Transcription of Elucidation – S1S4 – Dr. Pritesh Kumar

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On last week’s episode of Anslinger: The untold cannabis conspiracy we discussed the first major breakthrough discovery of marijuana and how a human interacted with the drug. We also dove into Harry Anslinger’s personal life from the perspective of his great grand niece Mary Carniglia.
His great grand niece, Mary, wholeheartedly believes that Anslinger was more likely to have been manipulated by larger stakeholders than operating as the true brains and force behind the regulations and research created. She may or may not be correct in her assumption, but we do know that the bulk of the brains behind narcotic regulations laid in the hands of one very important Government Committee.

The Committee on Drug Addiction is probably one of the most essential pieces in this twisted story. And this committee is likely one of the top reasons that the pharmaceutical industry had the ability to proliferate opioid production and use while prohibiting cannabis altogether. But yet, of all the times I have heard people talk about the cannabis conspiracy, I have only heard one other person bring up this group of men.

The Committee on Drug Addiction officially formed under the National Research Council in 1929 but its foundation was laid years prior within an organization called the Bureau of Social Hygiene. The Bureau of Social Hygiene was established by John D. Rockefeller in either 1911 or 1913, the records are unclear. But it was financed by the Rockefeller Foundation, the Rockefeller family and individuals like Paul Warburg, who was a German-American banker, often credited with formulating our centralized Banking system an the Federal Reserve.

Around the time the Bureau of Social Hygiene formed, so did the Rockfeller Foundation with a mission of “promoting the wellbeing of humanity throughout the world.” And if I were to take an educated guess, I’d say the Rockfeller’s likely originally formed the Rockefeller Foundation as a means to progress medical and pharmacological research in the United States after America determined that they needed to invest in medical research to remain competitive in an international landscape. Because upon formation, the Rockefeller Foundation almost immediately funded Harvard School of Public Health and Johns Hopkins School of Public Health with a focus on epidemiology, also known as diseases.

The Rockefeller Foundation’s purpose of improving the wellbeing of humanity also paralleled with the purpose of is grantee, the Bureau of Social Hygiene, whose original mission was to study and prevent certain social conditions that may negatively impact society, like prostitution, narcotics, crime and delinquency. All very lucrative markets in today’s time.

And by 1921, the Bureau of Social Hygiene had created the original Committee on Drug Addiction as a response to the growing concerns of addiction. But by 1928, the Bureau had attained enough research to publish a report called The Opium Problem, which provided a thorough examination of drug addiction and the effects of morphine in the body. Soon after the report published, the Bureau of Social Hygiene appointed a new Executive Director to its board by the name of Lawrence Dunham. Mr. Dunham, apparently moved by the addiction reports, felt compelled to write to the National Research Council’s Dr. Vernon Kellogg to request that the Committee on Drug Addiction be moved under the organization and leadership of the National Research Council. Mr. Dunham felt that this transition would allow the Committee to investigate narcotics outside “purely scientific research.”

The proposal was approved by the National Research Council and in January 1929, the Bureau of Social Hygiene initiated the transition of the Committee on Drug Addiction and its remaining 3 year research budget of $186,500 to be taken over by the National Research Council, which in today’s money is $2.7 million over a three year span.

The initial board of the Committee on Drug Addiction consisted of 9 men, who all served without change in membership from 1929-1939. The group of men would commonly convene at the Cosmos Club in Washington DC, an upty white male establishment for the wealthiest and most influential citizens in America. This isn’t too surprising, considering who was funding the Committee.

Soon after establishment, the Committee on Drug Addiction nominated Commissioner Harry Anslinger to the board and by 1938, added Dr. Lawrence Kolb to organize addiction research at the Narcotic Farm in Lexington, Kentucky. Besides Anslinger, the board mostly consisted of doctors and professors who unanimously agreed that synthetic chemistry would be the foundation of their research and was the future of pharmaceuticals, which was great news for the Standard Oil giant Rockefeller, whose investments would be used to grow the processes.

This new Committee on Drug Addiction would expand their focus from opium to instead focus on four broader areas of research:
1. The analysis of chemical literature of addiction alkaloids,
2. The analysis of biological literature of addiction alkaloids,
3. The formulation of rules and regulations for legitimate use of alkaloids having addiction properties and the education of physicians and the public on the knowledge of these rules by means of medical schools, societies, journals, and drug manufacturing plants (which is also considered the basis of western medicine), and
4. The replacement of all present use of addiction alkaloids by substitutes having no addiction properties

This committee conquered the first three focus areas, but the forth focus area — finding the Holy Grail to morphine – well, this is still to be determined.

But even so, throughout the 1930s and beyond, the Committee on Drug Addiction was able to allocate tremendous time and resources towards advancing drug research, and really organic, synthetic and alkaloid chemistry as a whole. And according to Board Member, Pharmacologist and Director of the National Cancer Institute Dr. Voegtlin , it was of the utmost importance to “place alkaloid chemistry and alkaloid pharmacology on a sound basis in America even if it’s chief purpose fails.”

But what exactly did this research mean for the pharmacological and narcotic world? We’ve invited pharmacologist and toxicologist Dr. Pritesh Kumar to explain.

Annie: What is alkaloid chemistry and why was this so important in pharmacology?

Dr. Kumar: Well you know very simply put alkaloid chemistry is the study of all of the naturally occurring chemicals around us. And it’s importance, you know, I think you know this could be a conversation that could be on its own entirely, but briefly I’ll say I mean I think it’s incredibly critical that we study the natural compounds around us in order to better explain some of the phenomena that are occurring with these substances. And I’ll leave it at that. But I think it’s very important because you know a lot of the medications on the market now have been derived from plants to begin with.

And we need to better understand the process and what we can actually achieve when we start looking into the plants that are found in nature.

Annie: Yeah that makes sense definitely especially for ingesting them and taking them for you know different medical ailments. I didn’t realize that alkaloid chemistry because alkaloids aren’t in everything right. It’s only like I know that they’re highly prevalent and opioids are they found in cannabis as well?

Dr. Kumar: They’re found in a wide variety of plant species. And you know really in general alkaloids are really just any group of compounds that have some type of nitrogen atom. That’s what it really comes down to. So they’re very abundant in nature.

It could be particles. It could be teas. It could be different herbs. It could be different plant constituents. It could be a wide variety of things. There are some you know bacteria and fungi that are that actually produce alkaloids as well.

Annie: And nitrogen is like the it’s the most abundant element in our solar systems is that right.

Dr. Kumar: it’s definitely definitely the top three.

Annie: Yeah.

Dr. Kumar: But I mean obviously the atmosphere is you know very rich with nitrogen than compared to oxygen right.

Annie: So can you explain organic chemistry and why this understanding of organic chemistry was so essential as well the pharmacology?

Dr. Kumar: Organic chemistry is very important because it’s my thing in the study and by definition the study of organics which is the study of life and all of the chemical reactions related to life. Organic chemistry plays a very critical role in the development of anything from your common household chemicals, to drugs, to fuels, to foods, and different plastics. Really most of the chemicals.

And why that’s relevant to pharmacology is you know these reactions need to be investigated. They’re part of things that go into foods, plastics, drugs, and fuel and these also need to be studied for to ensure they are safe for human consumption.

Annie: So the I mean I know obviously organic chemistry has always existed but there was there wasn’t a ton known about it until the early 1900s, so I guess you could say that the combination of understanding more about organic chemistry and then studying and understanding more about alkaloid chemistry was a major breakthrough in our natural scientific world.

Dr. Kumar: Absolutely. You know it’s one of the major branches of chemistry history you know can be traced back to the truly ancient times when medicine, well when “medicine men” extracted chemicals from plants and animals to treat members of their tribes.

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And now back to the show.

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So with the Committee on Drug Addiction investigating alkaloid chemistry, the research also provided insight into a more boarder understanding of organic chemistry and the understanding of how humans can interact with nature.

As Dr. Kumar stated, organic chemistry can be traced back to ancient times, with the use of plants like cannabis, poppy plants and willow trees to treat different issues. But the rise in organic chemistry didn’t lend itself to pharmacology and our modern synthetic world until the late 1800s and early 1900s when research and analysis became more systematic. In addition to pharmaceuticals, organic chemistry provided an understanding of polymers and enzymes as large organic molecules that could also be used for industrial purposes like plastics, with petroleum being at the root of research.

Man J.D. Rockefeller had his hands in it all.

German Pharmaceutical giant Bayer, was one of the first pharmaceutical companies to initiate the synthetic pharmacology with the synthesis of drugs like heroin and Aspirin. A decade later a German scientist Paul Ehrlich synthesized Arsphenamine as a treatment for syphilis and used the compound in the world’s first chemotherapy.

You’ll notice that Germany, and in particular Bayer, was at the forefront of pharmaceutical breakthroughs in the latter half of the 1800s and early 1900s, and funny enough, Bayer is again today with the breakthroughs in cannabinoid research. But the funding allocated to the Committee on Drug Addiction would provide United States researchers with ample resources to study and develop alkaloid chemistry, most importantly providing the appropriate labor and equipment to study the field.

The motivation for studying Alkaloid chemistry seemed to have been for financial and competitive reasons, alongside national security. At the time, Germany had a strong opinion that the United States was not a competitor and never would be a serious competitor in the field of chemistry. But Germany, reprimanded for WWI, and forced to reduce industrial and pharmaceutical manufacturing across its country, was in a precarious position to lose their scientific dominance.

After WWI, the US and I presume, J.D. Rockefeller, saw an opportunity to pounce on a vulnerable Germany and the Committee on Drug Addiction, was one of those opportunities. Investigating alkaloid chemistry meant understanding what species, in particular, what plant species, contained nitrogen and how to synthesize nitrogen into useful products. With nitrogen being at the basis of forming important chemicals, like ammonia, for pharmaceuticals, fertilizers, and warfare, one can understand why this research was essential along the United States’ pathway to global dominance.

Beyond fertilizers and bombs, nitrogen is found in beneficial drugs like morphine, codeine, cocaine and penicillin. But it is not found in cannabis’ active molecules, which may have been one of the main factors in the slow development in understanding cannabis as opposed to opioids. Another factor is likely the complexity of the cannabinoid molecules and the inability of scientists to fully extract, isolate, elucidate and synthesize the molecules using the equipment that was available during the first half of the 1900s. Conversely, by 1895, scientists had already extracted, isolated, elucidated and synthesized opium’s active molecules into drugs like isolated forms of morphine and codeine and synthesized forms of heroin.

Annie: Can you explain where opium derivatives come from?

Dr. Kumar: Yeah sure so derivatives and opium in general is a natural product. However in opium poppy, morphine is the most abundant opiates found in that species.
Annie: So is morphine morphine is naturally occurring in the end opium kind of like cannabidolic acid would be occurring in cannabis?

Dr. Kumar: That is correct.

Annie: So what’s the extraction process for extracting morphine from opium.

Dr. Kumar: Without getting you know extremely technical, the process is very basic. The process begins with some type of general extraction with the basic alcohol solution. And the reason why that is you need a you need some type of solvent to dissolve the material in. Once it’s dissolved for a period of time you can filter it and then the alcohol can be removed through evaporation from filtration, which leaves a residue and that residue is morphine.

Annie: And then so historically they had turned morphine into heroin. What is that process?

Dr. Kumar: Well so that process actually occurs in our bodies. Believe it or not our body naturally converts morphine into into heroin. A lot of people don’t know that. And that’s really just through a metabolic process. When you ingest morphine our bodies convert that chemical compound into the same chemical structure as heroin.

Dr. Kumar: Heroin or diamorphine really, is referred to chemically, is approximately three times more potent than morphine and it’s made by combining morphine or opium with a chemical agent called Acetic anhydride. So really the increase in potency is what’s so attractive to a lot of these drug seekers and leads to down a path of addiction.

Annie: So Bayer Pharmaceuticals was the first pharmaceutical company to synthesize morphine into heroin. Can you explain the steps that it takes to get to that point in terms of extraction, isolation, elucidation and synthesis?

Dr. Kumar: Yes sure. So you know a natural point of interacting has a lot of challenges from the raw material consistency to developing a standardized protocol for extraction isolation and synthesis. So some of the steps that takes it very briefly.

Extraction. This is a very important part because you want to ensure that you’re getting a high level of compound yield out of that initial extraction procedure. So this first step is very critical and usually with new natural products what experiments naturally focus on are different solvents, alcohol solvents, a wide variety of solvents to see which is the most suitable solvent to extract this type of material and so that step one.

Isolation really is fine tuning, I like to call it fine tuning, or refining the extraction process. And what that means is, extraction essentially focuses on extracting all the compound into a solution. Isolation is very targeted and that focuses more on targeting one or two or three of the compounds in that mixture and purifying that.

Elucidation is more of a analytical and identification technique. Elucidation can be accomplished through either liquid chromatography or mass spectrometry to make sure you’re identifying the target calm down and matching it with its spectrum. And then the last part you actually synthesis?

Annie: Yes

Dr. Kumar: Synthesis is you know is very different than extraction, isolation and natural product purification. Synthesis is when you know what the targeted compound, the chemical structure is. And you can simply synthesize it with a list of chemical reagents and accomplish that through reactions.

Annie: So it’s no that you don’t necessarily use the natural product that has been extracted, instead you’re mimicking the chemical structure that you’ve discovered in that elucidation process.

Dr. Kumar: That’s correct for example morphine is one of the active ingredient in opium opium plan right. Once you know once the pharmaceutical world and chemist in general know of what structure is through you know mass spectrometry, through isolation, through these different analytical techniques, once you know what that chemical structure looks like, you can synthesize it without the plant at all.

Annie: So in the early 1900 late 1800’s. How difficult was it for these researchers to actually elucidate compounds not having the technology that we have today?

Dr. Kumar: You know that that’s a very good question. It’s a tough one to answer because you know back then the advanced liquid chromatography and mass spectrometry methods were not in place even though it is a very established technology. I think a lot of the difficulties that we’re faced back then are still faced today in in in the manner that for example you have a plant material and you’re looking to identify what is in there. It’s very challenging because there could be you know 10 compounds or other could be a thousand compounds in there that you know we don’t have reference standards for when we run the experiments or when we run the analytical assays to look to identify what compounds are in there. So I think some of the problems that we’re that they were facing the chemist were facing back then we’re still facing for some of those today to some extent.

Prior to advancements in elucidation technology like gas chromatography and mass spectrometry, which didn’t occur until the1950s and 1960s, scientists really played more of a guessing game when it came to understanding the molecular make up of plants, drugs and fuels. Structures were unraveled by degrading the molecules through chemical reaction until one could determine what element was left. This process seemed to work well for opioids but when it came to cannabis, the plant’s molecules were more difficult to separate.

We know now that cannabis is made up two primary cannabinoids – one intoxicating cannabinoid called Tetrahydrocannabinol, or THC and one NON-intoxicating cannabinoid called Cannabidiol, or CBD. Beyond these two primary cannabinoids there are also 100+ minor cannabinoids that interact in various ways with our endocannabinoid system. It’s a complicated system and researchers are just scratching the surface on understanding it, but our interviewee, Dr. Kumar, will provide us with a more in-depth understanding of this system and our body’s opioid system in the next episode.

Even though the cannabis plant’s molecules are complex, cannabis extraction research was underway. And actually, one of the 100+ minor cannabinoids, called Cannabinol or CBN, was the first cannabinoids in the cannabis plant to be extracted and isolated in the late 1800s, but it wasn’t until the 1930s that the structure of CBN was elucidated by a man named R.S. Cahn. But CBN was not first chemically synthesized in a laboratory until 1940 by a United States scientist named Roger Adams and a United Kingdom scientist named Lord Todd.

Roger Adams also was the first to extract cannabis’ non-intoxicating primary cannabinoid, cannabidiol or CBD. Two years later, in 1942, a different group of scientists extracted cannabis’ intoxicating cannabinoid, tetrahydrocannabinol or THC. But given the complexities of the cannabinoid structures, it would take another 21 years, with the support of technological advancements, before these two primary cannabinoids, THC and CBD, were actually isolated, elucidated and synthesized by an Israeli scientist named Raphael Mechoulam.

Given the lack of technology and the fact that I don’t believe that cannabis can be considered an alkaloid, as its extracted molecules do not contain nitrogen, it is no wonder that cannabis was not a focus of the Committee on Drug Addiction. We should also remember from our previous episode that the test subject in the medical trial on cannabis conducted in Germany experienced no addiction symptoms, so why would a committee focused on drug addiction care?

Instead in 1930, the Committee on Drug Addiction progressed their research on their four essential areas of focus we discussed earlier in this episode. And as they researched, the Committee questioned two major areas. The first question regarded the addictive relationship between morphine and codeine. Both molecules are naturally produced and extracted from the poppy plant, but as opposed to morphine, codeine was considered to be relatively less addictive with similar pain relieving properties. At the time, because codeine was less addictive, scientists hypothesized that chemical modifications of morphine would contribute to finding a non-addictive, pain-relieving drug.

According to Dr. Nathan Eddy, a researcher for the Committee on Drug Addiction, this hypothesis was incorrect because at the time the Committee had no idea that codeine was actually less addictive simply because it had less pain-relieving properties.

The second question the Committee pondered was why the demand for cocaine fell with the introduction of non-abusive local anesthesia called procaine, more commonly known for its trade name, Novocain. With the introduction of procaine, the availability of cocaine reduced, which may have led to reductions in abuse; therefore, the Committee determined that a synthetic substitute for morphine would lead to reductions in the abuse of morphine.

This determination to find a non-addictive synthetic morphine pushed the Committee’s hired researchers to produce all kinds of new synthetic drugs, which of course led to the question of how can the Committee and its funders protect and monetize these new drug discoveries? And just so you know, the funders of the Committee on Drug Addiction was mostly the Rockefeller Foundation, also included small grants from pharmaceutical companies including: E.R. Squibb, Merck & Co and Mallinckrodt Chemical Works. E.R. Squibb eventually merged with Bristol Meyers, forming Bristol Meyers Squibb, but all three pharmaceutical companies are still active in some capacity today.

After much deliberation, the Committee decided that when discoveries were patentable, the National Research Council would pay for the patenting costs and become the assignee on the discovery in an attempt to provide a service to the public. However, oddly enough, according to Dr. Nathan Eddy, the liaison for Committee on Drug Addiction and the director of the Committee’s pharmacology laboratory at the University of Michigan, this decision was against their original opinion on patenting products, which was that medicines should not be patented because it would not be in the best interest of science or the general public.

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And now back to the show.

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Annie: So the Committee on Drug Addiction had concerns over patenting the drugs that they synthesized and researched and ultimately they decided that the U.S. Government would be the assignee to these different patents. Can you explain the patent process for pharmaceuticals and how patents impact the natural derivatives of these synthesized drugs.

Dr. Kumar: So this is a very important question and it’s very relevant to this conversation. You know really patents in the pharmaceutical world or patents in general start with when somebody or an organization discovers what they believe to be a new chemical entity. You know some unknown structure whether that is plant derived or whether that is chemically synthesized into a new form that doesn’t exist. This process really is a process that is quite common in the pharmaceutical and biotech industry.

Essentially starts with new chemical discovery or synthesis. And then you can file a patent on that procedure to develop that that compound. So that’s one way that patents work on the chemistry side.

Another way on the pharmacological side, is a compound is discovered or derived from a plant and the specific experiments are done on that compound in animal models. Some absorption, distribution, excretion, metabolism studies are done with that compound so you have a safety and basic pharmacological profile on that compound and that can also be patented.

Essentially you know the new chemical and the discovery and the investigational new drug process fall into the same protocol for patenting and usually involves you know a good amount of assistance from the FDA and the review team and the researchers and chemists involved to accomplish that.

Now that’s the process. So your primary question is how does this process for pharmaceuticals impact natural derivatives, right?

 

Annie: Yes.

Dr. Kumar: So you know this is the critical question, which is still in the gray area, for example, can you patent a plant?
Can you patent the cannabis plant? Can you patent the opium plant? Well you can’t patent naturally occurring substances. You can certainly patent different formulations and ratios of compounds within those plants.

So that does impact to some degree natural derivatives, and the study of natural derivatives. For example, if you if you perform an extraction on a plant material and you isolate different compounds and then you develop a formulation and and add in, let’s say for example, just for the sake of this conversation, you add in two different additional compounds like tumeric and curcumin right. That is now a new formulation that can be patented.

The other way, well there are several ways, but the other primary way for patents is around the delivery mechanism.

So that same formulation I was referring to he formulated that into let’s say a transdermal patch or an inhaler. The delivery mechanism is novel and new. So that can be patented as well.

Annie: That’s like GW Pharmaceuticals has patented I think the delivery method for their Epidiolex Pharmaceuticals.

Dr. Kumar: That’s correct.

 

The decision of the Committee on Drug Addiction to patent drugs fostered drug research and the ability of pharmaceutical companies to protect, market and monetize their synthetic drugs. And over time, with Anslinger involved in the Committee, the group of the 11 men and a few salaried researchers, were able to create a process for federally regulating the plants that naturally produced these drugs as narcotics, while funding research to create genetically similar synthesized substitutes which could be manufactured and sold by only those who owned the intellectual property.

As Anslinger participated in the Committee on Drug Addiction he was routinely praised for his invaluable role in the Committee. While Anslinger sometimes butted heads with the Committee members, and didn’t necessarily want to participate in the scientific aspect of narcotics, he used the Committee as a way to wage his war on regulating drugs and controlling drug supply on an international level.

When the U.S. Public Health Service’s Narcotic Farm opened in 1935 in Lexington, Kentucky, with narcotic research lead by the Committee on Drug Addiction, the Committee was finally able to step outside of laboratory experiments and animal trials on monkeys and into the realm of clinical trials on prison inmates – trials that would support Anslinger’s enforcement strategies.

We know that the Committee on Drug Addiction had an obsession with opioid research, and for good reason. But what did they know about the way opioids interacted with the human body’s opioid system? And what did they know about the way cannabis interacted with the human body’s endocannabinoid system? You’ll find out on the next episode of Anslinger: The untold cannabis conspiracy.

Credits
Thank you for listening to this week’s episode sponsored by Anavii Market and Natural Hemp Oil.

If you like what you hear, please subscribe to our podcast, write a review and tell your friends to tune in. For more information visit thinkhempythoughts.com. It’s like Think Happy Thoughts, but hempy.

This podcast is written and produced by A. Rouse Production with facilities provided by the Media Collaboratory and audio support by Jake Mannino.

On the next episode of “Anslinger: The untold cannabis conspiracy,” we investigate the medical and therapeutic uses of cannabis. We also continue our conversation with Dr. Pritesh Kumar about the differences between the endocannabinoid and opioid systems in the human body and their physiological actions.

Dr. Kumar: So there’s some type of cross-interaction between the opiate and endocannabinoid systems. Also not only in the functional interaction side but when it comes to mediating behavioral responses related to addiction and possibly opening up new strategies for the treatment of opiate dependence.

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