Endocannabinoid System

CB1 Kinetics

When a receptor is overactive — because of a drug or disease — the body attempts to normalize activity by internalizing the receptor, hiding it from molecules at the cell surface. Internalization is a key homeostatic mechanism. But a receptor’s degree of activation doesn’t perfectly parallel the subsequent internalization. Some ligands are “biased,” preferring activation over desensitization, or vice versa.

Big Bellies: Pregnancy & Obesity

A mother’s diet while she’s pregnant is known to affect the child’s eventual food preferences. A new animal study from scientists in the U.S. and Brazil examines how a high-fat diet during pregnancy influences the offspring’s predisposition to obesity and related complications later in life, and this appears to be mediated by changes in the endocannabinoid system. The researchers showed that the biochemical response to a high fat diet depends on whether the offspring was male or female.

Singing Praises of the ECS

The endocannabinoid system forms part of what makes us feel pleasure — from the runner’s high, eating good food, and according to new research singing. Saoirse O’Sullivan’s group at University of Nottingham (UK) examined the effects of singing and dancing on endocannabinoid levels. Singing (in a group of people who like to sing) increased fatty acid ethanolamide concentrations by 30-50% in the blood — more than is typically associated with exercise.

ABHD6, an Exceptional Enzyme

2-AG is the most abundant endocannabinoid. It is derived from the lipid membrane that separates a cell from its environment — a cell will cut 2-AG out of its membrane, allowing the molecule to drift to neighboring cells. Upon meeting those neighbors, it slips into their membrane, where it binds to cannabinoid receptors and communicates a message. Those neighboring cells don’t send 2-AG back after the message is received, but instead cut up 2-AG to terminate the signal.

CB2 in Breast Cancer

Breast cancers are often classified by the receptors they express. The three most common breast cancer receptors respond to estrogen, progesterone, or epidermal growth factor. The latter include HER2-positive breast cancers. Identifying these receptors facilitates treatment. A study led by scientists in Spain indicates that the endocannabinoid system plays an important role in the treatment of HER2-positive cancer.

Orphan Receptors in Cancer

An “orphan receptor” is the term for a receptor in the body whose natural activator is not known. GPR55 is a G-protein coupled orphan receptor that interacts with the other cannabinoid system. CBD appears to inhibit GPR55, while endocannabinoids may activate it. Researchers in the UK and Italy collaborated on a study of GPR55 in pancreatic cancer.

Loss of Cannabinoid Receptors in Adenomyosis

Drawing of woman with abdominal pain
Adenomyosis is a menstrual complication that causes heavier bleeding and pain during a woman’s period. About one in five women suffer from it. As with most female diseases, it is poorly studied and consequently hard to treat. The endocannabinoid system (ECS) is known to be involved in reproductive tissues, and it is dysregulated in pathologies like endometriosis, so it makes sense to consider the ECS in this condition.

Anandamide Modulates Panic

Rainbow Boa Snake
Panic, as a mental health disorder, results from overactive stress hormones, hypersensitivity to certain neurotransmitters, and a desensitization to the parasympathetic system — which is supposed to quell the fight-or-flight reaction after a threat has disappeared. New research from Brazilian scientsts in São Paulo examined how endocannabinoids, specifically anandamide, plays a role in panic-like reactions in mice. Injecting various doses of anandamide into a brain region called the dorsomedial hypothalamus, they found that moderate doses suppress panic, but high doses have no effect.