa Rica) have claimed that the votes in Washington and Colorado state will have significant implications for current attempts to halt drug smuggling. Indeed, these votes may also even affect the stance of these nations with regards to the current War on Drugs.

Perhaps one of the more concerning news stories to come out in the days following the Colorado and Washington votes, and in relation to the Federal stance on possession and cultivation of marijuana, is the case against Chris Williams. Following the move by the state of Montana to legalise medical marijuana, Williams opened a marijuana grow-house. Due to Federal laws surrounding the cultivation of marijuana, as set out by the Controlled Substances Act of 1970, Williams faces a mandatory minimum jail sentence of 80 years. 

Though I would generally not desire to second-guess the Justice Department of the United States, this seems to be outrageously draconian. Though it is true that Williams turned down various plea bargains offered by the Justice Department, to me it seems that the application of the Controlled Substances Act of 1970 seems outdated, doubly so when contrasted with two states explicitly legalising cannabis for recreational purposes. Perhaps it is time the Drug Enforcement Agency (DEA) and other parties consider whether this act represents a legal anachronism in light of recent events and the comments of Attorney General Holder back in 2009.

As an aside, the issues of medical and recreational marijuana use in relation to the United States reminds me of one of my lecturers from undergraduate days. During our discussion of drug law in relation to the seeming aversion some countries and jurisdictions have towards harm minimisation, he vehemently declared that the current stance is "schizophrenic". No doubt that these are strong words, though perhaps not surprising when one reads of draconian sentences for actions that are ostensibly legal from an individual's position within a State's legislature. 

Until next time,
Nathan

An interesting article: Ketamine and depression

A few days ago, I came across an article published on YaleNews, regarding new evidence on how the drug ketamine may be used to alleviate the symptoms of depression in treatment-resistant patients. In this article, it was reported that small doses of ketamine may produce an immediate, albeit temporary, relief of symptoms of severe depression. Indeed, though the effect ketamine has on the symptoms of depression has been known for some time, the exact mechanism has allegedly eluded scientists until now.

Before delving into the proposed mechanism, it may be useful to first look at the drug itself. Ketamine is an general anaesthetic, and in combination with other sedatives, may be used to induce and maintain general anaesthesia. It is chemically related to other drugs with similar structures, namely tiletamine and phencyclidine, and as such is considered to be a dissociative anaesthetic. It has also found use in veterinary medicine, for inducing general anaesthesia in animals.

Oh ketamine, you crazy anaesthetic! Humans, animals, what won't you sedate?

As with many drugs prescribed for use in a medical setting, recreational use of ketamine is not unheard of. Since ketamine is used for anaesthesia, recreational doses are typically in the sub-anaesthetic range. The effects at this particular dose resemble two other well-known dissociatives, phencyclidine and dextromethorphan. As a recreational drug, ketamine is considered to have a short half-life, and acts as a hallucinogen.

Of particular note is that ketamine, like the related compounds mentioned above, can produce what is known as a "dissociative state", whereby an individual experiences a sense of depersonalisation. To put it more plainly, the user may experience a strong detachment from physical reality. Higher doses may cause users to experience an effect known as a "K-hole". This is where the degree of dissociation from reality becomes so severe, that the effects are considered to mimic catatonic schizophrenia, near-death experiences and out-of-body experiences.

Crystals of ketamine on a glass slide. Pretty.
(Photo courtesy of Wikipedia)

As I was reading about ketamine, and in particular, recreational use of this cute little chemical, I was surprised to find that Richard Feynman, an American theoretical physicist of some note, explored the use of marijuana and ketamine to study the nature of consciousness. Indeed, in his semi-autobiographical book "Surely You're Joking, Mr. Feynman!", he describes his experimentation with ketamine. After being given 10% of a normal dose, thereby avoiding induction of anaesthesia, the following effects are described:

"I got this strange kind of feeling which I've never been able to figure out whenever I tried to characterize what the effect was. For instance, the drug had quite an effect on my vision; I felt I couldn't see clearly. But when I'd look hard at something, it would be OK."

... 

"Although I had a feeling of complete disorientation, a feeling of an inability to do practically anything, I never found a specific thing that I couldn't do."

Certainly an interesting bit of information, though it is perhaps best if we depart this tangent and get back to the purpose for this post. The article published on YaleNews indicates that current evidence suggests that ketamine may, in fact, regenerate the synaptic connections between brain cells. This is interesting, as it is these connections that may be damaged by stress and psychological conditions such as depression. The specific mechanism which has been proposed is that administration of ketamine results in the release of the neurotransmitter glutamate, which is responsible for stimulating the growth of the connection between synapses.

The review article, co-authored by Yale professors Ronald Duman and George K. Aghajanian is titled "Synaptic Dysfunction in Depression: Potential Therapeutic Targets", is honest with regards to the efficacy of ketamine in the treatment of depression. As previously stated, ketamine may produce an immediate improvement in the symptoms associated with depression. However, in the YaleNews article, author Bill Hathaway notes that:

"The improvement in symptoms, which are evident just hours after ketamine is administered, lasts only a week to 10 days"

Though this recent article Duman and  Aghajanian does highlight specific limitations regarding the use of ketamine in the treatment of treatment-resistant depression, knowledge of the specific mechanism by which symptoms of depression are alleviated provides a viable avenue for future research into this field.

The short-term cessation of symptoms associated with depression reported by Duman and Aghajanian has been described in literature previously. Indeed, another article, published in the Journal of Biological Psychiatry, and authored by James Murrough et. al., describes a similar issue with the short-term effect of ketamine with regards to depression. In particular:

"[Though] ketamine was associated with a rapid antidepressant effect in TRD (Treatment-Resistant Depression)... future controlled studies will be required to identify strategies to maintain an antidepressant response amongst patients..."

In addition, the work of aan het Rot, et. al., studies the effect of sub-anaesthetic intramuscular doses of ketamine in relation to the treatment of depression and the side effects encountered. It was found that the administration of ketamine at the dose range reported in this article elicited minimal psychotic symptoms, as well as "significant but transient dissociative symptoms". This result is interesting, as aside from using the mechanism of ketamine in treating depression to explore alternate chemical treatments for depression, it may well be possible, if not practicable, to manage the symptoms of treatment-resistant depression with repeated infusions of ketamine over regular periods of time.

In case all this talk of depression was depressing, here's a... oh...

Another potentially interesting avenue of research regarding the use of ketamine in the treatment of psychological conditions comes a letter to the editor in the American Journal of Psychiatry. In this letter, Cusin et. al., describe two cases where ketamine was used to successfully treat Treatment-Resistant Bipolar II depression. In a slight parallel to the research of Duman and Aghajanian, it was found that the cessation of symptoms was temporary, though it was found that repeated doses of ketamine every few days allowed for a potential long-term treatment for this specific condition. It should be noted that this treatment was not without its problems. Several negative side-effects were reported, and included headaches, irritability, nightmares and mild dissociative states.

On that note, it may be prudent to note that though ketamine has a history of both medical and recreational use, some care should be taken with regards to novel therapeutic applications. Aside from a range of short-term side effects associated with the use and abuse of ketamine, other negative long-term effects have also been reported. Olney's lesions, associated with the long-term use of drugs like ketamine and phenylcylidine, are cytotoxic variations in brain structure that were discovered in rat models. However, the relationship between use of dissociatives and formation of these lesions is controversial, as no causal relationship has been found in the human model.

So there you have it. Recent work by Duman and Aghajanian has provided some new insights into the mechanism by which ketamine may treat the symptoms of depression. Though some limitations have been noted, this provides a new avenue for research into the treatment of depression and ailments.

Until next time,
Nathan

Voters back legalisation of recreational marijuana in Colorado and Washington

In the days since the recent election in the United States, some interesting news has come out of the states of Colorado and Washington. Both states, in a historic vote, have gained voter approval to legalise the recreational use, and small-scale possession of marijuana (or cannabis, if you prefer). Specifically, these amendments, I-502 in Washington, and Amendment 64 in Colorado, allow individuals over the age of 21 to legally posses up to one ounce of marijuana, and to grow up to six plants in their homes.

People celebrating the passing of Amendment 64 in Colorado
(Photo courtesy of Huffington Post)

These amendments may very well signify a significant and considerable challenge to the current War on Drugs, and current laws that allow for the incarceration of people convicted of possession of marijuana. In addition, this outcome will no doubt have the potential to be an issue for Federal authorities, in particular the Drug Enforcement Administraiton (DEA). Indeed, both states are holding off on plans to regulate and tax marijuana, pending a response from the United States Justice Department.

Indeed, medicinal use of marijuana is still illegal under Federal law, though the Obama administration has generally not pushed the application of this law. Currently, activists and supporters of this recent move to legalise marijuana are awaiting the response of a Federal appeals court, regarding whether marijuana's status as a Schedule 1 drug in the Controlled Substances Act will be altered. If successful, marijuana would lose its status as a dangerous drug with no accepted medical use.

Dried flower of the Cannabis Sativa plant, or marijuana, if you prefer.
(Photo courtesy of Wikipedia)

What alternate classification it would receive would be interesting. Schedule 2 drugs are substances regarded as having a high potential for abuse, accepted medical uses in the United States, and having a risk of causing severe psychological or physical dependence if abused.

Alternately, Schedule 3 drugs are regarded as having a lower potential of abuse than substances classified as being in Schedule 1 and/or Schedule 2. In addition, Schedule 3 substances are classified for acceptable medical use in the United States, and may potentially able to cause moderate psychological or physical dependence if abused.

There are two more schedules in the Controlled Substances Act, though in my opinion marijuana would most likely end up classified in Schedule 2 or Schedule 3.

Moving away from the Controlled Substances Act, it is of note that prosecutors in King and Pierce Counties, Washington, have moved to dismiss more than 220 misdemeanor marijuana cases in response to this vote. To quote King County prosecutor Dan Satterburg,

"Although the effective date of I-502 (the vote to legalise recreational marijuana use) is not until December 6, there is no point in continuing to seek criminal penalties for conduct that will be legal next month."

This move to retroactively apply this recent vote to current cases is, in my opinion, sensible. It will be curious to see, however, to what degree this retroactive stance will be applied. It should also be noted that possession of large amounts of more than one ounce of marijuana is considered a felony, though King County allows defendants to plead to a misdemeanor offence.

It was also curious to note a response by Kansas law enforcement officials regarding the legalisation of marjuana in Colorado and Washington. Specifically, citizens of Kansas venturing into Colorado to enjoy this relaxation of drug laws are warned to not attempt to bring marijuana back into Kansas. As reported by The Wichita Eagle, and quoting Josh Kellerman of the Kansas Highway Patrol:

“It’s still illegal in the state of Kansas... It is an arrestable offense. You can be taken to jail if you’re in possession of it.”

One potentially major impact of legalisation will be the effect on the local economies. Aside from Kansas warning its residence about bringing marijuana purchased in Colorado back into the state, the Huffington Post has reported that legalisation may result in a significant drop in the price of marijuana. This is expected to be a result of decreased costs associated with growing the drug in a now-legal environment. Further variations in price may occur in the near future as both states consider how to tax marijuana, and as fluctuations in demand occur.

In addition, this change in policy may prove to be a boon for the Washington and Colorado economies. The prospect of "Marijuana Tourism" may cause an increase in visitors to these states, and perhaps see an infusion of cash into their economies.

A view of the Seattle Hempfest, in the state of Washington
(Photo courtesy of gadling.com)

Not everyone is convinced that legalisation of marijuana will have a considerable effect on tourism and the local economy. Democratic Governor John Hickenlooper, who opposed the push in Colorado to legalise recreational use of marijuana, is quoted as saying in response to the passing of Amendment 64:

"They're going to flock here to buy marijuana as if they're going to take it back? On an airplane? That seems unlikely to me.''

There have also been a few interesting articles regarding whether the passing of Amendments I-502 and Amendment 64 will have an effect on Mexico's drug war. Legalisation of marijuana would quite potentially have an adverse impact on the income and power of Mexico's drug cartels, which have been responsible for a recent wave of violence, intimidation and murders in the region.

At any rate, it will be very interesting to see how this all plays out in the coming weeks, months and years. In particular, I will be curious to see the response of the US Justice Department and the Drug Enforcement Administration regarding application of Federal law.

Until next time,
Nathan

A Curious Australian Plant - Gympie Gympie

Recently I happened across an interesting article on the Australian Geographic website, detailing the existence of a rather curious plant native to northeastern Australia, Indonesia and India. Known by its scientific name dendrocnide moroides, or more affectionately as Gympie Gympie, this plant is alleged to be one of the most poisonous plants in the world.

Relatively common in Queensland and growing to between 1-2 metres in height, Gympie Gympie has heart-shaped leaves. More to the point, Gympie Gympie has heart-shaped leaves that are covered in tiny, hollow, silica-tipped hairs that are rather adept at penetrating skin. Contact with the stems and leaves of this plant is considered to be a bad idea, with the aforementioned hairs penetrating the skin and releasing a potent toxin known as moroidin. Unfortunately, physical contact is not the only method of falling victim to this frightful flora. Indeed, merely being in the presence of this plant is sufficient to cause itching, rashes, sneezing and a fair bit of pain.

The leaves of Gympie Gympie
(photo courtesy of Wikipedia)

Well, that doesn't look too scary, does it? For a plant, one may even say it looks downright boring. A closer look, however, paints a very different picture of this plant:

Tiny, painful needles, filled with the toxin moroidin
(Photo courtesy of Alan's Wildlife Blog)

These are the hairs that cover Gympie Gympie, and are readily shed into the air, to the discomfort and pain of those that pass by. The pain caused by contact with these hairs is described in some detail by M. Hurley (2000). It is mentioned that slight contact with these hairs produces "an extremely painful, burning sensation", and that severe contact causes "excruciating pain often requiring urgent medical attention and can cause death in humans... and dogs and horses". The Society for Growing Australian Plants (SGAP) also describes the pain caused by Gympie Gympie in one of their leaflets:

"The pain starts as a tingling sensation and develops into stabbing or radiating pain...being referred to other parts of the body"

In research undertaken by Robertson and MacFarlane (1957), references to several instances where the sting of this plant has been described in earlier articles. Indeed, as early as 1860, the sting of this plant has required horses to rest for several days prior to being suitable for use. In relation to horses, it is also noted that the sting of Gympie Gympie has been sufficient to kill, and alternately, causes horses to "become violent and have had to be shot".

In the Australian Geographic article mentioned previously, humans who have encountered Gympie Gympie have not fared much better. This article recalls a serviceman falling into the tree during military training in World War II, who spent three weeks in hospital. It also makes mention of a tale that I had encountered previously on the internet, where an unwitting fellow who committed suicide after using the leaf of a stinging tree for "toilet purposes".

Also curious is that the pain from the sting of this plant may persist for weeks and months, and may recur at points some years after the original exposure. It appears as though this recurrence may be related to mechanical trauma to the previously affected area, as well as exposure to the cold. I was unable to find any mention of whether this recurrence of pain is mediated by attempts at removing the hairs from the skin.

Aside from pain-inducing, hair-covered leaves, Gympie Gympie also produces pink/purple fruit, as seen below:

The fruit of Gympie Gympie

The principle compound responsible for the extreme pain caused by the sting of Gympie Gympie is known as moroidin. A bicyclic octapeptide, it is also found in the hollow, stinging trichromes of the Stinging Nettle (urtica dioica), and its structure is shown below:

Moroidin

One significant research project studying the sting of Gympie Gympie and the search for specific pain-producing substances present in this plant was undertaken by Robertson and MacFarlane. Indeed, as no specific pharmacologically active compound had been isolated from Gympie Gympie and related species of stinging trees, they selected laportea moroides (also known as dendrocnide moroides, Gympie Gympie) for study, as it was reported to give "the most vicious sting in both intensity and duration".

Of particular note in Robertson's and MacFarlane's research is their method in testing extracts of the leaves of the Gympie Gympie plant:

"Since pain appeared to be the primary effect of L. moroides action, the essential test was the reaction of human skin to the stinging hairs or extracts of the hairs. Other pharmacological actions were sought on a variety of tissues and preparations"

Not only were hairs and extracts of the hairs from L. moroides tested on humans to understand the underlying cause of the painful sting of this plant, a few other methods were used. Indeed, the stinging potential of this plant was also tested on:

• Guinea pigs and rabbits: both isolated sections of intestine from freshly killed subjects, but also the eye of what would appear to be live test subjects;
• Rats: in particular, the uterus of young, adult, female, virgin rats, which appear to have also been freshly killed;
• Anesthetised cats, where the effect of the sting on blood pressure was recorded

I offer no commentary on this manner of experimentation, except to say that bioethics requirements have evolved significantly over time.

Now, back to the chemistry. As mentioned previously, moroidin is a peptide composed of eight amino acids. These are, in alphabetical order:

1. Arginine
2. β-leucine: The (3R)-β-isomer of leucine
3. Glycine
4. Histidine
5. Leucine
6. Pyroglutamic acid: An amino acid derivative and lactam formed by the cyclisation of glutamic acid
7. Tryptophan
8. Valine

Above, we have seen the structure of moroidin. Now, let us have a second look, with the eight amino acids (or seven amino acids + one amino acid derivative, if you prefer) highlighted. It is also worth noting the carbon-nitrogen bond between tryptophan and histidine.

Another look at the structure of moroidin, with amino acids/derivatives highlighted

Now that we have an understanding of the excruciating pain that may be caused by contact with Gympie Gympie, it seems reasonable to know how to treat the sting of this plant. One method that is reported to be effective is to use a sticking plaster or hair waxing strip to remove the hairs from the skin. Otherwise, general analgesics are recommended for minor exposures to the plant, though in all instances it may be best to seek medical attention, regardless of the severity of the sting.

So there you have it. A bit of background on a rather curious Australian plant, the horrible pain that it causes, and the search for the compound responsible. In closing, I would proffer one last comment, in that it was exquisite fun to type (and mentally hear) the name "Gympie Gympie" again and again.

Off to stock up on hair waxing strips,
Nathan

An Update: Oleanders and giraffes no longer mix

Back in April I posted a discussion of a news article forwarded to me, regarding the unfortunate death of a giraffe at Reid Park Zoo, in Tucson. To recap, in an unfortunate series of events, a giraffe affectionately called Watoto, was inadvertently fed clippings from the highly toxic ornamental plant Oleander (Nerium Oleander), and died. A second giraffe, by the name of Denver, also ate the oleander trimmings, but luckily survived.

With a bit of luck, I was able to visit the Reid Park Zoo recently with my partner and his aunt, who is a volunteer at the zoo. I was able to pick her brain regarding the unfortunate death of Watoto, which she recalls with some sadness. She was, however, happy to indicate that the zoo is free from oleander, and that feeding time for the animals is controlled to ensure that such an event does not occur again.

Happy, healthy giraffes.

I must say, Reid Park Zoo is an amazing zoo for its size. The staff and volunteers at the zoo were very knowledgeable  the enclosures and habitats for the animals appear more than suitable to my untrained eye, and more importantly, a quick walk through the zoo would appear to confirm that no more oleander is present on the grounds of the zoo.

The rest of Tucson, not so much. Though I have encountered oleander whilst living in Sydney, and it is indeed a popular ornamental plant, I was surprised to see quite so many oleander plants. Then again, when you have saguaro cactus, barrel cactus, "jumping cholla" and "devil's claw" to worry about, I may glibly suggest they have other nefarious flora to be concerned with.

Until next time,
Nathan