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- Cannabis & You
There are approximately 483 natural components found within the Cannabis sativaplant1,
of which 66 have been classified as ‘cannabinoids’; chemicals unique to the plant.
The most well known and researched of these, delta-9-tetrahydrocannabinol (?9-THC), is the substance primarily responsible for the psychoactive effects of cannabis. The effects of ?9-THC may, however, be moderated by the influence of the other 482 components, most particularly by the cannabinoids2. The cannabinoids are separated into the following subclasses:
Like opiates, cannabinoids exert their effect by interacting with specific receptors, located within different parts of our brains and peripheral nerves. Two kinds of cannabinoid receptors have been found to date and are termed CB1 and CB23,4. A substance that occurs naturally within the brain and binds to CB1 receptors was discovered in 1992 and termed ‘anandamide’ (from the Sanskrit for ‘bliss’)5. Additional naturally occurring substances that bind to CB1 have since been discovered, and these, together with the receptors, are termed the ‘endogenous cannabinoid system’.
Cannabinoids are somewhat unusual drugs in that they are soluble in lipids (fats) rather than in water. Thus, with repeated dosage, cannabinoids tend to accumulate in fatty tissues and remain in the body for several days6. The actual effects that the cannabinoids have, reflect the areas of the brain they interact with. Interactions tend to occur in our limbic system (the motivational centre of the brain that affects memory, cognition and psychomotor performance) and mesolimbic pathway (activity in this region is associated with feelings of reward) and are also widely distributed in areas of pain perception3, 7.
Despite a rapid increase in our knowledge of the endogenous cannabinoid system, the field is still in its developmental stages. However, as described below, much research has focused on the many potential therapeutic uses of chemical replications of the cannabinoids, called ‘synthetic analogues’8.
The major differences between the cannabinoids are determined by the extent to which they are psychologically active. Three classes of cannabinoids, the CBG, CBC and CBD are not known to have such an effect. However, THC, CBN, CBDL and some other cannabinoids are known to be psychologically active to varying degrees1.
Interestingly, CBD may actually have anti-anxiety effects and lessen the psychotropic effects of THC1, although it is not clearly understood how9. That is, a plant with a greater percentage of CBD may attenuate the effects of the THC, which in effect, lowers the potency of the plant. Use of a cannabis plant with less CBD has been shown to have an increased psychological effect and incidence of anxiety reactions10,11. The non-psychotropic aspects of CBD are of particular interest in therapeutic settings and are discussed below12.
?9-THC is oxidized by exposure to air which reduces to form CBN1. CBN is only very weakly psychotropic and not unlike CBD, interacts with THC to attenuate its effects13. Cannabis that has been left out unused will have increasing amounts of CBN and decreasing amounts of THC and thus lose potency1.
Some cannabinoids, and thus their synthetic analogues, have clear therapeutic potential14. This should be clearly distinct from the use of natural cannabis. Studies have shown that the toxicity of synthetic analogues is low and they are unlikely to cause physical dependence15. However, when cannabis is smoked, hundreds of other chemicals interact and cannot be safely used. Thus, synthetic analogous of certain cannabinoids have been created in order to isolate their effect from the undesirable harmful effects of natural cannabis.
To date, hundreds of studies have analysed the clinical significance of these cannabinoids, yet even today their usefulness continues to be debated. Several studies have reviewed the literature in the area16-18. Although showing some anecdotal success, the therapeutic applications lack randomized clinical trials.