A new study published in the journal Current Biology has revealed that the well-studied nematode worms, Caenorhabditis elegans (C. elegans), react to cannabinoids and ingesting marijuana in a manner strikingly similar to humans.
“Cannabinoids make nematodes hungrier for their favored foods and less hungry for their non-favored foods,” said Shawn Lockery from the University of Oregon. “Thus, the effects of cannabinoids in nematodes parallels the effects of marijuana on human appetites.
“Nematodes diverged from the lineage leading to mammals more than 500 million years ago. It is truly remarkable that the effects of cannabinoids on appetite are preserved through this length of evolutionary time.”
In 2015, when cannabis became legal in Oregon, Lockery became inspired to conduct the new study. “At the time, our laboratory at the University of Oregon was deeply involved in assessing nematode food preferences as part of our research on the neuronal basis of economic decision-making.”
“In almost literally a ‘Friday afternoon experiment’ – read: ‘let’s dump this stuff on to see what happens’ – we decided to see if soaking worms in cannabinoids alters existing food preferences. It does, and the paper is the result of many years of follow-up research.”
People commonly associate ingesting marijuana or cannabis with stimulating appetite and cravings for high-calorie, tasty foods. This phenomenon is colloquially known as the “munchies.” This research explores the molecular mechanisms underlying these effects and uncovers intriguing similarities between nematodes and humans.
The active compounds found in cannabis are cannabinoids. Cannabinoids exert their effects by binding to specific proteins called cannabinoid receptors. These receptors are present in the brain, nervous system, and other parts of the body. They normally respond to endocannabinoids, naturally occurring molecules in the body. The endocannabinoid system plays crucial roles in various physiological processes, including eating, anxiety, learning, memory, reproduction, and metabolism.
The apparent similarities between the cannabinoid system in nematodes and that in humans and other animals at the molecular level intrigued the researchers. The researchers sought to determine whether the hedonic feeding effects of cannabinoids and ingesting marijuana were conserved across species.
The study first demonstrated that worms exposed to the endocannabinoid anandamide consumed more food. They also exhibited a preference for their favorite food. These effects were dependent on the presence of the worms’ cannabinoid receptors.
In a series of follow-up experiments, the scientists genetically replaced the C. elegans cannabinoid receptor with the human cannabinoid receptor. This resulted in the worms displaying normal responses to cannabinoids.
“We found that the sensitivity of one of the main food-detecting olfactory neurons in C. elegans is dramatically altered by cannabinoids,” Lockery said. “Upon cannabinoid exposure, it becomes more sensitive to favored food odors and less sensitive to non-favored food odors. This effect helps explain changes in the worm’s consumption of food, and it is reminiscent of how THC makes tasty food even tastier in humans.”
The discovery highlights the remarkable commonality between the effects of cannabinoids and ingesting marijuana in nematodes and humans. The researchers also found that the effects of anandamide rely on neurons involved in food detection.
“Cannabinoid signaling is present in the majority of tissues in our body,” said Lockery. “It therefore could be involved in the cause and treatment of a wide range of diseases. The fact that the human cannabinoid receptor gene is functional in C. elegans food-choice experiments sets the stage for rapid and inexpensive screening for drugs that target a wide variety of proteins involved in cannabinoid signaling and metabolism, with profound implications for human health.”
According to Lockery, these findings in worms are not only entertaining but also have significant practical implications.
“Cannabinoid signaling is present in the majority of tissues in our body,” he said. “It therefore could be involved in the cause and treatment of a wide range of diseases. The fact that the human cannabinoid receptor gene is functional in C. elegans food-choice experiments sets the stage for rapid and inexpensive screening for drugs that target a wide variety of proteins involved in cannabinoid signaling and metabolism, with profound implications for human health.”
However, the researchers acknowledge that many questions remain unanswered. How do cannabinoids alter the sensitivity of C. elegans olfactory neurons, which do not have cannabinoid receptors? They are also eager to investigate the effects of psychedelic substances on nematodes.
“Perhaps we can find a new set of similarities between humans and worms, now in the case of drugs that alter perception and psychological well-being,” said Lockery.
This groundbreaking study offers valuable insights into the molecular mechanisms of cannabinoid action from ingesting marijuana. It also paves the way for further exploration of the intriguing parallels between nematodes and humans.
The Cannabis plant is the source of cannabis, also known as marijuana, which is a psychoactive drug. It contains over 100 active compounds called cannabinoids, with the two most prominent being delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD).
THC is responsible for the intoxicating effects or the “high” associated with ingesting marijuana. CBD is non-intoxicating and known for its therapeutic properties.
People primarily attribute the appetite-stimulating effects of marijuana, commonly known as the “munchies,” to THC. When people consume marijuana, THC interacts with the endocannabinoid system. This is a complex cell-signaling system that plays a crucial role in various physiological processes. These include appetite regulation, pain sensation, mood, memory, and immune response.
The endocannabinoid system comprises endocannabinoids (naturally occurring compounds in the body), enzymes, and receptors such as the CB1 and CB2 receptors.
THC binds to the CB1 receptors. These are predominantly found in the brain and central nervous system. This binding leads to a cascade of events that contribute to appetite stimulation:
THC stimulates the release of ghrelin, a hormone that increases appetite. It also affects other appetite-regulating hormones, such as leptin and peptide YY.
THC can heighten the sense of taste and smell, making food more appealing and enjoyable. This heightened sensory perception can contribute to increased appetite and food consumption.
THC activates the brain’s reward system, increasing the release of dopamine, a neurotransmitter responsible for feelings of pleasure and motivation. This surge in dopamine makes eating more pleasurable and rewarding, leading to increased food intake.
THC can also modulate neural circuits that suppress appetite, effectively reducing the inhibitory signals that would otherwise limit food consumption.
Although people well-establish the appetite-stimulating effects of marijuana, the underlying mechanisms are complex. Researchers do not yet fully understand them. Studies are ongoing to further understand these mechanisms and explore potential therapeutic applications. These include treating appetite loss in patients with chronic illnesses, cancer, or eating disorders.
Nematode worms, also known as roundworms, are a diverse group of microscopic, unsegmented worms that belong to the phylum Nematoda. Over 25,000 described species inhabit various environments, including soil, water, plants, and animals.
Among the nematodes, Caenorhabditis elegans (C. elegans) is a well-studied model organism. It has contributed significantly to the understanding of various biological processes.
Some key features and facts about nematode worms include:
Nematodes are usually very small, ranging from less than a millimeter to several centimeters in length. They have a simple body structure with a cylindrical, elongated, and unsegmented body covered by a tough, protective cuticle.
Nematodes play essential roles in various ecosystems, acting as decomposers, predators, or parasites. Microorganisms can help recycle nutrients in the soil and regulate pest populations. They also serve as bioindicators for assessing soil health and quality.
C. elegans is a free-living nematode found in soil. Researchers widely use it as a model organism in biological research. This is due to its simplicity, transparency, short life cycle, and ease of genetic manipulation. Studies on C. elegans have led to critical insights into genetics, development, aging, neurobiology, and cell biology.
Some nematode species are parasitic, infecting plants, animals, and humans, causing various diseases. In humans, parasitic nematodes can cause conditions such as ascariasis, hookworm infections, trichinosis, and filariasis.
Nematodes exhibit considerable genetic diversity, which allows them to adapt and survive in a wide range of environments. Their genomic complexity varies significantly across species, with some nematodes having more genes than humans.
Nematodes can reproduce both sexually and asexually. C. elegans, for example, has two sexes: hermaphrodites and males. Hermaphrodites can reproduce through self-fertilization, while males can mate with hermaphrodites for cross-fertilization.
Nematode worms, despite their small size and simplicity, have significantly contributed to our understanding of biological processes. They continue to be valuable in various research fields, such as genetics, developmental biology, and neurobiology.
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