Elsevier

Fitoterapia

Volume 153, September 2021, 104992
Fitoterapia

Synergistic and antagonistic antioxidant effects in the binary cannabinoids mixtures

https://doi.org/10.1016/j.fitote.2021.104992Get rights and content

Abstract

From the group of nearly 120 cannabinoids identified in the hemp sativa and marijuana, CBG, CBD, THC and their acidic forms CBGA, CBDA and THCA are the most frequently studied. All these cannabinoids exhibit antioxidant activity manifested in the ability to scavenge free radicals, to prevent the oxidation process and to reduce metal ions. The paper reports and discusses the antioxidant properties of binary mixtures of the mentioned cannabinoids as regards their ability to scavenge free radicals. The paper shows that, depending on cannabinoid type in their binary mixture and their amounts ratio, an additive, synergistic and antagonistic effect of their antioxidant activity is observed. Binary mixtures of the tested cannabinoids in the full range of their molar ratios were used in the experiments. The presented results seems to be essential in terms of more and more numerous reports showing greater pharmacological effectiveness of binary cannabinoid mixtures compared to that of their individual components.

Introduction

In recent times one of the characteristic wellness trends is the utilization of different products containing hemp sativa ingredients. A fairly wide range of such products is commercially available: cannabinoid containing oils (e.g. CBD, CBG oils), food products (e.g. pure hemp oil, honey, flour), cosmetics (e.g. ointments, creams, lotions, gels) or sweets (e.g. chewing gums, protein bars, cookies, jelly beans). Despite a variety of such products, probably the most common are cannabidiol (CBD) and cannabigerol (CBG) containing oils, which are produced using hemp extracts or pure components. Apart from the mentioned oils recently, also oils containing acidic forms of these cannabinoids, cannabigerolic acid (CBGA) and cannabinolic acid (CBDA), which are precursors of CBG and CBD in the metabolic path of Cannabis sativa have become more and more common. They have gained popularity not only among people struggling with various health ailments, but also those who are looking for a neutral way to take care of their body and mind [1,2].

According to many studies [3,4], the bioactivity of cannabinoids results from both their ability to interact with the endocannabinoid system, which is important for various health systems in the body, and their antioxidant activity. As there are many reports proving greater pharmacological effectiveness of some binary cannabinoid mixtures in relation to that evoked by individual ingredients alone [[5], [6], [7], [8]] for this reason it was decided to answer the question about the antioxidant activity of cannabinoid mixtures. The question is justified as the antioxidant properties of the mixtures are not always the additive value of antioxidant activities of individual mixture components [9,10]. The paper presents and discusses the antioxidant properties of the six most common cannabinoids, CBG, CBD, THC, CBGA, CBDA and THCA (see Fig. 1), and their binary mixtures (CBG/CBD, CBD/THC, CBG/THC, CBG/CBGA, THC/THCA, CBD/CBDA, CBGA/CBDA, CBDA/THCA and CBGA/THCA). The experiments determined both the antioxidant properties of individual cannabinoids as a function of their concentration and the antioxidant properties of the above-mentioned mixtures differing in the ratio of the tested cannabinoids. Hence, the obtained results significantly extend the knowledge contained in [11] about the antioxidant properties of cannabinoids.

There are several reasons for including also the psychoactive THC and its precursor, THCA, in this study:

  • −

    their pharmaceutical activity is frequently used for treatment in the inpatient medicine;

  • −

    in some countries oils with THC and THCA are not included in the sales restrictions, and

  • −

    almost every CBD or CBG oil supposedly free from THC and THCA contains trace amounts of these compounds.

There are many spectrophotometric methods which can be applied for the estimation of compounds antioxidant activity. In these experiments the ABTS assay was used. This method was regarded as a direct, rapid, simple and reliable for antioxidant activity estimation of the cannabinoids and their mixtures being examined as the concentration changes of the ABTS cation radical are registered spectrophotometrically at the 744 nm wavelength which does not coincide with the spectrum of the tested cannabinoids and their oxidation products [12,13]. Hence, the concentration changes of the examined compounds and their derivatives in the measuring system do not influence on the reliability of measured antioxidant activity [14,15].

Section snippets

Materials

Methanol was supplied by the Polish Chemical Plant POCh (Gliwice, Poland). CBD, CBG, Δ9-THC, CBDA, CBDA and Δ9-THCA, 2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), di-potassium peroxdisulfate were purchased from Sigma Aldrich (Poznań, Poland). Deionized water was purified using on a Milli-Q system from Millipore (Millipore, Bedford, MA, USA).

Preparation of antioxidant solutions

0.001 M standard solutions of CBG, CBD, THC, CBGA, CBDA and THCA, all in methanol, were prepared. The volume ratios of

Results and discussion

Fig. 2, Fig. 3, Fig. 4 present the influence of the amount of examined cannabinoids in the one-component solutions and in their chosen binary mixtures (see Table 1) on the antioxidant activity of the measuring system. In the presented plots the cannabinoid amounts are expressed as the volume of cannabinoid solution in the examined systems – see Table 1.

Fig. 2, Fig. 4, Fig. 6 present also the expected curves (solid lines with open rings) constructed by figuring up of the experimental antioxidant

Conclusions

There are many examples of binary antioxidants binary mixture in which, depending on the mutual quantitative component ratio, both synergistic and antagonistic effects of antioxidant activity of the mixture components are observed [20,30]. As follows from the study both types of antioxidant effects are observed also in the case of binary mixtures of the cannabinoids under consideration. The mixtures of neutral and acidic forms of cannabinoids, CBG/CBGA, CBD/CBDA, THC/THCA, for which, in the

Declaration of Competing Interest

There are no conflicts of interest to declare.

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