Cold Ethanol Extraction of Cannabinoids and Terpenes from Cannabis Using Response Surface Methodology: Optimization and Comparative Study - PubMed
- ️Sat Jan 01 2022
. 2022 Dec 11;27(24):8780.
doi: 10.3390/molecules27248780.
Sai Uday Kumar Reddy Sagili 1 , Samuel Eichhorn Bilodeau 2 , Frederick-Alexandre Gladu-Gallant 2 , Douglas A MacKenzie 3 , Jennifer Bates 3 , Garnet McRae 3 , Sarah MacPherson 1 , Maxime Paris 2 , Vijaya Raghavan 1 , Valérie Orsat 1 , Mark Lefsrud 1
Affiliations
- PMID: 36557913
- PMCID: PMC9786071
- DOI: 10.3390/molecules27248780
Cold Ethanol Extraction of Cannabinoids and Terpenes from Cannabis Using Response Surface Methodology: Optimization and Comparative Study
Philip Wiredu Addo et al. Molecules. 2022.
Abstract
Efficient cannabis biomass extraction can increase yield while reducing costs and minimizing waste. Cold ethanol extraction was evaluated to maximize yield and concentrations of cannabinoids and terpenes at different temperatures. Central composite rotatable design was used to optimize two independent factors: sample-to-solvent ratio (1:2.9 to 1:17.1) and extraction time (5.7 min-34.1 min). With response surface methodology, predicted optimal conditions at different extraction temperatures were a cannabis-to-ethanol ratio of 1:15 and a 10 min extraction time. With these conditions, yields (g 100 g dry matter-1) were 18.2, 19.7, and 18.5 for -20 °C, -40 °C and room temperature, respectively. Compared to the reference ground sample, tetrahydrocannabinolic acid changed from 17.9 (g 100 g dry matter-1) to 15, 17.5, and 18.3 with an extraction efficiency of 83.6%, 97.7%, 102.1% for -20 °C, -40 °C, and room temperature, respectively. Terpene content decreased by 54.1% and 32.2% for extraction at -20 °C and room temperature, respectively, compared to extraction at -40 °C. Principal component analysis showed that principal component 1 and principal component 2 account for 88% and 7.31% of total variance, respectively, although no significant differences in cold ethanol extraction at different temperatures were observed.
Keywords: cannabinoids; cannabis; cold ethanol; delta-9-tetrahydrocannabinol; extraction.
Conflict of interest statement
The authors declare no conflict of interest.
Figures

3D plots showing the combined effects of sample (g)-to-solvent (g) ratio and extraction time (min) on the concentration (g 100 g dry matter−1) of total THC (A,D,G), total terpenes (B,E,H), extraction yield (C,F,I) for cold ethanol extraction of cannabis at −20 °C (A–C), −40 °C (D,E), and room temperature (G–H).

Principal component analysis plots for cold ethanol extraction of cannabis at various temperatures: −20 °C, −40 °C, and room temperature. Scree plot (A), loadings plot (B), and scatterplot (C).
Similar articles
-
Addo PW, Sagili SUKR, Bilodeau SE, Gladu-Gallant FA, MacKenzie DA, Bates J, McRae G, MacPherson S, Paris M, Raghavan V, Orsat V, Lefsrud M. Addo PW, et al. Molecules. 2022 Dec 12;27(24):8803. doi: 10.3390/molecules27248803. Molecules. 2022. PMID: 36557949 Free PMC article.
-
Boffa L, Binello A, Cravotto G. Boffa L, et al. Molecules. 2024 Feb 18;29(4):899. doi: 10.3390/molecules29040899. Molecules. 2024. PMID: 38398651 Free PMC article.
-
Multivariate classification of cannabis chemovars based on their terpene and cannabinoid profiles.
Birenboim M, Chalupowicz D, Maurer D, Barel S, Chen Y, Fallik E, Paz-Kagan T, Rapaport T, Sadeh A, Kengisbuch D, Shimshoni JA. Birenboim M, et al. Phytochemistry. 2022 Aug;200:113215. doi: 10.1016/j.phytochem.2022.113215. Epub 2022 Apr 26. Phytochemistry. 2022. PMID: 35483556
-
Al-Khazaleh AK, Zhou X, Bhuyan DJ, Münch GW, Al-Dalabeeh EA, Jaye K, Chang D. Al-Khazaleh AK, et al. Molecules. 2024 Jan 15;29(2):410. doi: 10.3390/molecules29020410. Molecules. 2024. PMID: 38257323 Free PMC article. Review.
-
Gouvêa-Silva JG, Costa-Oliveira CD, Ramos YJ, Mantovanelli DF, Cardoso MS, Viana-Oliveira LD, Costa JL, Moreira DL, Maciel-Magalhães M. Gouvêa-Silva JG, et al. Cannabis Cannabinoid Res. 2023 Jun;8(3):476-486. doi: 10.1089/can.2022.0076. Epub 2022 Jun 28. Cannabis Cannabinoid Res. 2023. PMID: 35763833 Review.
Cited by
-
Effect of Hemp Extraction Procedures on Cannabinoid and Terpenoid Composition.
Chacon FT, Raup-Konsavage WM, Vrana KE, Kellogg JJ. Chacon FT, et al. Plants (Basel). 2024 Aug 10;13(16):2222. doi: 10.3390/plants13162222. Plants (Basel). 2024. PMID: 39204658 Free PMC article.
-
Karangan A, Rahardjo SW, Widagdo AJ, Santoso SP, Ismadji S. Karangan A, et al. Data Brief. 2024 Jun 10;55:110623. doi: 10.1016/j.dib.2024.110623. eCollection 2024 Aug. Data Brief. 2024. PMID: 38993226 Free PMC article.
-
Alcantara KP, Malabanan JWT, Nalinratana N, Thitikornpong W, Rojsitthisak P, Rojsitthisak P. Alcantara KP, et al. Int J Mol Sci. 2024 Apr 26;25(9):4744. doi: 10.3390/ijms25094744. Int J Mol Sci. 2024. PMID: 38731964 Free PMC article.
References
-
- Khare S., Singh N., Singh A., Hussain I., Niharika K., Yadav V., Bano C., Yadav R.K., Amist N. Plant secondary metabolites synthesis and their regulations under biotic and abiotic constraints. J. Plant Biol. 2020;63:203–216. doi: 10.1007/s12374-020-09245-7. - DOI
-
- Schreiner M., Mewis I., Huyskens-Keil S., Jansen M., Zrenner R., Winkler J., O’brien N., Krumbein A. UV-B-induced secondary plant metabolites-potential benefits for plant and human health. Crit. Rev. Plant Sci. 2012;31:229–240. doi: 10.1080/07352689.2012.664979. - DOI
-
- Kabera J.N., Semana E., Mussa A.R., He X. Plant secondary metabolites: Biosynthesis, classification, function and pharmacological properties. J. Pharm. Pharmacol. 2014;2:377–392.
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources