Dr. Daniele Piomelli

Dr. Piomelli is a professor of Anatomy & Neurobiology at the University of California, Irvine. He runs the Piomelli lab which researches the messenger molecules that affect the function of the brain and organs. His goal is to understand how we experience pain, feel anxious, crave food, our sleep patterns, and inflammation as a result of brain signaling. Dr. Piomelli's research has led him to become an advocate for the use of medical marijuana.

Mapping the brain’s signaling has led Piomelli's research to focus on the endocannabinoid system. Our bodies naturally produce cannabinoids that work with the endocannabinoid system in order to regulate the messenger system in our body. Cannabis has cannabinoids that attach to the same cell receptors, resulting in similar effects. By increasing or decreasing the endocannabinoid system, Piomelli is discovering ways to treat pain, depression, and inflammation with the use of marijuana. His results have proven to be more effective with fewer negative effects than current prescription drug medication.

Piomelli comes from Naples, Italy; there his family owned a pharmacy for over 400 years. Keeping with his family tradition, Piomelli has taken pharmacology further in the search for new drugs. Piomelli states, "The study of the body's cannabinoid system is relatively young, scientifically speaking, but it's presenting promising opportunities for drug discovery... I feel we're on the forefront of a new frontier." Piomelli has been studying the endocannabinoid system since its discovery in the late 1980's.

In the 1990's, Piomelli published research in the scientific journal Nature which discussed how the endocannabinoid compound ‘anandamide’ is created. This “bliss molecule” triggers behavior with appetite, motivation, and pleasure. Piomelli found that it helps patients cope with stress and depression.

Piomelli advocates for the use of marijuana for medical purposes. He has also lamented the struggle he’s faced while researching marijuana due to its Schedule I drug classification. Piomelli states that cannabis can be difficult to dose correctly in its natural state as each flower has a different potency. Despite these hurdles, he still finds marijuana to be a powerful drug, meant to treat many conditions.

Source:

http://www.pharmacology.uci.edu/research/labs/piomelli.asp

https://www.som.uci.edu/features/feature-piomelli-05152012.asp

How THC Mimics a Messenger Molecule

   Behaviors such as the  munchies, fertility and where you left your car keys all relate to a messenger molecule named anandamide. This molecule contributes to messages in the brain regarding to pain, depression, appetite, memory and fertility. The molecular structure of THC is very similar to anandamide. The similarity allows it mimic functions that this messenger molecule does. Anandamide breaks down very quickly not allowing humans to get to a “natural high”. THC takes more time to break down giving a psycho-active high.

   Messenger cells like anandamide are like a “key” that can attach to a nerve cell receptor acting like a “lock”. Once the messenger cell find a good connection with a receptor it can attach and open the nerve membrane to allow chloride ions to enter the cell. This equalizes the charges inside and outside the cell and prevents the cell from firing a charge. The “key” must be removed to allow the nerve cell to work again. Enzymes work to break down the “key” messenger molecules after a certain amount of time. The nerve cells will cease to work if the messenger molecule remains.(Source) In 1992 an Israeli scientist Raphael Mechoulam was able isolate anandamide as the “bliss” messenger cell that THC emulates. He was the same scientist that isolated THC in 1964.(Source)

How THC mimic's Anandamide

Anandamide and Memory
   Anandamide has been shown to create or destroy short term memory nerve connections. In animal studies an increase in anandamide results in forgetfulness.(Source) Anandamide helps to retain information like where you parked your car. It allows you to forget things like what the women was wearing at the checkout stand.(Source)

   A famous experiment known as the Morris Water Maze shows what happens to short term memory when anandamide is inhibited. Mice are placed in a water test area with a platform so they can climb out of the water. The platform is removed once the mice remember where it was placed. The mice will naturally look for the platform and realize it isn't there. They will then focus on surviving by swimming. Mice with a drug to block the anandamide will perpetually continue to look for the platform. They will forget that the platform isn't there.(Source)

Anandamide and Fertility
   Anandamide acts as a signaling when an embryo attaches to the female uterus. In fact anandamide is at a higher concentration in the uterus than the brain. Sperm contain receptors that accept the anandamide molecule. It is theorized that disrupting the function of anandamide therefore could interfere with fertility. More research is need to further investigate the relation between fertility and drugs that act like anadamide.(Source)

Similar Sources to Anandamide
   Chocolate has a similar structure to anandamide much like THC. Daniele Piomelli studied this as a scientist at the Neuroscience Instititute in San Diego. He found that chocolate has three compounds that mimic anandamide. Chocolate and THC behave differently as a messenger.  Piomelli states, “The response to THC and to the chocolate anandamides are not at all the same, even if the concentrations could be made comparable.” Chocolate may create a blissful feeling while not giving a high.(Source)

   Recently Piomelli found a naturally occurring molecule in the body that mimics anandamide. Sn-2 arachidonylglycerol (2-AG) can lock into the same bliss receptors. It is unique in that it works at 170 times the concentration of anandamide. The 2-AG molecules are found in different parts of the brain. Piomelli theorizes that the functions of anandamide and 2-AG are complementary.(Source)


Source:
http://antoine.frostburg.edu/chem/senese/101/features/anandamide.shtml
http://thesilvertour.org/cannabis-professor-raphael-mechoulam-discovery-thc-1964-anandamide-1992
http://www.marijuanalibrary.org/981217.html#nfo
http://www.ncbi.nlm.nih.gov/pubmed/21684528
http://www.sciencedirect.com/science/article/pii/S0091305799001069
http://www.nature.com/nature/journal/v388/n6644/full/388773a0.html
https://www.exploratorium.edu/exploring/exploring_chocolate/choc_8.html

The Reason Behind Cannabis and the Munchies

For chemotherapy patients struggling to increase their appetite, marijuana can increase their desire to eat being beneficial. Tetrahydrocannabinol or THC which is the psychoactive part of cannabis has been found to be the factor to increasing appetite. There are a couple studies that show different reasons on why marijuana increases the “munchies”, and it may be a combination of the various factors.

Two studies showed that an increase in hedonic, or pleasurable taste, rather than a motivation to eat was increased with the use of cannabis. With exposure to taste and scent, dopamine is released with encourages the appetite for the food. Once THC is in the blood stream, it has been found to increase dopamine levels.(Source) and (Source)

In a study published in Proceedings of the National Academy of Sciences a research group led by Daniele Piomelli found that marijuana triggers the CB1 receptors in the gut, not the brain, to signal that a fatty food has been ingested. The saying of “You just can't eat one Lay Potato Chip” is correct in that when a fatty food is eaten, intestinal CB1 receptors send a message to the brain to stimulate the creation of endocannabinoids creating a chemical response of hunger increasing your appetite for fatty foods. (Source)

Another study shows how endocannabinoids are responsible for pre and post natal survival. Endocannabinoids are present in cow's milk, soft cheese and breast milk. The research showed that the cannabinoid receptors are stimulated by the cannabinoids in milk to encourage suckling leading to newborn survival. This response may hold a connection in later life to the encouragement of eating.(Source)

Another study showed the THC released the hormone ghrelin, which increases appetite. Both endocabbinoids and ghrelin effect the hypothalamus part of the brain. AMP-activated protein kinase, or AMPK helps regulate cell energy metabolism. THC and ghrelin increase appetite by stimulating the AMPK to allow the hypothalamus sense of food deprivation thereby increasing hunger.(Source)

Recently in February 2014 a study was published in Nature Neuroscience studied the increase in smell with cannabis. The study used the underlying basis that hunger leads to an increase in sensory perception which leads to an increase in food intake. The results in the study with mice showed that odor detection was increased with cannabis due to CB1 receptors affecting the olfactory bulb enhancing the sense of smell. This increased awareness to smell gives in turn the increase to hunger. The mice stayed longer smelling the food and ate more.(Source)

Cannabis and Obesity

Though the study finding show that caloric intake from marijuana goes up with the urge to eat, another study two studies show that marijuana users are one third less likely to be obese and have a lower rate of Type 2 Diabetes.(Source) Read more on this by clicking this link.

Source:

http://www.nature.com/neuro/journal/v17/n3/full/nn.3647.html

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3705914/

http://www.ncbi.nlm.nih.gov/pubmed/16185725

http://www.jbc.org/content/280/26/25196.full

http://www.pnas.org/content/108/31/12904

http://www.sciencedirect.com/science/article/pii/S0014299904007423

http://aje.oxfordjournals.org/content/early/2011/08/24/aje.kwr200.abstract?__hstc=9292970.2e518383c30fe9090ca33584378a6435.1409929942141.1411273921013.1411401471685.9&__hssc=9292970.1.1411401471685&__hsfp=210472818

Benefits of Cannabis for Schizophrenia

Schizophrenia is mental disability where the person has inappropriate thoughts, emotions, behavior feelings and actions causing an altered reality of delusions and hallucinations. (Source) Studies have found a theory that the human endogenous cannabinoid system is a major source of the causes of schizophrenia. (Source) The endogenous cannabinoid system is responsible in the brain to trigger signals relating to appetite, the feeling of pain, mood and memory as well as regulating phychoactive effects by cannabis from the most notable CB1, CB2 and Anandamide receptors of the nervous system (Source).

Studies have shown promising benefits of Marijuana to relieve Schizophrenia symptoms. Cannabis should not be a replacement for prescribed drugs for the condition without talking to your physician. The Drug Enforement Agency DEA has categorized cannabis as a schedule 1 drug, research for cannabis is lacking and conclusive evidence for benefits of Schizophrenia is still in progress.(Source) 

Here are a collection of studies regarding marijuana and Schizophrenia:

Markus Leweke of the University of Cologne in Germany conducted a study with 39 individuals with schizophrenia giving half cannabidiol (CBD) and the other half Amisulpride, an anti psychotic drug used for schizophrenia treatment. Cannabidiol is derived from the cannabis plant and is an antioxidant anti psycho-active part of the marijuana plant. The results showed that the symptoms equally went down for all subjects, with the people using cannabidiol (CBD) having less side effects. (Source)

Dr. Daniele Piomelli, professor of pharmacology at the University of California-Irvine has studied the anandamide receptors of the nervous system in the endogenous cannabinoid system. Dr. Piomellis theorizes with this study that cannabidiol CBD helps with schizophrenia by saying “What CBD seems to be doing is preventing anandamide from being destroyed”.(Source)

Raquel Levin and Fernanda F. Peres in Brazil did a study on mice with schizophrenia in which they gave Cannabidiol CBD to some mice and WIN55212,2 (synthetic cannabinoid agonist) to the other. Both were able to show positive results in improving sensory gating deficits. The results from the team were “Our results reinforce the role of the endocannabinoid system in the sensorimotor gating impairment related to schizophrenia, and point to cannabinoid drugs as potential therapeutic strategies.” (Source)

Future Studies

Currently, GW Pharmaceuticals is doing a study on their own GWP-42003 which is derived from cannabidiol CBD. They are doing the research in hopes of finding treatment with cannabis for schizophrenia. They have finished phase 1 and it shows promising results and they are now doing phase 2 (Source)

For medication to be introduced in the United States with cannabidiol CBD, it first needs to be FDA approved for study. The FDA has approved experimental use for CBD for the treatment of Dravet syndrome. Soon the FDA is set to allow it for clinical trials in showing safety and tolerability for CBD in children.(Source)

Source:

http://clinicaltrials.gov/show/NCT00628290

http://en.wikipedia.org/wiki/Schizophrenia

http://www.ncbi.nlm.nih.gov/pubmed/9130308

http://en.wikipedia.org/wiki/Endocannabinoid_system

http://www.thewire.com/politics/2014/06/its-hard-to-study-marijuanas-medical-benefits-when-its-illegal/373603/

http://healthland.time.com/2012/05/30/marijuana-compound-treats-schizophrenia-with-few-side-effects-clinical-trial/

http://www.leafscience.com/2014/03/18/drug-made-cannabis-treat-schizophrenia/

http://www.ncbi.nlm.nih.gov/pubmed/24567721

http://blog.norml.org/2013/12/16/study-cannabidiol-holds-promise-for-treating-psychosis/