Raphael Mechoulam, the man who first synthesized THC, the main ingredient in marijuana, and is often referred to as the “father of marijuana research,” recently gave a brief history of marijuana and its receptors in the central nervous system during a plenary talk at the 2014 meeting of the International College of Neuropsychopharmacology.
In Syria, hundreds of years ago, the drug was named ganzigunnu, meaning “the drug that takes away the mind.” It has also been called azalla, meaning “hand of the ghost.”
Among the 100 compounds in marijuana, the best-known ingredient is delta-9-tetrahydrocannabinol (delta-9 THC), which produces most of the well-known effects of the drug. There is another active ingredient, however, cannabidiol (CBD), which has calming and anti-anxiety effects, but is usually only present in very low levels.
In the human brain, inherent cannabinoid receptors respond directly to the ingredients in marijuana, in addition to other chemicals produced in the brain. They modulate calcium ions and decrease the release of many neurotransmitters.
THC acts at CB-1 receptors, producing the high. The CB-1 receptor is synthesized on demand, postsynaptically, and is transferred to the presynaptic terminal where it decreases calcium and transmitter release. Consistent with marijuana’s appetite-stimulating properties (“the munchies”), if the CB-1 receptor is blocked in animals, they lose their appetite and can die of hunger.
Also inherent in the brain, but in much lower levels, are CB-2 receptors, where activation does not cause a high. Levels of these receptors may increase dramatically in pathological situations however. Activation of the CB-2 receptor is anti-inflammatory and in the same way that the immune system acts against foreign proteins, CB-2 acts as a protector against non-proteins.
CBD, however, does not directly bind to any cannabinoid receptors, rather its actions are blocked by cannabinoid antagonists.
There are two chemicals in the brain (endogenous ligands) that act at the cannabinoid receptors – anandamide and 2-arachidonoylglycerol (2-AG). They are soluble only in lipids (fats), and have never been given to people. In animals, 2-AG has neuroprotective effects, decreases the size of a stroke by 60% and increases recovery from stroke.
Marijuana and CBD in particular have also had beneficial effects in people. Marijuana – both THC and CBD – decreases the nausea and vomiting associated with chemotherapy in children, has anti-inflammatory effects in rheumatoid arthritis (decreasing inflammatory marker TNF alpha), and has anti-diabetes and anti-convulsant effects.
In 2012, researcher F. Markus Leweke and colleagues showed that CBD was about as effective as the atypical antipsychotic amisulpride in alleviating the psychotic symptoms of schizophrenia. CBD’s other effects include reducing anxiety and improving psoriasis by increasing DNA methylation.
It seems possible that some of these myriad effects of marijuana and endogenous ligands at CB receptors could be exploited for clinical therapeutics, as Mechoulam endorses, but when and how that will take place remains an unanswered question.
With the passing of the Industrial Hemp Farming Act, though, as well as discussions to reduce the schedule of marijuana on the US Controlled Substances Act, that day may be sooner than we think.
In the meantime, if you feel you may benefit from the use of CBD now, consider some of our fully legal hemp-derived CBD products. Whether you’re looking to supplement your diet to aid with internal issues or trying to reduce the inflammation of psoriasis or RA, DiscoverCBD has got you covered.
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