Endocannabinoids -- The Brain's Cannabis -- Demonstrate Novel Modes of Action to Stress

July 20, 2005

Science Daily/American Physiological Society

Three separate research team reports -- one from Louisiana, one from Japan and one from Scotland -- are presenting independent research results pointing to involvement of endocannabinoids as a novel neural messenger in various stress-related situations with possible applications in eating, disease treatment and social behavior.

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."

https://www.sciencedaily.com/releases/2005/07/050720065810.htm

How cannabis affects appetite: Brain changes

July 17, 2018

Science Daily/Society for the Study of Ingestive Behavior

New research on how cannabis use alters eating behavior could lead to treatments for appetite loss in chronic illness, according to experts at Washington State University. Using a new procedure to dose lab rats with cannabis vapor, the researchers found how the drug triggers hunger hormones. They also identified specific brain regions that shift to 'hungry' mode while under the influence, according to a report they shared this week at the Society for the Study of Ingestive Behavior, an international meeting of scientific experts on eating.

"We all know cannabis use affects appetite, but until recently we've actually understood very little about how or why," explained Jon Davis, Ph.D., researcher in the Department of Integrative Physiology and Neurosciences at Washington State. "By studying exposure to cannabis plant matter, the most widely consumed form, we're finding genetic and physiological events in the body that allow cannabis to turn eating behavior on or off."

A recent wave of cannabis legalization for both medical and recreational purposes has stimulated research on its therapeutic potential. A family of compounds called cannabinoids, particularly delta-9 tetrahydrocannabinol (THC), are responsible for its psychological effects. The ability of THC to stimulate appetite is valuable since many illnesses cause extreme appetite loss which reduces quality of life and slows recovery.

For these new studies the scientists designed a vapor exposure system to mimic how people often consume cannabis. This allowed precise control of dosage while rats' meals were closely monitored throughout the day. Brief exposure to cannabis vapor stimulated a meal even when rats had recently eaten, suggesting that inhaling cannabis tricks appetite circuits in the brain into hunger mode.

"We found that cannabis exposure caused more frequent, small meals," stated Davis. "But there's a delay before it takes effect." That delay provided a clue to how the drug may act. Ordinarily, when the stomach is empty it releases a hormone called ghrelin, a message to the brain that it's time to look for food. The researchers found that the cannabis dose triggered a ghrelin surge. When they gave a second drug which prevented the ghrelin surge, cannabis no longer triggered eating. They also found changes in how the brain responds to the message. In small region of the hypothalamus responsible for sensing ghrelin, cannabis changed the genetic activity of brain cells that respond to the hormone.

The researchers are optimistic that deciphering that ways cannabis acts in the body to alter appetite can lead to new treatments for illness-induced anorexia. Severe appetite loss is a common symptom of many chronic illnesses, and is especially problematic in cancer, HIV/AIDS, heart disease, and some metabolic disorders. A targeted treatment that offers the beneficial effects on appetite without the broader effects on the mind and body could increase quality of life and speed recovery.

https://www.sciencedaily.com/releases/2018/07/180717094747.htm