## 3 Materials and Methods
### Cannabinoids LC-Q-Exactive-Orbitrap-MS Analysis  
The cannabinoids profile and content were evaluated by the procedure recently published by us [12]. Briefly, the oil samples for HPLC-Q-Exactive-Orbitrap-MS analysis were prepared by dissolving 100 mg of each oil in 10 mL of isopropanol. After adding the 1 \(\upmu\)g/mL of IS, 10 \(\upmu\)L of each sample were diluted in 890 \(\upmu\)L of initial mobile phase from which 2 \(\upmu\)L was injected. Chromatography was accomplished on an HPLC system (Thermo Fisher Scientific, San Jose, CA, USA) that was made up of a Surveyor MS quaternary pump with a degasser, a Surveyor AS autosampler with a column oven and a Rheodyne valve with a 20 \(\upmu\)L loop. Analytical separation was carried out using a reverse-phase HPLC column 150 \(\times\) 2 mm i.d., 4 \(\upmu\)m, Synergi Hydro RP, with a 4 \(\times\) 3 mm i.d. C18 guard column (Phenomenex, Torrance, CA, USA). The mobile phase used in the chromatographic separation consisted of a binary mixture of solvents A (0.1% aqueous formic acid) and B (acetonitrile). The gradient was initiated with 60% eluent A with a linear decrease up to 95% in 10 min. This condition was maintained for 4 min. The mobile phase was returned to initial conditions at 14 min, followed by a 6-min re-equilibration period (total run time: 20 min). The flow rate was 0.3 mL/min. The column and sample temperatures were 30 \({}^{\circ}\)C and 5 \({}^{\circ}\)C, respectively. The mass spectrometer Thermo Q-Exactive Plus (Thermo Scientific) was equipped with a heated electrospray ionisation (HESI) source. Capillary temperature and vaporiser temperature were set at 330 and 280 \({}^{\circ}\)C, respectively, while the electrospray voltage was adjusted at 3.50 kV (operating in both positive and negative mode). Sheath and auxiliary gas were 35 and 15 arbitrary units, with S lens RF level of 60. The mass spectrometer was controlled by the Xcalibur 3.0 software (Thermo Fisher Scientific). The exact mass of the compounds was calculated using Qualbrowser in Xcalibur 3.0 software. The FS-dd-MS2 (full scan data-dependent acquisition) in both positive and negative mode was used for both screening and quantification purposes. Resolving power of FS adjusted on 140,000 FWHM at _m/z_ 200, with scan range of _m/z_ 215-500. The automatic gain control (AGC) was set at 3 \(\times\) 10\({}^{6}\), with an injection time of 200 ms. A targeted MS/MS (dd-MS2) analysis operated in both positive and negative mode at 35,000 FWHM (_m/z_ 200). The AGC target was set to 2 \(\times\) 10\({}^{5}\), with the maximum injection time of 100 ms. Fragmentation of precursors was optimised as two-stepped normalised collision energy (NCE) (25 and 40 eV). Detection was based on calculated exact mass of the protonated/deprotonated molecular ions, at least one corresponding fragment and on retention time of target compounds [12]. Extracted ion chromatograms (EICs) were obtained with an accuracy of 2 ppm _m/z_ from total ion chromatogram (TIC) engaging the _m/z_ corresponding to the molecular ions [M + H]+ 315,23145 for CBD and THC, 311,20020 for CBN, 317.24716 for CBG and 311.2024 for CBN. In ESI- the molecular ions [M - H]- considered were 357.2164 for CBDA and THCA, while CBGA was detected by 359,22269.