Limited studies have explored different extraction techniques that improve cannabis extraction with scale-up potential. Ultrasound-assisted and microwave-assisted extraction were evaluated to maximize the yield and concentration of cannabinoids and terpenes. A central composite rotatable design was used to optimize independent factors (sample-to-solvent ratio, extraction time, extraction temperature, and duty cycle). The optimal conditions for ultrasound- and microwave-assisted extraction were the sample-to-solvent ratios of 1:15 and 1:14.4, respectively, for 30 min at 60 °C. Ultrasound-assisted extraction yielded 14.4% and 14.2% more oil and terpenes, respectively, compared with microwave-assisted extracts. Ultrasound-assisted extraction increased cannabinoid concentration from 13.2–39.2%. Considering reference ground samples, tetrahydrocannabinolic acid increased from 17.9 (g 100 g dry matter−1) to 28.5 and 20 with extraction efficiencies of 159.2% and 111.4% for ultrasound-assisted and microwave-assisted extraction, respectively. Principal component analyses indicate that the first two principal components accounted for 96.6% of the total variance (PC1 = 93.2% and PC2 = 3.4%) for ultrasound-assisted extraction and 92.4% of the total variance (PC1 = 85.4% and PC2 = 7%) for microwave-assisted extraction. Sample-to-solvent ratios significantly (p < 0.05) influenced the secondary metabolite profiles and yields for ultrasound-assisted extracts, but not microwave-assisted extracts.
