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Cannabinoid Report: NADA

October 28, 2019

N-Arachidonoyl dopamine (NADA) is an endogenous cannabinoid that acts as a potent agonist to the body’s CB1 and TRPV1 receptors. NADA was one of the later discovered endocannabinoids, along with 2-AGE and virhodamine. NADA was first proposed as an endocannabinoid in 2000 by T. Bisogno, D. Melck, Bobrov MYu, N. M. Gretskaya, V. V. Bezuglov, L. De Petrocellis, and V. Di Marzo. Later, in 2002, Huang et al. found that NADA activates vanilloid VR1 receptors as well. In that 2002 study, they discovered that NADA can be found in nervous tissues with high concentrations found in the cerebellum, hippocampus, and striatum. The lowest concentrations were found in the dorsal root ganglion.

Very little is known about the biosynthesis of NADA. In the 2002 study by Huang et al., evidence suggested that NADA is formed from arachidonic acid and dopamine or tyrosine with biosynthetic pathways that resemble those of arachidonoyl amino acids (which can suppress pain) or of dopamine. More evidence suggests that NADA is formed by the reaction between arachidonoylCoA and dopamine.

MEDICAL EFFECTS

One study showed that NADA is an agonist for the PPARγ receptor, and that PPARγ agonists have many positive effects on the cardiovascular system, such as reduction of blood pressure, cardiac protection, and benefits for atherosclerosis. NADA has also been proven to be a potent vasorelaxant. These findings imply that NADA, and other endocannabinoids, may be useful in the regulation of the cardiovascular system by relaxing blood vessels and allowing blood to flow more freely through the arteries.

Other studies have shown that NADA has antioxidant properties, which may be beneficial in regulating hypoxia-induced neurobehavioral deficits. NADA also has neuroprotective effects, may be able to mitigate certain symptoms of brain damage.

Another study showed that NADA may have useful anti-inflammatory properties. In fact, the study suggests that NADA may be able “to control the potential side effects induced by high levels of AEA at the inflammatory focus.” NADA is also thought to be helpful for pain modulation.

The anti-cancer and anti-tumoral effects of NADA are currently being studied. One study found that NADA and other N-acyl dopamines are cytotoxic to various types of cancer cells. As well, NADA has been shown to reduce FAAH activity (high levels of FAAH have been found in prostate cancer tissue and is often associated with higher severity of diseases.)

Currently, there is little known regarding the negative side effects of NADA.