Cannabinoids and Neuropathic Pain (2012)

IntroductionCannabinoids are drugs that are either derived from cannabis or that induce similar behavioural and physiological effects to cannabis.They fall into three classes: those that are produced by plants of the Cannabis genus, termed phytocannabinoids (plant cannabinoids); those that are produced within the body, termed endocannabinoids (endogenous cannabinoids); and those that are produced synthetically to mimic the pharmacology of naturally occurring cannabinoids.Cannabinoids stand in relation to cannabis as opioids such as codeine, pethidine, fentanyl, and methadone stand in relation to opium.While opium and opioids are used and abused recreationally, opioids have long been at the forefront of first line analgesia for acute and chronic pain indications.Similarly, while cannabis and synthetic analogues are drugs of abuse, cannabinoids also have beneficial therapeutic effects.While the therapeutic effects of cannabinoids do not yet approach those of opioids, there has been extensive pharmaceutical research into the use of cannabinoids for the treatment of pain.In contrast with opioids, however, there is mounting evidence that cannabinoids may be more efficacious in the treatment of chronic pain conditions, such as neuropathies, rather than acute pain. Cannabinoid pharmacology 2.1 A brief historyPhytocannabinoids are derived from the Cannabis species, primarily Cannabis sativa which originated in China and Central and South Asia.Two other species are known; C. indica and C. Ruderalis, and possibly a third; C. afghanica.Of these, C. sativa is the largest and most diverse genus (Clarke et al., 2002).Cannabis was probably first used as a medicinal herb in India around 800BC, and in Persia and Tibet by 500BC, purportedly as an anaesthetic during surgery, while the therapeutic properties of cannabis were first recorded in China as early as 200 AD.It wasn't until the nineteenth century, however, that the Irish doctor William O'Shaughnessy began the scientific investigation of the chemical properties of cannabis (Frankhauser, 2002).By 1900 various pharmaceutical companies in Europe were promoting cannabis based products for the treatment of migraine, menstrual cramps, whooping cough, asthma, and as a sedative and soporific.During the twentieth century, however, cannabis lost favor as a medicine due to combination of the development of better drugs, the instability of cannabis www.intechopen.comNeuropathic Pain 80 drug formulations, unfavorable economics, and legal restrictions on its availability (Frankhauser, 2002).Today, cannabis and cannabinoids are once again the subject of serious pharmaceutical development.More targeted drug formulations, a greater understanding of the evidence base for cannabinoid efficacy and safety for particular conditions, and the development of wholly new ways of manipulating the endocannabinoid system have lead to a resurgence of research.Following the initiation of the scientific study of cannabinoid chemistry in 1838 by O'Shaughnessy (Di Marzo, 2006a), the first purified cannabinoid, named cannabinol, was isolated in 1899, and by 1932, its structure had been partially described.In 1964 Raphael Mechoulam, at Hebrew University in Israel, described the structure of the principle pharmacologically active component of cannabis, delta-9-tetrahydrocannabinol (THC) (Mechoulam et al., 1965).Following this critical discovery, the study of the pharmacological effects of cannabis and cannabinoids accelerated from 1970 through to the 1990s.This period of cannabinoid pharmacology clarified the behavioural and physiological effects of cannabis and classical cannabinoids, in particular THC.It had already been discovered that opium derived opioids interact with an endogenous receptor system, mimicking the actions of endogenous opioids.It was hypothesised that a similar receptor binding system might underlie the effects of cannabinoids, and in 1988, Devane and colleagues (Devane et al., 1988) published an article describing and characterising binding sites for THC.This rapidly led to the discovery of a specific cannabinoid receptor, subsequently termed cannabinoid receptor I, or CB1, in 1990 (Herkenham et al., 1990a).A seminal study by Herkenham and colleagues (Herkenham et al., 1990a) used autoradiographical binding to describe the distribution of CB1 receptors throughout the rat brain.Soon afterward, a similar distribution of CB1 receptors was described for the human brain by Glass and colleagues (Glass et al., 1997).The results of these studies helped explain many of the psychoactive effects of cannabinoids that had been previously characterized.