Effect of solvent polarity on phenolic antioxidant extraction from Cannabis sativa L. leaves and inflorescences: mixture design optimization and HPLC-DAD/ESI-MS2 profiling

A new 2026 study shows that how cannabis is extracted can dramatically change which beneficial compounds are recovered. Researchers tested water, ethanol and acetone mixtures on Cannabis sativa leaves and inflorescences and found that solvent composition significantly affected total phenolics, cannabinoids and antioxidant activity.

Inflorescences produced their highest total phenolic content — 16.05 mg GAE/g dry weight — with an acetone-rich mixture, while leaves reached 13.65 mg GAE/g with one-third ethanol and two-thirds acetone. Chemical profiling identified 32 compounds, including phenolic acids, flavonoids, hydroxycinnamic acid amides, lignanamides and cannabinoid derivatives.

The extracts also showed notable antioxidant activity across DPPH, ABTS, FRAP, CUPRAC and TAC assays. The authors concluded that cannabis leaves and flowers may be valuable targeted sources of antioxidant phytochemicals for pharmaceutical, nutraceutical and cosmetic applications.

“Cannabis (Cannabis sativa L.) is a source of bioactive compounds with promising applications in the nutraceutical, pharmaceutical, and cosmetic fields.

Applying a mixture design approach with three solvents (water, acetone and ethanol), this study investigated how solvent composition modulates the recovery of phenolic compounds from cannabis inflorescences and leaves. Extracts were assessed for total phenolic content (TPC) and antioxidant activities using DPPH, ABTS, FRAP, CUPRAC, and TAC assays, and their chemical profiles were characterized by HPLC-DAD/ESI-MS2.

Solvent composition significantly affected extraction efficiency across plant organs. For inflorescences, the highest TPC value (16.05 mg GAE per g dry weight) was obtained with an acetone-enriched mixture (1/6 water-1/6 ethanol-2/3 acetone), whereas leaves reached their maximum (13.65 mg GAE per g DW) with 1/3 ethanol-2/3 acetone.

Multi-response optimization identified 1/3 water-1/3 ethanol-1/3 acetone for inflorescences and 50% water-30% ethanol-20% acetone for leaves as the optimal solvent mixtures.

HPLC-DAD/ESI-MS2 analysis identified 32 compounds belonging to several classes, including phenolic acids, flavonoids, hydroxycinnamic acid amides, lignanamides, and cannabinoid derivatives. These classes showed diverse content depending on the solvent and plant matrix. The acetone rich mixture produced the highest total cannabinoids (10.56 and 8.45 mg CBN equivalents per g dry weight) for inflorescences and leaves, respectively.

These results reveal clear organ and solvent-dependent selectivity in Moroccan Cannabis. These differences were reflected in the antioxidant activities, with extracts showing notable reducing and radical-scavenging capacities across DPPH, ABTS, FRAP, CUPRAC, and TAC assays.

These findings support the targeted valorization of cannabis leaves and inflorescences as sources of antioxidant phytochemicals for pharmaceutical and cosmetic applications.”

https://pubmed.ncbi.nlm.nih.gov/42751042

“The chemical diversity of Cannabis sativa metabolites has stimulated extensive research into their extraction and characterization. In this study, water, ethanol, and acetone were combined to enhance the extraction of phenolic compounds and antioxidants from Cannabis sativa L. leaves and inflorescences.

Multi-response optimization showed that each plant matrix required a specific optimal solvent mixture, confirming matrix-dependent extraction behavior: 1/3 water–1/3 acetone–1/3 ethanol for inflorescences and 50% water–30% ethanol–20% acetone for leaves. HPLC-DAD/ESI-MS2 enabled the tentative identification of several compound classes, including cannabinoids, hydroxycinnamic acid amides, flavonoids, and lignanamides. Inflorescences were characterized by higher total cannabinoid contents, whereas leaves contained higher levels of hydroxycinnamic acid amides. These differences highlight both the importance of solvent selection and the distinct chemical composition of Cannabis sativa L. organs.

Overall, these results support the potential valorization of the optimized Cannabis sativa leaf and inflorescence extracts as sources of antioxidant and bioactive compounds for prospective applications in natural cosmetic formulations, such as antioxidant creams, serums or other topical skincare products, as well as in nutraceutical formulations, including functional supplements enriched with plant-derived antioxidants. However, additional studies on formulation stability, bioavailability, efficacy, and safety are required before practical application.”

https://pubs.rsc.org/ra/article/doi/10.1039/d6ra05874d/1356587/Effect-of-solvent-polarity-on-phenolic-antioxidant

Cannabidiol and Other Non-Psychoactive Cannabinoids for Prevention and Treatment of Gastrointestinal Disorders: Useful Nutraceuticals?

ijms-logo“Cannabis sativa is an aromatic annual flowering plant with several botanical varieties, used for different purposes, like the production of fibers, the production of oil from the seeds, and especially for recreational or medical purposes.

Phytocannabinoids (terpenophenolic compounds derived from the plant), include the well-known psychoactive cannabinoid Δ9-tetrahydrocannabinol, and many non-psychoactive cannabinoids, like cannabidiol.

The endocannabinoid system (ECS) comprises of endocannabinoid ligands, enzymes for synthesis and degradation of such ligands, and receptors. This system is widely distributed in the gastrointestinal tract, where phytocannabinoids exert potent effects, particularly under pathological (i.e., inflammatory) conditions.

Herein, we will first look at the hemp plant as a possible source of new functional food ingredients and nutraceuticals that might be eventually useful to treat or even prevent gastrointestinal conditions.

Subsequently, we will briefly describe the ECS and the general pharmacology of phytocannabinoids. Finally, we will revise the available data showing that non-psychoactive phytocannabinoids, particularly cannabidiol, may be useful to treat different disorders and diseases of the gastrointestinal tract.

With the increasing interest in the development of functional foods for a healthy life, the non-psychoactive phytocannabinoids are hoped to find a place as nutraceuticals and food ingredients also for a healthy gastrointestinal tract function.”

https://www.ncbi.nlm.nih.gov/pubmed/32357565

https://www.mdpi.com/1422-0067/21/9/3067

Drug repurposing and emerging adjunctive treatments for schizophrenia.

“Schizophrenia is a frequent disorder, which substantially impairs patients’ quality of life. Moreover, the burden of illness for patients, their families and for the society, in general, is substantial.

Given the current failure of a number of mechanistically new drugs, repurposed compounds may serve as alternative and/or adjunctive agents for schizophrenic patients and for treatment refractory patients in particular. Anti-inflammatory drugs, as well as N-acetylcysteine, a precursor of the major antioxidant glutathione, hormones, glutamatergic and nicotinergic compounds, ‘nutraceuticals’ (e.g., ω-3 fatty acids) and cannabidiol, an endocannabinoid modulator, represent promising agents in this field.”

http://www.ncbi.nlm.nih.gov/pubmed/25866122

Prevention and Treatment of Colorectal Cancer by Natural Agents From Mother Nature.

“Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the United States after cancers of the lung and the breast/prostate. While the incidence of CRC in the United States is among the highest in the world (approximately 52/100,000), its incidence in countries in India is among the lowest (approximately 7/100,000), suggesting that lifestyle factors may play a role in development of the disease. Whereas obesity, excessive alcohol consumption, a high-calorie diet, and a lack of physical activity promote this cancer, evidence indicates that foods containing folates, selenium, Vitamin D, dietary fiber, garlic, milk, calcium, spices, vegetables, and fruits are protective against CRC in humans. Numerous agents from “mother nature” (also called “nutraceuticals,”) that have potential to both prevent and treat CRC have been identified. The most significant discoveries relate to compounds such as cardamonin, celastrol, curcumin, deguelin, diosgenin, thymoquinone, tocotrienol, ursolic acid, and zerumbone. Unlike pharmaceutical drugs, these agents modulate multiple targets, including transcription factors, growth factors, tumor cell survival factors, inflammatory pathways, and invasion and angiogenesis linked closely to CRC. We describe the potential of these dietary agents to suppress the growth of human CRC cells in culture and to inhibit tumor growth in animal models. We also describe clinical trials in which these agents have been tested for efficacy in humans. Because of their safety and affordability, these nutraceuticals provide a novel opportunity for treatment of CRC, an “old age” disease with an “age old” solution.”

http://www.ncbi.nlm.nih.gov/pubmed/23814530