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Hacking retrograde anandamide signaling


  • Key concept 1: Retrograde anandamide trafficking with dopamine conjugate of DHA may induce selective GPCR receptor heteromerization.
  • Key concept 2: Microglial Neuroprotection!
  • Key concept 3: CREB phosphorylation
  • Key concept 4: BDNF expression, a biomarker for learning-dependent synapse formation. (synaptogenesis) [1]

Synaptogenic endocannabinoids

  • Intracellular CB1/BDNF signaling mediate on-demand neuroprotection on excitatory (glutamatergic) synapses and in particular astrocytes. [2]
  • DHA supplementation improves mitochondrial function and neuronal survival (homeostasis). [3]
  • Anti-proliferative effects of DHEA on prostate cancer cell lines. [4]

Microglial activation

  • Inhibitory effect of the CB2 receptor on monocyte subpopulations and microglial activation. [5]
    • Anti-inflammatory role of anandamide and 2-AG signaling in LPS-stimulated microglial activation of endogenous CB2 receptor. [6]
    • Neuroprotection by inhibition of microglial activation. [7]
    • CB2 stimulation is proneurogenic on adult hippocampal neurogenesis PMC
  • Caffeine is a adenosine antagonist which potentiate CB1 receptor transactivation in the hippocampus PMID PMID


  1. [Parkhurst-2013]

    Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor.

  2. [Marsicano-2003]

    CB1 cannabinoid receptors and on-demand defense against excitotoxicity.

  3. [Stanley-2012]

    Update on lipids and mitochondrial function: impact of dietary n-3 polyunsaturated fatty acids.

  4. [Website2]
  5. [Martin-Moreno-2011]

    Cannabidiol and other cannabinoids reduce microglial activation in vitro and in vivo: relevance to Alzheimer's disease.

  6. [Website1]
  7. [Obregon-2005]

    Stimulation of cannabinoid receptor 2 (CB2) suppresses microglial activation.