## 2 Results and Discussion  
### Selection of Appropriate Level of Theory  
The first part of the theoretical prediction of spectra includes the selection of the appropriate level of theory. The structure optimization is carried out using the crystal structure deposited in the Cambridge Crystallographic Data Centre (CCDC) [18]. The alternative would be to select a compound structurally similar to the investigated one, usually some derivative or analog, and then determine the applicable theory level. Standard functionals, such as B3 LYP, CAM-B3 LYP, B3 PW91, M06-2X, and M05-2X, perform the optimization reasonably well for most organic compounds, but the subtle differences in structural parameters determine the success in the prediction of spectra. The authors have selected these five functionals to optimize LSD structure, starting from the crystallographic one (CCDC number: 1208523) [19; 20] (Figure 1). Before the optimization, it is necessary to remove the counter ions and co-crystallized solvent molecules or impurities. It should be kept in mind that impurities can influence the spectra of seized compounds, and that they can be important for determining their origin. The choice of basis set is also an important question to address. However, the 6-311++G(d,p) basis set is small, fast, and reasonably well performing for the optimization of organic compounds [21].  
The structure of LSD (Figure 1) consists of an indole ring and conjugated single and double bonds, which limit the free rotation around the bonds and lead to a stable structure. After the optimization is completed, the obtained structures are compared to the crystallographic one by determining the bond lengths and angle deviations. For each functional, the structures underwent a conformational search along the C-C-C(O)-N(CH\({}_{3}\))\({}_{2}\) fragment, which is the only routable part of LSD. These comparisons are quantified by the mean absolute error (MAE) as the average absolute value of the difference between experimental and theoretical parameters. A lower MAE value shows a higher resemblance between experimental and theoretical structural parameters. Tables S1 and S2 contain the complete list of crystallographic and optimized bond lengths and angles, while the MAE values are shown in Table 1. When MAE values are compared, it should be kept in mind that the bond angles are more reliable than bond lengths. Although all MAE values for bond lengths are between 0.0423 and 0.0444 A, the LSD structure optimized at B3 LYP/6-311++G(d,p) level of theory had the lowest MAE value for bond lengths. The second lowest MAE value is for the M05-2X functional. In terms of bond angles, the M05-2X functional (2.70\({}^{\circ}\)) had the lowest MAE value, while the highest was for B3 LYP (2.88\({}^{\circ}\)). Including dispersion interactions (B3 LYP-D3 BJ) lowers the MAE value for bond angles, but this value is still higher than the respective value for the M05-2X functional. This reasonably simple methodology leads to the conclusion that the M05-2X functional is suitable for the theoretical description of LSD structure and spectra prediction (Figure 1). The last section also checks applicability, in which two other LSD derivatives are optimized.  
Sometimes, it is beneficial to understand the stability of the psychoactive compounds through analysis of intermolecular interactions. This is a more complex task, as it requires some knowledge of substituents' electron donating/withdrawing properties, stereochemistry, and resonance. Still, it can be essential to determine the direction of signal shifts in IR, UV-VIS, and NMR spectra.  
Figure 1: Optimized structure of LSD (at M05-2X/6-311++G(d,p) level of theory) with the atom numbering scheme.