Chronic inflammatory joint disease represents an emerging public health issue, occupying a sizeable proportion of the adult population in the industrialized world. Recently, there has been a resurgence of interest in marijuana and its natural and synthetic derivatives, cannabinoid receptor agonists and antagonists, as well as chemically related compounds, for their therapeutic potential as both an anti-inflammatory and analgesic. Whilst the benefits of endocannabinoid-based treatments appear promising, very few studies have investigated the use of the self-assembled nanoparticles (NPs) for targeted drug delivery. In this study, the nanostructure mesophase behaviour of a series of mixed monoethanolamide lipids of oleoylethanolamide (OEA) and linoylethanolamide (LEA) into higher order NP structures for the encapsulation and delivery of drugs was investigated. In addition to drug encapsulation, active targeting through the conjugation of a synovium-targeting peptide, HAP-1, to the surface of these NP’s was used to facilitate selective accumulation of therapeutic agents the inflamed joint. The inhibitory cytokine effects of these targeted NPs was demonstrated in vitro, and in vivo using an adjuvant induced arthritis model of inflammation. The ability to deliver endocannabinoid based NPs to specific sites of the body mediating pharmacological endocannabinoid-like effects to influence key physiological pathways, provides a novel drug delivery system and medicinal potential to treat many diseases in many fields of medicine in which inflammation is a key feature of the disease.