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anandamide (anandamide)

✓ Approved

Yissum · CNR1

什么是 anandamide？

anandamide 是一种治疗药物，由Yissum研发。该药已获批，用于治疗相关适应症，给药途径：Unknown。

药物档案

商品名anandamide
公司Yissum
分子靶点CNR1, CNR2
给药途径Unknown
状态Approved
来源： ClinicalTrials.gov, Yissum

作用机制

分子靶点

anandamide 作用于 2 个分子靶点：

CNR1cannabinoid receptor 1 (CNR, CB1A)
CNR2cannabinoid receptor 2 (CX5, CB-2)
需要更深入的分析？Noah AI 可解释复杂机制并与同类药物比较。

治疗适应症

anandamide 针对 2 个适应症，涉及 1 个治疗领域。

治疗领域疾病/病症分期
Psychiatric disordersAnorexia nervosa✓ Approved
Psychiatric disordersBulimia nervosa✓ Approved

相关研究文献

PubMedCanadian journal of physiology and pharmacology2026-06-12

TRPV1, Endocannabinoid, and Opioid Systems in Analgesia: Molecular Mechanisms and Drug Development Strategies.

Benkhraba Kaoutar K, Castano Jesus D JD, Beaudry Francis F

Pain modulation relies on complex molecular interactions among ion channels, G protein-coupled receptors, and intracellular signaling cascades. The Transient Receptor Potential Vanilloid 1 (TRPV1) channel serves as a polymodal detector and integrator of noxious stimuli, linking sensory transduction with broader neuromodulatory systems. This review delineates the mechanistic crosstalk between TRPV1, endocannabinoid, and opioid pathways in nociceptive regulation. TRPV1 activation by heat, protons, or endogenous lipids induces calcium influx and engages protein kinase C (PKC), protein kinase A (PKA), and mitogen-activated protein kinase (MAPK) pathways that modulate channel phosphorylation and neuronal excitability. Endocannabinoids such as anandamide act as dual CB₁ and TRPV1 agonists, establishing feedback loops that adjust nociceptive thresholds, while μ-opioid receptor activation inhibits adenylate cyclase and TRPV1 sensitization through Gi/o-mediated signaling. Given the recent progress in cryo-electron microscopy and molecular modeling, simulation studies have been possible, revealing key structural determinants underlying key receptor interactions. Integrating pharmacophore modeling, molecular docking, and artificial intelligence-based screening enables rational design of multi-target ligands that exploit TRPV1-endocannabinoid-opioid synergy. This mechanistic framework supports the development of next-generation analgesics that achieve potent, sustained, and safe modulation of nociceptive signaling.

PMID 42276013
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PubMedThe journal of pain2026-06-11

Inhibition of endocannabinoid catabolizing enzymes MAGL and FAAH reduces the activity of CaV3 channels in nociceptors and pain hypersensitivity in a rat model of spinal cord injury.

Liu Huilin H, Sipple Erin E, Schutz Livia L, Gordon Chris C et al.

Development of chronic neuropathic pain is a severe secondary complication following spinal cord injury (SCI) and affects up to 60-70% of patients. Successful management of SCI-induced neuropathic pain is in many cases insufficient, leading to a severe decline in quality of life and increased risk for depression, anxiety, and addiction. Nociceptors' hyperexcitability and spontaneous activity contribute to the development/maintenance of SCI-induced neuropathic pain, and studies in rodent models of SCI have shown reduced pain hypersensitivity upon downregulation of nociceptors' hyperexcitability. Previous reports showed that CaV3 channels contribute, together with other mechanisms, to driving nociceptors' hyperexcitability and the development/maintenance of SCI-induced neuropathic pain in rodent models of SCI. Endocannabinoids can directly inhibit the activity of CaV3 channels. Accordingly, we hypothesized that inhibition of endocannabinoid catabolizing enzymes monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH), and subsequent increase in the levels of 2-arachidonoylglycerol and anandamide, could result in inhibition of CaV3 channels and reduced pain hypersensitivity following SCI. Using a combination of patch clamp electrophysiology in nociceptors in vitro and behavioral pharmacology in vivo combined with measurements of mechanical hypersensitivity and spontaneous pain in a rat model of SCI, we found that inhibition of MAGL and FAAH reduced the activity of CaV3 channels in nociceptors and mechanical hypersensitivity, while reduction of spontaneous pain was observed only upon inhibition of FAAH. Taken together, our data suggest that inhibition of MAGL and FAAH, with subsequent inhibition of CaV3 channels in nociceptors, may provide a strategy to reduce chronic neuropathic pain following SCI. PERSPECTIVE: CaV3 channels contribute to nociceptors' hyperexcitability and SCI-induced neuropathic pain. Our data demonstrate that inhibition of MAGL and FAAH reduces the activity of CaV3 channels in nociceptors and SCI-induced neuropathic pain, suggesting that inhibition of endocannabinoid catabolizing enzymes may represent a rational approach to reduce pain hypersensitivity following SCI.

PMID 42269804
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PubMedVeterinary record open2026-06-08

Effect of environmental temperature on oxidative status, inflammatory response and endocannabinoid system at oestrus in dairy cows.

Carbonari Alice A, Frattina Lorenza L, Burgio Matteo M, Cicirelli Vincenzo V et al.

Heat stress (HS) poses a significant challenge to dairy production under climate change, as it compromises fertility, productivity and overall health in cows. This seasonal observational cross-sectional study investigated how environmental temperature affects oxidative status, inflammatory responses and endocannabinoid system (ECS) in dairy cows, comparing winter and summer conditions. Sixty Italian Holstein cows, 20 per farm, were enrolled from three farms in southern Italy. In winter and summer, temperature‒humidity index (THI) was recorded using data loggers and blood samples were collected from each cow's coccygeal vein during oestrus. Serum samples were analysed to evaluate the oxidative status as reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP), inflammatory responses as tumour necrosis factor-alpha (TNF-α) and interleukin (IL)-10, and ECS as anandamide (AEA) and 2-arachidonoylglycerol (2-AG). Temperature‒humidity index was significantly higher in summer than in winter (p < 0.001), confirming HS exposure. Anandamide levels showed no significant seasonal variation, while 2-AG concentrations were significantly reduced in summer compared to winter (p < 0.01). Oxidative stress increased in summer, with lower BAP (p < 0.05) and higher d-ROMs (p < 0.001). Tumour necrosis factor-alpha and IL-10 were significantly higher in summer than in winter (p < 0.001 and <0.05). The study demonstrates that summer HS could alter oxidative balance, stimulates inflammatory pathways and modulates ECS activity in dairy cows. Reduced 2-AG suggests potential ECS involvement in thermal-stress adaptation. These findings provide a foundation for future research on nutritional or management strategies aimed at improving resilience to HS.

PMID 42254555
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PubMedImmunity, inflammation and disease2026-06-04

Dandruff Is a Low-Grade Inflammatory Condition Featuring Hyperproliferative Keratinocytes, Interleukin-17-Producing T Cells, and N-Acyl Ethanolamines.

Kendall Alexandra C AC, Mohamed Karishma K, Linley Holly H, Koszyczarek Marta M MM et al.

Dandruff features epidermal scaling but lacks overt signs of inflammation, such as erythema. Characterisation of its inflammatory profile may improve understanding of the underlying inflammatory mechanisms and therefore indicate alternative approaches for treatment. Full-thickness scalp biopsies were sampled from healthy volunteers and those with dandruff. Immunohistochemistry for Ki67 and keratin 16 was used to examine keratinocyte proliferation and differentiation. Mass spectrometry lipidomics was applied to profile scalp skin barrier lipids and lipid mediators. The presence of immune cells and their cytokine production was examined by flow cytometry. Cytokine and chemokine levels in scalp skin were analysed by cytometric bead array. Increased keratinocyte proliferation and aberrant keratinocyte differentiation were observed in dandruff relative to healthy scalp; however, this epidermal dysregulation was not mirrored by alterations to barrier lipid levels. Decreased numbers of innate lymphoid cells and reduced expression of CD86 on antigen-presenting cells, were the few cellular alterations observed in dandruff scalp, suggesting dandruff only subtly changes major skin immune cell populations. Despite this, increased proportions of interleukin-17-producing T-cells and increased C-C Motif Chemokine Ligand 17 (CCL17) levels were observed in dandruff scalp, indicative of a low-grade, mixed Type-2/Type17 inflammatory response. Increased levels of N-acyl ethanolamines, including the endocannabinoid anandamide, as well as linoleoyl- and oleoyl-ethanolamine, were also observed in dandruff scalp which could be responsible for suppressing inflammation to sub-clinical levels. These findings indicate that, contrary to being a mere flaking disorder, dandruff involves an altered inflammatory environment consistent with low-grade inflammation.

PMID 42237451
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PubMedTranslational psychiatry2026-05-29

Enhancing anandamide signalling through fatty acid amide hydrolase inhibition: An update on the pharmacological strategy for treating psychiatric disorders.

Couttas Timothy A TA, Hoffmann Anna E AE, Jieu Beverly B, Golla Felix R FR et al.

Endocannabinoids (eCBs) are lipid-derived neuromodulators that regulate numerous neurophysiological processes by modulating synaptic transmission. Synthesised on demand in response to increased postsynaptic intracellular calcium or activation of postsynaptic G-protein coupled receptors, eCBs are rapidly degraded, resulting in transient, tightly regulated signalling. Dysregulation in the endocannabinoid system (ECS), including altered peripheral and central eCB concentrations and/or cannabinoid-1 receptor (CB1R) expression, has been observed across psychiatric syndromes, including major depressive disorder, psychotic disorders, and post-traumatic stress disorder (PTSD). These associations have prompted growing interest in pharmacological strategies targeting the ECS. Though medical cannabis is increasingly prescribed for psychiatric symptoms, its clinical use remains controversial due to limited high-quality evidence, psychotropic side effects, and regulatory constraints. An alternative is to enhance the signalling of a principal eCB, anandamide (AEA), potentially offering more physiologically constrained CB1R engagement, by inhibiting fatty acid amide hydrolase (FAAH), the main enzyme degrading AEA and its congener, N-acylethanolamines (NAE), oleoylethanolamide (OEA) and palmitoylethanolamide (PEA). This review consolidates recent clinical evidence for FAAH inhibitors, examining their influence on AEA, safety and efficacy in ameliorating symptoms across a range of psychiatric conditions, including depression, anxiety, PTSD, and cannabis use disorder (CUD). Presently, only two compounds, PF-04457845 (JZP150) and JNJ-42165279, have progressed to Phase II trials, demonstrating modest clinical benefit in CUD, with no efficacy in PTSD or osteoarthritis pain. Herein, we discuss emerging insights, safety considerations, broader mechanistic implications, and future directions for FAAH-targeted therapeutics, advocating for a precision medicine approach to realise their potential in the treatment of psychiatric disorders.

PMID 42209468
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PubMedInternational journal of molecular sciences2026-05-27

Short Communication: The Peripheral Cannabinoid CB1 Receptor Antagonist AM6545 Modifies Cardiovascular Effects of Endocannabinoids in DOCA-Salt Rats.

Remiszewski Patryk P, Schlicker Eberhard E, Grzęda Emilia E, Weresa Jolanta J et al.

Peripherally restricted ('second-generation') cannabinoid CB1 receptor (CB1R) antagonists have been suggested to have therapeutic potential in numerous diseases. However, their effects on the cardiovascular system require further research. The peripheral CB1R antagonist AM6545 failed to modify the decrease in blood pressure (BP) elicited by inhibition of anandamide degradation in spontaneously hypertensive rats. The aims of the present study were to examine the effect of AM6545 on BP and its interaction with endocannabinoid-evoked effects in deoxycorticosterone acetate (DOCA)-salt rats. For this purpose, we applied methanandamide (MethAEA), a stable analogue of anandamide, and URB597, an inhibitor of its degradation, in urethane-anesthetized animals. AM6545 did not affect BP by itself. MethAEA elicited a biphasic effect (a rise in BP, followed by its fall); both phases were antagonized by AM6545. URB597 induced a monophasic hypotensive effect, which was abolished by AM6545 in DOCA-salt rats but further enhanced in control animals. AM6545 also unmasked an additional increase in BP after URB597 in both groups of rats. In conclusion, AM6545 modifies the cardiovascular effects of endocannabinoids in hypertension in a model-dependent manner. The cardiovascular effects of CB1R antagonists should be carefully evaluated when assessing their potential therapeutic significance, as they may unmask an increase in BP.

PMID 42196427
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