A set of chiral polyhydrochromenes was synthesized by clay-catalyzed reactions of monoterpenoids (−)-isopulegol, (+)-neoisopulegol and (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol 5 with aromatic and heteroaromatic aldehydes. These compounds resemble in structure phytocannabinoids, some of them demonstrated analgesic activity in vivo. Polyhydrochromenes containing amino groups were obtained through the interaction of (−)-isopulegol with 5-hydroxymethylfurfural, followed by substitution of hydroxy-group with bromine and further reaction with amines. The ability of all synthesized compounds to influence the endocannabinoid system was studied for the first time. Although the polyhydrochromenes did not significantly bind to CB1 and CB2 cannabinoid receptors and did not inhibit MAGL activity at the concentration of 10 µM, isopulegol derivative 2i containing 3-bromothiophene substituent inhibited FAAH activity with an IC50 value of 7.6 µM. Thus, this compound may increase endocannabinoid system activity.