The brain has nerve circuits that are part of the natural reward system for animals and humans.  Behaviors like sex or feeding activate these nerve circuits and therefore these behaviors feel good and are rewarding.  There are two types of chemical messenger molecules released from the nerves in these reward circuits: acetycholine and annandamide.  Acetylcholine released from nerve cells attaches to a “receptor” on target nerve cells; the receptor is called the nicotinic acetylcholine receptor.  This receptor gets its name from the fact that the active ingredient in tobacco, nicotine, also attaches to and activates the receptor.  This is one reason smoking cigarettes is pleasurable because nicotine activates the reward circuits. 

Annandamide is a molecule made by nerve cells that acts receptors called cannabinoid receptors (abbreviated CB receptors).  CB receptors are the same receptors activated by delta-9-THC, the active ingredient in marijuana smoke.  It is well known that delta-9-THC is an appetite stimulant (the “marijuana munchies”) and annandamide is the substance released from the brain that activates the reward circuits in response to feeding. 

A recent article on the newswire services summarizes new information that a drug used to treat nicotine addiction (Chantix) and an anti-obesity drug (Acomplia) may produce depression as an unwanted side effect because they disrupt the nerve circuits in the brain’s reward pathways.  Chantix is a drug that attaches to but does not activate the nicotinic acetylcholine receptor in the reward pathway.  Therefore, the receptor is blocked and can not respond to stimulation by the nicotine in cigarette smoke.  The individual taking Chantix as part of a nicotine cessation program, no longer experiences the rewarding effects of nicotine and this makes it easier to quit smoking.  The problem is that Chantix also blocks signals that come from other types of rewards and this might lead to depression. 

Acomplia is a drug that blocks CB receptors in reward pathways associated with feeding.  Patients taking Acomplia no longer find that eating is as pleasurable of rewarding and this will help obese patients lose wait.  However, CB receptors are also in the reward circuits and Acomplia may block pleasurable feelings associated with other kinds of rewarding behaviors.  Patients taking Acomplia may be at risk for developing depression. 

This new information highlights the challenges for modern pharmacologists interested in developing drugs for the treatment of disease.  Development of safe and effective drugs requires that scientists understand the complex functions of the human body and also understand the complex actions of drugs.  Pharmacologists have the specialized training to understand the complexity of the human body and to understand how drugs interact with the body.  This understanding helps to develop drugs that have beneficial effects without producing unwanted side effects. 

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