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Sam Harris, Religion & Drugs

What with my recent com­puter troubles (I’ve had to format at least once more since writing that post, by the way), I’ve not been able to post any­thing with much sub­stance in the past few weeks. To make that up to you, this post will a long one, albeit not my own words, so put the kettle on and dig out your reading glasses.

The End Of FaithThe fol­lowing passage is taken from Sam Harris’s book, The End Of Faith, and talks about religion’s role in keeping drugs illegal:

***

The War on Sin

In the United States, and in much of the rest of the world, it is cur­rently illegal to seek certain exper­i­ences of pleasure. Seek pleasure by a for­bidden means, even in the privacy of your own home, and men with guns may kick in the door and carry you away to prison for it. One of the most sur­prising things about this situ­ation is how unsur­prising most of us find it. As in most dreams, the very faculty of reason that would oth­er­wise notice the strange­ness of these events seems to have suc­cumbed to sleep.

Beha­viors like drug use, pros­ti­tu­tion, sodomy, and the viewing of obscene mater­ials have been cat­egor­ized as “vic­tim­less crimes.” Of course, society is the tan­gible victim of almost everything human beings do — from making noise to man­u­fac­turing chem­ical waste— but we have not made it a crime to do such things within certain limits. Setting these limits is invari­ably a matter of assessing risk. One could argue that it is, at the very least, con­ceiv­able that certain activ­ities engaged in private, like the viewing of sexu­ally violent por­no­graphy, might incline some people to commit genuine crimes against others. There is a tension, there­fore, between private freedom and public risk. If there were a drug, or a book, or a film, or a sexual pos­i­tion that led 90 percent of its users to rush into the street and begin killing people at random, con­cerns over private pleasure would surely yield to those of public safety. We can also stip­u­late that no one is eager to see gen­er­a­tions of chil­dren raised on a steady diet of methamphet­amine and Marquis de Sade. Society as a whole has an interest in how its chil­dren develop, and the private beha­vior of parents, along with the con­tents of our media, clearly play a role in this. But we must ask ourselves, why would anyone want to punish people for enga­ging in beha­vior that brings no sig­ni­ficant risk of harm to anyone? Indeed, what is start­ling about the notion of a vic­tim­less crime is that even when the beha­vior in ques­tion is genu­inely vic­tim­less, its crimin­ality is still affirmed by those who are eager to punish it. It is in such cases that the true genius lurking behind many of our laws stands revealed. The idea of a vic­tim­less crime is nothing more than a judi­cial reprise of the Chris­tian notion of sin.

It is no acci­dent that people of faith often want to curtail the private freedoms of others. This impulse has less to do with the history of reli­gion and more to do with its logic, because the very idea of privacy is incom­pat­ible with the exist­ence of God. If God sees and knows all things, and remains so pro­vin­cial a creature as to be scan­dal­ized by certain sexual beha­viors or states of the brain, then what people do in the privacy of their own homes, though it may not have the slightest implic­a­tion for their beha­vior in public, will still be a matter of public concern for people of faith.

A variety of reli­gious notions of wrong­doing can be seen con­ver­ging here — con­cerns over non­pro­cre­ative sexu­ality and idol­atry espe­cially — and these seem to have given many of us the sense that it is ethical to punish people, often severely, for enga­ging in private beha­vior that harms no one. Like most costly examples of irra­tion­ality, in which human hap­pi­ness has been blindly sub­verted for gen­er­a­tions, the role of reli­gion here is both explicit and found­a­tional. To see that our laws against “vice” have actu­ally nothing to do with keeping people from coming to phys­ical or psy­cho­lo­gical harm, and everything to do with not angering God, we need only con­sider that oral or anal sex between con­senting adults remains a crim­inal offence in thir­teen states. Four of the states (Texas, Kansas, Oklahoma, and Mis­souri) pro­hibit these acts between same-​​sex couples and, there­fore, effect­ively pro­hibit homo­sexu­ality. The other nine ban con­sen­sual sodomy for everyone (these places of equity are Alabama, Florida, Idaho, Louisiana, Mis­sis­sippi, North Car­o­lina, South Car­o­lina, Utah, and Vir­ginia). One does not have to be a demo­grapher to grasp that the impulse to pro­secute con­senting adults for non­pro­cre­ative sexual beha­vior will cor­relate rather strongly with reli­gious faith.

Jesus once got 5000 people totally baked with only an eighth of weed

Jesus once got 5000 people totally baked with only an eighth of weed

The influ­ence of faith on our crim­inal laws comes at a remark­able price. Con­sider the case of drugs. As it happens, there are many sub­stances — many of them nat­ur­ally occur­ring — the con­sump­tion of which leads to tran­sient states of inor­dinate pleasure. Occa­sion­ally, it is true, they lead to tran­sient states of misery as well, but there is no doubt that pleasure is the norm, oth­er­wise human beings would not have felt the con­tinual desire to take such sub­stances for mil­lennia. Of course, pleasure is pre­cisely the problem with these sub­stances, since pleasure and piety have always had an uneasy relationship.

When one looks at our drug laws — indeed, at our vice laws alto­gether — the only organ­izing prin­ciple that appears to make sense of them is that any­thing which might rad­ic­ally eclipse prayer or pro­cre­ative sexu­ality as a source of pleasure has been out­lawed. In par­tic­ular, any drug (LSD, mes­caline, psilo­cybin, DMT, MDMA, marijuana, etc.) to which spir­itual or reli­gious sig­ni­fic­ance has been ascribed by its users has been pro­hib­ited. Con­cerns about the health of our cit­izens, or about their pro­ductivity, are red her­rings in this debate, as the leg­ality of alcohol and cigar­ettes attests.

The fact that people are being pro­sec­uted and imprisoned for using marijuana, while alcohol remains a staple com­modity, is surely the reductio ad absurdum of any notion that our drug laws are designed to keep people from harming them­selves or others. Alcohol is by any measure the more dan­gerous sub­stance. It has no approved medical use, and its lethal dose is rather easily achieved. Its role in causing auto­mobile acci­dents is beyond dispute. The manner in which alcohol relieves people of their inhib­i­tions con­trib­utes to human viol­ence, per­sonal injury, unplanned preg­nancy, and the spread of sexual disease. Alcohol is also well known to be addictive. When con­sumed in large quant­ities over many years, it can lead to dev­ast­ating neur­o­lo­gical impair­ments, to cir­rhosis of the liver, and to death. In the United States alone, more than 100,000 people annu­ally die from its use. It is also more toxic to a devel­oping fetus than any other drug of abuse. (Indeed, “crack babies” appear to have been really suf­fering from fetal-​​alcohol syn­drome.) None of these charges can be leveled at marijuana. As a drug, marijuana is nearly unique in having several medical applic­a­tions and no known lethal dosage. While adverse reac­tions to drugs like aspirin and ibuprofen account for an estim­ated 7,600 deaths (and 76,000 hos­pit­al­iz­a­tions) each year in the United States alone, marijuana kills no one. Its role as a “gateway drug” now seems less plaus­ible than ever (and it was never plaus­ible). In fact, nearly everything human beings do — driving cars, flying planes, hitting golf balls — is more dan­gerous than smoking marijuana in the privacy of one’s own home. Anyone who would ser­i­ously attempt to argue that marijuana is worthy of pro­hib­i­tion because of the risk it poses to human beings will find that the powers of the human brain are simply insuf­fi­cient for the job.

And yet, we are so far from the shady groves of reason now that people are still receiving life sen­tences without the pos­sib­ility of parole for growing, selling, pos­sessing, or buying what is, in fact, a nat­ur­ally occur­ring plant. Cancer patients and para­ple­gics have been sen­tenced to decades in prison for marijuana pos­ses­sion. Owners of garden-​​supply stores have received similar sen­tences because some of their cus­tomers were caught growing marijuana. What explains this aston­ishing wastage of human life and material resources? The only explan­a­tion is that our dis­course on this subject has never been obliged to func­tion within the bounds of ration­ality. Under our current laws, it is safe to say, if a drug were invented that posed no risk of phys­ical harm or addic­tion to its users but pro­duced a brief feeling of spir­itual bliss and epi­phany in 100 percent of those who tried it, this drug would be illegal, and people would be pun­ished mer­ci­lessly for its use. Only anxiety about the bib­lical crime of idol­atry would appear to make sense of this retributive impulse. Because we are a people of faith, taught to concern ourselves with the sin­ful­ness of our neigh­bors, we have grown tol­erant of irra­tional uses of state power.

Our pro­hib­i­tion of certain sub­stances has led thou­sands of oth­er­wise pro­ductive and law-​​abiding men and women to be locked away for decades at a stretch, some­times for life. Their chil­dren have become wards of the state. As if such cas­cading horror were not dis­turbing enough, violent crim­inals — murders, rapists, and child molesters — are reg­u­larly paroled to make room for them. Here we appear to have over­stepped the banality of evil and plunged to the absurdity at its depths.

The con­sequences of our irra­tion­ality on this front are so egre­gious that they bear closer exam­in­a­tion. Each year, over 1.5 million men and women are arrested in the United States because of our drug laws. At this moment, some­where on the order of 400,000 men and women lan­guish in U.S. prisons for non­vi­olent drug offences. One million others are cur­rently on pro­ba­tion. More people are imprisoned for non­vi­olent drug offences in the United States than are incar­cer­ated, for any reason, in all of Western Europe (which has a larger pop­u­la­tion). The cost of these efforts, at the federal level alone, is nearly $20 billion dollars annu­ally. The total cost of our drug laws — when one factors in the expense to state and local gov­ern­ments and the tax revenue lost by our failure to reg­u­late the sale of drugs — could easily be in excess of $100 billion dollars each year. Our war on drugs con­sumes an estim­ated 50 percent of the trial time of our courts and the full-​​time ener­gies of over 400,000 police officers. These are resources that might oth­er­wise be used to fight violent crime and terrorism.

In his­tor­ical terms, there was every reason to expect that such a policy of pro­hib­i­tion would fail. It is well known, for instance, that the exper­i­ment with the pro­hib­i­tion of alcohol in the United States did little more than pre­cip­itate a ter­rible comedy of increased drinking, organ­ized crime, and police cor­rup­tion. What is not gen­er­ally remembered is that Pro­hib­i­tion was an expli­citly reli­gious exer­cise, being the joint product of the Woman’s Chris­tian Tem­per­ance Union and the pious lob­bying of certain Prot­estant mis­sionary soci­eties. The problem with the pro­hib­i­tion of any desir­able com­modity is money. The United Nations values the drug trade at $400 billion a year. This exceeds the annual budget for the U.S. Depart­ment of Defense. If this figure is correct, the trade in illegal drugs con­sti­tutes 8 percent of all inter­na­tional com­merce (while the sale of tex­tiles makes up 7.5 percent and motor vehicles just 5.3 percent). And yet, pro­hib­i­tion itself is what makes the man­u­fac­ture and sale of drugs so extraordin­arily prof­it­able. Those who earn their living in this way enjoy a 5,000 to 20,000 percent return on their invest­ment, tax-​​free. Every rel­evant indic­ator of the drug trade — rates of drug use and inter­dic­tion, estim­ates of pro­duc­tion, the purity of drugs on the street, etc. — shows that the gov­ern­ment can do nothing to stop it as long as such profits exist (indeed, these profits are highly cor­rupting of law enforce­ment in any case). The crimes of the addict, to finance the stra­to­spheric cost of his life­style, and the crimes of the dealer, to protect both his ter­ritory and his goods, are like­wise the results of pro­hib­i­tion. A final irony, which seems good enough to be the work of Satan himself, is that the market we have created by our drug laws has become a steady source of revenue for ter­rorist organ­iz­a­tions like Al Qaeda, Islamic Jihad, Hezbollah, Shining Path, and others.

Even if we acknow­ledge that stop­ping drug use is a jus­ti­fi­able social goal, how does the fin­an­cial cost of our war on drugs appear in light of the other chal­lenges we face? Con­sider that it would require only a onetime expenditure of $2 billion to secure our com­mer­cial sea­ports against smuggled nuclear weapons. At present we have alloc­ated a mere $93 million for this purpose. How will our pro­hib­i­tion of marijuana use look (this comes at a cost of $4 billion annu­ally) if a new sun ever dawns over the port of Los Angeles? Or con­sider that the U.S. gov­ern­ment can afford to spend only $2.3 billion each year on the recon­struc­tion of Afgh­anistan. The Taliban and Al Qaeda are now regrouping. War­lords rule the coun­tryside beyond the city limits of Kabul. Which is more important to us, reclaiming this part of the world for the forces of civil­iz­a­tion or keeping cancer patients in Berkeley from relieving their nausea with marijuana? Our present use of gov­ern­ment funds sug­gests an uncanny skewing — we might even say derange­ment — of our national pri­or­ities. Such a bizarre alloc­a­tion of resources is sure to keep Afgh­anistan in ruins for many years to come. It will also leave Afghan farmers with no altern­ative but to grow opium. Happily for them, our drug laws still render this a highly prof­it­able enterprise.

Anyone who believes that God is watching us from beyond the stars will feel that pun­ishing peaceful men and women for their private pleasure is per­fectly reas­on­able. We are now in the twenty-​​first century. Perhaps we should have better reasons for depriving our neigh­bors of their liberty at gun­point. Given the mag­nitude of the real prob­lems that con­front us-​​ — ter­rorism, nuclear pro­lif­er­a­tion, the spread of infec­tious disease, failing infra­struc­ture, lack of adequate funds for edu­ca­tion and health care, etc. — our war on sin is so out­rageously unwise as to almost defy rational comment. How have we grown so blind to our deeper interests? And how have we managed to enact such policies with so little sub­stantive debate?

***

Letter To A Christian Nation Wise words indeed. Sam Harris is a philo­sopher, neur­os­cientist and the kind of atheist who takes no shit from anyone. The rest of his book tackles the irra­tion­ality of belief, the damage it can do to society and high­lights the reasons why reli­gious tol­er­ance is cer­tainly a bad thing. This book should be on everyone’s reading list, but if you’re looking for a more concise attack on irra­tional belief, I’d also recom­mend Sam Harris’s other book, Letter To A Chris­tian Nation. Weighing in at just over 100 pages, this is more of an essay than a book, so you’ll finish it in one afternoon.

If you’re one of those rare kinds of people with an atten­tion span longer than 10 minutes, you might also like to watch The Four Horsemen — a dis­cus­sion between Sam Harris, Richard Dawkins, Daniel Dennet & Chris­topher Hitchens. It’s two hours long, so you might want to preroll before­hand. ;)

Posted in Essays, Legislation | Tagged athiesm, books, faith, Legislation, prohibition, religion, sam harris, sin |

Computer Problems

It’s been one hell of a week.

My com­puter has decided that now would be a great time to die, with only a few weeks to go before my final uni­ver­sity dead­lines. Error message after error message came thun­dering onto the screen faster than I could tell the com­puter “Ok”, as though my acknow­ledge­ment of the situ­ation would make the slightest bit of dif­fer­ence. After failing to run a system restore, I decided to rein­stall Windows. I was 100% con­fident that this would fix all of my prob­lems in one fell swoop. If only…

Practice safe surfing

Prac­tice safe surfing

My first mistake was trying to rein­stall Windows XP Pro­fes­sional instead of Home edition, putting two dif­ferent install­a­tions of Windows on the same machine and solving nothing. Stupid mistake, but I had to move on — there’d be time to deal with a rogue Windows install­a­tion when everything else was back up and running. Time to rein­stall XP Home Edition! Easy enough, should you have a working XP Home Edition CD at your dis­posal. Unfor­tu­nately, mine was scratched in such a manner than each time I tried to rein­stall it, random, but dif­ferent, files refused to copy across on each of the several occa­sions I attempted it. Some time later, I bit the bullet and made the always painful decision to format the bastard. But first, I needed to back up all my shit, including Coffeesh0p code and plenty of stuff for this blog, which is no easy task if you can’t boot up your com­puter in the first place. Luckily, I decided against smashing that XP Pro­fes­sional CD into the wall earlier and cutting myself with the shards, so I thought I’d try and install that again. 39 minutes later, my com­puter was back up from its death bed, but still not fit for duty. Before I could operate format, I needed to get all my stuff backed up onto another PC on the network, but then the next hurdle cropped up — appar­ently, I wasn’t author­ised to access the files on my own pissing com­puter! Just in case any of you encounter a situ­ation as shitty as this, you have to log onto your other Windows install­a­tion in safe mode, log into the admin­is­trator account and set your­self as the owner of the files in ques­tion, which is far from a simple task.

Even­tu­ally, everything was rescued and the com­puter formatted, but it’s still not working prop­erly. I suspect it may have some virus or other, but I’ll have to live with it until my exams are over.

As a result, my cus­tomer service went down the pan, so I apo­lo­gise to anyone that sent me an email last week.

In other news, you’ve all been very kind with the new rating system I installed. So far, there’s 14 ratings, only two of which are not five stars. Thanks! :) Hope­fully, I’ll be able to post a bit more once this damn project is over…

Posted in Personal | Tagged computer, customer service, virus, windows |

Herbal Photography

It’s been a busy week here at Coffeesh0p Studios (my bedroom). First off, we’ve been bat­tling with hosting issues since the weekend. Turns out we’d exceeded our band­width limit for Feb­ruary, taking both Coffeesh0p and this blog down until I forked over more money. It’s kind of like the internet equi­valent of being kid­napped and held to ransom.

I’ve also been taking pic­tures for some of the new products I men­tioned a while ago, so I thought I’d share some here. At the moment, the product images on Coffeesh0p are pretty small, most of them being around 200 px wide, so I’ve picked a few of my favourite full size pics and dis­played them below. Click on each for the full res­ol­u­tion version.

Amanita MuscariaWe’ll finally be stocking plain ol’ Fly Agaric caps in the next few days. Up until now, the only Amanita mus­caria we’ve sold has been pre­pack­aged, so it’s hard to display them in their full glory. This single cap will be turned into a thumb­nail image only 50 x 50 px. Seems such a shame. :(
This picture of Salvia divinorum leaf has been des­per­ately needed for quite some time. Although we’ve always sold salvia leaf, the picture was terrible.Salvia Leaf
Damiana ExtractSince most extracts look pretty unap­pealing, this chunky Damiana 4x extract really stood out.
This is one of our new smoking mix­tures, Blaze. Looks as deli­cious as it smells!Blaze
Posted in Drugs | Tagged amanita muscaria, blaze, coffeesh0p, damiana, hosting, new products, photography, Photoshop, salvia divinorum |

JWH-018 Toxicology

ToxicSince my last post about the spice behind Spice (and other smoking mix­tures such as Smoke, Serenity Now, K2, Sence, etc), it has been brought to my atten­tion that some initial tox­ic­o­logy testing has been done on the syn­thetic can­nabinoid JWH-​​018. Before we get down to the details however, here’s some pretty weird back­ground inform­a­tion — the sponsor and pro­vider of these studies wishes to remain anonymous! Unfor­tu­nately, this makes the whole thing a lot less cred­ible, but since this is the only inform­a­tion we have right now, let’s hope someone else can verify these things at a later date. So far, one pro­fessor (who also wishes to remain anonymous) thinks these are real, but as of yet, no one is willing to put their name down on any kind of formal state­ment. If you, or anyone you know, has the rel­evant expertise to look over these studies, please drop me a line!

(Quick Update — A lot of people have been dis­cussing and linking to this post, but there remains some sus­pi­cion that I have some­thing to gain by saying the JWH-​​018 isn’t that harmful. Firstly, JWH-​​018 is now illegal in the UK. Secondly, as I men­tioned just above this, if I have got any­thing wrong, please pick me up on it! If it turns out my ana­lysis of the data is incor­rect, I will correct it!)

Feel free to invent your own con­spiracy the­ories, but for now, let’s take a look at the data. You can down­load the PDF doc­u­ments in this Zip file [2.04 MB]

CYP450 Inhibition Assay

This first assay looks at the effect of a drug on spe­cific enzymes in your liver. These Cyto­chrome P450 enzymes are respons­ible for meta­bol­ising the vast majority of drugs you might put in your body, so if you’ve got too much of one drug in your system (ie paracetamol/​acetaminophen), then other drugs that are also meta­bol­ised by these enzymes (ie alcohol) may compete for these enzymes and so hang around in your system for longer. As you can imagine, it’s important to under­stand how one drug may affect the meta­bolism of another, in case of any dis­as­terous drug-​​drug interactions.

Results: JWH-​​018 will prob­ably interact with the meta­bolism of other drugs, so more in vivo work is necessary.

hERG Binding Assay

hERG stands for human Ether-​​à-​​go-​​go Related Gene. This gene codes for a par­tic­ular type of potassium channel found on heart tissue. This channel pumps potassium ions out of the heart muscle cells and are crit­ical in coördin­ating the heart’s elec­trical activity. Unfor­tu­nately, these chan­nels are a prime target for drugs to bind to, dis­rupting their func­tion. This can lead to “Long QT Syn­drome”, asso­ci­ated with fainting and can lead to sudden death, so you can see why these kinds of tests are important. Here’s a typical ECG recording showing what’s called the “QT interval” shown in blue, which lasts for longer than it should do if these chan­nels are disrupted.

QT Interval

Results: JWH-​​018 does not inter­fere with these chan­nels. That’s a good thing.

Cytotoxicity Assay

This simple test essen­tially looks at how many cells die when you perfuse them with a drug. The more cells that die, the more toxic the drug.

Results: JWH-​​018 is not cyto­toxic at low concentrations.

GreenScreen HC Genotoxicity Assay

This assay looks at how much a drug will inter­fere with our DNA. Typ­ic­ally, any­thing that damages DNA is bad news, being poten­tially car­ci­no­genic, making the rationale behind this test glar­ingly obvious. This test was also per­formed in the pres­ence of a frac­tion taken from liver cells, which will break down the drug. This not only checks if the drug will damage DNA, but also its break­down products.

Results: JWH-​​018 does not damage DNA, so shouldn’t give you cancer.

Rat Repeat Toxicity Assay

Guess what happens in this exper­i­ment. A number of ren­agade lab rats looking for a bad time are rounded up and prom­ised free drugs (kind of like Pleasure Island from Pinoc­chio; that shit was scary!). The rats are then dosed up and observed. Ini­tially, they appear leth­argic (read: totally baked) but a few of them died at higher doses. This appears to be down to prob­lems breathing rather than organ tox­icity, but only affected the male rats, who appeared more sens­itive to the com­pound. The drug didn’t appear to accu­mu­late in their systems either, but they did lose some weight, prob­ably because they couldn’t be arsed to eat. JWH-​​018 showed a huge potency and was found to be tachy­phylactic (my new favourite word — it means that more of a drug is required to reach the same state fol­lowing an initial dosage).

Results: According to FDA guidelines, the human equi­valent dose is 0.016 mg/​kg but it should be tested in other species before this can be seen as reliable!

Rat Pharmacokinetics

Data is col­lected on a number of dif­ferent “phar­ma­cokin­etic” aspects of the drug, such as how it is absorbed, dis­trib­uted throughout the body, meta­bol­ised and excreted, which can help with the design of future clin­ical trials.

Results: JWH-​​018 is dis­trib­uted well throughout the rat’s tissues. Meta­bolism and excre­tion are normal, with a plasma half-​​life of approx­im­ately 2 hours

Summary

Well, from the looks of these tests, JWH-​​018 seems to be pretty safe, but unless you want to piss off Ben Gol­dacre, it would be wise not to rely on this “test tube data” entirely. Also, like I said before, we don’t know where this data has come from, clouding the issue even further.

Feel free to ask any ques­tions in the comments.

Big thanks to Alfa @ Drugs​-Forum​.com for letting me know about these studies. You can read all about JWH-​​018 on their Drugs Wiki.

COM­MENTS IN THIS THREAD ARE NOW CLOSED. YOU CAN CON­TINUE DIS­CUSSING SYN­THETIC CAN­NABIN­OIDS HERE OR INDI­VIDUAL SMOKING MIX­TURES HERE.

Posted in Drugs, Pharmacology | Tagged CyP450, cytotoxicity, genotoxicity, hERG, JWH-018, safety, spice |

JWH-018, Spice & Me

The Spice smoking mixture range has been one of the most popular “herbal” smokes ever, and now it’s no suprise why.

To get an idea of just how popular these mix­tures are, just take a look at this data from Google’s keyword tool:

That’s over 37,000 searches a month for these three search terms alone — Spice is def­in­itely a cus­tomer favourite. I also get no less than 500 emails a day from Russia asking if I can ship it there by the kilo. So what’s behind it all?

This paper [PDF; 246 kB] has some inter­esting things to say. It turns out that the Spice blends all contain JWH-​​018 as well as two com­pounds based on CP 47497 — all of them syn­thetic can­nabin­oids. These are man made chem­icals designed to tickle the same receptors as THC, the active com­pound in can­nabis, so it’s no wonder these smoking mix­tures are so powerful. The dif­fer­ence in potency between the Spice blends appears to be accounted for by increasing levels of these CP 47497 homologues.

jwh-018

Since this dis­covery, Spice has been banned in several coun­tries, including Austria and Germany. The BBC also reported on it and had the fol­lowing to say:

The UK drugs reg­u­lator, the Medi­cine and Health­care products Reg­u­latory Agency (MHRA), is under­stood to have iden­ti­fied JWH018 in products avail­able in the UK. It is cur­rently in order to determine whether or not it should be clas­si­fied as a medi­cinal product — which would mean it should only be avail­able from a doctor.

The UK Advisory Council on the Misuse of Drugs, which advises the gov­ern­ment on whether a drug should be made illegal, is also aware of the sub­stance, and is invest­ig­ating it.

The Spice man­u­fac­turers make no mention of these syn­thetics on their pack­aging, so a lot of herb-​​enthusiasts feel some­what betrayed. Rightly so, I suppose — not being told just what you’re smoking exactly. People have the choice to put things in their body and some Spice smokers might make a dif­ferent decision if they had all the facts in hand.

But, why?

The typical reac­tion to this news seems to be the disgust about putting any of these “unsafe” man-​​made com­pounds into their body, as though mother nature was some kind of safety net. “These plants have thou­sands of years of safe use”, they say! But let’s take a closer look…

Take Kratom, for instance. Kratom con­tains a powerful com­pound called mitra­gynine, which acts upon the opioid receptors; the same targets for opium and its deriv­at­ives. One alkaloid in kratom, although present in much smaller quant­ities, is 7-​​hydroxymitragynine, which is appar­ently 17x more potent than morphine! While I wouldn’t call this plant harmful, com­pared to other drugs like cocaine and heroin, it wouldn’t say it was harm­less either. The opioid receptors are a dan­gerous set of receptors to be messing with — the mu subtype respons­ible for the classic euphoria that accom­panies opiate use also stops you breathing if you tickle them too much. Opiates are also addictive, just like kratom can be if you take too much. While this plant may have seen thou­sands of years of respons­ible, mod­erate use, this is no reas­sur­ance at all towards its safety.

Now days, people gen­er­ally don’t toil in the field every day that Newton sends — we have more free time and money to spend than ever before. We can now afford to use large quant­ities of kratom every day, as well as other entheo­gens from around the world, but we don’t have any inform­a­tion about this level of exposure to kratom itself or in com­bin­a­tion with other stuff. For all we know, taking a mixture of kratom and Salvia divinorum daily could make your eye­balls explode after day 300, or chronic kratom use might give you some kind of evil super­power. Looking at paracetamol as a rather boring example, if you take the odd one every now and then, you’ll be fine, but if you take 8 pills a day every day for a year, you’ll likely end up with some serious con­di­tion. There’s also the fact that modern chem­istry can create powerful extracts of these entheo­gens. Who’s to say they’re safe, just because they come from a plant? And what about any other drugs we might be on? Being on a selective sero­tonin reup­take inhib­itor like Prozac for depres­sion isn’t uncommon in today’s society — combine them with the “per­fectly safe” Ban­is­teriopsis caapi vine, itself a monoamine oxidase inhib­itor, and you have a poten­tially fatal com­bin­a­tion of drugs in your system. I bet there are many more con­train­dic­a­tions we haven’t even considered.

What about plants like can­nabis and tobacco? They’ve also been used respons­ibly for thou­sands of years, but it’s only when so many people start to take these things that we real­ised “Actu­ally, smoking is bad for us”. Besides, our current medical know­ledge means we’ve only recently been able to dia­gnose these kind of things. I’m not sure I want to trust any data from a period when epi­lepsy might have been down to a demonic pos­ses­sion. How many adverse health effects could we identify in these ancient entheogen users based on what we know today?

So, while we can be uncer­tain of the long term effects on health of JWH-​​018 and friends, it seems we can’t actu­ally be certain about the safety of most of the things we happily consume. Yes, they may turn out to be super toxic (although prob­ably not, if they’re given to lab rats), but at least they only act on your can­nabinoid receptors. Kratom tends to be pre­pared as a tea — once you’ve drunk it, you’ve drunk it. If you’ve taken too much, you’ll realise when its already in your blood. It would be much harder to over­dose on these syn­thetics due to the speed at which they get in your system — if you’re too stoned, you won’t want to smoke any more, never mind being phys­ic­ally able to. The can­nabinoid receptors they target are also much safter than the opioid targets of kratom. Can­nabinoid receptors seem play a mod­u­latory role, rather than being majorly important, so messing with them doesn’t have as drastic an effect. Smoking too much might make you feel a bit sick and dizzy for a while, but you cer­tainly won’t stop breathing.

In all, I think Spice is in the wrong for not making this clear in the first place, but then I’m not suprised they didn’t want to list these com­pounds in the current polit­ical climate. Maybe when the gov­ern­ment real­ises that it is our right to put things into our own bodies, listing these ingredi­ents wouldn’t be an issue.

Even with this new inform­a­tion however, I’ll still be using the stuff. It’s great!

Posted in Drugs | Tagged banisteriopsis caapi, cannabinoids, contraindications, JWH-018, kratom, safety, spice, spice diamond, spice gold, spice silver, synthetics |

Synthesis of Salvinorin-A

Salvinorin-A Synthesis

Any hard­core chem­ists out there might be inter­ested in this paper, pub­lished in Organic Letters by a team of researchers from Niigata Uni­ver­sity. It details the syn­thesis of one of nature’s cra­ziest com­pounds, Salvinorin-​​A, found in Salvia divinorum.

For a bit more back­ground and phar­ma­co­logy, you might want to check out my Salvia present­a­tion.

Inter­esting stuff!

Posted in Drugs | Tagged chemistry, salvia diviorum, salvinorin-a, synthesis |

Cannabis Reclassification

Cannabis

Cannabis is now Class B

Don’t worry though! Our awesome Smoking Mix­tures do the trick and are totally legal!
According to our gov­ern­ment, amphet­amine (speed) is as bad for us as can­nabis — what other message could reclas­si­fic­a­tion send?

Your typical can­nabis smoker tends to

  1. stay indoors
  2. chillax
  3. get through a lot of crisps

Your typical whizzkid tends to

  1. go out a lot
  2. get some­what over­con­fident and aggressive
  3. listen to awesome drum ‘n’ bass
  4. approach the speed of light (literally*)

*Not lit­er­ally

I’m not neces­sarily knocking amphet­amine or it’s users, just pointing out that drugs are a class apart. Oh no, wait.

Check out the (now out of date) graph below, placing drugs from most harmful on the left to least harmful on the right.The score assigned to each drug takes into account harm to your­self and to society as a whole, and what’s that… alcohol and tobacco are more harmful than the class A drugs LSD and ecstasy! Con­sid­ering that the link between can­nabis and schizo­phrenia is as tenuous as ever (why isn’t the Neth­er­lands one big psych ward?), why is our gov­ern­ment ignoring it’s own sci­ent­ists? Reli­gion has more regard for evid­ence than Mr. Brown (and that’s saying some­thing!) If you want to learn more about just how stupid our current clas­si­fic­a­tion system is, you can watch this episode of BBC’s Horizon, which tackles each drug in turn. (49 mins)

Posted in Legislation | Tagged alcohol, amphetamine, cannabis, horizon, reclassification, tobacco |

Coffeesh0p Is Doing Great

So, I’ve been playing around with Excel (read: pro­cras­tin­ating) a lot lately and pro­duced these lovely looking graphs. Since they do look ever so lovely, and without revealing too much, I thought I’d post them here, along with a healthy dose of good advice. Also, the second two show the first month’s results from my little article exper­i­ment.

The X axis rep­res­ents the months from Jan 2007 until Dec 2008. The extra­pol­ated curves of best fit do not take into account December’s data.
Orders
I guess this first graph shows we’re here to stay — this is the number of orders placed with us each month. While the number of orders placed last month is a little lower than November’s data, this is con­sistent with most other e-​​commerce sites, who all see a slump in traffic (and sales) over the hol­i­days. Who’d have thought people would prefer to spend time with their fam­ilies rather than shop online? The same thing also occurs during December of last year. Still, not bad for a reces­sion.

Traffic

This graph shows overall traffic to the site. Internet mar­ket­eers may be inter­ested to learn that the dis­tinct peaks rep­resent my limited foray into social book­marking. Notice how the same months in the pre­vious graph do not show any similar increases in the amounts of orders placed. This just goes to show that social book­marking is shite for e-​​commerce.

One final point: traffic dropped sig­ni­fic­antly in December — far more than you’d expect over the hol­i­days. For­tu­nately, this was exactly as I’d planned. December was when I moved all the old art­icles over to this blog, and art­icles are big traffic-​​generating machines. Take note, budding mar­ket­eers — article mar­keting can really drive traffic to your site! Compare the month of December on both graphs so far though — while traffic dropped sig­ni­fic­antly, the number of orders decreased only slightly. There are also plenty of other things you can do with old static content, so make sure you don’t let things stagnate.

conversion-rate

This final graph shows each month’s con­ver­sion rate — that is, the per­centage of vis­itors who go on to place an order. December’s data shows a sig­ni­ficant increase as soon as I moved those art­icles, which just goes to show — traffic isn’t everything! It sur­prised me that before then, the con­ver­sion rate was still con­tinu­ally on the rise. I must have been doing some­thing right. Unfor­tu­nately though, many, many things can affect your con­ver­sion rates, none of which have a par­tic­u­larly large effect. Here’s a great post on 108 ways you can increase your con­ver­sion rates.

Why I should Be Worried

There’s no doubt about it — our little herbal highs hobby is kicking some ass, but it’s not all good news. More orders means more work, and right now me and my girl­friend are in the last term of our final year at uni­ver­sity, so time is not some­thing we have in abundance.

We might have to hire someone…

Posted in Internet Marketing | Tagged article marketing, coffeesh0p, conversion rates, e-commerce, traffic |

How To Grow Salvia Divinorum: A Rough Guide

Green Fingers

Buying Your Plant

The most expensive part of growing Salvia Divinorum on a organic/​semi-​​organic basis is actu­ally buying a cutting or whole plant. I managed to get my plant for £12 including postage and pack­aging. After this follows compost and a suit­able size pot.

There are many places to find salvia plants/​cuttings, not only at local plant nurs­eries, but all over the internet; there’s at least one salvia plant on ebay at any one time. It’s worth noting that prices can vary sig­ni­fic­antly with little vari­ation in quality, so make sure you shop around.

Try and buy a plant locally if you can. If not, def­in­itely buy from a website based in your home country to min­imise the time it spends in an envelope.

Growing A Cutting

When your cutting arrives, remove it from it’s pack­aging extremely care­fully and let it sit in luke warm water. Assuming your cutting already has roots, leave it in the water for a couple of hours. If no roots are present, leave it in the water for a week or so until there’s enough root growth present to allow for potting.

After it’s sat in water for a while, it’s time to plant it. You’ll need a pot at least 20-​​30cm wide to allow your cutting to grow without having to be repotted every couple of months. The first thing to do is place some gravel or broken crockery into your pot up to about 5cm from the bottom. This thin layer allows for superior drainage after watering. After that, fill the pot up with your loam based compost avail­able from any gardening store and dig a little hole in the centre where your plant will sit. Next, take your cutting, splay out the roots gently with your fingers and place the cutting into the hole you provided. Back­fill the hole with more compost and com­press down lightly around the stem of your plant.

Trav­el­ling through the mys­teries of the postal service and being stuck in some soil is thirsty work for a plant. Imagine you have been slaving away all day in the blis­tering sun, doing vast quant­ities of manual labour. How badly are you gagging for a pint at your local? This is how your plant is feeling right now. Although your plant needs a drink, don’t feel obliged to buy it any peanuts. Now your plant is potted, give it enough water so that excess water will drip from the bottom of the pot.

From here, I advise you to put the plant in a humid envir­on­ment, at least at first, to promote healthy growth. Just like a fat kid loves cake, Salvia Divinorum loves indirect sun­light. This can be any­where such as a light room with no direct sun blazing down on it all day, or even dir­ectly in the sun, but behind a net curtain. Provided your plant is not exposed to too much direct sun­light, it will do all right.

Leave it a few weeks and your cutting will start turning into a fully-​​fledged plant. Keep an eye on the compost, making sure it doesn’t dry up. Water once a week in summer and once every two weeks in winter. Just be careful to never over water your plant, or root rot could set in.

Growing & Maintaining A Plant

Growing an estab­lished plant is almost the same as growing a cutting. Salvia Divinorum can be very flex­ible about its growing con­di­tions, but a quick change in con­di­tions will most likely piss your plant right off. You have to con­sider that your plant has already been growing for prob­ably quite some time in certain con­di­tions, which it is now used to. These includes, but is not limited to, dif­ferent light levels, compost, humidity, etc so it is very important to find out as much as you can about these con­di­tions from the plant’s pre­vious owner, then try to match those con­di­tions as best you can. Once the plant has been repotted and is begin­ning to settle into it’s new envir­on­ment, then you can slightly alter it’s envir­on­ment a little each day until you have it growing in con­di­tions easy for you to maintain.

The growth of the plant at first will be slow. Remember, it’s been shoved in an envelope for a few days with no light, so it’ll need to recover from that trau­matic exper­i­ence before it will even think about new growth. This can take up to around 2 weeks before any pro­gress can be seen.

Look out for the leaves and edges of the plant turning brown, this means it is NOT in the right con­di­tions. There are many things it could want, but chances are it’s some­thing to do with humidity. Try misting the leaves if your envir­on­ment is not very humid, or con­sider building a humidity tent or moving the plant into the bath­room, where people use the shower fre­quently. The stem, and pos­sibly the leaves should return to normal in a couple of weeks. If not, cut the leaves off at the stem to facil­itate new growth.

Some­times the leaves might turn a yel­lowish colour. Never fear, it just means your plant could do with some more sun. This could be because other leaves on the plant are blocking out light, in which case, feel free to remove those other leaves and do with them what you will.

If your plant is wilting, it simply means it could do with more water. And if it’s bent, try rotating the pot 180 degrees. Plants will grow towards the sun, which could be causing the bowing in the stem.

Miscellaneous Tips

Auto­matic Watering — One method for ensuring your plant always has enough water is by setting up a low main­ten­ance auto­matic watering system. You’ll need some organic rope (NOT plastic), a drill and a tray. Firstly drill two holes near the base of your pot in the side and push your rope into one side and out the other. Make sure there is plenty of slack inside the pot. The next step is to pot your plant or cutting as described above, only this time, wrap the slack from the rope around the root system of your plant before you pack it out with soil. You should now have one plant in its pot with two bits of rope hanging down from either side. Finally, place a couple of bricks, a lump of wood, or some other object into your tray and fill the tray up with water. Place your pot onto the bricks, wood, or whatever and allow the two pieces of rope to dangle into the water. This will auto­mat­ic­ally deliver enough water to the plant all the time.

Pinching — Pinching is a method to promote bush­i­ness and outward growth in your plants instead of growing too tall. At the tip of each branch, there is a section called the apical mer­istem. This is where all the new growth comes from and is respons­ible for reg­u­lating a plant hormone called indole-​​3-​​acetic acid (IAA). This hormone pro­motes the growth of the main stem and inhibits side­ways growth from nodes along the stem. If this hormone weren’t present in the plant, it would grow out­wards instead of upwards, so it follows that if you remove the apical mer­istem, this hormone will no longer be pro­duced and your plant will bush out instead of grow tall.

When your plant has reached the desired height, cutting off the top of the main stem with a clean sharp pair of scis­sors will safely stop the plant from growing taller, while max­im­ising leaf output.

Posted in Drugs | Tagged cultivation, cuttings, growing, pinching, salvia divinorum |

Animal Testing & Species Differences

Today, I thought I’d share another one of my essays I had to do recently. This one looks at animal testing, prob­lems con­cerning species dif­fer­ences and what we can do to avoid them. This essay is a little more sciency than my other one on living forever, so I’ll include the ref­er­ences this time. Here goes:

The use of non-​​human animals in the drug devel­op­ment process can attract cri­ti­cism due to the issue of species dif­fer­ences. How sig­ni­ficant is this problem and what strategies can be employed to min­imise the impact of species differences?

lab ratAnimal testing is a major tool in the drug devel­op­ment process, required by law before any new drug can enter the market. Animal models are set up to not only test the efficacy of a com­pound for its intended effect, but also to observe any poten­tial side effects, to cal­cu­late a safe dosage for humans and to check for any addic­tion poten­tial. Although animal testing is a legal require­ment, imple­mented for our own safety, it is still only a model; a sub­sti­tute for human physiology, whose results could be com­pletely erro­neous if they were derived from a poorly planned exper­i­ment. Dif­fer­ences between species are always a concern when setting up an appro­priate animal model, and a lot of time is spent agon­ising over them to ensure any results obtained are both accurate and applic­able to humans. When it comes to exper­i­mental design, species dif­fer­ences can be broadly clas­si­fied into the fol­lowing cat­egories: anatomical/​physiological dif­fer­ences, dif­fer­ences in meta­bolism and sub­sequent tox­icity, phar­ma­co­lo­gical dif­fer­ences and behaviour.

Anatomical/physiological Differences

This is perhaps the most obvious class of species dif­fer­ence. It is no good testing a drug on an animal and looking for effects that are phys­ic­ally impossible for the animal to mani­fest. Any tests carried out on one species with implic­a­tions for another must only test parts of the physiology common to both species, or identify an ana­logous symptom that cor­res­ponds to the effect you are looking for.

A prime example of this kind of dif­fer­ence crops up when invest­ig­ating the emet­o­genic poten­tial of a drug – unfor­tu­nately, evol­u­tion has not provided rats with a vomiting reflex, so an dif­ferent model would have to be devised looking for an altern­ative beha­viour or using another species with a physiology closer to ours.
chicken-anatomy

Metabolism & Toxicity Differences

Dif­ferent species also meta­bolise drugs dif­fer­ently – either via dif­ferent meta­bolic path­ways or with dif­ferent kin­etics. As such, a drug toxic to one species may have little effect on another, which is par­tic­u­larly important when trying to determine the tox­icity in humans. A drug’s LD50, the amount required to kill 50% of sub­jects in a par­tic­ular sample, is usually given in mg/​kg of body mass, scaled up from animal exper­i­ments. If a drug’s tox­icity or phar­mokin­etics are only determ­ined from one animal species and extra­pol­ated for the average human, the data would not take into account any dif­fer­ences in meta­bolism that may be present, res­ulting in poten­tially extreme inaccuracies.

For example, dogs should never be given coffee or chocolate, as they are poor meta­bol­isers of theo­bromine1, a xanthine alkaloid occur­ring nat­ur­ally in both, as well as being a meta­bolite of caf­feine. As little as 50g of chocolate can result in theo­bromine pois­oning for small dogs, while humans can meta­bolise it fast enough without issue.
Sim­il­arly, meta­bolism of NSAIDs shows a huge vari­ation across dif­ferent species. The plasma half-​​life of aspirin ranges from 1 hour in ponies up to 37 hours in cats2, due to their poor glucuronid­a­tion ability, while dogs are more sus­cept­ible to aspirin’s gastrointest­inal side effects3.

One final example would be the varying MPTP tox­icity between species. MPTP can be formed as an unin­tended byproduct in the man­u­fac­ture of MPPP, a syn­thetic opioid with great poten­tial for abuse. MPTP on its own is not harmful, but MPP+, the natural meta­bolite of MPTP, is a potent neur­o­toxin. MPP+ is pro­duced via MonoAmine Oxidase B in neuroglia and the capil­lary endothelia com­prising the blood-​​brain barrier, and results in rapid-​​onset Par­kin­so­nian symp­toms barely indis­tin­guish­able from typical Parkinson’s disease4. These symp­toms are also reduced by L-​​DOPA, a drug com­monly used in Parkinson’s disease. Rats, however, are almost entirely immune to MPTP tox­icity, most likely due to a dif­ferent level of expres­sion of MAO B5. Mice, on the other hand, do produce MPP+, but clear it from their brain in a matter of hours, unlike the primate brain, in which clear­ance can take days.

Pharmacological Differences

The chem­ical path­ways and their asso­ci­ated protein machinery will not neces­sarily be struc­tur­ally identical, or indeed act in the same way. Path­ways may be more or less complex, depending on the species, with more or less scope for mod­u­la­tion by other factors. Receptors too may also differ in struc­ture, ligand affinity and the type of G pro­teins they may couple with. All of these factors may be of huge import­ance when designing a drug with a par­tic­ular molecular target in mind.

A few inter­esting cases have res­ulted from these types of dif­fer­ences. For a while, Leptin was the­or­ised to sup­press hunger, as knockout mice that did not express leptin or its asso­ci­ated receptor got fat. Giving leptin to those that could not express it them­selves, but still pos­sessed the appro­priate receptor, caused them to lose weight6 – a poten­tial gold mine if the results were also applic­able to humans. Unfor­tu­nately, they were not. Leptin showed little effect in humans, as weight prob­lems tended to concern signal trans­duc­tion rather than a lack of leptin7, in much the same way as insulin-​​resistant diabetes.

Another, rather more serious example is that of TGN1412, a mono­clonal anti­body with not only a high affinity for the human CD28 receptor, but a strong agonist ability too. Ori­gin­ally intended to help patients with rheum­atoid arth­ritis and B cell chronic lymph­o­cytic leuk­aemia, TGN1412 was ini­tially tested on animals and an appar­ently safe dosage cal­cu­lated. Of the 6 volun­teers hos­pit­al­ised, each given a dose 500 times smaller than that given to their animal coun­ter­parts, 4 developed mul­tiple organ failure as a result of cytokine storm8. Hope­fully, this example high­lights the import­ance of species dif­fer­ence; that it is a real issue and not just a the­or­et­ical concern.

Behavioural Differences

hedgehog ballThe final cat­egory, and perhaps least obvious, is that con­cerning animal beha­viour. Unfor­tu­nately for us, animals are not able to clearly express their feel­ings, so we are left to try and inter­pret that beha­viour, which can be par­tic­u­larly dif­fi­cult. Humans seem to have an intrinsic pen­chant for anthro­po­morphism – we are always uncon­sciously trying to attribute char­ac­ter­istics that are uniquely human, such as complex emo­tions or inten­tion, onto animals and even non-​​living objects. Chil­dren are espe­cially guilty of this, smacking a rock, perhaps, as a pun­ish­ment because it tripped them up. It is only as we grow older and put in a little more thought that we realise that perhaps the rock was not to blame. With animal models, we must also put in that extra thought when it comes to inter­preting an animal’s beha­viour, instead of opting for the instinctive, human­ised interpretation.

Other prob­lems are encountered when we assume a par­tic­ular beha­viour is a result of a par­tic­ular effect. For example, in the tail flick assay, designed to measure effects on nocicep­tion, anal­gesia is asso­ci­ated with an increased latency in moving the tail away from a heat source. Approving a new drug as an anal­gesic based on only this inter­pret­a­tion could be dis­astrous if the increased tail flick latency was instead due to a loss of muscle control or paralysis.

One final thought con­cerning animal beha­viour, is that some beha­vi­oural responses may be unique to the species in ques­tion. For example, a hedgehog might curl up into a ball as a typical fear response. While this may be easy to inter­pret, other idio­syn­cratic responses may not.

Strategies

A number of strategies have been devised for com­bating the issues species dif­fer­ence brings up, ranging from simple common sense to the rather more complex. An in-​​depth know­ledge of the species under invest­ig­a­tion is a good start. Exper­i­ence and famili­arity with a par­tic­ular species will nat­ur­ally lead to a better ability to read an animal’s beha­viour, just as we become better at reading the people around us the longer we spend in their company. Someone new to animal work will be more likely to anthro­po­morphise, drawing instead from their exper­i­ence with other people, whereas someone with ample exper­i­ence could make a more accurate judge­ment. Another benefit from exper­i­ence is that any of the more subtle dif­fer­ences between that species and us is more likely to spring to mind, redu­cing the risk of some­thing important being over­looked. For example, rat models are a useful tool when studying the intest­inal bioavail­ab­ility of drugs, but are a poor choice when it comes to intest­inal meta­bolism9.

Another strategy to reduce the risks imposed by any unknown or over­looked dif­fer­ences, and one that is required by law, is to test on more than one species. Doing so greatly reduces the chances that any observed response is unique to one species in par­tic­ular, and is there­fore likely to be exhib­ited by humans too.

Although there are an incred­ible number of indi­vidual species, some pro­teins remain rel­at­ively con­served. Working with these spe­cific pro­teins that share a great deal of sim­il­arity between their human coun­ter­parts will likely lead to more reli­able results. For example, the mus­car­inic receptor family has remained much the same throughout evol­u­tion such that the human and rat receptors share a very similar agonist/​antagonist profile10. It is very likely that some­thing acting on rat mus­car­inic receptors will elicit the same response in humans, making this an accurate model.

More recently, the latest tools and tech­niques of the genetic engineer promise to make animal models even more rel­evant. Genetic manip­u­la­tion has already delivered knockout animals, not expressing par­tic­ular genes, and trans­genic animals, expressing genes belonging to another species, but in 2008 a chi­meric mouse with 90% human hep­ato­cytes (liver cells) was pro­duced11. Until now, the best tool for studying the effects of drugs on the liver would be to use actual human liver (another strategy for over­coming species dif­fer­ences is to use human cells if pos­sible), but the chi­meric mouse has already shown great poten­tial. The liver is mainly respons­ible for the phar­ma­cokin­etics of a drug, as it is the primary place that drugs are meta­bol­ised, which has sub­sequent effects on the tox­icity and efficacy of that drug. The chi­meric mouse has shown a similar phar­ma­cokin­etic profile to the human donor, as well as human-​​specific meta­bol­ites not ordin­arily found in mice, making this an excel­lent model with which to study phar­ma­cokin­etics and tox­icity. This advance­ment brings with it all the bene­fits of testing drugs on an actual human target, without any of the ethical con­sid­er­a­tions raised with human testing.

We humans are an animal species like any other, and we may have our own species-​​specific responses that are impossible to capture or anti­cipate with any animal model. It is important to remember that an animal model is just that – a model. Species dif­fer­ences will always be an issue; there are even idio­syn­cratic reac­tions to drugs within the same species, such as some humans being allergic to peni­cillin, so we can never elim­inate these dif­fer­ences com­pletely. Increasing research, aware­ness, cri­ti­cisms from the animal rights cam­paigners and new genetic tech­niques will con­tinue to help us reduce the severity of these issues until they can be reduced no further.

References

  1. Kahn CM, editor. The Merck Veter­inary Manual. 9th Ed. New Jersey: Merck & Co., Inc; 2008.
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