Hello and welcome back to SAR! I have written and rewritten this post a few times now and I think I have landed on a format I am happy with. When we talk about the impact of medicine on history its important to get the context right, and I think I have found a way to talk about our topic. So what is it? No chemical is more important to the world of medicine than Opium, okay maybe Penicillin, but today we will say its Opium. Principally an analgesic (anti-pain), the Opium Poppy allowed for humans to take away pain in great degrees and further development on the natural chemicals has opened up surgery and post-op recovery. While we tend to look at the recent Opioid Epidemic as the only issue regarding Opiates, history reveals to us a very similar precursor. Also please head over to u/jtjdp post about morphine derivatives here! She does an amazing job explaining the higher level concepts of medicinal chemistry that I just wouldn’t do justice. Alright, enough quibbling, let’s get to the good stuff.
Disclaimer: this post is not designed to be medical advice. It is merely a look at the chemistry of medications and their general effect on the body. Each person responds differently to therapy. Please talk to your doctor about starting, stopping, or changing medical treatment.

How Much do you Know About Pain?

To be alive is to feel pain, and emo sentiments aside, this is one of the biggest biological properties of the central nervous system. When you think about it, how does the body take external stimuli and allow you to recognize it? The answer is the sensory nervous system which is responsible for sensing many different types of stimuli: temperature, pressure, pain, and chemicals. These sensory neurons carry the information from the extremities and transmit it up the spinal cord into the brain for processing. From there the brain alerts you to the issue allowing you to correct whatever problem is causing the pain. Let’s take a look:
​
https://preview.redd.it/36yiuubbjw4b1.png?width=660&format=png&auto=webp&s=a8dc870ed6d879d67dce1eb126b86ba5acb9bc69

• We call these receptors Nociceptors and activation of these neurons in the periphery leads to a signal being sent towards the spinal cord. Those peripheral nerves eventually complex with the Dorsal Horn of the spinal cord and interface with the central nervous system to transfer the pain signal. This signal is then sent Ascending to the Thalamus where the pain signal is recognized and initiates a response (such as pulling your hand away from the hot stove). But that’s not the full story, the brain also sends signals back down Descending to modify the incoming signal and dampen it. Its this modifying that makes pain fade over time when you aren’t focusing on it—otherwise the brain would be overwhelmed by the repetitive signal and continuously think injury is still happening. Now let’s divide this process into its two parts, first up the Ascending pathway.

​
https://preview.redd.it/w6751owcjw4b1.png?width=896&format=png&auto=webp&s=122f8b2c615f741d848ed0171a574b1353a34038

• As the Action Potential travels from the periphery towards the Spine it causes the influx of Calcium into the Presynaptic Neuron. This neuron is what carries the original signal to then transfer into the Spine for further traveling. Eventually we reach the Synapse where the finger-nerve and spine meet and we get the transfer of information via Neurotransmitters. In this case, two chemicals are released: Glutamate and Substance P (which literally stands for Substance Pain). Glutamate will activate two receptors (AMPA and NMDA) which are Excitatory and stimulate the continuation of the pain signal up to the brain. Substance P activates the NK1 receptor which enhances the frequency of the pain signal (the throbbing) and the intensity of the pain burst. So to simplify, Glutamate allows the signal to be passed up to the brain but depending on the strength of the original pain signal more or less Substance P is released which modulates the strength and attention-grabbing nature of it. Okay great, we sent the pain pathway up and it will get processed in multiple different parts of the brain. But the brain can’t have that signal stinging it so it must send information back down to dampen that pain signal. This is where that aforementioned Descending pathway comes in. Above you can see how the blue line reaches down out of the brain and back into the spine to turn ‘off’ the signal. This is the basis of Analgesia or pain relief.

​
https://preview.redd.it/audgj8kfjw4b1.png?width=668&format=png&auto=webp&s=c3b58c520e8298e20f787d70e053948c3817c565

• Okay so now we have to divide the action of the Descending pathway which acts to dampen and modulate the original signal coming into the brain. Now, normally at rest this Descending neuron is inhibited so any fresh incoming signal is not inhibited from the get go but once that pain signal does come in, we get the good stuff! In response to pain the brain releases substances called Endorphins which activate the mu Opioid Receptor (MOR) located on the Descending pathway. Now MOR are inhibitory in nature so they are inhibiting the inhibitory resting state of neurons, or in other words, are allowing the Descending neuron to activate. And this is an important fact to recognize, Opiates do not inhibit pain, they inhibit the physiology of the nervous system that prevents modulation of the pain signal.
  • Once the inhibition is inhibited, the Descending neuron is free to release two neurotransmitters onto the nerve that was carrying the original pain signal. Both Norepinephrine and Serotonin are released to activate their respective receptors which inhibit the release of Substance P and Glutamate thus decreasing the incoming pain signal. Likewise MOR receptors are found directly on the incoming nerve and further prevent the release of Glutamate and Substance P as well as being found on the Ascending neuron preventing the activation of the NMDA/AMPA and NK1 receptors. The result: dampened incoming signal and decreased pain sense being sent to the brain.

The Stars Align in the Shape of a Poppy

​
https://preview.redd.it/nfygsi0hjw4b1.png?width=731&format=png&auto=webp&s=60c0b13cdad3d7b7b64f78d6294465f081839f61
To start our story about Opiates we need to turn to the great precursor—Opium. Opium itself is not a chemical but rather a really thick liquor (called latex) that contains a high concentration of Morphine (and some Codeine). There are 38 species of Poppy plants but only two produce Opium is great enough supply that it is worth farming them and humans have been cultivating these varieties for as long as we have known about the plants. When humans settled into Mesopotamia (near modern day Iraq), Poppies were one of the few plants grown in plots as large grain or vegetable fields (meaning that they were thought of as valuable as food). Throughout the Greek age of medicine (pre-500 BCE) through the Islamic medicinal revolution (500 BC-1500 AD), Opium was a major component of treatment, assisted suicide, and poison. In fact its through the rise of the Muslim Caliphates that we see the export of Opium to other parts of the world, especially through the Mediterranean Sea once the Crusaders return. Opium trading to the East via the silk roads was an almost continuous affair since time immemorial and Pakistan was a major growing area for the Eastern Poppy trade.

• By the time after the Crusades (11-13th centuries), we start to see the West’s fixation on Opium. For many reasons Europe didn’t develop many psychoactive plants to the same degree as more humid/hot climates like Africa, the Middle East, and India. This is why the importation of Opium (and also Marijuana) was such a trade commodity and staple in the development of Western medicine. During the Renaissance and the revival of Greek philosophy we start to see the re-fascination with Opium and by the 1600s we see merchants importing Laudanum into Europe for recreational and medicinal use. The standard use of Tincture of Opium (which is Opium dissolved in ethanol, a DEADLY combination) was a particularly favorite preparation which was prescribed to the lowest day-worker all the way up to kings.
  • The importation and use of Opium exploded in the late 1700s once the British conquered a major Poppy growing region of India. This region (western India and most of Pakistan) was originally slated to grow cotton like the American colonies but the region wasn’t wet enough to sustain the plant—it could however grow copious fields of Poppy plants to create Opium. Throughout the 18th century the British Raj became the largest exporter of Opium to Europe and after the discovery that Mercury and Arsenic may not be safe, Opium took over their duties. By 1780 almost all major remedies incorporated the use of Opium in some capacity and with the huge supply, it was incredibly cheap.

​
https://preview.redd.it/1cspu1ukjw4b1.png?width=578&format=png&auto=webp&s=4e81b6d401a1806f39592e802b0bd5ab6df9a2e8

• Poppy wasn’t only important to the British for its medicinal properties but also to bolster the huge amount of loss they were incurring in global trade to one trade partner—China. After she made contact with China in the mid-1500s, Britain starting to import HUGE amounts of tea as the Brits became literally addicted to the substance. By 1800 a full 15% of the ENTIRE British Empire’s revenue was being spent on importing tea, that’s 30 million pounds per YEAR, leading to a massive trade deficit. This means that more money was being sent to China literally enriching a foreign country while the British public was getting their fix on the black stuff. Oh and just in case you think things haven’t changed, Britain still accounts for 42.6% of the world’s tea consumption—seriously Brits, ever heard of coffee? Anyways, all this money leaving the British economy to be spent on non-Empire sustaining commodities was a major national security risk for the British. It would be different if they were importing gunpowder like the Dutch were or Silver as the Spanish had but literally they were consuming the riches they were spending the money on.
  • Remember too that the British were not in the best position by the turn of the 19th century—they had just lost their colonies in the Americas, involvement in the Napoleonic Wars killed a generation of men, and the push to develop industries over public health led to a focus on fast growth rather than smart growth. One of the results of the Napoleonic Wars was the British occupation of the Island of Java which developed a very potent Opium which was traded with Chinese merchants regularly. Soon British merchants realized they could rebalance the trade deficit by selling Javanese Opium into China but the small island was unable to produce enough Poppies to meet the demand. So Britain turned to another one of its colonies, India.

​
https://preview.redd.it/iiu2j8emjw4b1.png?width=707&format=png&auto=webp&s=d6f54a00fe47739db6545be913c186e4560195d4

• India by the end of the 1700s was a bit of a challenge. The British hold on the subcontinent was firm but they couldn’t grow the cash crops they wanted. Indian cotton was nothing compared to Egyptian or Southern American (i.e. Virginia/North Carolina/Georgia) cotton and the Indian tobacco was known for being bitter. But by the 1770s the British government realized that Poppy was an easy crop to grow and the demand across the border with China was an easy market; British traders brought their cargo to small islands off the coast of China where it was sold for silver. Initially the Chinese didn’t mind the sale of Opium in their territory—when the British traders collected the silver from the sale they would almost immediately use it to buy Chinese goods, thus driving tax revenue for the Chinese government.

​
https://preview.redd.it/andjwt0qjw4b1.png?width=644&format=png&auto=webp&s=730782fa74a65c111a62f05024445656b81f9811

• But if you buy Opium, people are going to use that Opium. By the 1810s all trade with foreigners was restricted to just one port, Canton, and slowly the city started to develop a habit for the drug. The use of mind altering substances was curtailed pretty quickly for hundreds of years in China—the Ming Dynasty banned tobacco in 1640 and the Qing banned Madak (a powdered Opium containing tobacco) was similarly banned in 1729. But by 1790 more and more Chinese citizens were becoming addicted to the substance; what started as a recreational drug slowly became a crippling addiction that took hold over Canton. For a rigid society, the crippling Opiate addiction was a moral corruption for the Qing government and forced them to curtail Opium importation in 1780 and then an outright ban in 1796.

​
https://preview.redd.it/mw9oflprjw4b1.png?width=879&format=png&auto=webp&s=5640d0bc425726fbd471b8dcf8954222afc49fc5

• Knowing just how devastating the Opium was having on the inhabitants of Canton, as well as how it spread further inland, British merchants kept peddling their drug. Older ships with larger hulls were converted into floating warehouses and parked just outside of navigable waters. Once set up, Opium smugglers would pull up, purchase the Opium and avoid any oversight by the Chinese government to prevent the sale of the drug. Following their mother country, American merchants started to sell Turkish Opium, an inferior variety, at a much cheaper rate leading to drug peddling competition with more and more tons of Opium being sent into China. This drove down the price of Opium considerably which ultimately increased the demand.
  • This demand eventually led to reversal of trade, meaning that more silver was leaving China to pay for Opium than the British were using to pay for Chinese goods. American and European traders could show up in Canton with holds full of Opium, sell it off for a profit, and then make a tidy silver profit to bring back to Europe. Likewise the importation of cheap machine-made cotton, furs, clocks, and steel into China driving down domestic profits.

Let’s Look at the Drugs a Bit

​
https://preview.redd.it/y4uwbc1tjw4b1.png?width=548&format=png&auto=webp&s=71f79278925a92ea052d1ae390a495f0496966b2
https://preview.redd.it/pf709wmujw4b1.png?width=918&format=png&auto=webp&s=91cdf3fdd56db4beb95f07f340d24bb7ef7e9cf3
Stepping away from the history a bit, let’s introduce the Family. Okay so we understand how pain is sent to the brain and how it modulates but there is so much more to the mu Opioid Receptor and that’s not the only kind of Opioid receptor that we have. The two most clinically useful receptors are the Mu and Kappa Opioid Receptors (KOR) because they result in analgesia but there is a Delta Opioid Receptor (DOR) that is worth mentioning. The majority of the Opiates that we know and love are Mu agonists but there are some very interesting Kappa agonists that are worth mentioning as well.
​
https://preview.redd.it/eg9toikwjw4b1.png?width=587&format=png&auto=webp&s=027d16b15bd7e195205513a3034eb5610ba88537

• Above is a chart that shows the binding affinities of select Opiates to the Mu receptor. The smaller the number is, the more tightly they bond. Now affinity is different than potency—potency is a measure of how much drug (in g) is required to produce the same effect. So even though morphine has a higher affinity than fentanyl, fentanyl has a MUCH more potent effect (which is why it can be so dangerous, you only need a little). Now many of the opiates cause the same effect so I want to spend more time on what makes them all so different:
• First up we have the 5-Ring Morphinians which are derived from the natural product Morphine. These structures have 5 component parts: an aromatic benzene ring (A), a completely saturated bridge ring (B), a partially unsaturated ring with an alcohol attachment (C), a piperidine heterocycle above the rest of the structure (D) and finally a ether linkage between the top and bottom of the structure to keep it fairly rigid (E). Truthfully we are only going to focus on two locations—firstly the top alcohol (red circle) can be methylated to form Codeine, a natural Prodrug of Morphine. A Prodrug is one that is biologically inactive but goes through an initial metabolism once ingested that makes it active.

​
https://preview.redd.it/hx3zwwcyjw4b1.png?width=725&format=png&auto=webp&s=bf238a61c14c183cf081da027074a3eb1a11b1f0

• In fact it’s this initial metabolism of Codeine that makes it very interesting. In order for Codeine to exert any pain relief it needs to be converted to Morphine which actually exerts the desirable properties. This is done by the liver enzyme CYP2D6 which is a pretty minor pathway for Codeine—only about 10% of the Codeine is actually converted to Morphine to have some action. Because of this 2D6 dependent pathway we have to be careful about administering drugs that might inhibit the 2D6 pathway because that would mean we are preventing codeine from being active. Drugs like Fluoxetine (Prozac) and Paroxetine (Paxil) are strong 2D6 inhibitors and so if we administered Codeine to someone taking this drug they’d never get any benefit from the Codeine. In addition there are genetic/ethnic differences that pharmacists can account for such as 2D6 activity. If you are someone with very little 2D6 activity then you would also not convert Codeine to Morphine and thus get no action from the drug—this may be a reason why some people say Codeine doesn’t work for them. Another reason could be that they are Rapid Metabolizers and quickly convert the Codeine to Morphine and thus get a massive hit quickly after ingestion—in that cause you’d need a much smaller dose than another person for the same effect.

​
https://preview.redd.it/cvbelexfkw4b1.png?width=919&format=png&auto=webp&s=ed6f1683761a69b87bd0de12834a76c1f089a31f

• A different drug that is the opposite of Codeine is Hydromorphone (Dilaudid) which has a Ketone on ring C. This ketone and the lack of the double bond on this ring increases the lipophilicity of the drug and increases its ability to penetrate into the brain and thus have a greater effect. In fact Hydromorphone is 5-10x more potent than Morphine due to its greater ability to penetrate into the brain and increased receptor affinity for the mu receptor. Because the A ring OH is not capped with a methyl group, we don’t need to rely on 2D6 to metabolize Hydromorphone into an active drug form which again increases the activity of this drug compared to Codeine.
• So combine these two structural changes—the capped OH on ring A as seen in Codeine and the increased affinity found with the ketone in Hydromorphone and we get Hydrocodone (Norco, Lorcet). Well in this case you’d get a drug that has very good affinity for the mu receptor (better than codeine) BUT is still reliant on the small 2D6 pathway for activation (worse than morphine). In this regard only about 10% of Hydrocodone is active at a time. We can see this effect in the relative doses for equivalent effect: to match the effect of 30mg of Morphine, we’d need only 7.5mg of Hydromorphone (more active) but need 200mg of Codeine (less active).

​
https://preview.redd.it/la2oqttgkw4b1.png?width=845&format=png&auto=webp&s=0155a6506a5038a6dad7987572a8eabaab75205a

• This brings us to our last drug of this class, Oxycodone which has a special OH group found on Ring B. What you’ll notice is that Oxycodone has that capped OH on ring A so it requires metabolism through 2D6 just like Codeine and Hydrocodone. When it is uncapped it becomes Oxymorphone which has 3 times as much effect as Morphine BUT that extra OH makes Oxycodone an exclusive Mu receptor agonist. Unlike the other drugs which may go to other receptors causing side effects (more on this later).

​
https://preview.redd.it/ftdg9l8jkw4b1.png?width=489&format=png&auto=webp&s=e2ceeb6172294b69574f5b929d0a218f481c7e41
https://preview.redd.it/yos35mojkw4b1.png?width=677&format=png&auto=webp&s=0e72e94694147c303defe123d88b048e6ca3369a

• Next up I want to look at some Mu opioid receptor Antagonists or those than inhibit the function of the opioid receptor. Looking at the first two drugs, Naloxone and Naltrexone, we can see that they have the structure similar to Hydromorphone so they would have incredible brain penetration and affinity for opioid receptors BUT they contain that funky Nitrogen tail. Now normally there is a short methyl tail that is required for the function of Morphine but by adding a bulkier tail the drug is able to fit inside the receptor but prevent activation. What’s most important about these two drugs is that they have much more affinity for the receptor than other opiates. We can see this effect in the graph above: when no Naloxone is present, Fentanyl occupies the opiate receptor about 75% of the time. But as soon as Naloxone is administered that number drops swiftly (within minutes)--this is because Naloxone has a higher affinity for sitting in the receptor than Fentanyl. Think of it like the bully Naloxone coming up and pushing the poor defenseless Fentanyl off the swings so the bully can play on it (except in this instance Fentanyl is causing an overdose and we need to save someone’s life).

​
https://preview.redd.it/61dx2mwokw4b1.png?width=594&format=png&auto=webp&s=4740b8395ca83304d5e0a756004b119976c621f2

• Buprenorphine is similar but it is a Partial Agonist instead of being a full antagonist. Buprenorphine is not a 5-ring Morphinian byt a 6-ring Oripavine that has a few different modifications. The biggest additions is that it has the bulky Nitrogen tail found in full Antagonists but it has this funky C ring tail which fights the antagonism. The result is a tug of war between the antagonism of the Nitrogen tail and the agonism of this new C-ring tail resulting in Partial agonism—so if you took Buprenorphine you’d notice a markedly decreased pain relieving ability but importantly there is a ceiling effect, its much harder to overdose on Buprenorphine than other full agonists. In addition in the second graph we can see that Buprenorphine has the greatest affinity for the receptor than our other agonists which prevents someone from taking a more potent opiate while taking Buprenorphine. In this case the bully is already sitting on the swing and scaring away the other kids thus preventing them from having a turn (and potentially causing an overdose). This does mean that if someone was taking a more potent drug (like Fentanyl) and then took Buprenorphine, it would cause withdrawal just like Naloxone or Naltrexone.

​
https://preview.redd.it/x9wcb8xqkw4b1.png?width=912&format=png&auto=webp&s=d09a59a927363d3864eebfd29cb05215e9f0234b

• Speaking of withdrawal, let’s take a look at how that happens. Remember that the pain signal is caused by the activation of AMPA and NMDA receptors from the peripheral nerve. AMPA is a type of receptor called a G-Protein Coupled Receptor or GPCR which in this case is linked to an Excitatory G-protein which leads to the activation of the nerve. When AMPA is activated, the G-protein (Ga) activates an enzyme called Adenylate Cyclase (AC) which increases the production of pro-activity cAMP—or in simpler terms—when AMPA is activated, it leads to an increase in levels of pro-pain molecule cAMP. The Opioid receptor is also a GPCR but it is linked to an inhibitory G-protein which prevents the action of Adenylate Cyclase and thus leads to a decrease in cAMP levels. So Opiates prevent pro-pain cAMP signaling from continuing.
  • In the second graph we can see how tolerance forms. Initially (A), Adenylate Cyclase and cAMP levels are not affected by having opiates even though their ability to push along the pain signal is blocked. After a few hours, the leftover cAMP is degraded and cAMP levels start to drop significantly (B). In response to these levels going down, the activity of Adenylate Cyclase starts to increase and increase (C) which raises the level of cAMP. This rise in Adenylate Cyclase activity opposes the action of the opiate which necessitates the need for increased doses of Opiates and is why tolerance forms. As sustained inhibition of Adenylate Cyclase continues, the body upregulates Adenylate Cyclase activity to create more cAMP and to combat this we increase the dose.
  • Now what if after years of taking an Opiate we suddenly administer Naloxone, an Opiate antagonist. Well after weeks to months of taking an Opiate, the level of Adenylate Cyclase activity is WAY above baseline. When you administer the antagonist, suddenly Adenylate Cyclase is able to produce a TON of cAMP that normally is blocked which leads to a MASSIVE amount of downstream signaling. The result is intense nausea and vomiting, stomach cramps, fever, anxiety, insomnia, and cravings. Thankfully the withdrawal process ends after about 72 hours but is one of the worst experiences someone can go through which is why proper down-tapering of Opiates is extremely important.

A Change in Trade Policy

​
https://preview.redd.it/bb4eb0ltkw4b1.png?width=628&format=png&auto=webp&s=321048bd5d5edf8877aede887c3fcb7aa387a0e4
Oh, you’re still here. Neat! So by the 1820s the Qing dynasty was running into many problems regarding Opium. Firstly they needed the Opium taxes to fund their efforts to put down the White Lotus Rebellion and retain power. But after almost 30 years of trade the effects on Chinese communities could not be ignored along with local officials operating under the imperial trade department, the Hong, profiting from bribes to allow Opium. Regardless of initial efforts things were getting out of hand for the Qing government. In 1800, about 4000 chests of Opium or 560,000 pounds entered the country but by 1830 that number exploded to 20,000 chests or about 3 million pounds. But more than the amount of Opium actually entering the country was the incessant rudeness of the British government to open trade.

• One of the “problems” for the British traders was how clamped down trade was with China. By 1800 all trade was limited to just Canton and the Hong was a strict master of trade. Foreigners were not allowed to appeal decisions made by the Hong and only Chinese traders could sell goods further inland than Canton. Traders chafed against this extreme oversight and sent hundreds of letters to the Hong requesting special dispensations which were summarily denied. Things changed significantly in 1834 when the Chinese trade was de-monopolized away from the East India Company allowing any private trader to get involved in the Eastern trade.

​
https://preview.redd.it/cvbkq7vukw4b1.png?width=669&format=png&auto=webp&s=9340d153989a2f8c32a72792554f86be77e1f4eb

• In August of 1834, the British sent Lord William John Napier to Macau as superintendent of Chinese trade with the explicit order to follow all Chinese regulations. Thinking he knows best, Napier decided that the restrictive Chinese trade system was too restrictive and sent a letter to the Viceroy of Canton. This was unheard of—NO foreign traders were allowed to speak directly with Chinese officials and the Viceroy refused to accept it. So why not double down by ordering two British ships to BOMBARD two Pearl River forts as a show of force? Luckily Napier died of Typhus almost directly after else it would have resulted in a full blown war.
• In 1839 the Qing government appointed Lin Zexu as the Opium czar to completely eradicate the Opium trade from China. Lin banned the sale of Opium in China completely, set up rehabilitation centers for those affected by the drug, and put addicts to work to distract them while detoxing. Lin demanded that all Opium supplies must be surrendered to Qing authorities and any Chinese citizen disobeying the order would be punishable by death. He even went as far as closing the Pearl River Channel, trapping British traders in Canton and seizing their Opium warehouse stockpiles.
• The replacement for Napier was Admiral Sir Charles Elliot who protested the seizure of the Opium stockpile but knew that they could do nothing. He ordered all Opium ships to flee and prepare for battle which caused Lin Zexu to beseige a group of traders inside a Canton warehouse. Elliot convinced the traders to cooperate with the Chinese government and surrender their stock, saying that the British government would compensate for the lost Opium (which he had no authority to do). During April and May 1839 the British (and American) traders to surrender 20,000 chests of Opium which was burned for three days outside Canton. Following the burning, trade resumed to normal except no more Opium was allowed. Like many other instances of the government removing legitimate sale of a drug, the black market increased markedly.
• In July 1839 a new scandal rocked the British-Chinese trade system; two British sailors became drunk and beat a man death outside of his village. In response, Superintendent Elliot arrested the two men and paid compensation to the villager’s family for the loss of the man but Elliot refused to hand over the sailors to the Qing government. Lin Zexu saw this as a blatant disregard for Chinese law—afterall traders needed to understand that they can’t just come to China and violate Chinese law as they saw fit. Elliot offered to hold a trial on a British ship in front of Chinese officials to show that the men would not get off free. This incident would start the smoldering.
  • On September 4th, Elliot sent two ships to Kowloon to buy food and provisions from Chinese peasants. While approaching the harbor, three Chinese war junks gave permission to the two British ships to trade but that permission was rescinded by the commander of Kowloon fort. Elliot fumed against the slight and said that if the British were not allowed to trade by 3pm, he would fire on the fort. 3pm passed and the British opened fire on the fort causing the Chinese junks to return fire. The fighting continued for 7 hours until nightfall and Elliot had to prevent the British officers from pressing the attack, thus ending the Battle of Kowloon. Having driven off the Chinese ships, the British purchased the supplies they needed while the Kowloon commander claimed that both ships were sunk and 50 British sailors killed.
  • The reaction in Britain was about as much as you expect. Prime Minister Palmerston sent out letters to the Governor General of India to prepare marines to invade China and another letter to the Chinese Emperor telling him that Britain would send a military force. He sent a letter to Superintendent Elliot to set up a blockade on the Pearl River and capture Chusan Island. He also instructed Elliot to accomplish the following objectives:
    • Demand the respect as a British envoy from the Qing Government.
    • Secure the right for British law to be doled out on British subjects
    • Get recompense for destroyed British property, especially the illegal drugs that they destroyed
    • And most important, End the Canton System thus opening up China to free trade for the first time, ever.

Alright this is where we will leave things off for now, on the brink of war with China. Stay tuned!

Howdy Arena goers! Once again it is I, Vixin, the guy who will play Mono Black decks against all reason and probably to his own detriment.
​
Since the bannings and the new season I've taken a break from ladder. With my finish from last month I definitely feel a lot less pressure to actually climb, so instead I've been grinding Traditional Standard events (hereafter referred to as leagues) in order to build my collection and get my daily games in. I've included some screenshots below, but I've played about 20 leagues and 100 matches with this deck and maintained about a 72% win rate overall. I got a lot of comments on my last post asking for an updated list since the bannings so I figured I'd share. With that in mind, let's get the list and talk about some cards!
​
A note on leagues: I am well aware of the difference in competitive level between leagues and ladder, especially higher up on ladder. That being said, more often than not I faced meta in the leagues and can definitely speak to meta matchups and play patterns. In addition, I also gained the insight that this deck is very strong against rogue matchups. You have a lot of different interaction and flexibility to be ready for anything, which can definitely translate to ladder performance.
​

The List:

​
Creatures (16):
4x Evolved Sleeper
2x Ayara's Oathsworn
4x Tenacious Underdog
3x Sheoldred, the Apocalypse
2x Sheoldred
3x Phyrexian Fleshgorger
​
Non-Creature Spells (18):
3x Cut Down
2x Go for the Throat
3x Sheoldred's Edict
4x Liliana of the Veil
3x Sorin the Mirthless
1x Invasion of Fiora
​
Lands (26)
23x Swamp
1x Takenua, Abandoned Mire
2x Mirrex
​
Sideboard (15):
1x Cut Down
2x Go for the Throat
2x Glistening Deluge
2x Graveyard Trespasser
4x Duress
1x Invasion of Fiora
3x Breach the Multiverse

Interlude: A Farewell to Fallen Brothers

​
Some of you may notice that there are several cards missing from the list that I talked way, way up in my last post: Jadar, Fell Stinger, and Concealing Curtains. Unfortunately, the context of the format completely changed with the bannings, and these cards are no longer as well-positioned as they previously were. There were a lot of incidental values and synergies between these cards and both Invoke Despair and Reckoner Bankbuster, as well as the fact that they're a lot stronger in a format dominated by slow, grindy Rakdos than in the much more open field we're facing today. It very well may be possible these cards will see play again, but for now, in the current format, they're just not optimal. No one is more disappointed than I.
​

Deck Overview

​
The name of the game is efficient threats, value generation, and disruption--and we've got it all. This deck can curve out, it can play the grind game, it can disrupt those pesky combo decks. With the loss of Invoke and Bankbuster this deck definitely leans a little more aggressive, but it's still at its heart a midrange deck. Get a couple of good threats out there, get your planeswalkers ticking up, and outlast everyone on your way to the top. The biggest deal in this deck is managing what you're spending your mana on. You have a lot of sinks in this deck, and making sure you weave in Sleeper activations and get in damage with Underdog when it's the right time to do so is a skill you're going to need to perfect, or else you may find yourself with no cards, too much mana, and you're staring down an Atraxa on field and another in hand.
​
​

Individual Card Choices

​
Evolved Sleeper
I have a love/hate relationship with this card. Every time I play it, I wish it was something else, but every time I go back to the collection and scroll through all of the cards in Standard I have to come to terms with the fact that, while it does everything in a very cumbersome manner, this card does a lot. Early damage, mana sink, value generation, stonewall defender, this card is so darn flexible that it's essentially unreplaceable. This card is a solid 1 drop, 2 drop, 4 drop, and 7 drop, since those are the breakpoints of all the different ways you can spend your mana on it at once. However, if you play it on turn 1, that ALSO means it's a solid 3 and 6 drop. If you count those numbers, that means Evolved Sleeper can fit in essentially anywhere on your curve, and it is very, very difficult to replace that kind of flexibility.
There's something to be said of knowing when to dump mana into sleeper when to just leave it alone like a ticking time bomb. It's hard to explain in text which is the correct move in which situation. Gaining a sense of the right time to evolve your boy is both difficult and necessary.
​
Tenacious Underdog
Another love/hate relationship for me. Underdog's just a simple, easy guy. He's above rate, he comes back, he draws you cards, he gets in damage, he keeps on punching. Another example of a hyper-flexible threat that is difficult to replace. With the need to be both aggressive and grindy (since you can't predict what you'll face on ladder or in leagues), Underdog just does it slightly better than other options.
​
Ayara's Oathsworn
This is a flex slot that I wanted to try a new card in, and it's doing alright so far. In many ways, the Menace on this creature is a lot more important than the scaling. Being able to attack around big blockers to either get in damage or hit Planeswalkers (very important!) is a surprisingly big deal. Even then, the scaling is pretty good. This thing can get very big very quickly and makes your opponent have to decide which time bomb of a creature they want to spend their removal on, and we are VERY happy to put our opponents in difficult positions. That being said, this could easily be something else.
​
Liliana of the Veil
Hoo boy. HOOOOOOOOOOOOOOOOOOOO boy. This card is nuts. This card is fantastic. You wanna talk flexibility? Liliana has your back. Removal with a threat attached, disruption and pressure against control and ramp opponents, Liliana is good in basically every matchup. Playing her in the ramp/control matchup turns the game into a question of "can your opponent afford to get rid of your Liliana?", to which the answer is often "no, not really". Curving Sleeper into Underdog/Ayara into Liliana means your opponent is going to have to look long and hard at their hand and figure out what they value more: their life total, or their ability to play the game. If they remove your creatures with Ossify or Binding, you'll rip their hand apart and blow up their lands. If they get rid of Liliana, you bash their face in. Liliana is such a scary card for your opponent to deal with, even in the hard aggro matchups. If you can have Liliana and another removal spell or two, you'll stonewall their early aggression and start to deprive them of precious resources. An absolute champion of a card, earning her voice line the prized position at the top of this post.
​
Sorin the Mirthless
This is our flex slot at 4--it's either this or Phyrexian Obliterator. I started seeing way more hard control (Esper / Azorius) later on so I chose Sorin, but either choice is justifiable. In Sorin's favor, he's once again a flexible, value-oriented guy. He can provide blockers, cards, whatever you need to stay in the game against a variety of opponents. By no means is he as strong as Liliana, not by a long shot, but he's good enough to earn a slot when the context of the format is right.
​
Invasion of Fiora
Sometimes you just gotta blow everything up. Like the 1-of Farewell in a lot of Mono W lists, Fiora provides a panic button available to you, and you have enough dig to be able to find it. Wiping the board comes up a surprising amount--you have few ways of answering a Herd Migration or multiple Wedding Announcements otherwise. And, very occasionally, you get to flip this thing, and Marchesa is pretty good!
​
Duress
It's a very close toss up between Duress and Pilfer in the side. Duress is better against a wider swath of matchups, but Pilfer is better against specifically the ramp decks (knocking out an Atraxa, Archangel, or Etali is super good). For now Duress is good enough against Ramp and great against everything else, so we run it over Pilfer, but it's very close.
​
26 Lands
This is the new normal, folks. You NEED to hit your land drops, and given the variety of mana sinks in your deck we're happy to flood. Pump up those sleepers, weave in those underdogs, we're happy to be able to play our cards.
​
Honorable Mentions:
Gix, Yawgmoth Praetor - Once again, our praetor boy is pretty good but didn't seem to quite be doing enough the times I played him. If he went off, it was usually because we were already winning, and he doesn't do enough from behind.
​
Phyrexian Obliterator - This guy is a WALL, so if you're seeing more aggro in your format (Soldiers, Legends, ESPECIALLY Mono Red), slot this guy in instead of Sorin and start sweeping up the silly aggro players.
​
Breach the Multiverse - No longer a main deck worthy card, Breach now belongs in the sideboard. It's powerful, absolutely, but you can no longer expect to make it to turn 7 against a random opponent. Bring this in against Ramp, planeswalker control, and other midrange matchups.
​
​

Matchup Discussion

​
5 Color Ramp - Even
The new boogeyman of the format, winning your first match or two in a league essentially guarantees you're going to see a bunch of tri-color lands and Atraxa further on. What's the gameplan? Liliana, that's what. Try and present an early clock with a backup Liliana, requiring them to have drawn a lot of removal (meaning they'll have to topdeck their threats) or else you'll rip their hand apart. Side in Breaches (to pretend we're the ramp deck), PilfeDuress, and an extra Invasion over removal and Sorin / MOM Sheoldred.
​
Esper Legends - Slightly Favored
I haven't seen this deck anywhere near as much as I thought I would, but we seem to have a pretty good time against it. There's been a trend overall away from Thalia which is great for us--curving a Cut Down or Throat into a Liliana on their Raffine turn is pretty strong. Deluge isn't as good out of the side, but with fewer Thalias running around Invasion of Fiora is more viable. Side out Ayara's Oathsworn and Sorin for a bit more removal.
​
Esper / Azorius Control - Even / Slightly Favored
The control matchup is super skill based, as your prime avenue for victory is identifying the windows between their counterspells to slam a threat. Both Sleeper and Underdog pull double duty as dual value generators/threats so they can get you a lot of resources over the course of the game--don't be afraid to just Underdog, hit for three, and pass! Your planeswalkers are great in this matchup, especially Liliana, just make sure you have a solid chance of landing them on the board before you go to play 'em--if your opponent left up two mana, don't just slam the Liliana into their Make Disappear. Side in some combination of Trespassers, Breaches, and Duress / Pilfer over removal, MOM Sheoldred (though try to keep some planeswalker sacrifice around), and Ayara's Oathsworn on the draw.
​
Azorius Soldiers - Unfavored
Golly I hate this deck. They have an intense ability to flood the board and get around blockers, so you're going to have to rely heavily on your sweepers in the side. Problem is, they can grow bigger than your Deluges SUPER quickly, meaning you have to time it just right. Some of these decks have been slotting in the 3/4 with the spell-cancelling ability that makes soldiers when it attacks, and that thing doesn't die to Deluge OR Cut Down. Tricky matchup, luckily we don't see it that much. Side in sweepers and removal for Sorin and Oathsworn.
​
Mono White and Orzhov Midrange - Even / Slightly Favored
The only truly dangerous card in this matchup is Wedding Announcement. If you don't have an established clock or a leveled-up Sleeper out before they drop that, they can swarm you pretty quick. The tokens also nullify Liliana's sacrifice ability somewhat, so this is actually the only matchup we tend to side her out in. The upside of all the tokens is MOM Sheoldred almost always snipes their planeswalkers in the backrow, so not playing into their Wandering Emperor turn and responding with a Sheoldred is a solid swing. They only tend to run one Loran so flipping Sheoldred is a solid win-con, and their Planeswalkers are great for Breaching. The Orzhov variant is a bit trickier since they have Breaches too, but it's essentially the same thing. Side in sweepers, Breach, and Duress for Liliana, creature-spot removal, and some Underdogs (exile based removal means this guy doesn't come around often).
​
Selesnya Enchantments - Even / Slightly Favored
This is another deck that I thought was going to be big and haven't really seen. Enchantments in general is a bit harder to deal with now that Invoke is banned, but we can usually control the board enough to the point of just winning in the value game. The real dangers are Wedding Announcement (again) and Katilda's flying, so try to keep track of if you have a plan for a giant flyer and you should be fine. Side in sweepers and spot removal for Sorin, Oathsworn, and an Underdog or two.
​
​

Closing Thoughts

Mono-Black had to adapt and evolve to match the sudden shift in the meta, but it still have a wide variety of efficient, valuable threats to take over a game. The flexibility and consistent mana base coupled with value and disruption is a big draw to the color combination (plus you get to flex on aggro decks with your 4 black symbol monster of an Obliterator). Try it out and let me know what you think. Hopefully, later in the month, I'll be speaking to you from high mythic again!
​
​
​
https://preview.redd.it/hqejz8ukuv4b1.png?width=952&format=png&auto=webp&s=7fb4f6a6bac61624d49a4028d5e73f033c92868f
https://preview.redd.it/9ass3ocfuv4b1.png?width=1907&format=png&auto=webp&s=81c79605a9e7474fc266cfcec7b0d085a929e155

- Hey everyone, my name is Joon and I am a GrandmasteChallenger player on the NA server. I also achieved the Master rank in 100 games on the Korean server. I currently have 5 accounts in 5 roles in MasteGM Elo and I constantly play Solo Q to keep up with meta changes (No Season 3-High Elo-washed up player coaching here 😉). I am also a CLOL collegiate coach for Ryerson University-TMU and verified both on Pro Guides (https://www.proguides.com/coach/joon) and the League Coaching subreddit.
Why Choose Me?
- More than anything I am very proud of the work and progress that I have achieved with all of my students over the course of years of coaching. I would encourage you, my potential new students, to have a look at the student progress page on my server, where many of my students post frequently showing the tremendous progress that they have made since they started coaching with me (https://discord.gg/SUrJuazdBz). My approach to each student is individual and I can quickly identify your strengths and weaknesses. Unlike many other coaches, my goal is not to push you to play my playstyle or my champions but to highlight YOUR strengths in your gameplay and minimize any weaknesses you might have.
Pricing
- Each coaching session takes 1 hour and costs $30 per session.
Do you offer bundles and plans?
- Absolutely, I include a FREE 1-HOUR session for a bundle of 5 sessions. (5 Hours + 1 Free)
Is there a trial session?
- Yes, a trial session lasts around 15 minutes, in which I will review and analyze your OP.GG and watch one of your recent VODs of choice. During the trial session, I will focus on the common fundamental mistakes that you often make as well as point out some windows of opportunities that you tend to miss.
Rank Proof
Unlike many other "High Elo" coaches out there with no proof or accounts dating back to Season 6 or other prehistoric times when the game was completely different, I grind Solo Q on multiple high elo accounts and servers constantly while reaching top GM+ ranks on every lane from top to bot on different servers (NA, EUW, KR) every season. In the last 2 seasons, I have climbed to Grandmaster + in every role. Accounts are posted on my discord for proof with screenshots and have my students added on my accounts as they tend to refer to my games for their own improvement.
Grandmaster
Challenger
Pro Guides Reviews
https://preview.redd.it/y2t042i2jv4b1.png?width=1094&format=png&auto=webp&s=74cd047816a8a465e6793303a938a9559f56f315
Grandmaster
Rank 4 Rumble 64% winrate on champion and 60% winrate overall Grandmaster
https://discord.gg/kB25pSwMEM - My accounts posted on my server
What can I expect from the sessions?
- A Session's format will depend on what you and I both believe would be a better fit for you based on your learning style (practical, theoretical, observing, etc.) and will consist of:

• VOD Review
• 1v1 Custom Practice (to apply the theoretical knowledge of mechanics, wave management, trading patterns, recall timers, solo kills etc.)
• Co-Piloted Live Game
• Champion-Specific Coaching
• Duo game with Commentary
• You can expect Guaranteed Improvement in every aspect of the game such as trading, jungle pathing and ganking routes, wave management, objective control, team fighting, split pushing, increasing your lead, mid and late-game macros, etc.
• No longer will you run around the map cluelessly after the laning phase is over and question yourself on your next move, you will have ALL YOUR QUESTIONS ANSWERED.
• Ever wondered how smurfs can 1v9 games in your elo? You will learn how to gain and how to push your advantages like a smurf focusing on resource accumulation and keeping your in-game tempo high and close-out games early as well as how to come back from unwinnable games.

- Your dedication to improving combined with the knowledge I can provide you will result in the growth of Divisions and even Tiers.
❗This is an example of a Full Coaching Session with me: https://www.twitch.tv/videos/1257158400
Recent Achievements:
My recent students climbed from

• Diamond 2 to Master 190 LP in 2 Sessions (MID) (Updated 300 LP)
• Master 50 LP to 800 LP Challenger (MID)
• Diamond 3 to Master 250 LP 3 Sessions (ADC)
• Diamond 1 to Master 10 LP 1 Session (ADC) (Updated 200 LP)
• Diamond 3 to Master 100 LP (JG) (Updated 300 LP)
• Platinum 3 to Master 200 LP (Jungle, Mid, Top)
• Gold 3 to Master 300 LP (Top Renekton, Fiora)
• Platinum 3 to Diamond 3 in 3 sessions and 3 weeks (JG)
• Gold 3 to Diamond 4 in 5 sessions
• Iron 2 to Gold 3 in 6 sessions (Mid, Jungle)
• Bronze 4 to Silver 1 in 1 month (ADC)
• Platinum 4 to Platinum 1 in 3 weeks (Renekton) (Updated Diamond 2)
• Diamond 2 to Grandmaster 480 LP in 2 sessions! (TOP Riven Updated 600 LP)
• Platinum 1 to Diamond 1 in 3 weeks (ADC)
• Silver 2 to Plat 3 in 3 weeks (TOP) (Updated Diamond 1!)
• Silver 4 to Plat 4 in 1.5 months (MID)
• Gold 4 to Plat 4 in 3 sessions (MID) (UPDATE - PLAT 2!)
• Silver 1 to Diamond 4 in 2 months (JG)
• Diamond 2 to Master in 5 sessions (MID)
• Platinum 1 to Diamond 2 in 4 sessions (SUPP)
• Gold 1 to Plat 3 in 1 Session (ADC)
• Platinum 4 to Diamond 4 (ADC) and many more

Recent Students reaching Grandmaster from Diamond 2 and Diamond 1 from Platinum 3
Master for Top and ADC students (NA and EUW)
All of these achievements and more you can see posted by my students in my Discord Group (https://discord.gg/SUrJuazdBz)
- Imgur links to students' progress (Names Blurred for Privacy): https://imgur.com/gallery/Supm2J1-
Availability
- I am available practically 16-17 hours a day as I am a full-time League of Legends Coach
- Session lasts for 1 hour and the price is $30 per session
- COACHING ON ALL SERVERS AND TIME ZONES
- BUNDLE TAKE 5 SESSIONS + 1 HOUR Session Free
- FIRST SESSION IS FREE (15 mins)
Contact Details
My Discord is Joon#7556
DISCORD SERVER: https://discord.gg/uhvrcH5yYS
Proguides Review Page: https://www.proguides.com/coach/joon
VOUCH POST: https://www.reddit.com/LeagueCoaching/comments/nkx9td/vouch_post_for_joons_coaching