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Chemical Characterization and Biological Potential of the Essential Oils from the Flowers of Two Cannabis sativa L. Cultivars from Komga, South Africa

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“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.”

https://pubmed.ncbi.nlm.nih.gov/42280118

https://www.mdpi.com/1420-3049/31/11/1814


Cannabidiol corrects sleep deficits and reduces spontaneous seizures in Angelman syndrome model mice

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“The off-label use of cannabidiol (CBD) has outpaced investigation. We assessed the effects of CBD in Angelman syndrome model mice lacking the Ube3a gene and found that chronic injection of CBD increased rapid-eye movement sleep during the dark cycle, restored “Siesta”, improved sleep homeostasis, and reduced spontaneous seizures following flurothyl kindling.”

https://pubmed.ncbi.nlm.nih.gov/42265437

“Cannabidiol (CBD), a major non-psychoactive and non-psychotomimetic phytocannabinoid constituent of cannabis, is gaining attention for its medical benefits. The multitarget and complex pharmacological nature of CBD in the central nervous system makes it a unique candidate for treating a wide range of complex neurological and psychiatric conditions, including seizures and sleep deficits.”

“This study primarily suggests that CBD restores REM sleep deficits in AS model mice. One hypothesis is that this effect may be related to CBD’s ability to enhance acetylcholine signaling, a central regulator of REM sleep. CBD’s ability to reduce the frequency of SRS, beyond its effects on induced-seizure suppression, further strengthens the preclinical evidence supporting its potential for clinical translation.” 

https://www.nature.com/articles/s41386-026-02462-7

Therapeutic Drug Monitoring of Cannabinoids: Therapeutic Reference Ranges for Delta-9-tetrahydrocannabinol in Medical Cannabis, Nabiximols, Dronabinol and Nabilone

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“Medical cannabis, nabiximols, dronabinol and nabilone are used for various medical conditions.

Despite their pronounced pharmacokinetic variability and complex concentration-effect relationships, therapeutic drug monitoring recommendations are lacking. We aimed to identify therapeutic reference ranges based on blood concentration-clinical effect relationships. Studies reporting blood concentrations and clinical effects/adverse effects or assessing cannabinoid receptors 1 and 2 occupancy were selected through a systematic literature search in the MEDLINE database via PubMed. Twenty-three articles were selected for vaporized/smoked medical cannabis, three for nabiximols, nine for dronabinol and one for nabilone. No article was identified for delta-9-tetrahydrocannabinol-dominant cannabis extracts.

For vaporized/smoked medical cannabis, an orienting therapeutic reference range of 15-30 ng/mL delta-9-tetrahydrocannabinol was identified for pain reduction in diabetic peripheral neuropathy, while concentrations of <20 ng/mL delta-9-tetrahydrocannabinol were significantly correlated with intraocular pressure reduction and 7.5-10 ng/mL with improvement of tic symptoms. Half-maximum effective concentrations of 7-29 ng/mL delta-9-tetrahydrocannabinol were reported for “high” effects.

For nabiximols, a preliminary therapeutic reference range of 1-10 ng/mL delta-9-tetrahydrocannabinol was determined for treating neuropathic pain and spasticity in adults with multiple sclerosis. For chemotherapy-induced nausea and vomiting, a preliminary therapeutic reference range of 1-5 ng/mL for nabilone and 5-15 ng/mL delta-9-tetrahydrocannabinol for dronabinol was assessed.

In conclusion, relatively low concentrations may be sufficient to achieve therapeutic effects across all substances studied, with medical cannabis demonstrating these effects at lower concentrations than typically observed in recreational use. Nevertheless, adverse effects at therapeutic reference ranges cannot be excluded.”

https://pubmed.ncbi.nlm.nih.gov/42269696

https://www.thieme-connect.de/products/ejournals/abstract/10.1055/a-2853-4984

Endocannabinoid system and skeletal muscle health: insights from cannabidiol

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“The endocannabinoid (EC) system is a complex network comprising endogenous ligands, enzymes responsible for their synthesis and degradation, and various receptors (including CB1 and CB2).

Present in many peripheral tissues, including skeletal muscle, EC system is now recognized to influence key physiological processes such as insulin sensitivity, mitochondrial metabolism, protein homeostasis and muscle development. Alterations in this system are associated with a variety of pathologies, including obesity, type 2 diabetes, sarcopenia, cachexia and muscle dystrophies.

In this context, cannabidiol (CBD), a phytocannabinoid devoid of psychoactive properties, is attracting growing interest as a potential therapeutic agent.

This article provides an analysis of the mechanisms by which the EC system, and more specifically the CB1 receptor, influences skeletal muscle development and function, while exploring emerging data on the potential benefits of CBD in various pathological conditions affecting skeletal muscle.”

https://pubmed.ncbi.nlm.nih.gov/42264146

“The endocannabinoid system (ECS) is composed of endogenous ligands (AEA, 2-AG), enzymes for their synthesis or degradation, and receptors (e.g., CB1, CB2). It also includes exogenous molecules like cannabidiol (CBD) produced from Cannabis sativa. Widely expressed in peripheral tissues such, the ECS plays a central role in the regulation of key skeletal muscle physiological processes, including insulin sensitivity, mitochondrial metabolism, protein homeostasis and skeletal muscle development.

Dysregulation of this system is associated with the development of metabolic and muscular disorders, such as obesity, type 2 diabetes, sarcopenia, cachexia and muscular dystrophies.

In this context, CBD, a non-psychoactive phytocannabinoid, has emerged as a potential therapeutic agent capable of modulating ECS activity, thereby contributing to the restoration of skeletal muscle function and homeostasis.”

https://www.sciencedirect.com/science/article/pii/S2212877826000803?via%3Dihub

Combined peripheral cannabinoid CB1 and CB2 receptor activation abolishes cystitis-induced bladder hyperalgesia

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“Cannabinoid agonists may ameliorate bladder pain associated with interstitial cystitis/bladder pain syndrome.

Visceromotor responses (VMRs) to bladder distension were recorded in urethane-anesthetised control and protamine/zymosan-treated guinea pigs. The peripherally restricted preferential CB1 receptor agonist PrNMI and the selective CB2 receptor agonist 4Q3C each reduced cystitis-induced enhancement of VMRs at high intravesical pressures.

Co-activation of CB1 and CB2 receptors abolished cystitis-induced bladder hyperalgesia.

These findings indicate that simultaneous targeting of peripheral CB1 and CB2 receptors may provide clinically meaningful benefits for the treatment of bladder pain associated with cystitis.”

https://pubmed.ncbi.nlm.nih.gov/42247877

“Combined activation of peripheral CB1 and CB2 receptors using peripherally restricted agonists effectively reverses bladder hyperalgesia in a preclinical model of IC/BPS.

These findings provide strong support for the development of peripherally acting combination therapies targeting both cannabinoid receptors as a strategy to treat bladder pain and associated symptoms in IC/BPS, while minimising central cannabinoid-related side effects.”

https://www.autonomicneuroscience.com/article/S1566-0702(26)00066-4/fulltext

Industrial Cannabis, Cannabic Residue or Industrial Cannabis Waste? Perspectives on the Utilization, Reutilization, and Recycling of Cannabis

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“Introduction: Cannabis sativa L. is an annual herbaceous plant with a long history of multipurpose use, including food, textile, and medicinal applications. The progressive legalization in several countries has significantly increased its large-scale cultivation, consequently generating a substantial amount of biomass waste. This scenario calls for innovative and sustainable strategies to valorize Cannabis residues, aiming at promoting the circular economy and technological innovation.

Materials and methods: An integrative review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Systematic searches were performed in SCOPUS, PubMed, and SciELO, complemented by specialized platforms such as CANNUSE and CONSENSUS. Peer-reviewed empirical studies were included if they addressed the utilization, reutilization, or recycling of C. sativa by-products or residues for the development of industrial products, processes, or inputs. The analysis considered thematic and commercial domains, geographic origin, and biomass type.

Results: A total of 262 studies were included, with 144 retrieved from indexed databases and 118 from alternative methods. The most commonly explored residues were stems (48.2%), seeds (21.0%), and postextraction residuum (9.7%). The majority of applications were related to technology and innovation (37.5%) and industrial sectors (36.9%). A total of 328 technologies were identified, highlighting applications such as textile fibers, bioplastics, biofuels, functional foods, adsorbents, and natural cosmetics. Italy, China, and the United States led in scientific production. Leaves (7.0%) and roots (0.9%) were significantly underexplored despite their bioactive potential.

Discussion: The findings demonstrate a growing global interest in the valorization of C. sativa residues, with promising applications in bioeconomy, regenerative agriculture, phytoremediation, and energy transition. The integration of traditional knowledge and green technologies is a key strategy to enhance sustainability and socioterritorial inclusion. Nonetheless, regulatory gaps and a lack of robust clinical and toxicological studies limit the use of by-products in food and feed chains.

Conclusion: The residual biomass of C. sativa holds high technological, environmental, and economic value. Strategic valorization demands regulatory advancement, the development of green technologies, and the strengthening of multidisciplinary research. Industrial Cannabis emerges as a driver of ecological, social, and economic transformation toward sustainable circular production systems.”

https://pubmed.ncbi.nlm.nih.gov/41652844

https://journals.sagepub.com/doi/10.1177/25785125261421439

Harnessing Cannabis sativa as a dual-use platform for biohydrogen production and pharmaceutical synthesis: a hypothesis and theory

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“Cannabis sativa, long established as a cornerstone of the pharmaceutical and industrial fiber markets, represents a radical and underexplored platform for renewable energy innovation.

In this Hypothesis and Theory framework, we introduce a novel, patented (Provisional Patent No. 63916615) dual-use bio-refinery paradigm. This model harnesses engineered cannabis photosynthesis to drive green hydrogen production without compromising its established value as a high-yield medicinal crop.

By strategically redirecting photosynthetic electron flow toward oxygen-protected hydrogenase activity, it is possible to generate molecular hydrogen at commercially relevant scales while maintaining plant viability.

Unique to this model is the ability to leverage over $10 billion in existing controlled-environment agriculture (CEA) infrastructure, bypassing the capital-intensive barriers that have hindered traditional algal biohydrogen systems. We outline a tripartite circular economy strategy that integrates hydrogen capture during the vegetative phase with the subsequent harvest of therapeutic cannabinoids and industrial biomass.

This convergence of synthetic biology, clean energy, and biomedicine positions cannabis as a uniquely versatile multipurpose crop capable of fueling both the pharmaceutical industry and the global transition to a sustainable hydrogen economy.”

https://pubmed.ncbi.nlm.nih.gov/42245109

“The global transition toward a net-zero carbon economy necessitates the development of scalable, carbon-negative energy sources. While hydrogen (H2) is a premier clean energy carrier, biological production methods have traditionally struggled with economic viability due to low feedstock density and high infrastructure costs. We propose that Cannabis sativa, a crop already optimized for high-density biomass and metabolic output, serves as the ideal biological “factory” to overcome these hurdles.”

“Cannabis sativa stands at the intersection of the most disruptive shifts in modern industry: the legalization of medicinal biotechnologies and the urgent need for carbon-negative energy transition.

By adopting this patented dual-use framework, we can transform one of the world’s most valuable crops into an engine for a sustainable, hydrogen-powered future.”

“Collaborative frameworks between synthetic biologists, agricultural engineers, and regulatory bodies will be essential to advance this platform toward commercial viability.”

https://www.frontiersin.org/journals/plant-science/articles/10.3389/fpls.2026.1833491/full

The Use of Cannabis sativa L. for Pest Control: From the Ethnobotanical Knowledge to a Systematic Review of Experimental Studies

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“Background: Despite the benefits that synthetic pesticides have provided in terms of pest and disease control, they cause serious long-term consequences for both the environment and living organisms. Interest in eco-friendly products has subsequently increased in recent years. 

Methods: This article briefly analyzes the available ethnobotanical evidence regarding the use of Cannabis sativa as a pesticide and offers a systematic review of experimental studies. 

Results: Our findings indicate that both ethnobotanical and experimental procedures support the use of C. sativa as a pesticide, as remarkable toxicity has been observed against pest organisms. The results included in the systematic review of experimental studies (n=30) show a high degree of heterogeneity, but certain conclusions can be extracted to guide further research. For instance, promising pesticide properties were reported for most of the groups of species tested, especially Arachnida and Insecta; the efficacy of C. sativa as a pesticide can be derived from a wide variety of compounds that it contains and possible synergistic effects; it is crucial to standardize the phytochemical profile of C. sativa plants used as well as to obtain easily reproducible results; appropriate extraction methods should be explored; and upper inflorescences of the plant may be preferred for the production of the essential oil, but further studies should explore better other parts of the plant. 

Conclusion: In the coming years, as new findings are produced, the promising potential of C. sativa as a pesticide will be elucidated, and reviews such as the present one constitute useful basic tools to make these processes easier.”

https://pubmed.ncbi.nlm.nih.gov/34612729

https://journals.sagepub.com/doi/10.1089/can.2021.0095

The potential of Allium sativum and Cannabis sativa extracts for anti-tick activities against Rhipicephalus (Boophilus) microplus

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“The efficacy of Allium sativum and Cannabis sativa against Rhipicephalus microplus ticks was evaluated using the adult immersion and the larval packet test. In addition, an in silico approach was utilized by performing a docking study in order to identify the active ingredients from both plants.

Results showed a comparatively high lethal effect of A. sativum and C. sativa on egg laying (index of egg laying = 0.26 and 0.24, respectively), egg hatching (33.5 and 37.1, respectively), and total larval mortality (100%, both), at 40 mg/mL.

When applied to cattle which had been inoculated with larvae ticks, it was observed that a 45% solution of both herbal extracts significantly reduced the number of ticks by 96 h post treatment.

We analyzed in silico 27 known active molecules from both plants and identified in the PubChem database to explore the hypothesis that the effect found on ticks was based on inhibition of acetylcholinesterase (AChE).

Vitamin E and cannabidiol are the most potent AChE inhibitors with docking scores of -15.85 and -14.38, respectively.

Based on these findings, we conclude that A. sativum and C. sativa may potentially be used for the control of R. microplus, and should be further investigated as a potential supplement to or replacement of synthetic acaricides.”

https://pubmed.ncbi.nlm.nih.gov/32886258

https://link.springer.com/article/10.1007/s10493-020-00540-z

Cannabidiol-thiosemicarbazone exhibits dual tyrosinase inhibition and antioxidant activity in human skin-derived cells

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“The search for modulators of melanogenesis with improved biological compatibility remains an active area of investigation, as existing tyrosinase (TYR) inhibitors are often limited by low potency, instability, or cytotoxicity.

Here, we investigated CBD-TSC1, a cannabidiol-based thiosemicarbazone derivative, as a TYR-targeting scaffold.

Structural characterization confirmed a single, stable E-isomer, and pKa profiling together with kinetic analyses indicated reversible mixed-type inhibition of human TYR, involving interactions with both free enzyme and enzyme-substrate complexes. CBD-TSC1 exhibited higher inhibitory activity than CBD and kojic acid under the tested conditions while maintaining low cytotoxicity in G361 melanoma and HaCaT keratinocyte cell lines. In addition, CBD-TSC1 reduced intracellular oxidative stress at low micromolar concentrations. In zebrafish larvae, treatment with CBD-TSC1 resulted in a dose-dependent reduction in melanin content, comparable to that of kojic acid under identical experimental conditions, supporting an association between thiosemicarbazone modification and the observed biological activity.

Overall, CBD-TSC1 demonstrated consistent activity across biochemical, cellular, and zebrafish-based assays under the tested conditions. Although the mechanistic relationship between TYR inhibition, redox modulation, and melanogenesis regulation remains to be fully clarified, the present findings support further investigation of cannabidiol-based thiosemicarbazone derivatives as modulators of TYR-related pathways.”

https://pubmed.ncbi.nlm.nih.gov/42235859

“CBD-TSC1 is a novel cannabidiol-thiosemicarbazone hybrid with dual anti-melanogenic activity.”

“Thiosemicarbazone modification is essential for superior enzymatic and redox performance.”

https://www.sciencedirect.com/science/article/abs/pii/S0960894X26001745?via%3Dihub