anandamide

Targeting the Endocannabinoid System for Management of Chemotherapy, HIV and Antiretroviral-Induced Neuropathic Pain

Chemotherapeutic drugs (used for treating cancer), HIV infection and antiretroviral therapy (ART) can independently cause difficult-to-manage painful neuropathy. Paclitaxel, a chemotherapeutic drug, for example is associated with high incidence of peripheral neuropathy, around 71% of the patients of which 27% of these develop neuropathic pain. Use of cannabis or phytocannabinoids has been reported to improve pain measures in patients with neuropathic pain, including painful HIV-associated sensory neuropathy and cancer pain. Phytocannabinoids and endocannabinoids, such as anandamide and 2-arachidonoylglycerol (2-AG), produce their effects via cannabinoid (CB) receptors, which are present both in the periphery and central nervous system. Endocannabinoids are synthesized in an “on demand” fashion and are degraded by various enzymes such as fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MGL). Various studies, including those from our group, suggest that there are changes in gene and protein expression of endocannabinoid molecules during chemotherapy-induced neuropathic pain (CINP), HIV and antiretroviral-induced neuropathic pain. Analysis of endocannabinoid molecule expression in the brain, spinal cord and paw skin using LC-MS/MS show that there is a specific deficiency of the endocannabinoids 2-AG and/or anandamide in the periphery during CINP. Various drugs including endocannabinoids, cannabidiol, inhibitors of FAAH and MGL, CB receptor agonists, desipramine and coadministered indomethacin plus minocycline have been found to either prevent the development and/or attenuate established CINP, HIV and antiretroviral-induced neuropathic pain in a CB receptor-dependent manner. The results available suggest that targeting the endocannabinoid system for prevention and treatment of CINP, HIV-associated neuropathic pain and antiretroviral-induced neuropathic pain is a plausible therapeutic option.

Early adolescence MK-801-induced behavioral and gene expression alterations are reversed by anandamide hydrolysis inhibition: differential modulation by cannabinoid receptor 1 and 2

Elevating anandamide levels restore depression-like phenotype and alterations in micro-RNAs in rats exposed to early life stress

Elevation of anandamide by URB597 mitigates cocaine-seeking behaviour during abstinence

Enhancing anandamide prevents a stress phenotype via β-catenin in the PFC in a rat model of PTSD

Modulation of anandamide tone as an effective strategy for in vitro and in vivo stimulation of autophagy in Alzheimer's disease

Cortical miR-16 involvement in the antidepressant effects of pharmacological elevation of anandamide in a rat model for depression

FENS Forum 2024

Dual effect of anandamide and its endogenous precursor 20:4-NAPE on DRG neuronal excitability and nociception

FENS Forum 2024