Recovery of cannabinoids from <i>Cannabis sativa</i> flowers using modifier/water leaching method

<p dir="ltr">In Press - Pre-proof available available: <a href="https://doi.org/10.1016/j.seppur.2025.136141" target="_blank">https://doi.org/10.1016/j.seppur.2025.136141</a> </p><p dir="ltr">Abstract:</p><p dir="ltr"><i>Cannabis sativa</i> L. is a recognised medicinal plant containing a diverse array of phytocannabinoids, which are largely responsible for cannabis' therapeutic efficacy in treating psychiatric syndromes, chronic pain and epilepsy. The global market for cannabinoid products is rapidly expanding, necessitating high throughput and sustainable cannabinoid extraction processes to meet this growing demand. Liquid-liquid extraction (LLE) is a superior candidate for industrial cannabinoid isolation but there are still many knowledge gaps regarding its application in drug-type cannabis chemotype and minor cannabinoids recovery. This study filled these gaps by developing an efficient and scalable leaching method to recover cannabinoids from drug-type cannabis flowers using green modifier/water leaching solutions. The impacts of different cannabis forms (i.e., fresh (primarily acidic forms) and heat-treated (primarily decarboxylated forms)), modifier/water systems (i.e., ethanol/water and methanol/water), modifier contents (i.e., 0–100 % <i>v</i>/v) and solid-to-liquid ratios on the leaching efficiency of 15 of the most common cannabinoids were investigated. Results showed that leaching conditions of either ≥50 % <i>v</i>/v ethanol/water or ≥ 70 % v/v methanol/water were required for the efficient recovery of ∆(Jin et al., 2020⁹⁾-tetrahydrocannabinolic acid A (∆Jin et al. (2020)⁹-THCAA), the primary cannabinoid in fresh cannabis, while either ≥70 % <i>v</i>/v ethanol/water or ≥ 80 % v/v methanol/water leaching solutions were required for complete recovery of ∆(Jin et al., 2020⁹⁾-tetrahydrocannabinol (∆Jin et al. (2020)⁹-THC), the predominant cannabinoid in decarboxylated cannabis. The stability of cannabinoids in alcohol/water leachates for up to 40 d was also evaluated, the results of which suggests that alcohol/water leachates containing ∆(Jin et al., 2020⁹⁾-THCAA required rapid processing to the next liquid-liquid extraction stage or cool-storing to enhance its stability in solution. Furthermore, this study successfully utilised Hansen Solubility Parameters (HSPs) to predict the experimental leaching trends of cannabinoids, indicating that HSPs is an effective tool for screening alternative solvent systems for cannabis processing.</p>