Cannabis sativa is known among many cultures for its medicinal potential. Its complexity contributes to the historical application of various parts of the plant in ethno-medicines and pharmacotherapy. C. sativa has been used for the treatment of rheumatism, epilepsy, asthma, skin burns, pain, the management of sexually transmitted diseases, difficulties during child labor, postpartum hemorrhage, and gastrointestinal activity. However, the use of C. sativa is still limited, and it is illegal in most countries. Thus, this review aims to highlight the biological potential of the plant parts, as well as the techniques for the extraction, isolation, and characterization of C. sativa compounds. The plant produces a unique class of terpenophenolic compounds, called cannabinoids, as well as non-cannabinoid compounds. The exhaustive profiling of bioactive compounds and the chemical characterization and analysis of C. sativa compounds, which modern research has not yet fully achieved, is needed for the consistency, standardization, and the justified application of Cannabis sativa products for therapeutic purposes. Studies on the clinical relevance and applications of cannabinoids and non-cannabinoid phenols in the prevention and treatment of life-threatening diseases is indeed significant. Furthermore, psychoactive cannabinoids, when chemically standardized and administered under medical supervision, can be the legal answer to the use of C. sativa.

Cannabis sativa L. is a medicinal plant cultivated globally due to its remarkable historical and scientific relevance. Through the consumption of its flowers, also referred to as inflorescences, which contain a high content of cannabinoids, terpenes and polyphenols, the therapeutic properties of C. sativa can be harnessed. This study therefore aimed to determine the chemical profile, antioxidant and anti-inflammatory activities of the essential oils (EOs) obtained from the fresh and dried flowers of two C. sativa cultivars, Lifter and Cherrywine, grown in Komga, South Africa, to assess which cultivar has greater biological potential. The chemical profiles of the hydro-distilled EOs were analyzed by gas chromatography–mass spectrometry (GC-MS), while the in vitro antioxidant and anti-inflammatory activity of the EOs was analyzed using the DPPH and EAD methods, respectively. The identified constituents from the EOs were molecularly docked against NOX2 and NIK (NF-κB-inducing kinase) protein, which are implicated in oxidative stress. The afforded EOs were yellow (pale and bright yellow) in color with a sweet to mildly sweet aroma description. A total of 51 constituents were identified in both fresh and dry oils from the Lifter cultivar, while the Cherrywine cultivar contained a total of 44 constituents. Eighteen compounds, were found to be the main chemical constituents consistent in the flower EOs of both cultivars, notably, caryophyllene (10.71–19.96%), levo-β-pinene (1.37–13.21%), humulene (5.88–9.77%), caryophyllene oxide (4.32–7.49%), D-limonene (1.40–5.48%), α-pinene (2.22–5.22%), nerolidol (0.63–4.97%), cis-β-ocimene (0.22–4.37%), linalool (1.12–4.28%), selina-3,7(11)-diene (0.15–4.23%), humulene-1,2-epoxide (1.23–3.32%), guaiol (0.17–2.60%), (+)-β-selinene (1.20–2.51%), trans-α-bergamotene (0.68–2.37%), β-ocimene (0.90–2.27%), fenchol exo- (0.15–1.27), terpineol (0.14–1.38%) and α-terpineol (0.19–0.75%). The fresh Lifter flower oil (LFO) showed 50% inhibition at 100 μg/mL, with an IC₅₀ of 69.50 ± 4.05 µg/mL against DPPH, suggesting moderate to low radical scavenging activity. The maximum percentage inhibition response of DLFO, CFO and DCFO remained below 50% at all concentrations. The antioxidant activity of fresh LFO may be attributed to its overall chemical composition. The flower oils showed in vitro inhibition of protein denaturation; however, the high standard deviation relative to the mean IC₅₀ values limited the ability to rank the samples’ potencies. Further in silico studies on the putative constituents in the Lifter and Cherrywine cultivars revealed β-bisabolene and α-curcumene as potential molecular targets, with binding energy scores of −7.7 and −7.9 kcal/mol, respectively. Thus, the study findings highlight the promising biological importance of C. sativa inflorescences in the management of oxidative stress-related conditions. Further studies may investigate the influence of environmental growing conditions on their chemical composition, total ROS analysis, pharmacokinetic properties, and in vivo efficacy against oxidative damage to DNA, proteins and lipids. Evaluating the toxicity of the flower EOs is also recommended.

Cannabinoids and cannabinoid-like substances, traditionally linked to Cannabis sativa , are now being identified in a diverse range of natural sources, including non-cannabis plants, fungi, microorganisms, and marine organisms. This review explores the variety of cannabinoids and cannabinoid-like compounds, as well as their interactions with the endocannabinoid system. The objective is to thoroughly investigate these compounds and emphasize how different natural sources influence and/or modulate the endocannabinoid system, which has significant implications for therapeutic advancements. By examining the chemical structures, biological functions, and therapeutic potential of these compounds, we can greatly enhance the pharmacognostic dimensions of cannabinoid research. This approach may also uncover new bioactive compounds that could be utilized as precursors for drug development and therapeutic progress extending beyond those derived from cannabis.

Cannabis sativa L. is an aromatic medicinal plant with various biologically active classes of compounds such as cannabinoids, polyphenols, and terpenes. Unlike the widely investigated inflorescence and leaf, the stembark of C. sativa has been overlooked regarding its medicinal potential. This study, therefore, was aimed at determining the chemical composition and antioxidant activity of the essential oils (EOs) obtained from the fresh and dried stembark of two C. sativa cultivars, Lifter and Cherrywine, grown in Komga, South Africa, with a view to ascertaining the more promising cultivar. The chemical profiles of the hydro-distilled EOs were analyzed by gas chromatography-mass spectrometry (GC-MS), while an in vitro antioxidant activity assessment of the EOs was performed using DPPH and H₂O₂ spectrophotometric methods. The identified constituents from the EOs were molecularly docked against NOX2, a protein implicated in oxidative stress. The afforded EOs were colorless with a mild skunk-like odor. A total of thirty-two constituents were identified in both fresh and dry oils from the Lifter cultivar while the Cherrywine cultivar contained a total of forty-two constituents. The EOs of both cultivars contained twenty compounds, notably Cannabidiol (0.25–85.03%), Caryophyllene oxide (1.27–19.58%), Caryophyllene (0.64–16.61%), Humulene (0.37–8.15%), Octacosane (3.37–6.55%), Humulene-1,2-epoxide (0.45–5.78%), Nerolidol (0.32–4.99%), Palmitic acid (1.45–4.45%), Tetracosane (1.75–2.91%), Dronabinol (0.86–2.86%), Cannabinol (0.54–1.64%), 7-epi-γ-eudesmol (0.53–1.00%), Guaiol (0.37–0.66%), Linoleic acid (0.22–0.60%), γ-Selinene (0.15–0.48%), β-Eudesmol (0.34–0.50%), and Linalool (0.24–0.30%). The dried Lifter stembark oil (DLSO) gave the best antioxidant activity among the four investigated cannabis oils, exhibiting the lowest IC₅₀ values of 21.68 ± 1.71 and 26.20 ± 1.34 µg/mL against DPPH and H₂O₂ radicals, respectively. The notable antioxidant activity of the DLSO may be attributed to the higher number (30) of constituents compared to the fresh Lifter stembark oil (LSO) with 11 constituents. Additionally, the DLSO showed a unique chemical profile comprising monoterpenes, oxygenated and hydrocarbon sesquiterpenes. Further in silico studies on the putative constituents in the Lifter cultivar revealed Cannabinol, Cannabidiol, and Linalool as the promising constituents based on their higher binding energy scores of −9.7, −8.5, and −6.5 kcal/mol, respectively, compared to L-Ascorbic acid (−5.7 kcal/mol). It can be inferred from this study that the EOs from the stembark of C. sativa contain promising compounds, such as Cannabinol, Cannabidiol, and Linalool, which might be responsible for the displayed antioxidant activity of the oils. Thus, the study findings underscore the biological importance of C. sativa stembark in the management of oxidative stress-related conditions.