Interview to Prof Mauro Maccarrone, Professor of Biochemistry and Director of Biomedical Science at the University of Teramo, Italy

JH:  Professor, you carry out research on endocannabinoids.  Tell us how you came to do this and what these compounds are.

MM: After having graduated in Biology and having achieved a PhD in Enzymology in Italy, I moved to Utrecht in Holland, where I achieved a PhD in Bio-organic chemistry and was hired as a University researcher.  When I came back to Italy I carried out research in biochemistry at Tor Vergata in Rome and then at Teramo, where I was appointed Professor of Biochemistry.  Right from the start I investigated arachidonic acid derivatives, at first leucotrienes and prostaglandins, and now compounds belonging to the last generation of these derivatives - endocannabinoids.  These are naturally occurring compounds that regulate a number of functioins, including reproduction (they enable implantation of the fertilized egg in the uterus) and various nervous circuits, such as the striatal circuits that are altered in Parkinson's disease. 

JH:  What kind of studies do you carry out in your laboratory? Do you co-operate with neurologists?

MM:  In the last 4-5 years my laboratory has developed a series of methods to determine endocannabinoid concentrations in the body.  They have enabled us to establish how endocannabinoid concentrations change in the presence of neurodegenerative diseases, such as Parkinson's disease.  We co-operate with researchers of the European Centre for Brain Research  (CERC) / Santa Lucia Foundation in Rome and with the Neurology Department at the Neuroscience Institute of the Tor Vergata University in Rome. 

JH:  Have you carried out studies specifically in Parkinson's disease?

MM:  Yes, we have.   We have carried out studies in an animal model of Parkinson's disease and have discovered that an  endocannabinoid, anandamide, increases in the central nervous system in the presence of parkinson-like lesions.  Other studies have shown that this is the case also in monkeys and we have found high anandamide concentrationis also in the cerebrospinal fluid of untreated patients with Parkinson's disease. 

When an inhibitor of anandamide degradation was administered to rats with parkinson-like lesions their motor deficits improved considerably.

JH:    What does this mean?

MM:  We believe that the increase in anandamide is a defense mechanism i.e. that it is neuroprotective and that symptom improvement is achieved via a correction  of striatal nervous circuit imbalance.  Our last discovery is that anadamide reduces the levels of another endocannabinoid that has the opposite effect i.e. negative effects on nervous circuits -  2-arachidinonoylglycerol.

JH:  Could anandamide degradation inhibitors be used to treat Parkinson's disease?

MM:  We think so.  For instance, they could be useful to compensate the progressive loss of efficacy of levodopa over time.   They are currently being investigated in man in clinical trials designed to evaluated their safety and efficacy in anxiety. However, investigators must proceed with caution, as their safety profile will have to be assessed in-depth.  A selective antagonist of type 1 cannabinoid receptors, rimonabant, is effective in promoting body weight loss (by about 10% in one year), but can also cause even severe depression, showing that it indeed does influence nervous circuits.  Also repercussions on fertility will have to be investigated.  This aspect is obivously less important in Parkinson's disease as most patients with this disease are not young.   

In any case we shall continue research interacting closely with clinicians, because our ultimate aim is not to broaden knowledge about the cannabinoid system in a series of publications, but to achieve something tangible that helps patients.

JH:  One last question before closing.  What about cannabis i.e. marijuana?

MM: Marijuana is a substance that has a structure that differs from that of naturally occurring brain endocannabinoids, but is nevertheless able to stimulate the same receptors.  This is how it has similar effects to endocannabinoids, which however are potentially dangerous.  I believe that the best way forward is to modulate the concentrations of naturally occurring endocannabinoids, rather than to resort to external substances.