Anandamide

Anandamide is an ubiquitous neurotransmitter found throughout the brain as well as the body; in fact, there are two main types of receptor, CB-1, found in the brain, and CB-2, present in the rest of the body.  It plays multiple roles, in the regulation of pleasure, motivation, and reward receptors, in the uterus and embryo (with peaks of levels at ovulation), regulation of appetite and feeding, the immune system, etc.   The effect of paracetamol (acetaminophen) is even proposed to be related to anandamide stimulation.  Multiple anandamide-like molecules were found in chocolate.

The most potent stimulator of anandamide, however, is the cannbinoid plant, Cannabis sativa, and its delta 9 tetrahydrocannabinol.  It is a stable analogue of the brain’s neurotransmitter anandamide that attaches to both types of receptors.  This substance is said to overwhelm anandamide receptors and cause multiple side effects related to attention, memory, concentration, time perception, and appetite, as well as xerostomia.

Anandamide is broken down by an endogenous enzyme, fatty acid amine hydrolase (FAAH.)  There happens to be a mutation that creates an enzyme which is deficient in breaking down anandamide, leading to continued high levels of anandamide in the blood and making the owner of a double mutation (homozygous) in the enzyme resistant to the effects of cannabinoids.  These people are said to be normally less anxious and more optimistic than people without the mutation.

About 20 percent of Americans have homozygous mutations in the FAAH gene, and about 40 percent of a people said to represent a tribe in Nigeria also have the homozygous mutation.  Whether this has any effects on society as a whole is unknown and possibly unanticipated.

The number of locations in which anandamide receptors are found in the body suggests the cannabinol could have many, many uncertain side effects, but there are no indications that others are being overlooked.  We know that cannabinol impairs memory and concentration, raises the heart rate, stimulates appetite, may cause drowsiness, and so on, but despite the ubiquity of the receptor, nothing that could kill you.  Despite all these side effects, some people seem to enjoy using it.  They must be appreciating the known effects of anandamide in the brain related to pleasure, reward, and motivation.

There are a number of states that have decided to go against the federal prohibition on marijuana, even going so far as to legalize the general sale of the drug.  Most have, however, limited marijuana to quasi-medical uses.  The federal government’s agencies have taken an inconsistent approach to state initiatives, but have recently appeared to back off of a more hostile attitude and abjure small raids.  There are even programs to legitimize the bank deposit of funds earned by the sale of marijuana in the few states that have legalized that sale.

All of this represents a societal shift that has taken at least fifty years more than was originally expected.  The comedian Lenny Bruce is said to have commented that marijuana would soon be legalized “because all the lawyers smoke it.”  That was in 1960.