decarboxylation cbd vs thc

December 15, 2021 By admin Off

Experimental results for the decarboxylation…

Concentration (mM) of (A) CBDA…

No competing financial interests exist.

Structures of major cannabinoids in…

Keywords: Cannabis sativa; UHPSFC/PDA-MS; cannabinoids; decarboxylation; kinetic analysis.

Conflict of interest statement.

Experimental results for THCA-A, Δ 9 -THC and CBN at 110°C.

Concentration (mM) of (A) THCA-A…

Introduction: Decarboxylation is an important step for efficient production of the major active components in cannabis, for example, Δ 9 -tetrahydrocannabinol (Δ 9 -THC), cannabidiol (CBD), and cannabigerol (CBG). These cannabinoids do not occur in significant concentrations in cannabis but can be formed by decarboxylation of their corresponding acids, the predominant cannabinoids in the plant. Study of the kinetics of decarboxylation is of importance for phytocannabinoid isolation and dosage formulation for medical use. Efficient analytical methods are essential for simultaneous detection of both neutral and acidic cannabinoids. Methods: C. sativa extracts were used for the studies. Decarboxylation conditions were examined at 80°C, 95°C, 110°C, 130°C, and 145°C for different times up to 60 min in a vacuum oven. An ultra-high performance supercritical fluid chromatography/photodiode array-mass spectrometry (UHPSFC/PDA-MS) method was used for the analysis of acidic and neutral cannabinoids before and after decarboxylation. Results: Decarboxylation at different temperatures displayed an exponential relationship between concentration and time indicating a first-order or pseudo -first-order reaction. The rate constants for Δ 9 -tetrahydrocannabinolic acid-A (THCA-A) were twice those of the cannabidiolic acid (CBDA) and cannabigerolic acid (CBGA). Decarboxylation of THCA-A was forthright with no side reactions or by-products. Decarboxylation of CBDA and CBGA was not as straightforward due to the unexplained loss of reactants or products. Conclusion: The reported UHPSFC/PDA-MS method provided consistent and sensitive analysis of phytocannabinoids and their decarboxylation products and degradants. The rate of change of acidic cannabinoid concentrations over time allowed for determination of rate constants. Variations of rate constants with temperature yielded values for reaction energy.

Structures of major cannabinoids in Cannabis sativa.

UHPSFC/PDA (220 nm) chromatogram of a mixture of cannabinoid standards. Peak assignment: (1)…

Concentration (mM) of (A) THCA-A and (B) Δ 9 -THC as a function…

UHPSFC/PDA (220 nm) chromatogram of…

Concentration (mM) of (A) CBDA and (B) CBD as a function of time…

Experimental results for THCA-A, Δ…

Experimental results for the decarboxylation of (A) CBDA in extracts at 110°C; (B)…

Figures.

Ultimately, the ideal decarboxylation process uses the least heat possible to retain more of the plant’s therapeutic cannabinoid and terpene compounds. Terpenes, especially, can be vulnerable to evaporating off when exposed to high heat.

A number of scientific studies have analyzed different decarboxylation temperatures and their effects on the cannabinoid acids. Researchers have studied temperatures ranging from 176ºF to 293ºF and plotted decarboxylation rates for up to 120 minutes in a decarboxylation chart.

In the wild, THCA protects cannabis leaves from damaging UV-B light radiation. Some research also suggests THCA induces cell death in cannabis leaves. In humans, un-decarboxylated THCA can have numerous health benefits:

What Is the Process of Decarboxylation?

Decarboxylation after extraction does have some unique challenges including more time-consuming extraction times and lower yields. Despite these obstacles, precision commercial ovens can produce premium and delicately decarbed products.

Decarboxylation occurs over a period of time with the application of heat, which means decarboxylation can occur at varying rates depending on time and temperatures. The trick is to decarboxylate cannabis at the ideal temperature to avoid cannabinoid degradation or combustion.

Currently, Ardent is prototyping a high-powered decarboxylator fitted with a digital screen display that can hold up to five pounds of marijuana in a single cycle. The Indy is set to produce 2,240 grams at once or about 336,000 mg of THC allowing commercial operations to elevate their activation process.

Decarb ovens are built for a quick cleanup. Its stainless steel construction and airtight seal allow for minimal aroma leakage and complaints from neighbors. Popular oven makers include Cascade Sciences, SH Scientific, Thermo Fisher Scientific, Sheldon Labs, and Precision Quincy, which can be found in the United States and Europe.

When cannabis matter undergoes the heating process, the cannabinoid acids’ molecular structure changes. When decarboxylated, the acids lose one carboxyl group (-COOH) as carbon dioxide while retaining one hydrogen atom.

Cannabis decarboxylation is a crucial component of activating the psychoactive compounds found in cannabis and hemp plants. Decarboxylation happens organically for smokable plant material, as the heat from the flame does the work. For consumables, tinctures and salves, however, it is a more careful process that occurs earlier in production.

Medical patients treating their symptoms with oral or topical medical marijuana must ensure their cannabis is decarboxylated. Commercial manufacturers take care of the extraction and decarboxylation process to ensure the infused product is ready to consume after purchase.

Decarboxylation Temperatures For Cannabis.

The decarboxylation reaction is important because the heating process converts tetrahydrocannabinolic acid (THCA), the non-psychoactive cannabinoid acid, into the highly intoxicating THC compound that produces euphoria. Decarbing cannabis also converts cannabidiolic acid (CBDA) into CBD which is tamer when compared to the effects of THC.

Decarboxylation after extraction can degrade many of the more volatile terpenes with lower boiling points but is necessary for many extraction methods. Special techniques must be used to prevent terpene loss during pre-extraction or post-extraction decarboxylation. Unfortunately, because these techniques are often difficult and costly, most cannabis extractors do not take the time to preserve terpenes. Terpenes can also be ruined in extraction and post-processing. Hydrocarbon extraction does not require decarboxylation so terpenes can be preserved.

Cannabis users and manufacturers vary in decarboxylation temperatures and methods. Generally, lower decarboxylation temperatures take longer to fully decarb. Exposing marijuana to high decarboxylation temperatures for a long time will degrade the active compounds.

Decarboxylation ovens feature temperature controls to within plus or minus .5 degrees celsius. Manufacturers can check temperatures on built-in and easy-to-read LED displays and set the timer for ultimate precision and a reliable decarbing session.

CBDA, the non-decarboxylated precursor to the CBD compound, is found in trace amounts in the cannabis plant. Like THCA, not as much research has been performed on CBDA compared to CBD and THC research. New evidence, however, suggests that CBDA can have plenty of health benefits when the plant is kept in its raw form:

To Decarb Or Not To Decarb? That Is The Question.

Each cannabinoid and terpene has a different decarboxylation temperature. For instance, THCA requires temperatures to be about 220ºF for about 30 to 45 minutes before the compounds begin decarboxylating. Full decarboxylation time can vary depending on the material and amount needed to decarb.

Decarboxylation is one of the most important processes when making edibles, tinctures, and other consumable goods, because there is no heat added during consumption of these products. Decarbing activates the plant’s most essential cannabinoids: tetrahydrocannabinol (THC) and cannabidiol (CBD). For smokeables, decarboxylation prior to consumption is not necessary, as it happens when the flame or electric heating element hits the plant.

No, decarboxylation methods do not destroy CBD or THC, for that matter, if done right. High temperatures can scorch cannabis rendering the kief, concentrates, or bud unusable, but a uniform heat can convert raw cannabis compounds into their psychoactive counterparts. Decarbed cannabis actually increases the concentration of cannabinoids such as CBD and THC.

Decarboxylation is a crucial step in the consumption process, but not all cannabis will or should be decarbed. Much of today’s cannabinoid research has focused on the two main cannabinoids: THC and CBD. More recently, however, researchers have set their sights on the potential therapeutic application of non-psychoactive cannabinoid acids such as THCA and CBDA.

THC and CBD function as partial agonists or agonists of the endocannabinoid system (ECS). Consuming decarboxylated cannabis can have effects on multiple body functions determined by the ECS such as sleep, appetite, pain, inflammation, immune response, and mood. Decarbed THC and CBD can then be infused when cooking a small or large volume of cannabis infused products.

Depending on the product type a manufacturer is producing, decarboxylation before making oil is acceptable. Decarboxylation after cannabis extraction is also regularly performed. By definition, decarbing creates THC from THCA, and prevents the creation of cannabinoid acidi isolates.

Efficient production of Δ 9 -THC, CBD, and CBG from cannabis is important for the development of dosage formulations to facilitate the successful medical use of cannabis. These neutral cannabinoids do not occur at significant concentrations in the plants. Cannabis synthesize primarily the carboxylic acid forms of Δ 9 -THC, CBD, and CBG, namely, Δ 9 -tetrahydrocannabinolic acid A (THCA-A), cannabidiolic acid (CBDA), and cannabigerolic acid (CBGA). These acidic cannabinoids are thermally unstable and can be decarboxylated when exposed to light or heat via smoking, baking, or refluxing. As a result, the requisite forensic analyses are usually expressed as the sum of the acidic and neutral forms of the cannabinoids. Reports also show that Δ 9 -THC itself readily oxidizes to cannabinol (CBN) with oxygen and light during the decarboxylation process. 6.

2 Waters Corporation, Milford, Massachusetts.

Results: Decarboxylation at different temperatures displayed an exponential relationship between concentration and time indicating a first-order or pseudo -first-order reaction. The rate constants for Δ 9 -tetrahydrocannabinolic acid-A (THCA-A) were twice those of the cannabidiolic acid (CBDA) and cannabigerolic acid (CBGA). Decarboxylation of THCA-A was forthright with no side reactions or by-products. Decarboxylation of CBDA and CBGA was not as straightforward due to the unexplained loss of reactants or products.

1 National Center for Natural Products Research, School of Pharmacy, University of Mississippi, University, Mississippi.

Methods: C. sativa extracts were used for the studies. Decarboxylation conditions were examined at 80°C, 95°C, 110°C, 130°C, and 145°C for different times up to 60 min in a vacuum oven. An ultra-high performance supercritical fluid chromatography/photodiode array-mass spectrometry (UHPSFC/PDA-MS) method was used for the analysis of acidic and neutral cannabinoids before and after decarboxylation.

Associated Data.

LC is another chromatographic technique commonly used for decarboxylation studies because it is capable of detecting both neutral and acidic cannabinoids. No decarboxylation or derivatization is necessary using this technique. Veress et al. 10 studied the generation of Δ 9 -THC by heating dried extracts of cannabis over a range of temperature and time, and the products were analyzed by high-performance liquid chromatography/diode-array (HPLC/DAD). Maximum formation of Δ 9 -THC was observed in ∼5–10 min at 145°C followed by a significant loss at longer times possibly due to evaporation of Δ 9 -THC. Dussy et al. 6 also heated pure THCA-A in an oven for a fixed time (15 min) at 120°C, 140°C, 160°C, and 180°C. The reaction products were also analyzed by HPLC/DAD. Conversion of THCA-A was complete at 160°C; however, formation of an oxidation product, CBN, was observed at 160°C and 180°C. Thus, the conversion of the acid to Δ 9 -THC was never perfectly complete without loss or degradation of starting material. In this study, the molar sum of Δ 9 -THC and THCA-A measured by HPLC/DAD was always higher than the total Δ 9 -THC measured by GC, indicating an incomplete decarboxylation reaction. More recently, Perrotin-Brunel et al. 11 studied the kinetics and molecular modeling of the decarboxylation of THCA-A using HPLC. The proposed pseudo -first-order, acid catalyzed keto–enol mechanism for the decarboxylation process was found to be >95% efficient. The major problem with the HPLC/DAD analysis of acidic or neutral cannabinoids is the low molar absorptivity of these components, which results in relatively high limits of detection and restricts DAD detection to low wavelengths where there is often strong background absorbance from the eluant components, especially during gradient elution experiments. This problem can be overcome by using mass spectrometric detection.

Most of the previously reported decarboxylation results emphasized only the conversion of THCA-A to Δ 9 -THC. In the current studies, decarboxylation studies of three acidic cannabinoids, namely, THCA-A, CBDA, and CBGA, were carried out over a range of temperature and time to determine the most appropriate conditions for complete decarboxylation. Beside the neutral and acidic cannabinoids from decarboxylation reaction, the possible oxidation product (CBN), the isomerization product Δ 8 -tetrahydrocannabinol (Δ 8 -THC), and tetrahydrocannabivarin (THCV) were also quantified simultaneously. In addition, the kinetic analysis, including the determination of decarboxylation reaction rate constants and reaction energies, was conducted based on the decrease in acidic cannabinoid concentrations over a range of time.

1 National Center for Natural Products Research, School of Pharmacy, University of Mississippi, University, Mississippi.

1 National Center for Natural Products Research, School of Pharmacy, University of Mississippi, University, Mississippi.

1 National Center for Natural Products Research, School of Pharmacy, University of Mississippi, University, Mississippi.

Optima-grade isopropanol and acetonitrile were purchased from Fisher Scientific. Deionized water was generated by the Millipore Milli-Q water purification system. Regular-grade carbon dioxide was obtained from New Air.

1 National Center for Natural Products Research, School of Pharmacy, University of Mississippi, University, Mississippi.

Introduction: Decarboxylation is an important step for efficient production of the major active components in cannabis, for example, Δ 9 -tetrahydrocannabinol (Δ 9 -THC), cannabidiol (CBD), and cannabigerol (CBG). These cannabinoids do not occur in significant concentrations in cannabis but can be formed by decarboxylation of their corresponding acids, the predominant cannabinoids in the plant. Study of the kinetics of decarboxylation is of importance for phytocannabinoid isolation and dosage formulation for medical use. Efficient analytical methods are essential for simultaneous detection of both neutral and acidic cannabinoids.

1 National Center for Natural Products Research, School of Pharmacy, University of Mississippi, University, Mississippi.

The plant Cannabis sativa, in the form of crude drugs, marijuana, hashish, or hash oil, is the most widely consumed and popular recreational/medicinal botanical drug product in the world. 1 The legal status of cannabis varies significantly from state to state within the United States and also from country to country. As a result of the rampant use and confounding legal issues, there has been a significant case load increase seen in forensic laboratories. Therefore, cannabis is now one of the most thoroughly studied and analyzed plant materials. More than 100 cannabinoids have been isolated and identified in cannabis 2 along with the primary psychoactive component, Δ 9 -tetrahydrocannabinol (Δ 9 -THC). In addition to Δ 9 -THC, there are other components of cannabis that have been shown to be medically beneficial. For example, cannabidiol (CBD) and cannabigerol (CBG) can moderate or influence the psychoactive effects of Δ 9 -THC. 3,4 Studies of cannabis have also investigated the potential benefits of phytocannabinoids as anticancer, antiemetic, sedative, and palliative agents for several other disease states and symptoms. 3,5.

Mohamed M. Radwan.

1 National Center for Natural Products Research, School of Pharmacy, University of Mississippi, University, Mississippi.

Supercritical fluid chromatography (SFC) is a mild separation technique by which decarboxylation of the acid cannabinoids can be avoided. 12 It is fast, cost-effective, and able to provide the resolution necessary to separate neutral and acidic cannabinoids simultaneously. 13 Thus, ultra-high performance supercritical fluid chromatography (UHPSFC) with photodiode array (PDA) and mass spectrometry (MS) detections was used the first time to our knowledge to conduct a decarboxylation study of phytocannabinoids in a solvent extract of cannabis.

To understand the decarboxylation reactions that can occur with phytocannabinoids, efficient analytical methods are necessary to determine the concentration variations of decarboxylation reactants (acidic cannabinoids) and products (neutral cannabinoids) over time. Many analytical instruments have been applied to analyze cannabinoids in cannabis. 3,6,7 Among them, gas chromatography (GC) and liquid chromatography (LC) are the most commonly used techniques.

GC is ideal in some ways for these low molecular weight (280–360) neutral cannabinoids. However, the labile acids cannot be analyzed by GC without decarboxylation or derivatization. 8 Hewavitharana et al. 9 reported the decarboxylation reaction conducted in a heated GC injection port and suggested that this process can provide a means of complete conversion of the acids to neutral cannabinoids. Likewise, Dussy et al. 6 also studied the decarboxylation of pure Δ 9 -tetrahydrocannabinolic acid A (THCA-A), however, the generation of Δ 9 -THC was maximal at an intermediate temperature (225°C) but with only 65% conversion. At 300°C, a significant loss of Δ 9 -THC was observed, although no CBN, a possible oxidation product, was observed. Thus, the use of a GC injection port to convert THCA-A to Δ 9 -THC was not satisfactory under the experimental conditions of that particular study. In summary, GC analyses are complicated by the need for decarboxylation or derivatization of the acid cannabinoids before analysis. Moreover, both decarboxylation and derivatization techniques are subject to efficiency issues.

3 Department of Pharmaceutics and Drug Delivery, School of Pharmacy, University of Mississippi, University, Mississippi.

Conclusion: The reported UHPSFC/PDA-MS method provided consistent and sensitive analysis of phytocannabinoids and their decarboxylation products and degradants. The rate of change of acidic cannabinoid concentrations over time allowed for determination of rate constants. Variations of rate constants with temperature yielded values for reaction energy.

4 Division of Pharmacognosy, Department of BioMolecular Science, School of Pharmacy, University of Mississippi, University, Mississippi.

Ikhlas A. Khan.

1 National Center for Natural Products Research, School of Pharmacy, University of Mississippi, University, Mississippi.

Nine cannabinoid reference standards, namely, CBD, Δ 8 -THC, THCV, Δ 9 -THC, CBN, CBG, THCA-A, CBDA, and CBGA, were isolated in-house at The National Center for Natural Products Research, University of Mississippi, from cannabis plant materials (structures are shown in Fig. 1 ). The identity and purity of the isolated standards were established by infrared spectroscopy, nuclear magnetic resonance, and liquid chromatography/quadrupole time-of-flight.