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PhD Thesis: Regina Mangieri

Dissertation Abstract:
The endocannabinoid anandamide as a modulator of stress-coping behavior and positive affect

By Regina Anne Mangieri
Doctor of Philosophy in Pharmacology and Toxicology
University of California, Irvine, 2008
Professor Daniele Piomelli, Chair

The endogenous CB1 cannabinoid receptor ligand anandamide is a lipid-derived neurotransmitter found throughout the body. Anandamide can be released by pharmacological stimulation, but little is known about its physiological regulation and functions. Studies of the exogenous plant-derived cannabinoid agonist ∆9-tetrahydrocannabinol (∆9-THC) suggest that activation of the cannabinoid system can, among other things, increase feeding, reduce pain perception, and alter mood. It is unclear, however, what are the specific physiological functions of the endogenous cannabinoid anandamide.


A. To identify and further examine physiological and pharmacological stimuli, which increase levels of anandamide.

B. To characterize the behavioral effects associated with the elevation of anandamide levels, with the goal of understanding how anandamide signaling might be involved in mood and stress-related disorders.

Summary of Results

(1) Anandamide is increased in rat midbrain following foot shock stress, and partially mediates a form of foot shock stress-induced analgesia. (Chapter 2) 

(2) Pharmacological agents that inhibit anandamide degradation elevate brain anandamide levels and produce diverse effects on affective- and stress-related behaviors in rodents, including:

  • prolongation of stress-induced analgesia (Chapter 2),
  • reduction of anxiety-like behavior (Chapter 3), 
  • enhancement of active stress-coping behaviors (Chapter 4), and 
  • reversal of physiological effects induced by chronic stress (Chapter 5).

(3) Anandamide is increased in the plasma of humans following a pleasurable stimulus (alcohol drinking cues) and may modulate this state of positive arousal (Chapter 6).