Published on November 21, 2014 by Professor Gary L. Wenk, Ph. D. in Your Brain on FoodStudies suggest that people who user moderate amounts of marijuana show no personality disturbances. This finding raises the important issues of how much does the term “moderate” imply, how long have the people in these studies been smoking marijuana and at what age did they begin smoking. In contrast, people who are heavy users of marijuana for a prolonged period of time were characterized as suffering from apathy, dullness, lethargy, and impairment of judgment, i.e. the classic amotivational syndrome. Whether the amotivational syndrome exists or not is still controversial; there are still too few poorly controlled small studies that do not allow a definitive answer. Also, most people who use marijuana do not develop this syndrome. Why does this syndrome only develop in some long term users? The answer lies in understanding the behavior of our brain’s own marijuana system. Our human brain produces its own endogenous marijuana-like chemicals. One of them is call 2-AG and is the most abundant of the endogenous marijuana-like chemicals; the other is called anandamide. 2-AG and anandamide are made from the fat in our diet. Indeed, when we consume lots of fat our brain rewards us by releasing 2-AG and anandamide. Yes, our brain loves it when we consume fat; it makes us feel happier and induces us to eat more fat. You can thank your brain’s marijuana system for this. 2-AG and anandamide induce their effects in the brain by attaching to proteins called receptors. This happens similar to a key fitting into a lock. However, the brain’s response can be a little more complicated. If we repeatedly insert our key (marijuana) into the lock (receptor protein) too many times or too often the brain does something really strange: it takes away the lock. Thus the person needs to smoke more and more in order to find the reduced number of locks. Are there any long term consequences to having fewer working marijuana receptors (locks) in the brain? Until recently, no one really knew the answer to this question. Then, in 2006, a drug called Acomplia was introduced in the UK market for the treatment of obesity. Acomplia was invented based upon the recognition that marijuana induces “the munchies,” a strong craving for high-calorie foods. This well-known side effect of marijuana indicated that the brain’s feeding center possessed endogenous marijuana receptors. Acomplia was designed to block these receptors, and thus block cravings for high-calorie food. Acomplia worked very well as an anti-obesity drug but it had a very nasty side-effect: it caused severe depression and suicidal thoughts. The drug was withdrawn from the market. The actions of Acomplia taught neuroscientists an important lesson about the role of our brain’s endogenous marijuana system: we need it to function normally in order to experience everyday pleasures. If the endogenous marijuana receptors are blocked 24-hours each day, day after day, we lose the ability to experience pleasure and become apathetic and depressed. Overall, the symptoms of the amotivational syndrome are very similar to the symptoms of depression. Long term use of marijuana may, depending upon many factors such as genetics and age, ultimately produce a condition in the brain that is very similar to that produced by long term use of Acomplia leading to the condition known as amotivational syndrome.