The adsorption of psychoactive drugs (PADs) onto sodium-exchanged montmorillonite (Na—Mt) was investigated under two pH conditions. At pH = 2.5, the adsorption was performed through cation exchange and the three PADs were intercalated within the Na—Mt layers. However, the adsorption capacity was lower than the theoretical cation exchange capacity of Na—Mt due to the impact of the acidic conditions on the adsorbent. At pH = 7.5, only Codeine was protonated and its adsorption through cation exchange resulted in the highest amount adsorbed among the tested PADs. Diazepam was adsorbed through weak electrostatic interactions, whereas Oxazepam appeared to be intercalated within Na—Mt layers despite its neutral charge. Consequently, the variation in pH strongly impacts the affinity of PADs for Na—Mt. These initial results highlight the impact of raw clay on the fate of these contaminants within environmental compartments and could pave the way for a green solution to the removal of PADs from wastewater effluents.