Music:
Member Since: 7/19/2006
Band Website: myspace.com/kaosincontrol
Band Members: Agent 86
Influences: Finding the Responsible Agent
Figuring out how the drug exerts these myriad effects has taken a long time. In 1964, after nearly a century of work by many individuals, Raphael Mechoulam of the Hebrew University in Jerusalem identified delta-9-tetrahydrocannabinol (THC) as the compound that accounts for virtually all the pharmacological activity of marijuana. The next step was to identify the receptor or receptors to which THC was binding.Receptors are small proteins embedded in the membranes of all cells, including neurons, and when specific molecules bind to them--fitting like one puzzle piece into another--changes in the cell occur. Some receptors have water-filled pores or channels that permit chemical ions to pass into or out of the cell. These kinds of receptors work by changing the relative voltage inside and outside the cell. Other receptors are not channels but are coupled to specialized proteins called G-proteins. These G-protein-coupled receptors represent a large family that set in motion a variety of biochemical signaling cascades within cells, often resulting in changes in ion channels.In 1988 Allyn C. Howlett and her colleagues at St. Louis University attached a radioactive tag to a chemical derivative of THC and watched where the compound went in rats' brains. They discovered that it attached itself to what came to be called the cannabinoid receptor, also known as CB1. Based on this finding and on work by Miles Herkenham of the National Institutes of Health, Lisa Matsuda, also at the NIH, cloned the CB1 receptor. The importance of CB1 in the action of THC was proved when two researchers working independently--Catherine Ledent of the Free University of Brussels and Andreas Zimmer of the Laboratory of Molecular Neurobiology at the University of Bonn--bred mice that lacked this receptor. Both investigators found that THC had virtually no effect when administered to such a mouse: the compound had nowhere to bind and hence could not trigger any activity. (Another cannabinoid receptor, CB2, was later discovered; it operates only outside the brain and spinal cord and is involved with the immune system.)As researchers continued to study CB1, they learned that it was one of the most abundant G-protein coupled receptors in the brain. It has its highest densities in the cerebral cortex, hippocampus, hypothalamus, cerebellum, basal ganglia, brain stem, spinal cord and amygdala. This distribution explains marijuana's diverse effects. Its psychoactive power comes from its action in the cerebral cortex. Memory impairment is rooted in the hippocampus, a structure essential for memory formation. The drug causes motor dysfunction by acting on movement control centers of the brain. In the brain stem and spinal cord, it brings about the reduction of pain; the brain stem also controls the vomiting reflex. The hypothalamus is involved in appetite, the amygdala in emotional responses. Marijuana clearly does so much because it acts everywhere.Over time, details about CB1's neuronal location emerged as well. Elegant studies by Tamás F. Freund of the Institute of Experimental Medicine at the Hungarian Academy of Sciences in Budapest and Kenneth P. Mackie of the University of Washington revealed that the cannabinoid receptor occurred only on certain neurons and in very specific positions on those neurons. It was densely packed on neurons that released GABA (gamma-aminobutyric acid), which is the brain's main inhibitory neurotransmitter (it tells recipient neurons to stop firing). CB1 also sat near the synapse, the contact point between two neurons. This placement suggested that the cannabinoid receptor was somehow involved with signal transmission across GABA-using synapses.
Sounds Like: vibration of any substance
Record Label: Elite Media
Type of Label: Indie
