Endocannabinoids -- The Brain's Cannabis -- Demonstrate Novel Modes Of Action To Stress

Tulane, LSU team on stress-related shutdown

The team from Tulane and Louisiana State Universities, led by Shi Di, found that in both physiological and psychological stress situations, stress hormones act on the brain to stimulate the release of endogenous cannabinoids from neurons in the hypothalamus, which act as a local messenger within the hypothalamus to shut down the neuroendocrine stress response.

One explanation for this hormone feedback regulation of the stress response might be to prepare the brain to mount another response in case of the onset of another possible stressor. The endogenous cannabinoids may serve to link the stress response with other neuroendocrine functions controlled by the hypothalamus, such as feeding.

Di says that the "actions of the endocannabinoids on the synaptic circuits that control the activity of the hypothalamic neurons serve to rapidly inhibit hormone secretion from the pituitary gland, providing a rapid negative feedback mechanism for the regulation of neuroendocrine function during stress."

Japanese team finds inhibition of excitatory and inhibitory synaptic transmission

In an in vitro study, a multi-center Japanese team led by Atsushi Soya focused on the supraoptic nucleus (SON) where vasopressin and oxytocin are synthesized. They found that a synthesized cannbinoid (CP55,940) inhibited both excitatory and inhibitory synaptic transmission and that a balanced input can produce sustained changes in neuronal activity without damage to neuronal homeostasis.

"Our next step is to investigate cannabinoids' effects in various stress conditions," Soya said. "Endocannabinoids may have possible involvement in stress-induced responses such as the changes of autonomic, endocrine and immune function."

Furthermore, Soya added, "cannabinoids are relevant to potential relief in such disease situations in the brain as multiple sclerosis and epilepsy, or feeding disorders. In these, their effects are similar to marijuana, except for the possible dangers of accidentally using the natural products at higher dosages."

Scottish team seeks social behavior answers

Nancy Sabatier of the University of Edinburgh, noted that "cannabis, or marijuana, is a drug that is widely abused because of the effects it can have on our mood and our social behavior. Cannabis works this way because it acts like substances that are produced inside our brains that are messengers between brain cells. Our work involves trying to understand what these substances, endocannabinoids, are for."

She said they are particularly interested in how endocannabinoids influence oxytocin cells in the brain, because because OT within the brain is involved in social behavior. "We have found that oxytocin cells produce endocannabinoids, and can release these to switch off other inputs to the oxytocin cells themselves. We are looking at what stimuli will cause oxytocin cells to release endocannabinoids to understand why this system might be important."

Sabatier noted that most related experiments are carried out in rats, "but we think that the basic ways in which these circuits work is very similar in all mammals. These brain circuits are very old in evolutionary terms, and they govern behaviors that are of fundamental importance to most species."

Editors note: Di, Soya and Sabatier are presenting each of their team's research at the American Physiological Society's 2005 Conference, "Neurohypophyseal Hormones: From Genomics and Physiology to Disease," plus the latest developments toward clinical applications, July 16-20 in Steamboat Springs, Colorado.

In addition, Shi Di is participating in the symposium, "Pressure/volume regulation of VP/OT release," chaired by Tom Cunningham of the University of Texas Health Science Center, and Leo Renaud of the Ottawa Health Research Center, Canada.

Shi Di, Victor Marcheselli, Nicolas Bazan, Jeffrey Tasker. Di and Tasker are at the Neurobiology Division and Cell & Molecular Biology Department at Tulane University, New Orleans; Tasker is also at the Neuroscience Program; Marcheselli and Bazan are at the Neuroscience Center, Louisiana State University Health Sciences Center, New Orleans. "Rapid glucocorticoid-mediated endocannabinoid release and opposing regulation of glutamate and GABA inputs to hypothalamic magnocellular neurons." Funded by NIH.

Atsushi Soya, Ryota Serino, Tatsushi Onaka, Takeshi Terao, Jun Nakamura, Yoichi Ueta. Soya and Ueta are at Dept. of Physiology School of Medicine, University of Occupational & Environmental Health (UOEH), Kitakyushu; Serino is at the UOEH Dept. of Internal Medicine; Onaka is at Division of Integrative Physiology, Dept. of Physiology, Jichi Medical School; Terao is at Dept. of Psychiatry, Oita University School of Medicine; and Nakaura is at UOEH Dept. of Psychiatry.

Nancy Sabatier, Gareth Leng, University of Edinburgh, Scotland. "Cannabanoids inhibit excitatory responses of supraoptic neurons to stimulation of OVLT in vivo."