Analysis of Anti-Cancer and Anti-Inflammatory Properties of 25 High-THC Cannabis Extracts

Abstract

Cannabis sativa is one of the oldest cultivated plants. Many of the medicinal properties of cannabis are known, although very few cannabis-based formulations became prescribed drugs. Previous research demonstrated that cannabis varieties are very different in their medicinal properties, likely due to the entourage effect—the synergistic or antagonistic effect of various cannabinoids and terpenes. In this work, we analyzed 25 cannabis extracts containing high levels of delta-9-tetrahydrocannabinol (THC). We used HCC1806 squamous cell carcinoma and demonstrated various degrees of efficiency of the tested extracts, from 66% to 92% of growth inhibition of cancer cells. Inflammation was tested by induction of inflammation with TNF-α/IFN-γ in WI38 human lung fibroblasts. The efficiency of the extracts was tested by analyzing the expression of COX2 and IL6; while some extracts aggravated inflammation by increasing the expression of COX2/IL6 by 2-fold, other extracts decreased inflammation, reducing expression of cytokines by over 5-fold. We next analyzed the level of THC, CBD, CBG and CBN and twenty major terpenes and performed clustering and association analysis between the chemical composition of the extracts and their efficiency in inhibiting cancer growth and curbing inflammation. A positive correlation was found between the presence of terpinene (pval = 0.002) and anti-cancer property; eucalyptol came second, with pval of 0.094. p-cymene and β-myrcene positively correlated with the inhibition of IL6 expression, while camphor correlated negatively. No significant correlation was found for COX2. We then performed a correlation analysis between cannabinoids and terpenes and found a positive correlation for the following pairs: α-pinene vs. CBD, p-cymene vs. CBGA, terpenolene vs. CBGA and isopulegol vs. CBGA. Our work, thus, showed that most of high-THC extracts demonstrate anti-cancer activity, while only certain selected extracts showed anti-inflammatory activity. Presence of certain terpenes, such as terpinene, eucalyptol, cymene, myrcene and camphor, appear to have modulating effects on the activity of cannabinoids.

Screening System of Cannabis sativa Extracts Based on Their Mitochondrial Safety Profile Using Cytochrome c Oxidase Activity as a Biomarker

“…According to this study, THC and CBD standards inhibited the cytochrome c activity in bovine heart membranes with similar concentration response curves. This discrepancy between the effect observed with pure cannabinoid standards and correlation studies with complex samples has also been reported in Cannabis sativa strains with high THC content, and could be due to other molecules, such as terpinene [ 30 ]. Indeed, it has been shown that the combination of THC and CBD is more effective for multiple sclerosis treatment [ 31 ] and pain relief [ 32 ].…”

Characterization of the Antitumor Potential of Extracts of Cannabis sativa Strains with High CBD Content in Human Neuroblastoma

“…In previous studies on breast and lung tumor cell lines, THC was seen to have a dose-dependent, inhibitory cell proliferation effect [ 35 , 36 ] through its actions on the EGFR pathway. However, this dose-dependent effect has not been observed in other studies on tumoral cell lines, which exposed the cells to plant extracts with high THC content; however, the higher inhibition of cell growth was described [ 37 ].…”

“…This action of the Cannabis sativa plant extracts used in our study was not only mediated by the cannabinoid receptor’s activity, but also by its effect on the mETC complexes, among others, which promote oxidative stress. Moreover, the use of plant extracts has demonstrated higher antitumoral effects than cannabinoids by themselves [ 37 ]. However, the content of the antioxidants used in these extracts was not considered.…”

Comprehensive Profiling of Terpenes and Terpenoids in Different Cannabis Strains Using GC × GC-TOFMS

“…Most of the compounds identified in this study have previously been reported to possess therapeutic effects [13,14,16,32,[40][41][42][51][52][53][54][55]59]. For instance, linalool is neuroprotective [60], antiinflammatory [61], and antidepressant [62]; pinene possesses an anxiolytic effect [63], ameliorates memory impairment [64], and acts as an analgesic [65]; bulnesol has anticancer [66] and antianxiety properties [67]; humulene acts as an anti-bacterial and antitumor [68,69] agent and inhibits gastric lesions in gastritis [70]; myrcene possesses sedative, analgesic, and antipsychotic properties [13]; and limonene has antibacterial, anxiolytic, immunostimulant, and antidepressant effects [14].…”

“…The number of compounds detected in each terpene and terpenoid region varied in all six cannabis strains. In Pink Kush, Afghani Drifter, Blue Dream, Ultra Sour, and Western Frost, the number of sesquiterpenes (33,32,25,37, and 28, respectively) was highest followed by sesquiterpenoids (28, 19, 17, 34, and 18, respectively), monoterpenoids (12, 11, 11, 28, and 11, respectively), and monoterpenes (5, 5, 10, 16, and 9, respectively). In Reeferman's Rockstar, the number of sesquiterpenoids was 36, which was the highest followed by 33 sesquiterpenes, 14 monoterpenoids, and 6 monoterpenes.…”