By RQS Editorial Team


Humans have used cannabis for thousands of years. In ancient times, we figured out some of its holistic applications and utilised it as a source of paper, rope, and food. But only in the last century have we really started to unveil some of its deepest secrets.

We owe it to certain chemists, biologists, and other scientific researchers for taking the daring steps to acquire our current understanding of the herb.

There are a few well-known individuals that helped to discover the chemicals within the plant and elucidate how they work in the body. But none of these names receives more praise than Dr Raphael Mechoulam.

Unfortunately, Mechoulam passed away in March 2023 after a lifetime devoted to cannabis research. His six-decade career was marked by perseverance and dedication, resulting in millions of patients benefiting from his work.

Raphael Mechoulam was a founding member of the International Cannabinoid Research Society (ICRS) and a renowned figure in the field of cannabinoids. In a statement released by the society after his passing, Mechoulam was affectionately referred to as "Raphi", demonstrating his approachable and kind personality in addition to his brilliance as a scholar. Mechoulam's engaging public conferences around the world were a testament to his knowledge and passion for cannabis research.

Mechoulam and His Latest Discovery: EPM301

Dr Mechoulam broke a lot of ground during his career. From discovering and isolating THC to unveiling key endocannabinoid system components, modern researchers truly stand on the shoulders of this academic giant. In his latest discovery, he managed to create a cannabinoid acid known as EPM301 that shows great promise as a future pharmaceutical.

In 2020, the year in which he celebrated his 90th birthday, Mechoulam found a way to stabilise previously volatile cannabinoid acids. In certain instances, these compounds exert more potent effects than their "activated" counterparts, but their lack of stability makes them poor candidates for research and application. That was until Mechoulam got his hands on them.

What Are Cannabinoid Acids?

Cannabinoid acids are naturally occurring compounds synthesised within the glandular trichomes of cannabis plants—those shiny little structures that form a glistening “frost” on the surface of buds.

It might surprise you to know that raw cannabis contains very little THC and CBD. Instead, these cannabinoids start out life as cannabinoid acids. For example, CBD (cannabidiol) exists as cannabidiolic acid in raw weed flowers. It possesses a different molecular structure to CBD, in that it features an additional group of hydrogen, oxygen, and carbon atoms, known as a carboxyl group.

When you pack CBD-rich flowers into a bowl and apply a flame, you harness the power of heat to convert CBDA into CBD before inhaling the smoke. Through a process called decarboxylation, the additional carboxyl group ejects from the molecule, creating CBD.

What Are Cannabinoid Acids?

Whenever we smoke, cook, or vape cannabis, we convert all of those cannabinoid acids into their corresponding cannabinoids. But are we missing out when it comes to cannabinoid acids?

Indeed, cannabinoid acids bring their own traits to the table. Because they have different molecular structures, they’re able to influence the body and the endocannabinoid system in a different manner. Ongoing research[1] continues to explore the potential of cannabinoid acids, with a particular focus on their effects on immune response, mood, stomach discomfort, and degenerative diseases.

Despite their unique and promising properties, cannabinoid acids pose a big problem for companies looking to develop them as medicines and supplements. It’s not only heat that decarboxylates them and changes their structure. Long-term storage and UV exposure can agitate a cannabinoid acid and convert it into an activated cannabinoid as well. Well, that was until the father of cannabis research came along and did what he does best: revolutionise cannabis science.

What Are Cannabinoid Acids?

EPM301 & CBDA

Mechoulam worked at various labs and with various teams during this career. Most recently, he spearheaded the medical team for EPM, a pharmaceutical group working to develop novel therapeutics from synthetic cannabinoids.

EPM has turned their research efforts toward cannabinoid acids. Reshef Swisa, the CEO of the company, has stated[2]: “While the entire industry is working on the compounds that decarboxylate from the plant after it starts drying up, we were more interested in looking into what happens on the plant itself”.

Swisa has also highlighted why a lot of pharmaceutical companies aren’t really paying attention to cannabis. He claims that they don’t show much interest because these businesses can’t patent the formula for a natural molecule.

On top of this, he has identified perhaps the biggest challenge when it comes to working with cannabinoid acids: “The cannabis acids are very unstable, meaning they break apart into cannabinoids very easily. If you tried to take them from the plant or tried to consume them, the heat of your body would break them down and they would decarboxylate”.

However, the team at EPM supports the view that cannabinoid acids offer more potent effects than their resulting cannabinoids. To tackle the issues of patentability and volatility, EPM recruited the genius mind of Mechoulam.

During his research role at the company, Mechoulam overcame the hurdle of cannabinoid acid breakdown. He developed a technique that modifies the acids and keeps them stable enough to make them usable on an industrial scale.

Mechoulam took CBDA and stabilised it using a chemical process called esterification. This procedure enables the carboxyl group to maintain a grip on the rest of the CBD molecule, meaning it keeps CBDA intact in situations that would otherwise pull the chemical apart.

Not only did this discovery increase the stability and therefore usefulness of the cannabinoid acid, but it allowed EPM to patent this form of CBDA, which they called cannabidiolic acid methyl ester, or EPM301.

EPM301 and Its Potential Uses

Cannabis researchers are currently exploring the potential of CBDA for a variety of conditions, including neuropathic pain[3] and Dravet syndrome[4].

Mechoulam himself gave a glimpse into the ongoing research[5]: “We compare our compound not only to cannabinoids but to the existing drugs that are applied today”, adding, “So, for example, in IBD [inflammatory bowel disease] we compared our compounds to two conventional products: one is the prednisone (the steroids) and one is a biological drug. And in both of them, we managed to prove that the activity of our compound is very similar to the common one”.

The legendary researcher had an optimistic outlook when it came to his latest creation. He hoped that, within the next few years, it would reach a similar status in the market as CBD.

Swisa has also shared his hopes about the potential future applications of EPM301. In general, the signs look good that this synthetic cannabinoid acid will find its way into clinical settings.

EPM301 and Its Potential Uses

Mechoulam: Who Was the Father of Modern Cannabis Research?

Mechoulam’s discovery has led to a cannabinoid acid revolution. Once again, his genius paved the way toward a future of cannabis-based medicine. Although impressive, this finding barely scratches the surface of this man’s contributions to the world of cannabis science.

Entering the World of Weed

Born in Bulgaria, Mechoulam’s parents took him to Israel in 1949. Here, he earned a master’s degree in biochemistry from the Hebrew University of Jerusalem in 1952, followed by a PhD in chemistry from the Weizmann Institute in Rehovot.

Mechoulam clearly had a penchant for chemicals from the get-go. Eventually, he’d find himself applying this knowledge within the field of cannabis. He recalled the start of his cannabis journey as a fateful bus ride in 1964. After receiving 5kg of hash from the Israeli police, he was tasked with transporting it back to his laboratory at the Weizmann Institute. His team had already discovered the chemical structure of CBD back in 1963, and now they had an entire brick of cannabis chemicals to play with.

Discovery and Synthesis of THC and Other Cannabinoids

It didn’t take long for Mechoulam to work his magic. He successfully isolated THC[6] from this same lump of hash alongside his research partner Yehiel Gaoni. In a paper titled “Isolation, Structure, and Partial Synthesis of an Active Constituent of Hashish”, the two documented the process of obtaining and discovering the psychotropic cannabinoid from the crude material.

Although Mechoulam and Gaoni deserve all the credit for this discovery, it’s important to remember that they were continuing the decades-long work of researchers before them. Such efforts include those of Robert Cahn, who first isolated CBN[7]a product of THC degradation. One year later, in 1965, the two were also the first to synthesise THC[8] in the form of dl-Δ1-tetrahydrocannabinol. Mechoulam and his team also discovered the chemical structures of other cannabinoids over the next decade, including CBG, CBC, and several cannabinoid acids.

Discovery and Synthesis of THC and Other Cannabinoids

Unveiling the Endocannabinoid System (ECS)

After the discovery of THC, various animal and human studies confirmed that THC was indeed the main psychotropic component of cannabis. However, researchers didn’t know how the cannabinoid managed to produce these effects.

Scientists knew of the lipophilic nature of THC—that cannabinoids readily bind to fat. This knowledge gave way to a theory that the molecule acted non-specifically in the body. Some researchers believed that THC probably entered the high-fat environment of the cell membrane, where it floated around and altered consciousness through a non-specific mechanism of action.

Mechoulam’s work swiftly changed this view. In the 1980s, the father of cannabis research and his colleagues determined that cannabinoids work through a specific mechanism in the body[9]. This finding catalysed the hunt for cannabinoid receptors in mammalian tissue.

Researchers discovered two G-coupled protein receptors that make up what we now know as the canonical endocannabinoid system. They discovered the CB1 receptor (where THC binds to produce its effects) in 1988, and the CB2 receptor in 1993.

The presence of cannabinoid receptors in mammalian tissue then drove attention toward finding the endogenous signalling molecules that bind to them. Mechoulam passed the finish line in the first place, leading a research team that concluded anandamide (the bliss molecule) serves as a CB1 activator, and that 2-AG also works to regulate the endocannabinoid system.

Mechoulam also contributed massively to cannabinoid research by designing and synthesising a range of novel synthetic cannabinoids that are used to target endocannabinoid receptors during research. These include:

  • HU-210: A synthetic analogue of THC that targets CB1 and CB2
  • HU-308: A molecule designed to target CB2
  • HU-580: A synthetic form of CBDA that displays more potency than the natural molecule, and targets serotonin receptors

A Legendary Figure in Cannabis Science

Mechoulam made a name for himself within the field of cannabis science. His discoveries have not only led to a better understanding of the cannabis plant, but a more thorough view of the human body and its systems.

We owe a lot to this hard-working academic. Mechoulam received numerous “Highly Cited Researcher Awards”, and ranks among the top 1% of researchers in the world for cited papers in a specific domain of study.

The scientific publisher BioMed Central interviewed Mechoulam in 2020, asking him about his thoughts on the future of cannabis research[10]. He stated he’d like to see more human clinical trials regarding cancer and further exploration of the expanded endocannabinoid system. Hopefully, the doctor’s wishes will come true in the near future.

External Resources:
  1. Cannabis Pharmacology: The Usual Suspects and a Few Promising Leads - PubMed https://pubmed.ncbi.nlm.nih.gov
  2. Father of cannabis research plans a new revolution nearly 60 years later - The Jerusalem Post https://www.jpost.com
  3. An evaluation of the anti-hyperalgesic effects of cannabidiolic acid-methyl ester in a preclinical model of peripheral neuropathic pain https://bpspubs.onlinelibrary.wiley.com
  4. Pharmacokinetics of Phytocannabinoid Acids and Anticonvulsant Effect of Cannabidiolic Acid in a Mouse Model of Dravet Syndrome https://pubs.acs.org
  5. More Potent Than CBD, THC: Dr. Raphael Mechoulam Explains His Latest Discovery https://www.forbes.com
  6. Isolation, Structure, and Partial Synthesis of an Active Constituent of Hashish https://pubs.acs.org
  7. 174. Cannabis indica resin. Part III. The constitution of cannabinol - Journal of the Chemical Society (Resumed) (RSC Publishing) https://pubs.rsc.org
  8. A Total Synthesis of dl-Δ1-Tetrahydrocannabinol, the Active Constituent of Hashish https://pubs.acs.org
  9. The 90th Birthday of Professor Raphael Mechoulam, a Top Cannabinoid Scientist and Pioneer https://www.ncbi.nlm.nih.gov
  10. The father of cannabis research: Q&A with Raphael Mechoulam - On Health https://blogs.biomedcentral.com
Disclaimer:
This content is for educational purposes only. The information provided is derived from research gathered from external sources.

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Privacy Policy - Royal Queen Seeds

To ensure a safe online environment and guarantee adequate data protection, we strictly comply with all legal requirements. In this privacy statement, we provide information about how and for what purpose data is collected, safety measures, storage periods and contact details.


COMPANY NAME: SNORKEL SPAIN, SL (hereinafter ROYAL QUEEN SEEDS)

C/ Vilar d'Abdelà, 5 (nave 1) CP: 08170 de Montornès del Vallès

+34 937 379 846

support@royalqueenseeds.com


The present Privacy Policy sets out the terms on which we will treat personal data at ROYAL QUEEN SEEDS; this includes any personal data collected through our website https://www.royalqueenseeds.com/ as well as any other data we process in the course of our business activities.

ROYAL QUEEN SEEDS collects the following personal data for the purposes listed below:

SECTION 1 – PERSONAL INFORMATION WE COLLECT

1.1 Account purchases

Account purchases can only be made if you are in possession of a personal account. When you create an account or purchase something from our shop, as part of the buying and selling process we collect the following personal information that you provide to us:

This information is required for delivery. In addition, when you browse our shop, we automatically receive the Internet Protocol (IP) address of your computer. Based on this information, we can optimise your online experience and at the same time protect our online environment.

Purpose of data collection

We collect and store account-related data for the following purposes:

(a) to carry out obligations arising from any contracts between you and us, and to provide you with information, products and services that you may request from us;

(b) to set up, manage and communicate with you about your account and your orders;

(c) to conduct market research and analysis;

(d) to confirm your age and identity, and to detect and prevent fraud.

1.2 Newsletters

With your explicit permission, we may send you newsletters about our shop, new products and other updates. We send newsletters based on your explicit consent. In the event that you purchase a product, and in accordance with current regulations, we may send you commercial communications in accordance with the legitimate interest of our company, always about products or services similar to those you have purchased or contracted. In any case, you may exercise your right of opposition through the channels announced in this Privacy Policy. The following information is collected in relation to the newsletter:

We do not need to know the sex of the person in order to send the newsletter (data minimisation: by law we must ask for data that is strictly necessary to provide the service, and in this case knowing the sex is not necessary to send the newsletter).

Purpose of data collection

The data collected is used to:

(a) personalise our emails, including your name and gender;

(b) provide gender-specific content.

You can withdraw your consent at any time by using the link provided in the newsletter or the contact information provided in section 2.

1.3 Customer service and contact form

In order to provide appropriate support, our customer service employees have access to information related to the account. Consequently, their support will be highly effective and friendly. The data provided in our contact form is used by our CRM provider, SuperOffice. We will only use your details to respond to your message.

SECTION 2 – LEGITIMATE INTEREST

If you have purchased any of our products, please note that we may process your personal data for promotional purposes, based on Royal Queen Seeds' legitimate interest only to offer you products or services from our company and about products or services similar to those you have purchased. You may exercise your right to opt out of future messages by the means set out in this Privacy Policy or through any notification you receive.

2.1 How do you withdraw consent?

If you change your mind, you can withdraw your consent for us to contact you for the purpose of collecting, using, or disclosing your data at any time by reaching out to us at: support@royalqueenseeds.com.

SECTION 3 – DISCLOSURE

We may disclose your personal information if we are required to do so by law or if you breach our Terms of Service.

SECTION 4 – HOW LONG DO WE KEEP YOUR DATA?

At Royal Queen Seeds, we will not retain your data for longer than is necessary for the purposes described in this Policy. Different retention periods apply for different types of data; however, the longest period we will normally hold any personal data is 10 years.

4.1 Account information

Data relating to the account remains relevant for as long as the consumer is in possession of an account. Therefore, the data remains documented for as long as the account exists. When our customers delete an account, the associated data will be deleted within a reasonable period of time. Requests regarding the inspection or correction of stored personal data or the deletion of an account can be sent to support@royalqueenseeds.com.

4.2 Newsletters

In the event that you give us your consent to inform you about our products or services, we will keep your data until you express your wish not to receive any further communications from us. However, we regularly (every month) carry out a relevance check. Registered customers (and their personal information) will be deleted whenever customers do not reply to our request. In addition, our newsletter mailing has an opt-out feature. Consumers can withdraw their consent by using this opt-out feature.

SECTION 5 – COOKIES

Cookies are small information files that notify your computer of previous interactions with our website. These cookies are stored on your hard drive, not on our website. Essentially, when you use our website, your computer displays its cookies to us, informing our site that you have visited before. This allows our website to function more quickly and remember aspects related to your previous visits (such as your username), making your experience more convenient. At Royal Queen Seeds, we use two types of cookies: functional and analytical.

5.1 Functional Cookies

Functional cookies are used to enhance your online experience. Among other things, these cookies track what is added to your shopping cart. The use of these cookies does not require prior authorization.

5.2 Analytical Cookies

Analytical cookies are used for research and market analysis. The data collected with these analytical cookies is anonymous, making it unusable for third parties. The use of these cookies does not require prior authorization.

SECTION 5 – THIRD-PARTY SERVICES

Third-party services are required to conduct transactions and provide our services. In general, the third-party providers we use will only collect, use and disclose your information to the extent necessary to enable them to perform the services they provide to us.

However, certain third-party service providers, such as payment gateways and other payment transaction processors, have their own privacy policies regarding the information we must provide to them for your transactions.

We encourage you to read the privacy policies of these providers so that you can understand how these providers will handle your personal information.

In particular, certain suppliers may be located or have facilities located in a different jurisdiction than yours or ours. Therefore, if you choose to proceed with a transaction involving the services of a third party, your information may be subject to the laws of the jurisdiction in which that service provider or its facilities are located.

Once you leave our website or are redirected to a third-party website or application, you are no longer governed by this Privacy Policy or the Terms of Service of our website.

Web analytics service (anonymous data)

On this website we have integrated an element of a web analytics service (with anonymisation functionality). Web analytics can be defined as the gathering, processing and analysis of data about the behaviour of visitors to websites. An analytics service collects, among other things, data about which website a person came from (the so-called referrer), which sub-pages they visited or how often and for how long they visited a sub-page. Web analytics is mainly used for website optimisation and for a cost–benefit analysis of internet advertising.

Courier service

To complete deliveries we use a courier service. This courier service carries out the delivery between our company and the consumer's home. To complete these logistics, the company requires access to the consumer's name and address information.

Mailing service

Royal Queen Seeds uses a third-party mail service provider to send its newsletter. This provider has access to limited account information related to opt-in consent (e.g. email address).

Marketing services

Royal Queen Seeds has the support of a company that specialises in marketing and communication activities. Their access to personal information is very limited and mostly anonymous.

Payment services

At Royal Queen Seeds we use external payment services to handle our transactions (e.g. credit card payments).

SECTION 6 – SECURITY

To protect your personal information, we take reasonable precautions and follow industry standard best practices to ensure that it is not inappropriately lost, misused, accessed, disclosed, altered or destroyed.

If you provide us with your credit card information, the information is encrypted using secure socket layer technology (SSL) and stored using AES-256 encryption. Although no method of transmission over the internet or electronic storage is 100% secure, we follow all PCI-DSS requirements and implement additional industry standards that are commonly accepted. Information related to the account is protected with a hashing method. This method transforms the information into a generated hash. As a result, confidential information is protected and invisible, even to us. In addition, our databases are exceptionally protected against unauthorised access. For example, access to the database is only possible and permitted via approved IP addresses (e.g. from Royal Queen Seeds headquarters). Other attempts and addresses are rejected at all times.

Furthermore, data is anonymised as much as possible, so it cannot be directly linked to a specific consumer. With this data, however, we may be able to carry out market research and analysis. In addition, the third parties concerned (e.g. mailing service) are examined prior to our collaboration, comply with the GDPR from the EU and receive a processing agreement. Within Royal Queen Seeds, employees are assigned different access permissions. Specific permission provides access only to information that is strictly required to perform a task. Digital security measures are subject to change and must meet high requirements to ensure the safety of online customers. That is why, at Royal Queen Seeds, we appoint a security officer. Regular verification and improvement of security measures (where necessary) are part of the role.

SECTION 7 – CHANGES TO THIS PRIVACY POLICY

We reserve the right to modify this Privacy Policy at any time, so please check back regularly. Changes and clarifications will be effective immediately upon being published on the Website. If we make substantial changes to this policy, we will notify you here that it has been updated so you will know what information we collect, how we use it and under what circumstances, if any, we use and/or disclose it.

SECTION 8 – YOU HAVE THE RIGHT TO: