Although it may not be obvious during these Trump-rattled times, we’re in the midst of a psychedelic revival. There is more interest than ever before in experimenting with LSD, magic mushrooms, ayahuasca, ketamine, and other psychedelic drugs.
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.
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.
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.
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.
The endocannabinoid system is fundamental to addiction, but not in obvious ways. All sorts of cannabinoids appear to have anti-addictive properties: CBD, THCV, Rimonabant, THC. But Rimonabant acts by blocking the CB1 receptor, THC activates it, and CBD primarily functions in other ways.
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.
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.