Cannabinoids are a class of neurotransmitters made naturally by the body. One cannabinoid, Delta-9 tetrhydrocannabinol (THC) is the psychoactive ingredient in marijuana.
Cannabinoid receptors are widely distributed in the brain,1 but are most dense in structures involved in thinking and memory, attention and bodily movement.2 Cannabinoids also play a central role in regulating appetite.3 In addition, they facilitate tissue protection and immunity, fight inflammation4 and alleviate pain and nausea.5
One of the structures cannabinoids act on is the hippocampus, the site of short-term memory formation. Scientists say cannabinoids strengthen the connections between neurons to lay down new memories. This might seem counter-intuitive, since marijuana has a well-known (and well-deserved) reputation for short-term memory loss. However, as Dr. Rachel Wilson, a Cal-tech researcher explains, “It is probably a case of too much of a good thing …. When cannabinoids are abundant, every experience becomes strongly linked in our minds. But when everything is marked for memory, the system is overwhelmed, and nothing is remembered.”6
Cannabinoids also play a role in the brain’s feedback systems. According to Stanford researcher Dan Madison, there are two kinds of brain cells: principal cells and “inter-neurons.” Principal cells are like a superhighway for communication, whereas inter-neurons are like traffic signals along the highway, adjusting the flow. “Cannabinoids are a way for the principle cells to regulate the traffic lights,”says Madison.7
Marijuana affects this regulatory function in addition to its impact on the dopamine system. Dopamine and cannabinoids are known to interact with one another. For example, according to a 2007 Stanford study published in Nature, a cannabinoid shortage is a possible byproduct of the dopamine-depletion seen in Parkinson’s disease. Without enough dopamine, brain cells apparently can’t produce sufficient cannabinoids to maintain proper movement.8 (Interestingly, amphetamines help relieve some of the symptoms of Parkinson’s.9)But how dopamine and cannabinoids affect each other isn’t well-understood yet.
Cannabinoids have long been suspected to play a role in craving, as they are involved in brain circuits regulated by leptin, a hormone involved in hunger and satiety.10The lower the leptin in the circuits, the higher the production of natural cannabinoids.11 Another hormone that works with leptin, ghrelin, is produced in the stomach. Originally, it was thought that ghrelin worked through the hypothalamus to stimulate hunger, but more recently it was discovered that ghrelin works directly in the ventral tegmentum area (VTA), a key part of the reward system, to activate the dopamine system. Suppression of ghrelin causes experimental animals to suppress their feeding and food-seeking.12
One study investigating alcohol cravings reported that there are four subtypes of craving and the leptin/ghrelin system is involved in two of them. According to Otto Lesch, professor of psychiatry at the University of Vienna, “We know that these four different mechanisms are caused by different biological mechanisms. They have different long-term courses and they profit significantly differently from different pharmaceutical compounds. Therefore, it is very important to define basic workings of these different craving mechanisms in order to develop better models to proof new medications.”13
1. New Support For Pot As Painkiller, San Francisco Chronicle, October 27, 1997.
2. Scientists Find Way To Block Effects of Marijuana, Reuters, April 12, 2001.
3. Marijuana-like Substances In Brain Trigger Appetite, Associated Press, April 11, 2001.
4. Researchers Buzzing About Marijuana-derived Medicines, Baltimore Sun, November 5, 2004.
5. New Support For Pot As Painkiller, San Francisco Chronicle, October 27, 1997; Medical Promise In Marijuana Patch New York Times, January 30, 2000; Marijuana’s Effects: More Than “Munchies,” New York Times, January 29, 2002; Medical Pot Cuts Pain, Study Finds, San Francisco Chronicle, February 13, 2007.
6. Marijuana’s Effects: More Than “Munchies,” New York Times, January 29, 2002.
7. Nerves Need Marijuana-like Substances To Stay In Touch, Studies Find, San Francisco Chronicle, May 20, 2001.
8. Natural Brain Substance Linked to Parkinson’s Symptoms, San Francisco Chronicle, February 8, 2007.
9. Amphetamines Relieve Parkinson’s-like Symptoms, newscientist.com, July 24, 2006.
10. Marijuana-like Substances In Brain Trigger Appetite, Associated Press, April 11, 2001.
11. Alcohol Cravings For Some Alcoholics Influenced By the Appetite-Regulating Peptide Leptin, medicalnewtoday.com, May 31, 2007.
12. Hormone Linked to Brain’s Craving for Food and Other Energy Sources, medicalnewtoday.com, November 15, 2006.
13. The Brain: Malleable, Capable, Vulnerable, New York Times, May 29, 2007.