The Isolation of Natural Products: Morphine and Other Alkaloids

In the early 19th century, we were still in the habit of searching for plants with medicinal properties. But we were finally beginning to develop the capacity to identify active ingredients within those plants, isolate them, and purify them, such that they could be administered in the form of pills and powders. The class of molecules that initiated this sea change was alkaloids, the most notable of which was morphine. How did we identify morphine and ascertain its properties? Once isolated, how was it tested? It's actually a pretty crazy tale, so pull up a chair and have a listen!
Script by Vittorio Farina
Animation by Cyrene Domogalla: cyrenedomogalla.myportfolio.com/
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[@soonycaesaer8728]

Can't belive we are getting this for free

[@higorjr4101]

This guy is amazing and insane haha

[@blindwatchmaker2345]

i had to pay for my heroin and opioids 😒😒😁

[@iridiumFalcon]

I get my morphine freee

[@winstonjamir143]

not sure if anyone gives a shit but if you guys are stoned like me during the covid times you can stream pretty much all of the new series on InstaFlixxer. I've been streaming with my gf for the last couple of months xD

[@maxwellonyx9559]

@Winston Jamir definitely, I have been using InstaFlixxer for months myself =)

[@johnwong8146]

This was an incredible amount of interesting information packed in about 13 minutes. You are amazing. Thank you for making this!

[@chillazchillazius7634]

It looks like as if you put way more effort into the visual storytelling part in this one. I like that approach very much.

[@ProfessorDaveExplains]

That's because I've got a pro animator working on this series!

[@chillazchillazius7634]

@@ProfessorDaveExplains very nice work! I work in Motiongraphics and 3D Animation and I know how much work that is. He or she is doing a great job and you should keep doing it that way if you can in my opinion!

[@cyrenedomogalla5127]

@@chillazchillazius7634 thanks!

[@user-in8bz3kd7d]

​@@ProfessorDaveExplainsBrother, you are a genius, have you ever made oxytocin? I'm very curious about this, how is it extracted from the ergot fungus, I really want to extract it myself, can you teach me?

[@Felixkeeg]

Merck definitely deserves an episode for himself. The guy had isolated and characterized over 800 pure(!) compounds, which were up for sale at any time. And that was the mid 1800s

[@saturn1returns]

MDMA came from Merck too.

[@GazB85]

@@saturn1returns Not the original guy but the company did create it during WW1.

[@earlj9888]

@@GazB85 who was? Interesting stuff

[@earlj9888]

That old? MDMA

[@yessure5792]

what a legend!

[@truescotsman4103]

morphine is an amazing drug i have decades of experience using this drug to survive. i have somatoform disorder with chronic pain and about every 6-8 months i need a tiny dose to correct some imbalance in my endorphine system. after i take 2mg per day for about 5-7 days i still haven't developed a dependence and its job is done. my homeostasis returns and im able to cope and eat and go to work without constant multiple attacks of extreme abdominal pain requiring me to be in bed for anywhere from 4hrs to 2 weeks. the cycle repeats itself so im assuming im depleting my bodies own endorphins and somehow morphine stimulates my body to return to balance after i stop using it. im seeing the dr next week to discuss this effect. i have a feeling that my problem stems from taking 90mg a day of morhphine for about 9 years. changes occurred that are permanent.

[@thomasneal9291]

interesting. thanks.

[@christinearmington]

Very interesting. Thank you.

[@Cbd_7ohm]

Absolutely. The drug war is the biggest farce.

[@GazB85]

Your body can replace endogenous opioids, it's tolerance to exogenous mu agonist opioids that are the problem.

[@GazB85]

@@2nostromo You think it tastes disgusting? I think it's bitter, spicy and kinda grassy cause of the chlorophyll. Unfortunately it isn't a cure for your IBS, it just treats the symptoms. When you say 'addicted' do you mean dependent? Cause even doctor's get dependence and addiction wrong. Dependence ie where your body needs the substance and will go into withdrawal without it. Addiction is where you constantly increase the dose chasing the euphoria.

[@santicruz4012]

This is my favourite series in your channel!

[@soilmanted]

Although Friedrick Serturner later became a pharmacist, when he published about isolating morphine from Papaver somniferum, he was a pharmacists assistant. He did not have enough education to become a pharmacist. There was little to believe he ever would. However once he published, he gained a degree of fame which allowed him to pursue a further education, and eventually he became a pharmacist. Recent archeological evidence suggests that Papaver somniferum was one of the first plants cultivated, at the dawn of agriculture, about 8000 years ago.

[@franknblunt]

Papaver somniferum, enuff said😁pleasant dreams

[@tess7656]

Fuckin druggo 😂

[@beerpigs9764]

I cant get over how good these videos are such a dope playlist i definitely am gonna check out microbiology next

[@10000daddy]

Excellent job! This video must have taken a lot of work and time. I was reading about the morphine rule recently and this video has taught me new things.

[@xavierperez6739]

Excellent video, thank you for making these videos! It’s very thorough and I can’t tell you how appreciated that is.

[@ronokplays]

Especially the opening, amazing stuff man

[@Gman_4041]

Such quality content. We love you professor Dave!

[@brittanyjacobson5199]

Wonderful, very excited to be getting more in this series.

[@topiasr628]

Very facilitating! Also 👋 distant relative

[@AbhinavSingh04]

Congratulations for 1.2 million subscribers 🥳

[@vishnuprakashbharadwaj3211]

Hey! Professor Dave, could you make a video on metallurgical processes and isolation of metals?

[@toxikspeaks3523]

Yus! I'm here for it! Pleeaaaseee daaavvveee

[@mitch3384]

I worked in a copper smelter for a number of years, taking molten matte and refining it in a Pierce-Smith Converter from around 50% purity to about 90%. Also ran the anode furnace for a while, which takes copper from 90% to about 99%. If you're interested in that side of it, ask away. Super fun job if you don't mind hard work and heat.

[@RicoCreations]

Great way to present the field in a lay friendly level 👍🏼👍🏼Two thumbs up!

[@geraldomedrano5558]

Awesome video!!! Thank you for the lesson

[@davidhalliday616]

What a phenomenal video, great job

[@CJay-xq7dh]

You’ve gained me as a sub, what a great, informative video on this topic

[@dominiquedoeslife]

The fact that you used the term "complex dependency patterns" instead of misusing the word "addiction" tells me that you're both knowledgeable and unbiased. I just subscribed. Psychopharmacology was one of my areas of focus when I went to school for my psychology degree. Your channel is as informative and interesting as any of the classes I took at the private university I attended. (Edited and reposted this, because I'm a grammar nazi and I had made a spelling error in my original comment)🤦🏻‍♀️

[@grantflippin7808]

"Complex dependency patterns" sounds like something an addict would say to excuse their behavior...

[@hankhill3365]

@@grantflippin7808 both u are right tbh

[@BushyHairedStranger]

@@grantflippin7808 Heroin is awesome. You’re just afraid to try it because you’re already a slave to your ego. That said & known, if you ever tried Heroin, in place of talking shit about those who have, you’d know the power & the glory of the almighty King of Drugs! Smack City would make you slave numero uno!

[@grantflippin7808]

@@BushyHairedStranger imagine being addicted to hydrocodone (big pharma heroine) for your entire time at high-school. It only ended when my stash was stolen during a break in and had to experience the worst pain I have ever experienced from the withdrawal.

[@backstreetfan2887]

thank you for doing these

[@VerasakSahachaisaree]

Superb lecture, Prof. Dave. Thank so much.

[@avael2451]

Would be awesome to see this series continued into the 20th century by discussing the development of antibiotics and hormone drugs as well as their semisyntheses :D

[@ProfessorDaveExplains]

That's where it's headed!

[@catdurrant5694]

First channel that I have subscribed to in the first 10 seconds, purely based on the intro! Bring the science!

[@UNIRockLIVE]

Learning more with every upload

[@-azerima5039]

This video is so well made. I think a better title would help it loads.

[@michielvandemeent4454]

Great vid. One point however; the image at 1:50 shows eight structures, only two of which are actually alkaloids...

[@earlj9888]

Thank you for the information. The simple brakedown

[@DemDoolies]

Sure this dude was super irresponsible with his experiment, but I gotta give him credit for taking the morphine himself!

[@masterzoroark6664]

Well, yeah- gotta have balls to participate in your own experiment.

[@GazB85]

1.5 grains is 96mg Orally for a first timer at a recreational (Somnolent/Nodding.) dose it's only 20mg of morphine. So they would of all been fucked, unless Serturner had a tolerance, which I assume he did. The kid's could have too, considering how common laudanum (Opium Tincture) was back then and everything it was used for.

[@tinafoster8665]

@@GazB85 yes but the vinegar afterwards undoubtedly gave them a hangover which was really What affected them, the guy was super irresponsible with his experiment for not starting with just dried laudanum, n taking the same equivalent, say 30 mg of his dried laudanum to 30 mg of his morphine isolate, and give them to people who are actually suffering from diarrhea which is a lot of what laudanum was expected to do, to just give people opium extract without having any of the medical conditions which people took them for, it seems a little irresponsible for a pharmaceutical chemist LOL

[@HauntedHarmonics]

@@tinafoster8665 self administration was and is a huge part of medicinal chemistry, and without the self-experiments of chemists like Shulgin we’d likely still be decades behind in the field of chemistry that being said, yeah, it’s important to titrate doses up slowly. just giving yourself and 3 teenagers 50mg of mystery powder and seeing what happens probably isn’t the smartest move lol

[@BushyHairedStranger]

@@HauntedHarmonics you need to take into consideration the century this was work was happening, context applies to actions conducted. Albert Hofmann is responsible for one of the most important discoveries in World history. His work with Ergot Alkaloids is unprecedented and few Organic Chemists have surpassed his discoveries.

[@denguevirus135]

Waiting for the next video on this series

[@DakuHonoo]

woah i watched this due to a meme conversation about morphine and found such quality content, i'm subscribing, video's both informative and very well visually composed

[@SirElbert]

Thank you Prof. Dave

[@Guidus125]

fantastic video!

[@sydneyhunt6681]

Amazing and to the point wish more open spoken words to come 😁

[@godara2op566]

Thanks man I was feeling less motivated to study science as the science we study is too abstract. Problem solving is more prioritised than communication with the subject. Regards

[@zyern2822]

Seriously.

[@GazB85]

How did Serturner 'enrol' the animals? I like how he got the local kids involved. "Hey kid's, wanna try some pure morphine?"

[@BushyHairedStranger]

Sandoz Pharmaceutical(Novartis) made monumental strides in Alkaloid research. Specifically work with Ergotamines.

[@chris73brown]

Awesome. Thx for this

[@HitmanR97]

Dude, nice video!

[@brannonmcclure6970]

That is so informative. I am wondering about narcotics as well. Could we find other substances to medicinal interest? The night is short… .

[@lsd25records]

awesome video ... thanks.

[@thekeymaker-ey5rk]

Amzing doco 👏👏👏

[@AL4M1]

Great video !

[@choosen1130]

As a pharmacy student I really find this interesting

[@thomasrodriguez9864]

Randomly suggested video. I like it.

[@studybuddy9442]

He knows a lot about science stuff professor dave explains 😘

[@nathanielf48]

Very interesting although the poppy blowing in the wind is not an opium poppy

[@Talkwithtina808]

Omg, I'm in Mexico and just met a couple that was talking about this same thing.

[@dredank]

Did u ever make the narcotics video u mentioned with dia morphine

[@Yamoukawchowa]

It is time to use more of whole spectrum natural products extracts rather than isolated single molecule compound , much less modified synthetic compounds. Opioid crises are the outcome of these. Nature knows better how to modulate the toxicity and efficacy of whole extracts while humans just tinker pure compounds thinking the isolated compounds are the best forms. Now we know better. Single compounds are more potent but definitely more toxic.

[@fukpoeslaw3613]

I'm thinking of extracting furanocoumarines from grapefruit juice, I already asked my green grocer what he charges for 15 kg of white grapefruit (far to much: 37,50 euros) but how can I do that best?

[@garywood5882]

Professor Dave, could you do a vid on how to synthesize alpha methylphenethylamine ... asking for a friend...

[@iridiumFalcon]

I second this.. also asking for a friend

[@ronokplays]

I’d like to make content like this later in life. Such a goal

[@beckypots1]

I was told that in Iran the dried poppy is brewed into tea, 1 head per 4 people, is this a likely story? Would boiling water extract a paid relieving tea?

[@00bean00]

Dr , where is the thumbnail painting from? I would really like to find these

[@willsgarden6740]

Amazing video

[@rohanjagdale97]

Huge fan of you :)

[@AndreeaTrandafirFlagshipMed]

I am always amazed about the progress of medicine and I wonder how would I react if I could live for a day in different periods of the past but also in the future. I wonder how will our children or grandchildren think about medicine from the 2020s. 😅😂

[@masterzoroark6664]

Some probably will be baffled by the return of some to the make belief cures, but the fast acting to get the Covid vaccines will definetly impress them

[@rylandavis2976]

What's with him saying that nicotine is "extremely toxic" I'd love to see a research paper on that if you have a source. It's definitely not "extremely toxic" at least not in it's isolated form. Last i checked there was no evidence that nicotine was even really a real carcinogen although there is evidence that it can promote blood vessel growth in an already active tumor. Nicotine is actually pretty safe in safe doses probably within the ballpark of caffeine "toxicity" which mostly consists of stressing the circulatory system (when not in overdose). I'm pretty shocked that you would say it's "extremely toxic" given your previous toxicity is in the dose speech. We do not evidence for nicotine being extremely toxic at all in isolate forms. Things like nicotine gum show no widespread serious long term complications such as smoking. But if you have research showing different id love to see it

[@galileog8945]

What "research" do you need? Nicotine is an extremely poisonous compound. Its LD50 is 0.5 mg/Kg, which makes it more toxic than cyanide. It is all relative of course, but as far as chemicals go, very few things are more toxic than nicotine.

[@janedesign5758]

Same here, it is not toxic.

[@mattwaldren]

I recommend having a small pause or break throughout your videos, perhaps by separating the video into three separate parts/sections/chapters. Otherwise, to the viewer/listener, the video can come across as a gushing, unending torrent of information for 12+ minutes. Just trying to help. Otherwise, love the videos.

[@richardwilliamsiv3778]

Wish you had mentioned how aspirin and heroin are synthesized via the same reaction, using an agent that acetylates the starter natural product into what we call aspirin and heroin.

[@mohamadbaha6791]

rat randomly chiling in lab sertuner be like would not that make u a candidate for this experiment?

[@I-kd3cz]

thanks!!!!🎉

[@deliciousness8183]

Can anyone point me to the exact process of extracting morphine?

[@shaswatsatyam]

Thank you Professor dave for all your hard work.

[@TehGoldd]

Can you teach us how to hypothetically get pure morphine from dry Poppy pods

[@Eatmorepaper]

love how when youre talking about semisynthetic derivatives you convert morphine into morphine but its turned sideways

[@BRIANOKEEFFE1]

4:57 not opium poppy pod. Some other strain. Glitch in the,

[@dandylandpuffplaysminecraf8744]

Flanders poppy is one name. They grew in the trench warfare fields after the Great War. The field of Flanders were barren, poppies need light for the seeds to germinate so they outgrew all other plants creating a red field. The blood red poppies came to symbolize the war dead and wounded veterans. Paper poppies are worn on 11/11.

[@MilkoAtchev]

Regarding the %-ages of morphine that you mention at 5:07 - these are not morphine content in dry poppy pods, but morphine content in raw opium. On average morphine content in poppy pods is ~0.3%. Great content though!👍

[@BushyHairedStranger]

Milko Atchev the average claims to morphine content % vary wildly in the Poppy as mentioned in the video. There are cultivars that have been manipulated over decades to produce high concentrations in the latex.

[@ManpreetSingh-yt786]

How ammonia is precipitate

[@science_and_anonymous]

keynote: An alkaloid MUST contain basic nitrogen. If a phytochemical does not contain such, in the example of a flavonoid such as apigenin, it is not truly an alkaloid.

[@joesteadman343]

We went from blind experimentation to building space ships.... I wonder what tech other species have created?

[@tRumbewas]

Thanks

[@amritheshk7151]

Awesome

[@Gruwg2024]

“Sir Robert Robinson” what a legendary name

[@westurp9048]

That random ass rat that got added to the experiment 😂😂😭

[@pritammaji670]

Morphine is one of the best secondary metabolites🔥🔥🔥

[@flyback_driver]

What if he had given the vinegar too soon and produced 3-acetamorphine or diamorph. I know it's technically not anhydride but what if...

[@rastodulla1083]

Nice video, but you should correct information about poppy pods morphine content. Your numbers are probably correct for opium latex, but not for pods. Average dry poppy pods contain less than 1% of morphine (0.5% is common), only special breeded varieties could be up to 2%.

[@sydneyhunt6681]

Do you know how much calcium hydroxide to use ph ect before adding ammonium to get free base I find it all interesting stuff and yes I think the dead poppy heads have the levels you say

[@rastodulla1083]

@@sydneyhunt6681 In theory, morphine is not very soluble in water at pH 9.1 and should precipitate from a solution. But in practice, things are almost always different.

[@sydneyhunt6681]

@@rastodulla1083 I looked at loads of papers lol I get it needs ph 9.1 but how much or how high ph do you go with calcium hydroxide before you lower it with ammonium to 9.1 that information seems to be very hard to find lol anyway thanks buddy for getting back

[@rastodulla1083]

@@sydneyhunt6681 i saw somewhere online that it should be 11. iirc for decreasing pH back to 9, ammonium chloride should be used, not ammonium.

[@lostSempaiWissame]

Sooo interesting

[@Unraveled]

I can't believe how scientists just experimented on themselves and others just expecting to see what happened. Dangerous, but a little funny.

[@asraksabah3673]

Good

[@Brumbrumauto]

Haha how you pronounced the german name sounded hilarious. im german & i liked the video very much

[@traepetersen6199]

I can't believe they won't let you Fullscreen this

[@Meike164]

I can harvest opium in my back yard. I have a lot of pretty poppies

[@cyrenedomogalla5127]

Eeeeexcelent.

[@patldennis]

Tour has all of his sycophants convinced we isolate raw materials for synthetic DNA from natural sources bc we have no other alternative, rather than bc even though we can, it's just cheaper and easier to use a shortcut. I predict that for the ones that wander over here without paying attention this video will only fan the flames.

[@ProfessorDaveExplains]

Fortunately precisely none of them are interested in learning anything so they avoid my academic tutorials like the plague.

[@dredank]

So cancer has existed since man? Are there plants also carcinogenic to animals?

[@lion5452]

I have ammonia ???

[@s0umyendustudies]

And your hairstyle became like Newton 😍😂

[@infinitemonkey917]

You said synthetics aren't as efficient to make as natural alkaloids but isn't fentanyl a cheap to make synthetic ?

[@hankhill3365]

It's extremely potent so it ends up being worth the effort even tho fentanyl is not easy to make that's why it's all produced in super labs in China. But for morphine it would be so much easier to just let the plant do the synthesis for you.

[@infinitemonkey917]

@@hankhill3365 Yea, I guess the efficiency depends on a large scale operation. Apparently Mexican cartels now make their own.

[@chanceshaw812]

@@hankhill3365 You can find videos of Mexican drug cartel "cooks" making fentanyl in cow pastures and little shacks in the woods. Not scientists or chemists, just regular dudes in cowboy boots. No 'super labs' necessary lol. Very little fent comes from china anymore.

[@Sketch1994]

Who really believes bleeding opium when your skin is cut is good defense mechanism?

[@angelicazambrano]

Interesting, I wonder who had the bright ideas to chase the dragon for fun?

[@panosvrionis8548]

Power rangers said its morphine time.... Now I get it🙄🙄

[@KarlosEPM]

Mighty morphine

[@panosvrionis8548]

@@KarlosEPM 😎😎😝

[@flyback_driver]

9:07 yeah back in the day I used to take diacetylmorphine and eventually convert it into 6-acetlymorphine. I suppose I was conducting my own biochemical studies but jokes aside don't do heroin kids.

[@kg-Whatthehelliseventhat]

Good day, Would you mind replying to me? I could use some help with what you stated in your comment.

[@ruffhausmalinois]

Robert Robbie Robinson

[@disgracedrobertkelly898]

Watching this while drinking promethazine codeine slowly from my sprite while it turns into morphine in my liver feeling very relaxed, warm, cozy and sleepy all at the same time. I love all opioids except fentanyl and heroin.

[@radiobiologist]

Will it constipate you?

[@DIGITALVHS]

I love perpetually through the history of pharmacy and the discovery of drugs the chemist always seems to bioassay their product. I always think it's very neat they just eat the drug to find out what it's like for themselves. You can always say more than a rat I guess. And then there's albert Hoffmann

[@opiyumpharma5556]

Codiene is not technically not synthetic - It is an Opiate, produced in the poppy alongside morphine and thebaine, However due to the larger demand of codiene, for direct use or for further processing into other opioids, the large majority of morphine extracted from poppys is converted to codiene, around 80 to 90%

[@greenbanana311]

Yum.