THCV – The skinny cannabinoid (part 1)

THCV – Tetrahydrocannabivarin

Cannabis sativa: The Plant of the Thousand and One Molecules“ is the title of a paper by Andre et al. which eloquently shows the complexity and immense therapeutic potential of this plant. Cannabis sativa L. is most known for its cannabinoids and is the only plant that produces them in such high quantities. [1]

Besides phytocannabinoids (plant-cannabinoids) there are a vast number of other compounds such as terpenes, flavonoids, strereoids and fatty acids that all together have a synergistic effect on the efficacy of cannabis therapy. [2]

In the past, most of the research has been concentrated on the psychotropic compound delt-9-tetrahydrocanabinol (THC), while other „lesser “cannabinoids have been mainly overlooked. One of the overlooked minor cannabinoids is THC’s little brother, (THCV).

The two cannabinoid families

There are two major cannabinoid “families” that dominate the cannabis plant and the difference is only in 2 carbon atoms. The pentyls have a phenolic sidechain of five carbon atoms, while the propyls have only three. This difference is due to two different acids being used in the synthesis of phytocannabinoid precursors. If olivetolic acid is combined with geranyl pyrophosphate, we get cannabigerolic acid (CBGa). CBGa can then be converted to other cannabinoid acids depending on the acid sythethase that is present. THCa sythethase transforms it into THCa, CBDa synthethase into CBDa and CBCa synthethase into CBCa.

If instead of olivetolic acid, divarinolic acid is combined with geranyl pyrophosphate, we get cannabigerovarinic acid (CBGVa). The same acid synthetases that convert the pentlys also convert the propyls; THCa sythethase transforms it into THCVa, CBDa synthethase into CBDVa and CBCa synthethase into CBCVa

The discovrery of THCV

THCV was fist isolated in 1970 by Gill et al. by extracting it from a licensed cannabis tincture, that was available in UK at the time. The tincture was legally imported and made from Pakistani grown cannabis. The tinctures main constituents were THC (2,4%) and THCV (2%), an interesting 5:4 ratio, that can also be found in newer chemotypes (Doug’s Varin). [3]

As a side note, the propyl analog of CBD, cannabidivarin (CBDV) was isolated, as so many other cannabinoids, form hashish, by Vollner et al., in 1969. [4]

High THCV chemovars

THCV is inherently rare in the usual cannabis “strains” and it has been difficult to find chemovars with high percentages of this cannabinoid. Higher levels of this cannabinoid have been usually found in certain Asian and African landraces.

GW Pharma has developed their high THCV strain from selective inter-breeding of high 1:1 THC: THCV landraces (China, South Africa) and named (California orange, Malawi Gold) chemovars. By a selective process of self-pollination and cross breeding of the phenotypes with the highest levels of the propyl cannabinoids, they obtained a genotype with 96% of total propyl cannabinoids. [5]

One of the most well-known chemovars, with a high THCV, is the appropriately named Doug’s Varin. In tests done by Steep Hill Labs, they detected 19 % THC-A and a whopping 15% THCV-A. The main terpenes were beta-myrcene 1,5%, pinene 0,53 and limonene 0,48. They also performed an analysis on decarboxylated kief of this chemovar, and they measured 24,25% THCV and 21,13% of THC. The only measured terpene in the decarboxylated kief was beta-myrcene (0,38%), which shows us, how the monoterpenes are lost during this process. [6]

Recently, some chemovars have tested higher THCV values such as Jack el frutero (6%), Jack the Ripper (6%), Pink Boost Goddess (5%), and Black beauty (3-4%).

There might be other chemovars containing higher percentages of THCV, but sadly, a lot of analytical laboratories, still do not test for the presence of this cannabinoid.

THCV part 2

In the second part of this 2 part THCV article, I will be tackling the important question of THCV’s psychotropic effects (or lack thereof), its potential therapeutic applications in various diseases and if it really is the “skinny” cannabinoid.

References:

  1. Andre et al. Cannabis sativa: The Plant of the Thousand and One Molecules . 2016, Frontiers in plant science
  2. Roger Pertwee. The Handbook of Cannabis. 2014, Pages 14-19
  3. Gill et al. Preliminary experiments on the chemistry and pharmacology of cannabis. 1970, Nature 228:134–136
  4. Vollner, L., Bieniek, D., and Korte, F. (1969). Haschisch XX. Cannabidivarin, ein neuer Haschischinhaltsstoff. Tetrahedron Letters, 3, 145–147.
  5. P. M. de Meijer, E & M. Hammond, K. The inheritance of chemical phenotype in Cannabis sativa L. (V): regulation of the propyl-/pentyl cannabinoid ratio, completion of a genetic model. 2016, Euphytica. 210.
  6. THCV Update: Doug’s Varin Strain. 2014 http://steephilllab.com/thcv-update-dougs-varin-strain/

European Cannabis Events 2018

It is going to be a busy 2018 for cannabis expos and conferences in EU. I have compiled a list of some of the major Cannabis events in Europe this year. For clarity, I have divided them into 4 categories:

    • Cannabis Scientific Conferences
    • Business Conference
    • Expo & Conference
    • Hemp conferences

In each category, the events are listed by date. Which cannabis event are you going to participate in?

Cannabis Scientific Conferences Europe 2018

MAY

Cannabis Europa, 22 May, Barbican, London, UK

Cannabis Europa is the foremost arena to share knowledge and shape the future of medical cannabis in Europe. This is a uniquely European conference. There is no universal model for cannabis regulation and Europe has a clear opportunity to take a global leadership position. The conference is your opportunity to connect with influential leaders in science, policy and business. Gain unrivalled access to the most inspirational and forward-thinking figures in the industry. To navigate the future of European medical cannabis, industry leaders and regulators alike must share insights and innovations if we are to develop a truly successful, patient-focused sector.

JUNE

The International Annual Congress on Controversies in Cannabis-Based Medicines, 25-26 June, Vienna, Austria

It is our pleasure to invite you to participate in The International Annual Congress on Controversies in Cannabis-Based Medicines (Med-Cannabis2018) which will take place 25-26 June 2018 in Vienna, Austria.

A strong public and patient demand has led to the decision to allow cannabis products for medical use in most European countries. There is a lot of basic-science and clinical research on the potential use of cannabis products for chronic pain and cancer management as well as controversies on the potential harms.

This Congress will bring together researchers, clinicians, trialists, methodologists, industry professionals and representatives of the European Union and the European Medical Agency to update the current state of knowledge and of controversies and to outline some visions of the potential of cannabis based medicines.

ICRS Symposium, 30 June – 5 July, Leiden, the Netherlands

The 28th Annual International Cannabinoid Research Society Symposium on the Cannabinoids

Leiden, The Netherlands
Arrival date: June 30
Meeting: July 1- 4, 2018
Departure date: July 5

ICRS2018 will be our 28th annual Symposium. Another brilliant year of scientific progress!

Expo & Conference Europe 2018

JANUARY

 

Athens Cannabis Expo, January 12-14, 2018 | Faliro Sports Pavilion Arena (Tae Kwon Do) | Athens

The 1st International Cannabis Expo in Greece is happening! The purpose of the event is to inform the public about all the products and innovations that exist in the world of cannabis and the latest achievements in the medical, pharmaceutical and industrial use of cannabis. Come to get to know all the innovative companies that are active in the cannabis sector with many different products and services such as CBD (Cannabidiol), cosmetics, cocktails,  seeds, medical , vaporizers, clothing and many more.

FEBRUARY

Cannapa Mundi, 16-18 February, Rome Italy

Cannapa Mundi is the International Fair which has been bringing in Rome hemp fragrance and taste since 2015: the biggest event in Italy in exponential growth, the only officially recognized as International. In 2017: 7.500m², 120 stands, 23,000 attendances, 6,000 accredited professionals. In 2018: 9,000m², 150 stands, a relevant increase of visitors is expected.

MARCH

Spannabis Barcelona + International cannabis Forum, 9-11 March, Spain

Spannabis 15h Edition. What appeared to be a dream is now an outstanding reality: SPANNABIS, celebrating its eleven anniversary is consolidated as the most important Spanish cannabic event of the year, hand in hand with the Expocannabis fair in Madrid & Spannabis in Málaga.

APRIL

Konopex Ostrava, 20-22 April, Ostrava, Czech Republic

The Konopex Ostrava hemp expo will grow in the unique industrial area of Dolní  Vítkovice (- we call place WEEDkovice). Where we will again open the doors to the world of cannabis. There will be prepared exhibitions for you dedicated to cannabis, cannabis seeds, growing indoor and outdoor equipment and exhibitions focused on garden equipment and other curative herbs.You will find out lot of interesting information and news about usage of hemp in medicine, civil engineering, industry and livestock. Next you can look forward to a rich accompanying program including lextures, conferences and hemp exchange, where you can discuss and trade with respected experts. Finally, there will be workshops, competitions and afterparty ready for you.

CannaTrade ,27-29 April, Zurich-Oerlikon, Switzerland

We have the pleasure to welcome you to CannaTrade, the oldest hemp fair in Europe! The history of CannaTrade started 2001, in the fair halls of BEA Expo Bern, as a result of the Swiss Hemp Days in 1999 and 2000. The following editions of CannaTrade in 2008 and 2009 were presented at the exhibiton halls of Basel. Caused by the hemp related political situation, we decided to organize the fair CannaTrade in a two-years-rhythm. Until 2016, we did this successfully at Stadthalle Dietikon/Zurich.The next edition of CannaTrade takes place in the middle of Zurich!

MAY

Expo Canamo Sevilla, 11-13 May, Sevilla, Spain

Expocáñamo brings back to Seville the hemp culture fair, where you will enjoy a dynamic and comforting experience, you will dance with the best rhythms of reggae and rap, you will see the latest in cultivation technology, you will taste a wide variety of products with hemp and its derivatives and you can enjoy endless activities for your entertainment.

Indica Sativa Trade, 18-20 May, Bologna, Italy

Indica Sativa 2018

JUNE

BALKANNABIS EXPO, 1-3 JUNE, TECΗNOPOLIS ATHENS, GREECE

BALKANNABIS EXPO will host top cannabis traders, innovators, experts, industry professionals and scientists from all over the world in a rich and diverse 3-day programme that will include:

  • a large exhibition area and international trade show
  • two international conferences (Cannabis Science & Hemp Summit) with
  • keynote and guest speakers
  • cannabis culture workshops
  • networking spaces
  • masterclasses
  • market area
  • music and other artistic performances

MARY JANE BERLIN, 8 – 10 June, Arena Berlin, Germany

Mary Jane Berlin starts it third edition in Berlin – with over 6,500 m2 of hall space and 2,000 m2 of outdoor space is “Mary Jane Berlin” the leading German Cannabis exhibition with more than 200 national and international exhibitors. “Mary Jane Berlin” is not only an exhibition but also a festival. In combination with our exhibitors, food stalls, live concerts and lectures about cannabis’ therapeutic effects an extensive cultural and entertainment program is offered. As a visitor of Mary Jane Berlin, we inform you about the variety of THE green power plant – as food, cosmetic, building material, medicine and much more!

AUGUST

Green Cologne, 24-26 August, Cologne, Germany

Green Cologne starts with the biggest Cannabis Fair in Germany. The indoors as well as outdoors serves as an area for national and international exhibitors, speakers, musicians and food-trucks.

Get excited about the cannabis exhibitors from a wide variety of branches: Food, cosmetics, medicine and so much more! More than 200 exhibitors present their diverse product portfolio of this crop. Discover the innovative industry professionals’, physicians’, growers’ and scientists’ new knowledge on the fast-growing market of cannabis.

OCTOBER

Spannabis Madrid, 5-7 October, Madrid, Spain

Spain capital city will become from 5th to 7th of October the world cannabis capital by the hand of Spannabis. Spannabis will be held in Pabellón de Cristal of Casa de Campo, just a few minutes from Plaza de España. The results of the six previous fairs that we organized in Madrid suburbs, Leganés and Rivas, generated a great attendance of professionals and visitors. Because this edition will be held near the center of Madrid, we hope to have more attendance than in previous fairs.

Cultiva Hemp Expo, 12-14 October, Veinna, Austria

Cultiva Hemp Expo 2018

Cannapa in Mostra, 26-28 October, Naples, Italy

The association CANAPA in MOSTRA is pleased to present CANAPA in MOSTRA International Trade Fair of Industrial and Medical Hemp of Naples.

Hemp, known and used in all parts of the world, is recently returning to make space through a renewed social and economic interest.

In particular, we propose hemp as an ecological resource in the agricultural, energy, medical, recreational, textile, paper, green building and in every other possible field of application, trying to undermine the socio-cultural prejudices that oppose its real and massive reintroduction in the Italian context.

The fields of use of this plant are already very many, but with the advance of technology and scientific discoveries could become infinite, moreover the continuous demand for new eco-sustainable technologies imposes the need for new research on this extremely versatile material.

The intention of the association is to bring the general public and institutions aware of this potential and to bring to mind the long tradition that links our country to hemp, particularly the Campania region, trying to provide a place for aggregation , training and exchange for workers, experts, enthusiasts and anyone who is intrigued by this re-emerging industry in continuous turmoil and expansion.

NOVEMBER

Cannafest, 2-4 November, Prague, Czech Republic

The international trade show of cannabis and medical herbs Cannafest is the biggest cannabis fair in the world. Visitors can look forward to interesting expositions of exhibitors from all around the world. As usually, there will be cultivation technology, fertilizers, seeds, smoking accessories and vaporizers on display and on sale. People could also try and buy various hemp cosmetic products, clothing items or delicious hemp food, which shouldn’t be missed.

Business Conference Europe 2018

APRIL

ICBC Berlin, 11-13 April, Berlin, Germany

ICBC Berlin 2018

EuroAmerican Cannabis Business Conference, 1–2 November 2018, Prague, Czech Republic

EuroAmerican Cannabis Business Conference is an International Cannabis B2B Conference in the Heart of Europe

 

Hemp conferences Europe 2018

MAY

Hemp Food, Health & Beauty, May 25-26,The Palace at Nakło, Poland

This is a special invitation for you to join us May 25-26, 2018 for Hemp Food, Health & Beauty, part of the Hemp | 2020 Business Summit Series hosted by HempToday, the leading source for global business information about industrial hemp

We join with a group of independent entrepreneurs with strong bonds, and sharing key assets through which we strengthen our individual grass-roots businesses. We look for strategic and financial partners to join us as we work to synthesize our enterprises to further develop hemp industry value chains — from farming to processing facilities and product lines, B2B and B2C communications and marketing, sales and distribution channels.

To be held at HempToday’s center in the Palace at Nakło, Lelów, Poland, the Summit is an opportunity for current and future industry stakeholders to get up close and personal as we survey the vast opportunities in hemp food, health and beauty products worldwide, and explore investment and business opportunities together.

The aims of the Summit are to share knowledge and experiences, to foster business matchmaking among participants, to generate a body of content for broader distribution around the world, and to jointly explore the potential for hemp food, health and beauty products as an engine for sustainable local economic development.

We have invited entrepreneurs, consultants, investors, researchers and policy experts who’ll explore hemp’s market potential as a “super,” “nutritious” and “bio” food and health supplement, along with its promise in a wide range of topical, skin-care and beauty applications. We’ll look at value chain and economic development possibilities based on the production of hemp food and health products.

JUNE

International Conference of the European Industrial Hemp Association, 12 – 13 June, Maternushaus, Cologne, Germany

Specialists from all over the world will meet at EIHA 2018 in order to exchange information regarding the latest developments in hemp applications for fibres, shivs, seeds and oil as well as cannabinoids. Applications are biocomposites in automotive and construction, textiles, food, food supplements and pharmaceuticals. We are expecting again more than 300 international participants from more than 40 countries – we are looking forward to the biggest event on industrial hemp ever!

 

 

How much  ∆9-THC is in cannabis flowers?

The cannabis plant produces cannabinoids in the form of acids, like delta-9-tetrahydrocannabinolic acid (∆9-THC-A). It does not enzymatically produce a single molecule of delta-9-tetrahydrocannabinol (∆9-THC). That does not mean, that there is no ∆9-THC in the flowering tops; ∆9-THC-A and other acidic cannabinoids get converted into their neutral forms via heat, light or exposure to oxygen.

The presence and ratio of acid: neutral cannabinoids can also be an indicator of storage and age of the analysed cannabis. Improper storage can decrease the level of acidic cannabinoids, which in turn increases the level of neutral cannabinoids. Other volatile compounds, such as monoterpenes, are also susceptible to improper storage.

By doing a quick search and calculation from 15 analysed samples of type 1 (high THC) from Analytical 360’s archive website [1], the average ∆9-THC (compared to ∆9-THC-A) was 7,1% (2,4 – 12,4, n=15). From 5-10% of the total THC is usually in the neutral form, in properly stored cannabis.

If we compare this data to a study by Wang et al. [2], where they analysed DEA confiscated samples and samples from the University of Mississippi, the average % of ∆9-THC was 33,2% (19,2 – 54,7, n=11) in the DEA samples and 28,5% (10,5 – 41, n=6) in the Mississippi samples. While the number of samples analysed is relatively small, it can still give us an indication of the storage and handling of the plant materials.

Even worse results can be seen in a recently published study by Souleman et al. [3], where they analysed confiscated cannabis flowers and hashish. In the flower samples, 80% of the total THC was in the form of ∆9-THC and only 20% of ∆9-THC-A.

Another usually used indicator of cannabis poor storage is cannabinol (CBN), the oxidative product of ∆9-THC (or CBN-A). The samples form 360 analytical had no detectable CBN, while all the DEA samples had CBN present, on average 0,79 % (0,18 – 1,44, n=11). Only 2 of the 6 Mississippi samples had detectable CBN and no information on CBN levels was included in the Egyptian study.

In the discussion section of the same study they also commented that “marijuana, has shown a higher THC content than we expected based on the world drug reports.” If we compare the 11% total THC that hey reported, to the other newer published studies 12% [4] 13.9% [5] [ 14.88% [6], we can see, that it was in the lower end of potency for today’s standards.

A more indicative report, of the potency of the cannabis present on the market, can be gathered form analytical reports from laboratories. As an example, in the 15 samples analysed by 360, the average of total THC was 18% (13,25 – 23,22, n=15).

References:

1. Analytical 360 https://cbd.analytical360.com/

2. Wang YH, Avula B, ElSohly MA, Radwan MM, Wang M, Wanas AS, Mehmedic Z, Khan IA. Quantitative Determination of Δ9-THC, CBG, CBD, Their Acid Precursors and Five Other Neutral Cannabinoids by UHPLC-UV-MS. Planta Med. 2017 Dec 20.

3. Ahmed M.A. Souleman, Alaa El-Din M. Gaafar, Omar M. Abdel-Salam, Shaimaa A. El Shebiney. Determination of delta-9-tetrahydrocannabinol content of cannabis seizures in Egypt. Asian Pacific Journal of Tropical Medicine, Volume 10, Issue 3, March 2017, Pages 311-314

4. Mahmoud A.El Sohlya, Zlatko Mehmedica, Susan Fostera, Chandrani Gona, Suman Chandraa, James C.Churchb. Changes in Cannabis Potency Over the Last 2 Decades (1995–2014): Analysis of Current Data in the United States. Biological Psychiatry, Volume 79, Issue 7, 1 April 2016, Pages 613-619

5. D.J. Potter, P. Clark, M.B. Brown. Potency of delta 9-THC and other cannabinoids in cannabis in England in 2005: implications for psychoactivity and pharmacology. J Forensic Sci, 53 (1) (2008), pp. 90-94

6. W. Swift, A. Wong, K.M. Li, J.C. Arnold, I.S. McGregor. Analysis of cannabis seizures in NSW, Australia: cannabis potency and cannabinoid profile. PLoS One, 8 (7) (2013), p. e70052

7. Lewis, Melissa & Yang, Yi & Wasilewski, Ewa & A. Clarke, Hance & P. Kotra, Lakshmi. (2017). Chemical Profiling of Medical Cannabis Extracts. ACS Omega. 2. 6091-6103.

2nd annual Terpestival™ 2016 Hopland, CA

On the 23rd of July The Center for the Study of Cannabis and Social Policy (CASP) organized the 2nd annual Terpestival in Hopland CA.

The festival’s main goal is to  was designed to educate the public on the contribution of terpenoids to cannabis plant-based medicine. The keynote speaker was Dr. Ethan Russo who had a presentation entitled “Terpenoids and Cannabinoids.” There were several interesting panels all concentrated around the importance of terpenes in the hemp plant.

Total Terpene Aggregate Results

As the name suggest, in the The Terpene Tournament™,  the terpens were the stars of the show while cannabinoid content was not so relevant. All the flowers and CO2 concentrates were tested to determine the cannabinoid and terpene content. The  average flower terpene content was 1.4%, due to the loss of terpene content from harvest time. The average terpene content in concentrates was 9,7%.

An important take-away message from the event was that cannabis shouldn’t be defined only by the cannabinoid profile. Terpenes and other aromatic molecules give cannabis its distinct taste/smell and are very important not only for their medicinal value but also for the enhancement of the connoisseur experience. You can find more info on the event here.

Three new cannabinoids identified in Indian hashish

In a recently published article by Hanuš et al. (1), three new cannabinoids have been identified from a sample of Indian hashish; cannabiorcochromene,  cis-D9-tetrahydrocannabivarol and cannabinerol.

The main cannabinoids content in hashish samples seized in Israel and Czech Republic Lumír O. Hanuš, Rina Levy, Dafna De La Vega, Limor Katz, Michael Roman & Pavel Tomíček To cite this article: Lumír O. Hanuš, Rina Levy, Dafna De La Vega, Limor Katz, Michael Roman & Pavel Tomíček (2016): The main cannabinoids content in hashish samples seized in Israel and Czech Republic, Israel Journal of Plant Sciences, DOI: 10.1080/07929978.2016.1177983
Cannabiorcochromene, cis-D9-tetrahydrocannabivarol, and cannabinerol.

The study focused on identifying the main cannabinoid content of hashish samples from Morocco, Lebanon and India seized by Czech and Israel police forces. In the Indian sample from the Czech republic they also preformed a quantitative analysis of cannabinoids and terpenes which led to the identification of the three new cannabinoids. This brings the total number of cannabinoids identified in the cannabis plant to 120, although according to Dr. Hanuš lectures, the total sum is higher, amounting to 144 identified cannabinoids (Hanuš, march 2016).

Analysis of the the different hashish samples from Lebanon, Morocco and India also showed some interesting results. In Lebanese hashish the content of CBD was high and THC was low (2-3:1 CBD:THC ratio) while the Moroccan samples showed the opposite, high in THC and low in CBD (1:2-3 CBD:THC ratio). Indian hashish had a mixed range of ratios but showed higher
amounts of propylcannabinoids, such as D9-tetrahydrocannabivarin
(THCV) or cannabivarin (CBV). From the results of the analysis,  hashish of Lebanese origin was indicative of fiber-type phenotype and Moroccan pf the drug-type phenotype.

Refernces:

  1. Lumír O. Hanuš, Rina Levy, Dafna De La Vega, Limor Katz, Michael Roman,Pavel Tomíček (2016): The main cannabinoids content in hashish samples seized in Israel and
    Czech Republic, Israel Journal of Plant Sciences, DOI: 10.1080/07929978.2016.1177983