The endocannabinoid system is tonically active in control of pain, as demonstrated by the ability of SR141716A (rimonabant), a CB1 antagonist, to produce hyperalgesia upon administration to mice (Richardson et al 1997). As mentioned above, the ECS is active throughout the neuraxis, including integrative functions in the periacqueductal gray (Walker et al 1999a; Walker et al 1999b), and in the ventroposterolateral nucleus of the thalamus, in which cannabinoids proved to be 10-fold more potent than morphine in wide dynamic range neurons mediating pain (Martin et al 1996). The ECS also mediates central stress-induced analgesia (Hohmann et al 2005), and is active in nociceptive spinal areas (Hohmann et al 1995; Richardson et al 1998a) including mechanisms of wind-up (Strangman and Walker 1999) and N-methyl-D-aspartate (NMDA) receptors (Richardson et al 1998b). It was recently demonstrated that cannabinoid agonists suppress the maintenance of vincristine-induced allodynia through activation of CB1 and CB2 receptors in the spinal cord (Rahn et al 2007). The ECS is also active peripherally (Richardson et al 1998c) where CB1 stimulation reduces pain, inflammation and hyperalgesia. These mechanisms were also proven to include mediation of contact dermatitis via CB1 and CB2 with benefits of THC noted systemically and locally on inflammation and itch (Karsak et al 2007). Recent experiments in mice have even suggested the paramount importance of peripheral over central CB1 receptors in nociception of pain (Agarwal et al 2007)
Karl W. Hillig, a graduate student in the laboratory of long-time Cannabis researcher Paul G. Mahlberg at Indiana University, conducted a systematic investigation of genetic, morphological, and chemotaxonomic variation among 157 Cannabis accessions of known geographic origin, including fiber, drug, and feral populations. In 2004, Hillig and Mahlberg published a chemotaxonomic analysis of cannabinoid variation in their Cannabis germplasm collection. They used gas chromatography to determine cannabinoid content and to infer allele frequencies of the gene that controls CBD and THC production within the studied populations, and concluded that the patterns of cannabinoid variation support recognition of C. sativa and C. indica as separate species, but not C. ruderalis. The authors assigned fiber/seed landraces and feral populations from Europe, Central Asia, and Turkey to C. sativa. Narrow-leaflet and wide-leaflet drug accessions, southern and eastern Asian hemp accessions, and feral Himalayan populations were assigned to C. indica. In 2005, Hillig published a genetic analysis of the same set of accessions (this paper was the first in the series, but was delayed in publication), and proposed a three-species classification, recognizing C. sativa, C. indica, and (tentatively) C. ruderalis. In his doctoral dissertation published the same year, Hillig stated that principal components analysis of phenotypic (morphological) traits failed to differentiate the putative species, but that canonical variates analysis resulted in a high degree of discrimination of the putative species and infraspecific taxa. Another paper in the series on chemotaxonomic variation in the terpenoid content of the essential oil of Cannabis revealed that several wide-leaflet drug strains in the collection had relatively high levels of certain sesquiterpene alcohols, including guaiol and isomers of eudesmol, that set them apart from the other putative taxa. Hillig concluded that the patterns of genetic, morphological, and chemotaxonomic variation support recognition of C. sativa and C. indica as separate species. He also concluded there is little support to treat C. ruderalis as a separate species from C. sativa at this time, but more research on wild and weedy populations is needed because they were underrepresented in their collection.
The other 29 states that fully legalize the Medical use of all CBD products derived from either hemp or Marijuana are: Alaska, Arizona, Arkansas, California, Colorado, Connecticut, Delaware, Florida, Hawaii, Illinois, Maine, Maryland, Massachusetts, Michigan, Minnesota, Montana, Nevada, New Hampshire, New Jersey, New Mexico, New York, North Dakota, Ohio, Oregon, Pennsylvania, Rhode Island, Vermont, Washington and West Virginia. The territories of Guam and Puerto Rico also allow the use of CBD products on medical grounds.