How bioengineering correlates to cannabis?

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Medicine has evolved drastically, from our ancestors using natural remedies believed to have healing powers to now, the use of synthetic drugs, which target diseases far more effectively. It is believed that the next era of medicine will move away from management of genetic disorders, and towards the manipulation of genetics responsible for these diseases in the first place.

This is now more achievable than ever, as only a few years back, scientists discovered a genome editing technology that has revolutionised the possibilities of bioengineering. This system, known as clustered regularly interspaced short palindromic repeats, or simply as CRISPR, is derived from a bacterial defence mechanism against viral infections. Researchers found that they were able to manipulate the mechanisms to alter genetic sequences quite precisely in animal, plant and human DNA (if it is ethical that is).

Botanical gene manipulation isn’t a new thing at all as we have for many years now engineered crops through selective breeding techniques. These were however ineffective due to factors including trial-and-error and therefore took a very long time to achieve desired traits. The CRISPR system is however far more effective in terms of time, cost, and the specific effects it causes in organisms, making it very appealing for private and government research. The cannabis industry, in particular, is actually aiming to utilise these technologies as they are constantly figuring out ways to maximise, optimise or alter components found in the plant.

Ryan Lee, CEO, and founder of Chimera Genetic Resource Management praised genetic engineering of cannabis, stating that it “could make the cannabis resistant to things like mould, powdery mildew, and pests without any of the regular horticultural interventions”. He also expanded on the ideology that “Through biotechnology, you could even change the chemical pathways in the plant”, making it possible to alter the level of active compounds that grew within the crop. This would significantly help streamline the extensive use of filtration and separation techniques currently used in the drug’s manufacture process. Even more so, appropriate bioengineering could drastically speed up the manufacture of compounds like Cannabigerol (CBG), which can conventionally take up to 10 years to grow. Lee also added that this process could be shortened to just a few months… Not only would this be a huge advancement in the world of natural pharmaceuticals, but it could vastly increase the availability of natural drugs (which can currently be very expensive to buy) to many more people worldwide.

So where are we now?

At this moment in time, genetically modified cannabis just doesn’t exist in the industry. Studies and research have shown modern engineering technology to desirably alter the plant’s properties, yet these have not yet been adapted into industrial practice. Maybe because there’s still a grand global stigma over genetically modified organisms? Maybe because genetic modification is relatively new and not much research has investigated cannabis modification? The bottom line is that we have the technology here, ready to use… we just need to utilise more funding within this field.

The biotech industries interest in Cannabinoids?

From a drug of almost global illegality to a multibillion-dollar industry, cannabis has significantly progressed in the last two decades. This gradual movement caught the interest of many science-based industries to boost this market by tailoring their services towards cannabinoid research and production. One, that became a crucial part of this market was the biotechnology industry which focussed on prospecting the field of cannabinoids in society. Their main areas of interest revolve around the discovery of new health benefits from active bioproducts and, the introduction of improved methods of delivering these compounds into the human system. Consequently, this alliance of industries has led to efforts and advancements in tackling medical disorders, some of which were incurable before.

This blog will, therefore, concentrate on a few biotech companies which have or are believed to cause a great impact on the development of medical cannabinoid products. Many difficult terms will be used too so bear with me, I’ve hyperlinked most of them to help you understand what I’m on about!

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Cannabis takes over the biotech industry

Many companies have seen an opportunity to adapt their research, expertise or patented products in the cannabis market whilst others have invested in researching the plant since their establishment. For example, GW Pharmaceuticals was established in 1998 with the aim to research and develop cannabinoid-derived medication. They focused heavily on clinical trials, drug development and regulatory allowances but for years struggled to commercialise their medication because of the strict law surrounding cannabis. Fortunately, their research and trails were so extensive that they overcame regulatory clearance and became the first in the world to distribute cannabinoid-based medicine.

As mentioned, specialist biotechnology businesses found a profitable opportunity in the cannabis market and tailored their expertise towards its development. 22nd Century Group is one of these companies. The plant biotech firm originally focused on bioengineering of tobacco plants to lower the level of ‘harmful’ compounds like nicotine when smoked. The same problem is present when smoking cannabis as some compounds (e.g. CBD) are more desired in medicine than others (e.g. THC). Therefore, bioengineering of new cannabis strains which contain more of the desired compounds can support cannabinoid production companies like GW Pharmaceuticals. This can be through means of increasing yield and potency of the desired compounds but also improving the flow of the manufacturing process by lowering filtration steps needs to remove unwanted compounds.

Let’s jump back onto the topic of smoking as historically this was, and still is the main method of getting cannabis compounds into the human system. You do not have to be a doctor however to know that smoking in general, is a massive contributor to cardiovascular, pulmonary and cancerous diseases along with other difficulties. It shouldn’t, therefore, be a surprise that some biotechnological companies have recently been researching improved methods through which cannabinoid-derived medication can be consumed and absorbed. Lexaria Biosciences, for example, has developed the DehydraTECH™ technology which can be applied to bio-active compounds (including cannabinoids) which would otherwise be poorly absorbed by our stomachs. This technology is out-licensed to many pharmaceutical companies to improve the drugs taste and increase the rate of absorption, which in turn lowers the required dose needed for desired effects from the drug.

So, to sum things up, the biotech industry already has, and will continue to boost the development of the cannabis industry. They do this by directly impacting the properties of the drug or indirectly by research and making the public and government more aware of the medical benefits and more accepting of what it really is… just a plant with much medicinal potential. To top everything off, the recent involvement of the biotech industry (as well as other industries, e.g. medical, agricultural) in cannabinoids have really brought massive investments into cannabis in general, supplying scientists a whole load of funding to focus research more on the plant’s medical benefits.

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In my next blog, I will dive deeper into the analytical techniques hugely used in cannabinoid research, as well as mass manufacture. I will aim to help you all understand the complexity evolving these techniques.. purely because filtration refers to much more than just using a sieve to separate ‘water from sand’ (surely we all did this practical in primary school?). Above that, I’m sure you’ll find it interesting to learn scientists are able to achieve a pure compound from such a complex plant structure!

THC vs CBD: The O-C bond that makes a colossal difference

Historically, marijuana has been recognised as a ‘street’ drug for “getting high” and considered one, for which possession is illegal. Within the last decade, however, the demand for natural medicines has increased due to their wide range of health benefits. Consequently, this has prompted scientists to research and therefore uncover notable and empirical results proving that compounds derived from cannabis hold some medicinal properties.

So… surely you have heard about the psychological effects that a cannabis user experiences? If so, it must have got you wondering, what is it about this natural crop that can manipulate one’s psychological awareness? Well, the compound responsible for this ‘euphoria’ is THC which acronyms for delta-9-tetrahydrocannabinol (if you can manage the mouthful). This compound is considered the main psychoactive chemical out of approximately 500 chemical compounds naturally found in marijuana. Recently, much more attention has evolved around a compound, which has the same chemical makeup as THC, yet its effect on the body is vastly different. This compound, known as Cannabidiol (CBD) is made up of 21 carbon, 30 hydrogen and 2 oxygen molecules, just like THC. The two are nearly identical twins if you like. What differentiates them from one another however is the arrangement of a single atom, and this is illustrated below:

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To put things into perspective… an atom is approximately a million times smaller than a strand of your hair and so we’re talking about a microscopic difference! It is crazy to believe, but this minuscule difference is responsible for very different effects on our body.

The Endocannabinoid system and Cannabinoids

Before we dive further, it is important to understand how cannabinoids react with the body and the process they undergo.

So, the cannabinoid compound interacts directly with the endocannabinoid system (ECS), which is basically a network of receptors (complementary binding sites to cannabinoids) spread across parts of the human body. Currently, two of these receptors have been identified throughout the body and classed as CB-1 and CB-2. The CB1 receptors are predominantly found in regions of the brain responsible for mental and psychological alterations whereas their CB-2 counterparts are distributed throughout the immune and central nervous system.

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Now, the positioning of that atom between THC and CBD I mentioned earlier is what differentiates the effects that each of them has on the body. Both compounds bind to the CB-2 receptor similarly and hence impact the central nervous system similarly too. This reaction is what lead to an array of medical benefits associated with the two. The interaction with the CB-1 receptor, however, differs between THC and CBD. The molecular structure of THC allows for it to bind directly with this receptor, which in turn stimulates the release of chemicals responsible for “getting high”. In contrast, these stimulating chemicals are not released when CBD’s attempt to bind to the CB-1 receptor as their ability to bind in not as effective (Reggio, 2010). This is the main reason why CBD does not create psychoactive effects. Interestingly, CBD has also been found to hinder the bond between THC and CB-1 and thus neutralises the psychoactive effects caused by the THC.

THC and CBD content in medicinal marijuana

You should now have a sound idea on how and why the two differently affect individuals and through this, have realised that CBD’s are the components which are preferred in medicine.

CBD’s are mainly preferred as they offer more health benefits, do not cause psychoactive effects and currently are not illegal due to unclear laws around most of the world, unlike THC. So, for example, some states in the US have legalised the prescription of medical marijuana to patients in need. This means that they have allowed for the prescription of cannabis which is much more concentrated in CBD rather than THC. The concentration of these compounds in recreational marijuana differs, as THC tends to be much higher than CBD. So, in terms of medicinal use, the pharmaceutical producers want to omit the euphoria caused by THC by suppressing its presence in the herbal product.

Currently, CBD is therefore still in the grey area, but this is drastically changing with increasing studies and improving biotechnology for research and manufacturing. On this note, I will explore these biotechnologies in my next blog so stay tuned in… I’m sure you’ll find it interesting!

Cannabis – Class B drug or revolutionary medicine?

We live in a society where the current public and government perception of an array of controversial topics is decidedly offbeat. This disputable viewpoint, along with other factors, greatly contributes to the decisions made by influencers, and in some instances, prevents the use of valuable resources to their fullest potential. A strong example of this is Marijuana (commonly known as cannabis) and its application in society.

History & Law

For centuries, hemp, a strain of cannabis predominantly lower in tetra-hydro-cannabinol has been used in industry for fibres, oils and seeds. Recreational use of the drug has been practised for much longer than this, yet a majority of the world’s government put a ban on this form of misuse in the early 20^th century. Since then, a majority of these countries still enforce this law, even though we have since developed a better understanding of the active components, and the psychological (Walsh et al., 2017) and biochemical (Hill et al., 2017) effects that can be achieved from them. More emphasis evolved around the negatives of the drug, and the enforcement if one was found cultivating, possessing and distributing Cannabis, and thereby placing less attention on the medicinal benefits.

In recent decades, use of the drug has become more acceptable worldwide. Countries such as the Netherlands have allowed for the recreational use of the drug whilst some American states have legalised the use of cannabis for medicinal purposes only. The UK, however, has remained very hesitant on legalising the use of the plant for neither, recreational nor medicinal. The class B classification of the drug has remained the same since it was added to the Dangerous Drugs Act 1920 in 1928 and remains there till today. There was a slight movement towards acceptance between 2004 and 2009 when the drug dropped to a class C but this didn’t remain for long due to political and public safety factors. These factors seemed to have outweighed the public opinion as according to BBC news more people were in favour of this down classification (49% supported this movement whilst 36% didn’t).

Medicinal or Recreational cannabis?

It is important for laws to be set with the differentiation of ‘recreational marijuana’ and ‘medical marijuana’ in mind as their expected effects vary. Particularly more so, when patients who currently benefit medically from the drug in the UK have to commit criminal offences to obtain any form of cannabis. This ‘street’ cannabis is what causes harm to long-term users, as its manufacture does not comply under any standard operating procedures approved by regulatory bodies like the MHRA/FDA. This means that’s compounds may be used which greatly influence previously identified psychological harm (Di Forti et al., 2009). Could this also reason to the negative stigma around the plant?

Anyway… the difference between recreational and medicinal marijuana is quite simply segregated by the proportions of two relevant components:

Tetrahydrocannabinol (THC): The psychoactive compound of the cannabis plant which produces the ‘euphoria’ or high.
Cannabidiol (CBD): The substance that does not produce the high, yet has been recently found to hold many medicinal benefits.

Recreational marijuana is the type that is usually found on the streets. It is usually much higher in the psychoactive compound THC whereas its medicinal counterpart contains far more CBD. Use of the medicinal product, whether smoked, vaped or consumed, does not create the euphoria, yet gives the user relief from certain disorders. Extensive cannabinoid research has found benefits including pain control, multiple sclerosis, insomnia and has also been found to lessen disease symptoms including tremors in Parkinson’s disease (Grinspoon, 2018).

Where we are now?

As medicine and its application in society have improved over time, scientists have further studied CBD and other compounds in cannabis. A company recognised well in the field is GW Pharmaceuticals, who earlier this year became the first to have their cannabinoid-derived product approved for commercialisation by the FDA. The product (Epidiolex®), compromised of purified cannabidiol was created to treat two rare forms of epilepsy, Lennox-Gastaut syndrome and Dravet syndrome (FDA, 2018). Other preliminary uses for this drug have also been identified, yet not been approved by the FDA. Regardless of this, it is evident through FDA approval, that cannabis products have medicinal benefits… It’s just important to use the correct compounds in the correct manner to achieve the desired effects.

GW Pharmaceuticals, along with similar businesses will continue to undergo extensive research using state-of-art biotechnology to create medication cannabinoid-derived medication. I will get into more depth on the main active compounds found in cannabis in my next blog and explain their effect on the body.