anandamide (ATC-001) / Atticus Pharma - LARVOL DELTA

Endocannabinoid plasma concentrations and their relationship with clinical outcome and cannabis use in antipsychotic-naïve first episode psychosis. (PubMed, Psychiatry Res) - "Disturbances in the endocannabinoid system (ECS) have been reported in psychosis, with evidence suggesting consistent alterations in N-arachidonoylethanolamine (anandamide; AEA) and inconclusive findings for 2-arachidonoylglycerol (2-AG)...These findings suggest that higher baseline plasma AEA concentrations may be associated with a more favourable course of general psychopathology in early psychosis, potentially reflecting ECS involvement in stress- and anxiety-related symptom domains. Further studies are warranted to clarify the role of endocannabinoids in clinical outcomes and substance use trajectories in early phases of psychosis."

Clinical data • Journal • CNS Disorders • Mood Disorders • Psychiatry

Morphine causes distinct changes in the lipidome throughout the brain and body after acute or chronic administration: implications for novel endogenous lipid signaling systems involved in opioid reward and withdrawal. (PubMed, bioRxiv) - "Many of these studies are focused on the endocannabinoid (eCB) system, and its primary eCB ligands, Anandamide (AEA) and 2-arachidonoylglycerol (2-AG). Levels of AEA and 2-AG were largely unchanged; however, levels of the N -acyl GABAs, N -acyl valines, N -acyl taurines, and specific bile acids ( e.g. DCA, TCA) showed the most dynamic changes by treatment group. These results provide information on novel endolipid signaling pathways that may contribute to the unwanted side effects of opioids, such as dependence and withdrawal, and provide novel avenues for the development of therapeutic strategies."

Journal • Addiction (Opioid and Alcohol) • Substance Abuse

A phytocannabinoid-sensitive phosphorylation switch converts endocannabinoids into alternative lipid GPCR activators. (PubMed, bioRxiv) - "Endocannabinoids (eCBs) like anandamide and 2-arachidonoylglycerol are endogenous lipid ligands for CB 1 and CB 2 G protein-coupled receptors (GPCRs)...DGKQ showed noncanonical biphasic lipid kinetics and was inhibited by phytocannabinoids, most notably tetrahydrocannabinolic acid. Thus, eCBs are not only cannabinoid receptor ligands but also enzymatically adaptable lipid signals activating LPARs and MRGPRX4, thus linking metabolism of the distinct lipid LPA with Cannabis pharmacology."

Journal

Lipid Activation of a Thalamic GPCR Extends Working Memory Time-scales. (PubMed, bioRxiv) - "Cell-based assays confirmed that the endogenous cannabinoid anandamide (AEA), but not other closely related family members or derivatives, robustly activates Gpr12...Thus, while cannabinoids often impair memory, here we identify an AEA-Gpr12 signaling axis in thalamus that enhances memory, including in primates. These findings identify a lipidic signaling mechanism in thalamus that is sufficient to control and extend working memory duration."

Journal

N-terminal phosphatase of soluble epoxide hydrolase forms anandamide from anandamide phosphate. (PubMed, J Biol Chem) - "Enzyme kinetic analysis confirmed that species in this class, including arachidonoyl ethanolamide (anandamide) phosphate, were favorable N-phos substrates. The exogenous addition of anandamide phosphate inhibited VEC activation-associated expression of cell adhesion molecules at concentrations of 3 μM or more."

Journal • Inflammation

Atticus Pharma Awarded $2 Million NIH Phase II SBIR Grant to Advance Cutaneous Lupus Drug Candidate (Atticus Press Release) - "The grant will support further development of an endocannabinoid microparticle formulation for the topical treatment of cutaneous manifestations of lupus erythematosus, building on positive data from multiple animal models of lupus that showed resolution of lesions and dramatic improvements in skin and histopathology scores."

Financing • Cutaneous Lupus Erythematosus