Cannabinoids Cannabidiol (CBD) is one of the better-known and intensively studied phytocannabinoids. Acting as a mediator for the effects of THC, it is widely considered to be non-psychoactive in nature. However, research has indicated that CBD has a sedative effect, which may partly explain why strains high in CBD are known for their “stoned” effect rather than their “high”.
Cannabidiol (CBD) is one of the better-known and intensively studied phytocannabinoids. Acting as a mediator for the effects of THC, it is widely considered to be non-psychoactive in nature. However, research has indicated that CBD has a sedative effect, which may partly explain why strains high in CBD are known for their “stoned” effect rather than their “high”.
And if you follow the latest advances in dietary supplements for health and wellbeing you may already have heard of CBD products, even if you’ve never seen a cannabis plant. There is increasing and compelling evidence that adding CBD to your diet can potentially alleviate and protect against a variety of conditions.
CBD has the same chemical formula and molar mass as THC (C21H30O2, 314.46 g/mol), although the molecular structure differs slightly. Like THC and most other lipids, CBD is hydrophobic and lipophilic, meaning that it does not dissolve or emulsify readily in water, but will dissolve in fat (as well as most organic solvents, such as butane and alcohol).
In acidic conditions, CBD cyclises (forms a new carbon ring) to become THC. In alkaline conditions (when water is present) CBD oxidises to become cannabidiol-hydroxyquinone, which is as yet poorly-studied but may exert an inhibitory effect on the hepatic (liver) enzymes that are vital in the metabolism of ingested drugs.
Cannabidiol in the EC system
Although widely considered to have no affinity for the cannabinoid receptors, CBD has been shown in an at least one study to act as an inverse agonist of the CB2-receptor. An inverse agonist is a receptor ligand that induces an opposite response to an agonist; while THC increases the level of receptor activity above the intrinsic level found in the absence of any ligand, CBD reduces the level below this baseline. An antagonist, on the other hand, binds to a receptor and remains inactive, blocking the actions of nearby agonists.
The speculative new cannabinoid receptor, GPR55, may be influenced by the action of CBD. This receptor has been shown to respond to both CBD and THC, as well as the endocannibinoids 2-AG, anandamide and noladin ether, and has even been postulated as the CB3-receptor itself.
It is also thought that while CBD has little direct affinity for the cannabinoid receptors, it may have various indirect effects. These may arise due to its actions on other endocannabinoids (such as anandamide—CBD inhibits the degradation of this molecule, thereby increasing its endogenous levels and bioactivity), or on receptors that are not part of the endocannabinoid system but work in combination with it.
CBD’s effect on non-EC receptors
CBD is a full, but weak agonist of the transient receptor potential vanilloid type 1 (TRPV1), which plays an important role in the response to heat and noxious substances. TRPV1 is a nociceptor: when sufficient excitation of the receptor occurs, signals are sent to the brain, triggering a set of automatic responses including the sensation of pain.
Various cannabinoids including the endocannabinoids anandamide and N-Arachidonoyl dopamine (a CB1-receptor agonist) affect the TRPV1 receptor. Conversely, several vanilloids affect the cannabinoid receptors, including olvanil and pseudocapsaicin, but not including capsaicin itself. The close chemical similarity between many vanilloids and cannabinoids has led researchers to conclude that there is great therapeutic potential in researching vanilloid cannabimimetics (substances that mimic cannabinoids).
CBD has also been demonstrated to act as a 5HT1?-receptor agonist. This receptor regulates the expression of serotonin (5HT) in the central nervous system, and may explain many of CBD’s anxiety- and depression-relieving properties. Further, CBD’s modulatory effects on the Mu and Delta opioid receptors, which are involved in the analgesic and euphoric response, may add to the overall effect experienced by the cannabis user.
CBD has occasionally been described as being of even greater medical importance than THC. Its lack of psychoactivity is a great advantage as it can be safely used without fear of subjects becoming intoxicated and unable to function. Beyond this, it has numerous known beneficial properties, and no doubt many that are yet to be discovered.
CBD has an analgesic, antidepressant and anxyolitic (anti-anxiety) effect, and is also being explored for its neuroprotective properties. Neuroprotection, in which the structures of the brain and central nervous system are protected against damage (including further damage, in the case of degenerative illnesses such as Parkinson’s), is an area of medicine of huge and growing importance.
Cannabidiol and inhibition of cancer cell proliferation
Perhaps most excitingly, CBD has been shown to have an inhibitory effect on the proliferation of cancer cells. It is thought that CBD’s effect on the CB2- and TRPV1 -receptors may play a role here, through the induction of oxidative stress. Systemic biological functions produce reactive oxygen species (ROS) such as peroxides, oxygen ions and free radicals, which must usually be detoxified to mitigate damage to the cells.
If the body is unable to effectively detoxify these ROS, oxidative stress can increase until apoptosis (cell death) begins to occur. Oxidative stress has been implicated in the development of various progressive diseases including Alzheimer’s, Parkinson’s, and fragile-X syndrome, as well as cancer itself.
In normal cells, low levels of ROS are necessary to permit healthy cell signal transduction. If the cells in question are cancerous, high levels of ROS are required to allow for increased metabolic rates and rate of division and proliferation. Therefore, oxidative stress usually encourages cancer proliferation. However, it has been demonstrated that the oxidative stress induced by CBD can actually induce apoptosis in certain types of cancerous cells, particularly human breast carcinoma.
Availability as medicine
CBD is unscheduled in the USA and thus is legally permitted to be sold over-the-counter. Dixie Botanicals is a company specialising in hemp salves and supplements containing naturally-occurring CBD, and their products and many similar ones are on sale in various U.S. states. In Canada, however, CBD is a Schedule II drug and is technically only legally available on prescription, although there is no legal restriction in place limiting the permitted percentage of CBD, as exists with THC.