The War on Drugs - Medicinal Marijuana

Though I tend to only enter into political debates with my closest friends, I cannot help but comment on a clip that I found on YouTube. In short, Republican presidential candidate Mitt Romney is answering a question from an audience member regarding medicinal marijauna.

The clip:

And the quote:

"...And you know you know you hear that story, people who are sick needing medicinal marijuana, but marijuana is the entry drug for people trying to get kids hooked on drugs. I don't want medicinal marijuana, there are... synthetic forms of marijuana that are available for people that need it on prescription. Don't open the doorway to medicinal marijuana"

To begin with, marijuana has been used for medicinal purposes for a number of reasons. Primarily, marijuana (and select cannabinoids present in marijuana) have been shown to decrease the incidence and strength of nausea, and to stimulate hunger. These effects benefit those on chemotherapy or who are afflicted with AIDS, and has also been shown to have positive effects on patients with glaucoma. 

That marijuana has been used for medical purposes is of no surprise. Records from as far back as 4000 BCE have shown that marijuana has been used for medicinal purposes by the Chinese, during the Neolithic period. Even in relatively modern times, tinctures and extracts of marijuana have been used to treat pain and headaches, to aid in sleep, and so on.

Perhaps what irritates me most with Romney's comment on medicinal marijuana is that he refers to the spurious notion that marijuana is a gateway drug. For those unfamiliar, the Gateway Drug Theory proposes that the use of "softer" recreational drugs, like marijuana, alcohol and tobacco, leads to a dramatically increased risk of a user moving on to "harder" drugs like heroin, cocaine and so on. It is also posited that as a user moves on to "harder" drugs, that they will also move on to a life of crime in order to fund their drug habit. There are variations of the Gateway Drug Theory, but for now we will deal with Romney's concern, that marijuana (and other "soft" drugs) are used to hook children on "harder" drugs.

I won't deny that research into the Gateway Drug Theory is still ongoing, and that for every article criticising this theory, another article comes out shortly thereafter criticising the criticism, and so on. That being said, there are some fairly big holes in this theory. Namely, the theory itself relies on the post hoc ergo propter hoc logical fallacy. In the context of the Gateway Drug Theory: 

An individual tried a "soft" drug like marijuana. They then moved on to use a "hard" drug. Therefore, use of the "soft" drug caused them to use a "hard" drug at a later date. 

To put it another way, in this case correlation does not explicitly imply causation.

The main criticisms of the Gateway Drug Theory are detailed on the wikipedia page linked above. In summary, the more salient criticisms are:

• Due to curiosity and/or the pleasure-seeking behaviour of humans, some people will actively seek out and experiment with drugs. So-called "gateway" drugs are simply those that are more readily available;
• In the event that an individual seeks out recreational drugs that are illegal, they will be exposed to the black market for drugs. In this case, they will be exposed to readily available "harder" drugs. Therefore, the availability of different recreational substances on the black market is a possible cause for moving on to harder drugs, rather than use of a "soft" drug leading directly to the use of a "hard" drug, regardless of circumstance;
• Hyperbole and misinformation surrounding the nature of gateway recreational drugs causes teenagers and adults alike to distrust all anti-drug messages, thereby resulting in the individuals trying other, "harder" drugs at a later point;
• Drug dealers that have access to "harder" drugs will, due to the nature of their wares, be unwilling to engage in sales with those unfamiliar with gateway drugs. Therefore, those that buy from these dealers will already be acquainted with the "harder" drugs.

Another aspect of Romney's argument is that marijuana is addictive. Now, this is a tricky thing to deal with, as two separate forms of addiction exist. One is physical addiction/dependence, whereby continued use of a drug results in a physical need to continue usage, and has neurobiologic underpinnings. The other is psychological addiction/dependence, in which there is a strong behavioural aspect to the addiction.

The dependence potential of marijuana is interesting, in that it is reported as being less addictive than alcohol, tobacco, heroin, cocaine and select other recreational drugs. Nutt et. al (2007) provide an interesting comparison between various licit and illicit recreational drugs, with the following graph a concise summary of their findings:

In addition, a fascinating study by Coffey et. al.(2002) reveals that the symptomatology of marijuana dependence is poorly defined. Overall, marijuana dependence is a known phenomenon (recognised in the DSM-IV, section 304.30), and involves both physical and psychological dependence on the drug in question. 

In short, the argument that Romney uses is poorly constructed. It relies on the fact that marijuana is a gateway drug, which is still under debate. In addition, it posits that marijuana is addictive (which it is). What is not recognised is that a large number of recreational drugs (including legal drugs like tobacco and alcohol) have a higher dependence potential than marijuana.

I will cede, however, that the development of synthetic preparations of cannabinoids is a good thing. This allows dosage to be controlled, thereby ensuring that an adequate dose is provided to the patient. Furthermore, in patients that may require medicinal marijuana but do not want to experience the psychoactive effects of marijuana, well, the synthetic preparations of the cannabinoids present in marijuana provides a good middle ground.

In the end, contentious issues like the War On Drugs and medical marijuana will continue to be debated. Indeed, this is an area that I will come back to in the future. And as for Mr. Romney, well, he personifies my gripe with the aversion that many politicians have towards evidence-based policies, and those politicians that happily invoke populism and puritanism in order to win votes. Unfortunately, this is a phenomenon that is not limited to the United States of America, and seems to creep into politics, whether in Australia or abroad.

Thanks for reading,

Nathan

Acetonitrile, Or How I Learned To Stop Worrying And Love An Organic Cyanide Compound

Acetonitrile is a curious organic compound, widely used in analytical chemistry. A clear liquid at room temperature, it is completely miscible in water, and is used a an aprotic, polar solvent.

It is also known by another name: methyl cyanide.

Acetonitrile,a.k.a. methyl cyanide

When I first encountered it during my undergraduate studies, I was rather nervous handling it. Surely as a cyanide compound, one stray drop or errant exposure and I would be done for. With a bit of further reading, I was rather surprised that it had a significantly higher LD50 than other cyanide compounds.

First, a bit of an explanation. The LD50 of a compound is also known as the median lethal dose. In toxicology, it is defined as the dose of a compound that is required to kill half of a tested population over a specified test duration.

With that in mind, it was curious to see a clear and concise comparison of the relative toxicities of a range of aliphatic nitriles (Comparative Toxicologies of Aliphatic Nitriles). To put it plainly, the LD50 of the simple aliphatic nitriles, reported as an oral dose in mg/kg, is as follows:

• Acetonitile:          2460
• Propionitrile:        40
• Butyonitrile:         50

The following two nitriles are also included. Respectively they are propanedinitrile and vinylcyanide, and again, the LD50 is reported in terms of an oral dose in mg/kg:

• Malononitrile:      60
• Acrylonitrile:       90

 It can be seen that there is a massive difference in the reported median lethal doses of these compounds. This, of course, was a massive relief to me, as it meant that working with acetonitrile and appropriate PPE wasn't going to send me to an early grave.

But why is there such a difference in the LD50's of these simple organic cyanide compounds? Before we can answer this, we need to know why organic cyanide compounds, in general, are toxic. Upon ingestion, organic cyanides are metabolised in the liver, producing hydrogen cyanide. Hydrogen cyanide, of course, halts cellular respiration by inhibiting a specific enzyme present in the mitochondria, cytochrome c oxidase. Inhibition of this enzyme prevents cellular respiration, which ultimately leads to death of the cell.

So, what makes acetonitrile so special? Well, as it turns out, acetonitrile is metabolised rather slowly by the liver. This means that more acetonitrile can be excreted by the body before being metabolised in to hydrogen cyanide. Also, as the metabolism of acetonitrile is slow, this allows the body time to convert the toxic cyanide ion to the less-toxic thiocyanate ion. For those that are curious, this detoxification is governed by the rhodanese pathway (governed by the rhodanese enzyme present in the mitochondria).

As for the uses of acetonitrile, well, it makes a great organic, aprotic solvent, suitable for use in liquid chromatography. It is produced as a by-product of acrylonitrile manufacture, which leads to an interesting story. Back in 2008 my Honours project started, and methods were being developed and things were going swimmingly. My LC-MS/MS method used acetonitrile as an organic solvent/eluent, and I was getting good results.

Then it happened. And by "it", I mean the 2008 Olympic Games, which shut down the main source of the world's acetonitrile. Around the same time, Hurricane Ike also hit Texas, damaging one of the factories that produced acetonitrile in the U.S. Finally, the slowing economy at the time lead to a downturn in the production of acrylonitrile and related products. This produced a perfect storm, sending acetonitrile prices through the roof.

The gnashing of teeth and howls of dismay from researchers at this news was fierce. People called in favours to secure their own private supply of acetonitrile, lest they have to re-develop their methods with a cheaper solvent, like methanol. Such re-development is not necessarily an easy task, and would require the validation of a new method as well as starting a large number of experiments from scratch.

How many of my colleagues reacted at the news of the shortage.

How bad was the shortage? At my university we had a good relationship with one of the chemical supply companies. Despite being able to secure a suitable amount of acetonitrile, the price skyrocketed from approximately $300 per 4 litres to well over $600 per 4 litres. This meant that many researchers faced the choice of emptying their budget to ensure sufficient quantities of acetonitrile were available, or as mentioned previously, swap to a cheaper solvent. There are other alternatives to acetonitrile, like methanol, acetone and dimethyl sulfoxide, though they don't have quite the same properties.

In the end, production of acetonitrile came back to normal levels towards the end of 2009. Prices stabilised at around $400 per 4 litres, and life continued on as normal. Or at least until the next shortage comes around...

Well, there you have it. A little background on acetonitrile, cyanide poisoning and how for a short time a chemical shortage caused analytical chemists the world over to hoard their own supplies of acetonitrile.

Until next time,
Nathan

Organic stuff is good for you, right?

By presenting workshops and giving the occasional talk to high school students, I always make a point of allowing them to ask any relevant questions on science, chemistry and so on. I also try and ask them questions that make them think about the world and how it works. One of my favourite questions to ask is:

"Are organic things good for you?".

Most students surmise that I am referring to organic food, and respond with an emphatic "Yes!". This is a reasonable response, as depending on their year level, a number of students will not have encountered organic chemistry at this point in their schooling.

I then press the matter, and ask what does the term "organic" mean. In reply I'm told that it means that organic things are safe, natural, and so on. In response I ask whether they would eat arsenic, as it is naturally occurring. I explain that just because something is naturally occurring, it doesn't necessarily follow that it is safe.

The next question is whether they would ingest something like a cyanide salt, and receive an emphatic "No!" in response. This of course raises the question "Why?". After all, a compound like sodium cyanide is organic, and as the students have told me, organic things are safe and good for you.

At this point an explanation is in order, and discuss the different meanings attached to the word "organic". In particular, to scientists and chemists, "organic" describes a wide range of carbon-containing compounds, because hey, that's how we roll.

In short, it's always enjoyable to share knowledge during these workshops, and allowing the students to gain a more detailed understanding of the world around them.

Until next time,

Nathan

Workshops

As I've mentioned previously, I've had the opportunity to work on forensic science/chemistry workshops. Back in 2010 I was given the chance to help out one of my colleagues in setting up one of the workshops, and from there, took an active role in planning, setting up and running the workshops. Over time, I've been able to present to a range of people, young and old and from all walks of life.

Presenting workshops to high school kids is a highlight of my work at the moment. Sure, you can get a group of kids that have no interest in science, or a group that thinks it is a good idea to try and snort fingerprinting powder, but overall I've had a blast.

A typical workshop begins with a brief introduction to forensic science and how the portrayal of forensic science on television shows like CSI is often highly inaccurate. Afterwards, there is a hands-on demonstration of how to deposit fingerprints on suitable surfaces, how to develop these fingerprints with suitable fingerprint powders, and then how to lift the developed fingerprints with gelatine lifters.

Depending on the group and their interests, it's then off to the dark room and/or the microscope room. In the dark room, the students get to look at some of the cool bits of equipment available for use by undergraduate students and researchers. The Polilight is one such instrument, and allows me to show off the use of different coloured light sources in a forensic setting, and to also show fluorescence of fingerprinting reagents like Rhodamine 6G.

As an aside, the Polilight is an Australian invention, developed back in 1989. It was named by the Powerhouse Museum as one of the top 100 Australian inventions of the 20th century. Also, if you're ever in Canberra, around Dunlop, then you can visit Polilight Street. Cool, eh?

In the microscope room, students have the opportunity to view a range of items under different microscopes. They get a chance to compare and contrast different plant, animal and man-made fibres, and to look at the layers that make up a paint chip from a car.

The highlight for a reasonable number of students, however, is the mock crime scene. In the past, I was limited by the space available, though in recent months I've had the opportunity to make use of a larger and more suitable "Search Room". In short, a "Search Room" is typically used for collecting fibres from items of interest, and features a large, centrally located table in a very well-lit room. As such, I've had the chance to have some fun setting up the crime scenes, and have been able to draw a bit of inspiration from shows such as Dexter.

After all this is a quick Q&A session, answering any and all questions that the students have about university life, research, science, chemistry, drugs and poisons, autopsies and so on.

Here are a few shots of a crime scene I set up late last year, making full use of my fake blood recipe.

Oh the humanity! Or in the case, mannequinity!

Another view of the crime scene.

The right lighting conditions for murder most foul.

The possessions of the deceased.

Fake blood. Also, ouch!

More blood, and a different view of the crime scene.

I was always rather concerned about how gory this crime scene was, and how the students would respond. In the past I have had a few students who have become green around the gills when I mention blood, corpses or things of that nature. I shouldn't have worried though, as the students that got to experience this crime scene thought it was fantastic. Apparently more blood and gore the better, eh?

Well, hope you enjoyed all that. Until next time, warmest regards,
Nathan

Recipe time! Fake blood

One of the advantages of doing science marketing work and running forensic science/chemistry workshops is that it allows me to explore my creative side. When it comes to setting up a mock crime scene, one thing that is essential is a good fake blood.

I've had mixed success with the recipes I've found on the internet. Store-bought fake blood that is found on the shelves of dollar stores around Halloween is rather good, but I'm rather fond of my own recipe. Not only does it have a pleasant strawberry smell, it is also edible (I wouldn't go eating copious amounts of it though, as glycerine has a higher energy density than sucrose).

Materials
- 250 mL Glycerine/glycerol (available from supermarkets)
- Strawberry jelly powder (one sachet)
- Water
- Red food colouring
- Blue food colouring

Directions
1) Pour glycerine into microwave-safe bowl
2) Heat glycerine in microwave until hot (try not to set anything on fire). Shouldn't need more than about 30 to 45 seconds, but use your judgement.
3) Add jelly powder to hot glycerine, and mix with a wooden spoon until thoroughly mixed
4) Dropwise, add about 10 drops of red food colouring to mixture. Stir thoroughly.
5) Add a drop of blue food colouring and stir thoroughly. Add more until desired colour is achieved.
6) If the mixture is too thick, add small amounts of water until mixture has desired consistency.

Storage
If stored in an air-tight container, this mixture should be safe for use for weeks, if not months.

Preparation Time
This recipe should take about 10 minutes to make, from start to finish. 

Comment
Be aware that fake blood can stain, so take appropriate steps to ensure that you don't spray/spread this anywhere that will be difficult to clean. This fake blood can also be rather sticky, especially if left on a surface for a while. Also, as it contains glycerine, if you don't clean it up right away you may get ants and other insects taking advantage of a free meal.

A Brief Interlude - Some Music

Whilst working on my last post, I happened across a curious music video on YouTube.

I present you the song "I'm On Crack", by The Left Rights (a side project by Jimmy Urine and Steve, Righ? of Mindless Self Indulgence). Please be advised the song contains strong lyrics and potentially offensive content, so please bear this in mind before playing.

Until next time,
Nathan

Drugs Policy - Ecstasy

Though drugs policy is certainly a contentious issue, it is something worth commenting on. Walking through Sydney the other day, I happened across a poster regarding the production of ecstasy, and the nasty chemicals that are involved in its production.

This gave me pause. Certainly, harm minimisation and decreasing the incidence of recreational drug use (especially in teens) is ostensibly a worthy cause. However, this poster concerned me, not due to its portrayal of a clandestine laboratory, but the text associated with it:

"Made using drain cleaner, battery acid or even hair bleach. Then popped in your mouth"

Granted, a number of people would not necessarily understand the implications of this poster if it said:

"Made using sodium hydroxide, sulfuric acid or even hydrogen peroxide. 

Then popped in your mouth"

That being said, I feel that this poster is disingenuous, if only because it attempts to provoke fear, in particular, fear of chemicals. As mentioned in an earlier post, chemophobia is a tricky issue in modern society, where awareness of the health implications of exposure to toxic compounds is increasing. This awareness, however, has become associated with an irrational fear or distrust of, dare I say it, chemicals!

So, back to the poster. A wide range of synthetic routes are available for the production of MDMA from its precursors. The poster in question appears to reference a specific synthetic route, starting with isomerisation of safrole to isosafrole. Indeed, this method does involve the use of sulfuric acid, hydrogen peroxide and a strong base, as well as various other chemicals. In this regard, the poster is accurate, in that a clandestine laboratory may indeed use this particular scheme. 

At this point, we must ask ourselves what is the purpose of including the named chemicals in the above poster? It isn't to provide a cheat sheet a person on the street can use to start up their own little clandestine laboratory in suburbia. Again, it comes back to the use of scientific and chemistry-related terms to invoke fear, so as to scare off any would-be first time users of ecstasy, because hey, it contains chemicals.

To be blunt, and not to condone the production of recreational drugs, but one would imagine that a drug manufacturer would try not to actively poison their clientele. Of course, the use of adulterants and cutting agents to increase the bulk of a drug, or to alter its psychoactive effects are nothing new, and have been reported on. It is also unfortunately true that there have been reported fatalities due to ecstasy, whether due to overdose, adulteration and/or  polydrug abuse.

Back to the underlying element of chemophobia though. The three named chemicals in the above poster are sulfuric acid, hydrogen peroxide and sodium hydroxide. Though I dare say I don't often encounter sulfuric acid in everyday life, I do come into contact with hydrogen peroxide and sodium hydroxide. Regularly, in fact. Worse still, despite the warning of the poster, I put them in my mouth! Fear not, I don't swallow them. There is hydrogen peroxide in my mouthwash, and sodium hydroxide in various toothpastes. As for sulfuric acid, it is vital for a number of chemical reactions that produce a wide range of compounds, in particular those that are involve nitration in their synthesis.

Hmm... Perhaps this will make an interesting experiment for myself, and something I can report back on. I will endeavour to look at some everyday objects I encounter, and look at the chemicals that are present in them. 

Until next time, thanks for reading,

Nathan

On Chemophobia - Dihydrogen Monoxide

Perhaps one of the more interesting issues I encounter as a chemist is that of chemophobia, an irrational fear of chemicals.

In my experience it emerges as a lack of understanding of what chemicals are, the fact that everything in our world is composed of chemicals, and most important of all, a lack of understanding of the relationship between dose and effect.

In relation to dose, the German/Swiss alchemist Phillipus Aureolus Theophrastus Bombastus von Hohenheim, better known as Paracelsus, said it best:

"All things are poison, and nothing is without poison; only the dose permits something not to be poisonous" 

Or as it is more simply put:

"The dose makes the poison"

One of the advantages of working with high school students in forensic/chemistry workshops is that it allows me to gauge their understanding of the chemical world. Whether it be a discussion on what the term "organic" means, the painful debate over the safety of vaccinations, or what everyday objects contain, the questions and feedback I receive are truly fascinating.

Perhaps one of my favourite demonstrations draws on the rather popular Dihydrogen Monoxide (DHMO) hoax of years gone by. In my demonstrations, it begins by politely asking for volunteers from the audience, and if none are forthcoming, a bribe of crime scene tape works a charm. After the volunteers are assembled, I don my labcoat, goggles, and some nitrile gloves before continuing.

I then ask my volunteers to produce one of their hands, preferably their non-writing hand, before nervously producing a vial containing that dastardly compound, DHMO. After gingerly placing a drop on each of the volunteers' preferred and proferred hands, a short statement regarding the dangers of DHMO is read out. Ususally DHMO is switched out for the IUPAC name "oxidane", in order to throw off any students aware of the DHMO hoax.

Hide the children! It's oxidane!

The students are then questioned on any ill effects that they are experiencing following exposure. The effects I've had rattled off to me are curious, and have included anything from tremors, sweating and increased heart rate, to headaches, stomach cramps and dizziness. To quell any further worries, the ruse is revealed, and the students calm down significantly.

The goal of all this is to demonstrate that an awareness of chemistry, if not an active interest in it, combined with a healthy dose of skepticism, can prove invaluable.After all, it pays to be aware of the world around you, and to have at the very least a basic knowledge of how things work. This brings to mind a very salient quote by Neil Degrasse Tyson:

"If you're scientifically literate, the world looks very different to you"

In future posts, I will further discuss chemophobia and how people perceive chemicals, more broadly, chemistry.

Well, that wraps up this post. Thanks for reading!

Greetings to an electronic world

Greetings. This marks the first post on my blog.

My labcoat

 I am currently a PhD student, studying in the field of forensic toxicology. I was first drawn to science at a young age, with the gift of a chemistry set that would, in today's world, be seen as rather dangerous. In my mind, the chemicals were rather innocuous,  and allowed me to explore a world that exists parallel to our own, though on a much smaller scale. That chemistry set, that I still recall fondly, kindled a fire inside me to better understand our world. From simple experiments, like making pH indicators, crystallising compounds and so on, it provided much joy to me. It also allowed me to turn my hand bright orange, a result of an overzealous mind bored when the listed experiments were completed.

This fascination with science has not only lead to my current position as a PhD student in Sydney, but has also given me the opportunity to work with high school students, and present forensic science and chemistry workshops for those that are interested. The look of excitement and fascination on the faces of the students bestows a remarkable feeling, and I am glad to be able to have a chance to ignite and pass on a passion for science that a humble chemistry set ignited in me all those years ago. 

The research that I am currently working on pertains to urine testing for recreational substances, specifically, cannabis use. Though urine testing for a range of licit and illicit substances is well established, in recent years there has been an increasing problem with the use of adulterants to chemically alter urine samples in order to obtain a false negative. Currently, I am exploring a range of oxidising agents and their effect on urine samples that have been spiked with a key metabolite of delta-9-tetrahydrocannabinol (THC), 11-nor-9-carboxy THC (THC-COOH).

The key issue with the use of adulterants, in particular oxidising adulterants, is that they react with the metabolites present in a positive urine sample. These reactions render common methods to test urine samples ineffective. From immunoassays such as ELISA, to mass spectrometric techniques, these samples fly under the radar, as it were, for subtle changes to the structure of the metabolites of interest result in novel compounds that are not associated with a positive urine sample. Therefore, it has been the goal of my research to react THC-COOH with a range of oxidising agents, and to explore whether novel reaction products are formed, and if so, whether they are stable and suitable for incorporation into current testing procedures. 

Urine adulteration has therefore become an increasing problem for law enforcement agencies. This has been compounded by the availability of a number of oxidising agents, able to be bought online or at your local supermarket. On that note, from the fantastic Adult Swim cartoon Metalocalypse, some insight on this matter:

Pickles: Dudes, we party too hard, so our bodies are in terrible shape. We gotta trick the doctor by making it seem like we're in really good shape. And there's only one way to do that. Bleach. [holds up a jug of bleach] Here, drink this Murderface. [hands it to Murderface]

Skwisgaar: Uhh, maybe this ams a stupid question, buts, why don'ts we just pours bleach into our cups of...urines?

Pickles: [looking angry at the suggestion] No! Drink the bleach!

Nathan: Bleach is healthy. It's mostly water. And we are mostly water. Therefore, we are bleach.

Or if you prefer a clip:

As a sidenote, please don't drink bleach. Pretty please?

Results have been promising to date. A number of viable oxidising agents have been selected, including betadine, alkaline hypochlorite (bleach), potassium/sodium nitrite, and pyridinium chlorochromate. As THC-COOH is quite prone to oxidation, a number of viable intermediates and products have been isolated, and are in the process of being analysed. For the oxidising agents containing halogens, it appears that electrophilic aromatic substitution (EAS) produces mono-halogen derivatives of THC-COOH as intermediates, with the di-halogen (di-chloro and di-iodo) THC-COOH derivatives representing the ultimate products. For nitrite-based reactions, an unstable nitroso-containing derivative forms, which undergoes further reaction to produce a stable nitro-THC-COOH compound.

Well, that covers who I am and what I do. As for this blog, well, I intend to comment on the perception of science, chemistry and drugs within society, and to discuss fascinating articles and the like.

So, thank you for reading this far. I truly hope that you will find my writings and ramblings fascinating. With kindest regards,
Nathan