1. The Hemp Chronicle: DECARBOXYLATION OF TETRAHYDROCANNABINOLIC ACID
Motivation and Summary
The background of this study is as follows: On average hemp food stuffs contain up to 90% of the nonpsychoactive THCA. Nonetheless, regulation for THC limits in food often uses total THC = THCA + THC.
This leads to an overestimation of the content of psychoactive THC in hemp food.
The argument is that THCA can be transformed in THC after heating (decarboxylation).
This study analysed how relevant this conversion is in realistic scenarios.
The graph above shows the results for the complete decarboxylation depending on temperature and time.
One realistic example scenario demonstrates, that the total THC measurement method can lead to an overestimation of the content of psychoactive THC of ca. 60%.
To evaluate to what extent the THCA content of hemp food stuffs can influence their THC-levels, we performed a literature survey about the THCA carboxylation to THC (Fig. 1). In a second step we plotted these on a timetemperature graph using two different methods.
On the one hand, curve fitting with various mathematical functions was applied, where logarithmic trendlines had the best R-squared values of 0.99. This was in line with the behaviour of a first order reaction and research about reaction kinetics of the decarboxylation reaction proves this (Perrotin-Brunel et al., 2011).
After thorough research it became apparent that the most publications concerned with THCA decarboxylation to THC after heating, were papers describing HPLC or GC methodologies and mostly only had one timepoint and temperature where they measured THCA and THC.
The graph shows the results of the literature survey of studies which had at least two time-points and temperatures.
What the graphic means
Taking the combined trendline into account, it would need 3 hours at 100 °C to convert THCA fully into THC and 4 hours at 98 °C.
At high temperatures above 160 °C only about 10 minutes and at 200 °C only seconds are needed to convert THCA fully into THC.
It has to be pointed out that various techniques were used in the THC measurements e.g. Veress and colleagues (1990) used THCA in hexane on a glass plate whereas Taschwer et al. (2015) used confiscated cannabis and heated it in a closed cabinet. These differences could explain the discrepancy in some temperatures and times.
Moreover, the different cited papers use various units of THC measurement e.g. mg/g vs. percentages.
The graphic shows the assumed complete THCA decarboxylation to THC, where we used the peaks shown in the graph of Veress and colleagues (1990), for example, to indicate complete decarboxylation.
Side reactions affecting THC levels
It is important to note, that starting from ca. 157 °C THC evaporates.
Consequently, the peak THC levels given here, are only present in the sample for a short amount of time.
For instance, the highest THC content is reached at 145 °C after 7 min, but after 40 min the total THC amount is already halved (Veress et al., 1990). Taschwer and colleagues (2015) show in their experiments peak THC levels after 3 min heating at 150 °C, but a return to near zero THC percentages after 7 min.
Apart from THC evaporation, several other reactions occur when certain temperatures are reached.
For example, Dussy et al. (2005), were only able to convert a maximum of 70% THCA into THC. They mention polymerization and oxidation of THCA and THC to CBN and CBNA, respectively, as side reactions.
The THC degradation to CBN can already be considerable at temperatures between 85 – 100 °C (Repka et al., 2006).
Having these reactions, which reduce the THC content in mind, it is interesting that the THCA decarboxylation reaction starts at 90 °C (Veress et al., 1990; Peschel, 2010).
Implications of THCA decarboxylation to real live scenarios e.g. baking
One has to differentiate between the temperatures used to heat the oven, the temperature reached on the outside of the cake, which, for instance, has a proportion of hemp flour in it, and the temperature inside. It is reasonable to assume that relevant temperatures for THC-evaporation are reached (presuming oven temperatures with an average of 180 °C) only on the outside of the cake.
However, THCA and THC degradation will already play a role.
Inside the cake temperatures will not be higher than 100 °C as long as water is present in the cake. Using an average baking time of 45 min, the timepoints of the Veress et al. (1990) study and the above assumption that their peaks represent 100% decarboxylation, this would mean that only 1/3 of the THCA is converted into THC.
Coming back to the currently used total THC calculations for its limits, mentioned at the beginning of this paper, this would mean that instead of the actually present THC content in the heated hemp flour of ca. 33% (THC created through THCA-decarboxylation) + ca. 10% (original THC content in hemp flour) = ca. 43% (realistic THC content in heated hemp flour), using the total THC measurement method leads to an overestimation of 57%.
These calculations are only approximations, because the Veress study was carried out on heated glass plates and not with hemp flour cake in a regular oven. Nonetheless, they give an impression to what extent the total THC measurements overestimate the actual THC content.
Dussy, F. E., Hamberg, C., Luginbühl, M., Schwerzmann, T., & Briellmann, T. A. (2005). Isolation of Δ 9-THCA-A from hemp and analytical aspects concerning the determination of Δ 9-THC in cannabis products. Forensic science international, 149(1), 3-10.
Eichler, M., Spinedi, L., Unfer-Grauwiler, S., Bodmer, M., Surber, C., Luedi, M., & Drewe, J. (2012). Heat exposure of Cannabis sativa extracts affects the pharmacokinetic and metabolic profile in healthy male subjects. Planta medica, 78(07), 686-691.
Perrotin-Brunel, H., Buijs, W., Van Spronsen, J., Van Roosmalen, M. J., Peters, C. J., Verpoorte, R., & Witkamp, G. J. (2011). Decarboxylation of Δ 9-tetrahydrocannabinol: Kinetics and molecular modeling. Journal of Molecular Structure, 987(1), 67-73.
Peschel, W. (2010) Quality control of traditional cannabis tinctures: pattern, markers and stability. doi:10.3797/ scipharm.1603-02
Repka, M. A., Munjal, M., ElSohly, M. A., & Ross, S. A. (2006). Temperature stability and bioadhesive properties of Δ9-tetrahydrocannabinol incorporated hydroxypropylcellulose polymer matrix systems. Drug development and industrial pharmacy, 32(1), 21-32.
Taschwer, M., & Schmid, M. G. (2015). Determination of the relative percentage distribution of THCA and Δ 9-THC in herbal cannabis seized in Austria–Impact of different storage temperatures on stability. Forensic Science International, 254, 167-171.
Veress, T., Szanto, J. I., & Leisztner, L. (1990). Determination of cannabinoid acids by high-performance liquid chromatography of their neutral derivatives formed by thermal decarboxylation: I. Study of the decarboxylation process in open reactors. Journal of chromatography A, 520, 339-347.
Whittle, B., Hill, C. A., Flockhart, I. R., Downs, D. V., Gibson, P., & Wheatley, G. W. (2008). U.S. Patent No. 7,344,736. Washington, DC: U.S. Patent and Trademark Office.
Decarboxylation of Tetrahydrocannabinolic acid (THCA) to active THC
Authors: Kerstin Iffland, Michael Carus and Dr. med. Franjo Grotenhermen, nova-Institut GmbH
Hürth (Germany), October 2016
Woven into the fabric of the human body is an intricate system of proteins known as cannabinoid receptors that are specifically designed to process cannabinoids such as tetrahydrocannabinol (THC), one of the primary active components of Cannabis or marijuana.
Human breast milk naturally contains many of the same cannabinoids found in marijuana, which are actually extremely vital for proper human development.
Endocannabinoids have been detected in maternal milk and activation of CB1 (cannabinoid receptor type 1) receptors appears to be critical for milk sucking and activating oral-motor musculature.
Cell membranes in the body are naturally equipped with these cannabinoid receptors which, when activated by cannabinoids and various other nutritive substances, protect cells against viruses, harmful bacteria, cancer, and other malignancies. And human breast milk is an abundant source of endocannabinoids, a specific type of neuromodulatory lipid that basically teaches a newborn child how to eat by stimulating the suckling process.
Children who are breastfed naturally receive doses of cannabinoids that trigger hunger and promote growth and development.
There are two types of cannabinoid receptors in the body — the CB1 variety which exists in the brain, and the CB2 variety which exists in the immune system and throughout the rest of the body.
Each one of these receptors responds to cannabinoids, whether it is from human breast milk in children, or from juiced marijuana in adults.
This essentially means that the human body was built for cannabinoids, as these nutritive substances play a critical role in protecting cells against disease, boosting immune function, protecting the brain and nervous system, and relieving pain and disease causing inflammation, among other things.
And because science is finally catching up in discovering how this amazing cannabinoid system works, the stigma associated with marijuana use is, thankfully, in the process of being eliminated.
Breast Milk Reception
Recent research suggests that the endogenous cannabinoids (“endocannabinoids”) and their cannabinoid receptors have a major influence during pre- and postnatal development.
First, high levels of the endocannaboid anandamide and cannabinoid receptors are present in the preimplantation embryo and in the uterus, while a temporary reduction of anandamide levels is essential for embryonal implantation.
In women accordingly, an inverse association has been reported between fatty acid amide hydrolase (the anandamide degrading enzyme) in human lymphocytes and miscarriage.
Second, CB1 receptors display a transient presence in white matter areas of the pre- and postnatal nervous system, suggesting a role for CB1 receptors in brain development.
Third, endocannabinoids have been detected in maternal milk and activation of CB1 receptors appears to be critical for milk sucking by newborn mice, apparently activating oral–motor musculature.
Fourth, anandamide has neuroprotectant properties in the developing postnatal brain.
Finally, prenatal exposure to the active constituent of marihuana (Δ9-tetrahydrocannabinol) or to anandamide affects prefrontal cortical functions, memory and motor and addictive behaviors, suggesting a role for the endocannabinoid CB1 receptor system in the brain structures which control these functions.
Further observations suggest that children may be less prone to psychoactive side effects of Δ9-tetrahydrocannabinol or endocannabinoids than adults. The medical implications of these novel developments are far reaching and suggest a promising future for cannabinoids in pediatric medicine for conditions including “non-organic failure-to-thrive” and cystic fibrosis.
The endocannabinoid-CB1 receptor system in pre- and postnatal life – sciencedirect.com
3. The Medical Cannabis Council : A New Organisation established to support Australian Medical Cannabis
The Medicinal Cannabis Council provides a unifying voice for the Australian medical cannabis industry.
The Council provides a framework for best practice standards and supports the Australian industry in becoming a world leader in the research and production of safe, high-quality, scientifically backed medical cannabis products.
The objectives of the Medical Cannabis Council are to:
Foster national and international coordination and cooperation to promote the research, production, access and use of medical cannabis products;
Promote and support a high quality of medical cannabis research in Australia;
Promote and enhance Australia’s capability to produce and manufacture medical cannabis product’s;
Promote and enhance patient access to medical cannabis products;
Provide relief and support for patients seeking access to medical cannabis, including information, practical assistance and advocacy;
Promote public awareness of medical cannabis through education; and
Develop and enforce best practice, standards, and a code of conduct for producing, supplying and distributing medical cannabis products.
The Council and all its members adhere to five key underpinning principles:
This organisation is a new organisation and is set to become the working voice for the Australian Medical Cannabis Industry.
Its founders comprise a range of distinguished academics and business figures that are all working to develop the potential of an industry that could provide a value-added component for our health system, and a farm crop that can provide healthy nutrition, and a fibre suitable for paper production and garments.
i2P would support the concept of pharmacists joining this organisation for individuals, as well as their umbrella advocacy or marketing umbrella organisations.
Medical cannabis has the potential to drive future growth and revenue for community pharmacies through a wellness and health management program developed and delivered by clinical pharmacists.
One of the founding members, Prof Michael Katz, (a Director at Ripple Capital) has worked in the academic sector for both the University of Sydney and UNSW, where his focus has been on developing and implementing social investment projects and internship programs within the business faculties, as well as managing action research projects.
This includes initiating and managing the Medical Cannabis White Paper developed in collaboration with MGC Pharmaceuticals and Budding Tech.
MGC is an Australian publicly listed company whose shares have recently shown strong gains and may be of interest to those pharmacists wishing to add potential value to their share portfolio.
A recent report titled Clinical Evidence for Medicinal Cannabis: Epilepsy, Cancer and Multiple Sclerosis was Developed by the University of Sydney Community Placement Program in Partnership with MGC Pharmaceuticals.
It gives useful insights for the actual use of medical cannabis proven by local research.
It can be accessed here.