The work was dedicated to investigation of the influence of two endocannabinoids – arachidonoylethanolamide (AEA), also known as anandamide, and 2-arachidonoylglycerol (2-AG) on the parameters of miniature endplate potentials (MEPP) and evoked endplate potentials (EPP) of motor synapses at the early stage of regeneration during muscle reinnervation. 2-AG increased the amplitude of MEPP by 35%, and also increased the amplitude of EPP by 37%, without affecting quantal content of EPP or any other parameters of neurotransmitter secretion. This effect was prevented by vesicular acetylcholine transporter inhibitor vesamicol and by inverse agonist of CB1-type cannabinoid receptors AM251. AEA did not change the amplitude or any other parameters of MEPP, but reduced the quantal content of EPP by 27%. The inhibitory effect of AEA was prevented by AM251 and by the L-type Ca2+ channel blocker nitrendipine. Thus, it was established for the first time that in newly formed motor synapses AEA and 2-AG activate the same type of presynaptic cannabinoid receptors, but have different final targets, influence different parameters of quantal ACh secretion and have multidirectional effects on synaptic transmission. The presence of both facilitatory and inhibitory effects of endocannabinoids in regenerating synapses may serve to fine-tune and regulate synaptic transmission during their maturation.