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anandamide (anandamide)

✓ Approved

Yissum · CNR1

What is anandamide?

anandamide is a therapeutic agent developed by Yissum. It is approved for therapeutic indications via unknown.

Drug Profile

Brand Namesanandamide
CompanyYissum
Molecular TargetCNR1, CNR2
RouteUnknown
StatusApproved
Sources: ClinicalTrials.gov, Yissum

Mechanism of Action

Molecular Targets

anandamide acts on 2 molecular targets:

CNR1cannabinoid receptor 1 (CNR, CB1A)
CNR2cannabinoid receptor 2 (CX5, CB-2)
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Therapeutic Indications

anandamide is developed for 2 unique indications across 1 therapeutic area.

Therapeutic AreaConditionPhase
Psychiatric disordersAnorexia nervosa✓ Approved
Psychiatric disordersBulimia nervosa✓ Approved

Related Research Articles

PubMedBiochemical and biophysical research communications2026-10-11

Stage-dependent expression of CB1 and CB2 receptors and their vascular effects during the progression of diet-induced atherosclerosis.

Álvarez-Valadez María Del Rosario MDR, Virgen-Ortiz Adolfo A, Rodríguez-Hernández Alejandrina A, Limón-Miranda Saraí S et al.

Cardiovascular diseases (CVDs) remain the leading cause of global mortality, with ischemic heart disease and stroke representing the most common clinical manifestations. Atherosclerosis, a chronic inflammatory disorder of the arterial wall, constitutes the primary pathological basis of these conditions. Recent studies have implicated the endocannabinoid system (ECS), which includes cannabinoid receptors CB1 and CB2, their endogenous ligands, and metabolic enzymes, in the pathophysiology of atherosclerosis. In the present study, we explored the molecular and functional interactions between the ECS and diet-induced atherosclerosis in Wistar rats. Our results show distinct expression patterns of CB1 and CB2 receptors in the aortic wall, with significant downregulation observed in the advanced stages of atherosclerosis. Functional assays demonstrated stage-dependent vascular responses to selective CB1 and CB2 agonists, indicating that modulation of the ECS influences vascular tone and blood pressure. Additionally, biochemical analysis of endocannabinoids and their catabolic enzymes, including 2-arachidonoylglycerol (2-AG)/monoacylglycerol lipase (MAGL) and anandamide (AEA)/fatty acid amide hydrolase (FAAH), revealed dynamic alterations throughout the course of disease progression. These findings underscore the critical role of the ECS in vascular homeostasis and suggest that cannabinoid-based therapeutic strategies may hold potential for the management of atherosclerotic cardiovascular disease.

PMID 42858650
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PubMedFrontiers in cell and developmental biology2026-10-11

Integrated lipidomic and transcriptomic profiling of imiquimod-induced psoriasiform dermatitis.

Wisniewski Eva E, Du Wenwen W, Himelstein Jenna A JA, Szanda Gergő G et al.

Psoriasis is a chronic inflammatory skin disease characterized by keratinocyte hyperproliferation and immune dysregulation. Emerging clinical and experimental evidence suggests that endogenous lipid (endolipid) signaling systems, including the endocannabinoid system (ECS), represent a promising therapeutic target to treat psoriasis; however, comprehensive characterization of small-molecule endolipids and related proteins in psoriatic skin and their relationship to systemic changes remains limited. Here, we used the imiquimod (IMQ)-induced mouse model of psoriasis to perform combined lipidomic and transcriptional profiling of endolipid signaling in both skin and plasma. Targeted lipidomics revealed a striking divergence between tissues: most endolipids increased in inflamed skin but decreased in plasma, including the canonical ECS lipids anandamide and 2-arachidonoylglycerol. In contrast, selected lipid species, including taurine-conjugated metabolites (both N-acyl taurines and bile acids), were elevated in both tissues, indicating pathway-specific regulation. Targeted transcriptional analysis of whole skin showed reduced expression of key endolipid biosynthetic enzymes (Napepld, Dagla, Daglb) and the cannabinoid receptor Cnr1, while Cnr2 and ECS-related metabolic enzymes remained unchanged. Additional alterations were observed in transcripts involved in related endolipid signaling (Trpv1, Trpv4, Ppara, Pparg, Gpr55), bile acid metabolism (Fxr, Bsep, Fabp4, Fabp5, Cyp27a1, Cyp8b1), and inflammatory pathways (Cox-2). To resolve this apparent discrepancy between lipid levels and gene expression, we performed compartment-specific analyses of epidermal and dermal layers. These revealed a predominantly suppressive epidermal response across multiple ECS-related proteins, contrasted by a more variable dermal profile with selective preservation or upregulation, particularly of Cnr2. Together, these findings demonstrate that psoriasiform inflammation is associated with compartment-specific remodeling of endolipid signaling across skin and systemic compartments, underscoring the functional heterogeneity of epidermal and dermal layers. This dataset provides novel insights into the dysregulation of endolipid signaling systems in psoriasis and provides a foundation for the development of spatially informed, lipid-based therapeutic strategies.

PMID 42856670
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PubMedDiabetologia2026-10-05

Visceral fat endocannabinoid overproduction is associated with insulin resistance and tissue dysfunction in mice and humans.

Barbosa Romain R, Leemput Julia J, Passilly-Degrace Patricia P, Pointeau Océane O et al.

Visceral adipose tissue (VAT) dysfunction is a major determinant of obesity-related metabolic complications. Circulating endocannabinoids (ECs) correlate positively with visceral fat mass and metabolic risk, suggesting that adipose tissue-derived ECs may contribute to adipocyte dysfunction and systemic metabolic alterations. Although adipocytes possess the enzymatic machinery for EC synthesis, the depot-specific regulation of EC production and the contribution of insulin resistance to EC overproduction in metabolic diseases remain poorly defined. We quantified the dynamic production of the major ECs 2-arachidonoylglycerol (2-AG) and anandamide (AEA) and related N-acylethanolamines (NAEs) using ex vivo explants of VAT and subcutaneous adipose tissue (SAT) from obese mice and from individuals with obesity but without type 2 diabetes and those with both obesity and type 2 diabetes compared with their controls. Paired VAT and SAT samples from the same individuals were analysed. Mechanistic regulation of EC production was explored using pharmacological modulation, cannabinoid receptor type 1-deficient mice and cross-species transcriptomic profiling of VAT. 2-AG was the predominant species produced by human adipose tissue, with VAT exhibiting a 1.9-fold higher intrinsic production than SAT (p<0.001). Obesity alone did not significantly increase EC secretion from either depot. In contrast, VAT explants from individuals with type 2 diabetes showed an increase in EC production (1.7-fold for 2-AG [p<0.05] and 1.8-fold for AEA [p<0.05]) compared with control individuals, whereas SAT remained largely unaffected. AEA production by VAT was positively correlated with chronic glycaemic impairment (ρ=0.4786, p=0.003 for HbA1c; ρ=0.3445, p=0.034 for fasting plasma glucose). Comparative transcriptomic analysis of mouse and human VAT revealed that type 2 diabetes, but not obesity alone, was associated with the repression of insulin-sensitive adipocyte genes, activation of inflammatory and lipid mediator pathways, and upregulation of purinergic receptor expression, consistent with an increased availability of lipid precursors. Insulin resistance and severe adipocyte metabolic dysregulation, rather than adiposity alone, appear to be the primary determinants of depot-specific EC overproduction. Our findings identify VAT as a major source driving elevated systemic EC levels in type 2 diabetes, highlighting the therapeutic potential of specifically targeting visceral adipose EC signalling to mitigate downstream metabolic complications.

PMID 42831899
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PubMedPsychiatry research2026-10-02

Endocannabinoid plasma concentrations and their relationship with clinical outcome and cannabis use in antipsychotic-naïve first episode psychosis.

Martinez-Sadurni Laura L, Toll Alba A, Olivares-Berjaga David D, Rodriguez Natalia N et al.

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). Lower AEA concentrations have been associated with greater symptom severity, while the relationship between ECS and cannabis use remains unclear. However, the prognostic value of peripheral endocannabinoid concentrations for clinical outcomes and cannabis use in first-episode psychosis (FEP) remains largely unknown. This study examined whether baseline plasma endocannabinoid concentrations are associated with clinical outcomes and cannabis use at one-year follow-up in antipsychotic-naïve patients with FEP. Plasma AEA and 2-AG concentrations were measured in 58 antipsychotic-naïve patients. Psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS), and cannabis use was evaluated using Standard Joint Units to estimate THC consumption. Associations were examined using correlation and regression analyses adjusted for relevant covariates. Higher baseline AEA concentrations were associated with lower general psychopathology scores at follow-up. No significant associations were observed between endocannabinoid concentrations and total PANSS scores or positive and negative symptom subscales. Age emerged as a significant predictor of cannabis use at follow-up, while 2-AG showed a non-significant trend toward a higher likelihood of use. 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.

PMID 42826464
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PubMedbioRxiv : the preprint server for biology2026-10-01

A phytocannabinoid-sensitive phosphorylation switch converts endocannabinoids into alternative lipid GPCR activators.

Love Anna C AC, Kihara Yasuyuki Y, Mizuno Hirotaka H, Nagai Kazufumi K et al.

Endocannabinoids (eCBs) like anandamide and 2-arachidonoylglycerol are endogenous lipid ligands for CB 1 and CB 2 G protein-coupled receptors (GPCRs). Here, we show that phosphorylation of biologically important anandamide generates naturally occurring anandamide phosphate (AEAp), which switches GPCR ligand specificity to lysophosphatidic acid (LPA) receptors (LPARs) and the primate-specific bile acid sensory receptor MRGPRX4. The kinase responsible for anandamide phosphorylation was identified as diacylglycerol kinase (DGK) theta (DGKθ or DGKQ) using activity-guided brain fractionation, inhibitor profiling, recombinant reconstitution, and DGK isozyme screening. 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.

PMID 42818206
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PubMedbioRxiv : the preprint server for biology2026-10-01

Lipid Activation of a Thalamic GPCR Extends Working Memory Time-scales.

Brandt James Newton JN, Bonito-Oliva Alessandra A, Paknejad Navid N, Chen Celine C et al.

Working memory capacity is poorly understood. The ability to control and extend working memory time-scales provides the potential to alleviate cognitive decline in disease and aging. Through an unbiased genetic search, we previously identified a thalamic orphan receptor Gpr12 as a potent enhancer of working memory, however its activation mechanism remains poorly understood. Here, we describe the CryoEM structure of Gpr12, revealing a lipidic regulatory site enabling an activated signaling state. By surveying the native lipidic environment in mouse thalamus we identified a class of 20 carbon:4 double bond fatty acid eicosanoids as potential ligands. Cell-based assays confirmed that the endogenous cannabinoid anandamide (AEA), but not other closely related family members or derivatives, robustly activates Gpr12. In vivo imaging during behavior revealed that Gpr12 activation produces a striking molecular state - the persistent suppression of cAMP in thalamus that tracks the duration of memory maintenance. Notably, genetic or pharmacological manipulations that enhance the AEA-Gpr12 signaling axis are sufficient to prolong cAMP suppression and extend the temporal window of memory maintenance. Furthermore, AEA-mediated cAMP suppressions in thalamus support sustained neural activity in PFC, specifically during memory maintenance. 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.

PMID 42818673
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