Cannabidiol is rapidly becoming, with respect to medical use, “the more interesting cannabinoid,” according to a new and comprehensive review of the scientific literature published in the July issue of the journal Pharmacology and Therapeutics by Simona Pisanti, Anna Maria Malfitano and 10 additional colleagues.

The cannabis plant is known to contain over 90 unique chemicals, known as cannabinoids. Delta-9-tetrahydocannabinol (Δ9-THC or THC) is the primary compound and the most well-known; it was discovered and isolated first and is widely recognized as responsible for the psychoactive effects associated with the plant. Other cannabinoids have similar chemical structures but produce different pharmacological effects based on their interaction with the natural endocannabinoid receptor system in the body.

Cannabidiol (or CBD) is now recognized as the second compound of significance.

Among its characteristics of note is that it is most prevalent in hemp (cannabis bred for fiber or seed products for industrial use), has no psychoactive affects and no impact on motor function, memory or body temperature.

Of equal interest to researchers, CBD reduces some of the effects of THC, enhancing the “safety profile” of cannabis. In this capacity, CBD is referred to as “an entourage molecule.”

According to Pisanti, Malfitano et al: “CBD is undoubtedly the more interesting cannabinoid with a lot of reported pharmacological effects in several models of pathologies, ranging from inflammatory and neurodegenerative diseases, to epilepsy, autoimmune disorders like multiple sclerosis, arthritis, schizophrenia and cancer.”

The human body (along with other mammals) has a cannabinoid receptor system (often referred to as “endogenous,” meaning within the body.) The simple way of understanding receptors it to think of them as switches, in which they are activated by a specific chemical (in this case, a cannabinoid such as THC). The activation of the receptor produces specific effects based on their location in the body, and cannabinoid receptors located in areas of the brain, for example, associated with the well-known effects of cannabis.

But to understand CBD, it is more helpful to think of receptors as a knob, a dial, which can be turned one way or another to modulate the effect of the receptor (think in terms of a dimmer switch for lights). CBD lowers “receptor affinity with respect to” THC, and thus helps regulate “adverse effects like tachycardia [elevated heart rate], anxiety, sedation and hunger in humans and rats.”

CBD reduces anxiety associated with THC, thus a combination of both cannabinoids often has beneficial effects for a patient—thus the improvement of the safety profile and the concept of an entourage molecule.

This is just a starting point for understanding CBD.

It’s pharmacological action is both receptor-dependent and independent, meaning that while it mitigates the affinity or bonding of THC with receptors, it also has other biological effects on the body.

Consider this wide range of CBD applications, now supported by published research findings.

CBD is “a potential antipsychotic drug,” “an interesting possible durative drug for cancer, diabetes, inflammation and neurodegenerative disorders,” “an anticonvulsant,” a “neuroprotective antioxidant,” “analgesic” and an “anti-nausea molecule.” Research indicates that “CBD shows cytotoxicity [toxic to cells] in breast tumor cells and is cyto-preservative for normal cells.”

A lot of work remains when it comes to fully understanding how CBD affects the body; its pharmacodynamics remain unclear. More is known about its movement through the body, its pharmacokinetics—it is metabolized along the same routes as other cannabinoids but in different ways.

Nonetheless, like other cannabinoids it has a very low toxicity.

In laboratory studies, CBD produces a promising reduction of inflammation by acting on cannabinoid and on other receptor systems, mitigating the progression of various ailments.  In one set of studies, this effect resulted in improvement of lung functions in ways that would contribute to the treatment of inflammatory lung diseases. Another application of this property “support a role for CBD in inflammatory degenerative diseases.” CBD has shown an ability to reduce “pathological forms of inflammations that contribute to the progression of neurodegenerative (Parkinson’s and Alzheimer’s diseases, multiple sclerosis and HIV-associated dementia) and neoplastic diseases.”

While more needs to be learned about its effects on physiological immune response, promising research findings on CBD’s role in immunological anti-tumor responses alleviate potential concerns in this area.

Pre-clinical research shows that CBD has “neuroprotective, antioxidant, analgesic, anti-psychotic and anti-anxiety properties, not acting through the CB1 receptor but interacting with other targets that may be relevant in neurologic disorders.”

Recent studies “highlight that CBD is able to cope with oxidative stress, mitochondrial dysfunction, inflammatory changes, excitotoxicity, iron accumulation, and protein aggregation, all features of neurodegeneration.”

While progress is underway to understand the mechanisms of most of these effects, how CBD produces its analgesic effect remains something of a mystery.

There is also promising research indicating CBD can be helpful in treating schizophrenia by way of its impact on a key (NMDA) receptor hypofunction, and other research is investigating promising leads for use of CBD as an antipsychotic drug and for the treatment of clinical depression.

Another interesting effect of the nervous system involves CBD’s impact on sleep—it “stops anxiety-induced  [rapid eye movement] REM sleep suppression,” with little impact on NREM [non-REM] sleep.

“This is an important result for patients with post-traumatic stress disorder that often complain of having sleep disturbances, such as REM sleep abnormality and insomnia.”

In addition, CBD is showing promise in applications to the treatment of cardiovascular conditions, though experimental findings from the early stages of research are controversial due to their preliminary nature.  Yet the anti-oxidative and anti-inflammatory actions that are mediated by CBD can be applied to heart conditions characterized by inflammation and oxidative stress.

Some specific therapeutic applications of CBD will be reviewed in Part 2 of this column.

Previously in Pot Matters: Growing Support for Legalization in Washington State
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