What is CBD?

Cannabidiol (CBD) is an organic chemical compound produced by the Cannabis plant.  It has been found to have many therapeutic effects including antioxidant, anti-inflammatory, and neuroprotective. These properties make CBD useful in the treatment and prevention of a wide variety of conditions. Additionally, CBD is non-toxic and non-psychoactive, meaning users will not feel the “high” typically associated with smoked cannabis.

Science

Cannabis has been at the center of one of the most exciting – and under reported – developments in modern science.  Research on the effects of cannabis led directly to the discovery of a hitherto unknown biochemical communication system in the human body, the endocannabinoid system (ECS), which plays a crucial role in regulating our physiology, mood, and everyday experience.

The discovery of receptors in the brain that respond pharmacologically to cannabis – and the subsequent identification of endogenous cannabinoid compounds in our own bodies that bind these receptors – has significantly advanced our understanding of human biology, health, and disease.

It is an established scientific fact that cannabinoids and other components of cannabis can modulate many physiological systems in the human brain and body.  Cannabinoids are chemical compounds that trigger cannabinoid (and other) receptors.  In addition to phytocannabinoids produced by the plant, there are endogenous cannabinoids (anandamide and 2AG) that occur naturally in the body, as well as synthetic cannabinoids created by pharmaceutical researchers.

Extensive preclinical research – much of it sponsored by the U.S. government – indicates that CBD has potent anti-tumoral, anti-oxidant, anti-spasmodic, anti-psychotic, anti-convulsive, and neuroprotective properties. CBD directly activates serotonin receptors, causing an anti-depressant effect, as well.

In recent years, scientists associated with the International Cannabinoid Research Society (ICRS) have described a number of molecular pathways whereby CBD exerts a therapeutic impact.  A preclinical study by Dr. Sean McAllister and his colleagues at the California Pacific Medical Center in San Francisco reports on how CBD kills breast cancer by down-regulating a gene called ID-1, which is implicated in several types of aggressive cancer.  Thus, silencing the ID-1 gene is an excellent strategy for a cancer treatment.

“Cannabidiol offers hope of a non-toxic therapy that could treat aggressive forms of cancer without any of the painful side effects of chemotherapy,” says McAllister.

 

The images above are from an experiment by McAllister testing how CBD can stop the invasion of cancer cells in human cell lines. Compare the untreated breast cancer cells on the left to the breast cancer cells destroyed by CBD on the right.

 

Clinical studies conducted outside the United States have shown that CBD is an effective painkiller – particularly for peripheral neuropathy associated with cancer, multiple sclerosis, diabetes, arthritis, and other neurodegenerative conditions.

Sativex, a whole plant cannabis extract with equal levels of CBD and THC, is an under-the-tongue spray produced by GW Pharmaceuticals, a British company. Administered in repeatable, measurable doses, Sativex is clinically effective without causing psychoactivity. It has been officially approved as a medication for neuropathic pain in Great Britain, Canada, and more than 20 other countries. It is currently undergoing phase III clinical trials in the United States.

GW scientists determined that CBD is most effective therapeutically when administered in combination with whole plant THC. Cannabidiol interacts synergistically with THC.  CBD enhances THC’s painkilling impact, while muting THC’s psychoactivity. CBD can also neutralize unfavorable effects that THC may cause, such as anxiety and rapid heartbeat.

Scientific and clinical studies underscore CBD’s potential as a treatment for a wide range of conditions, including rheumatoid arthritis, diabetes, alcoholism, MS, chronic pain, schizophrenia, PTSD, antibiotic-resistant infections, epilepsy, and other neurological disorders. CBD has demonstrated neuroprotective and neurogenic effects, and its anti-cancer properties are currently being investigated at several academic research centers in the United States and elsewhere.

Conditions

Scientific research has shown that CBD may be therapeutic for many conditions, including (but not limited to) chronic pain, cancer, anxiety, diabetes, epilepsy, rheumatoid arthritis, PTSD, sleep disorders, alcoholism, cardiovascular disease, antibiotic-resistant infections, and various neurological ailments.

In compiling a list of conditions for which there is evidence that CBD-rich medicaments might be helpful, we examined hundreds of peer-reviewed articles in scientific journals. Relevant reports have been culled primarily from PubMed, the online service of the U.S. National Library of Medicine. To these highly technical reports, we have added articles from O’Shaughnessy’s, the journal of cannabis in clinical practice, and a few stories from general interest publications, such as Time and the Daily Beast.

Most of the PubMed material consists of abstracts on preclinical research involving single cannabinoid molecules, test tubes, petri dishes, animal experiments, and in some cases human cell line studies.

Although all mammals have cell receptors that respond pharmacologically to cannabinoid compounds, data from animal experiments and other preclinical research is not always applicable to human experience.

GW Pharmaceuticals has conducted successful clinical trials of Sativex, the whole plant CBD-rich cannabis extract, mainly for people suffering from neuropathic pain; summaries of this research are also included. There have been additional clinical studies with synthetic CBD in Brazil and Israel. Unfortunately, political constraints stemming from cannabis prohibition have obstructed clinical-oriented CBD research in the United States.

Most of the reports that follow pertain specifically to cannabidiol. Occasionally these articles examine the therapeutic potential of other plant cannabinoids – THC, CBDA (cannabidiol in its raw acid form), THCV, CBG, and CBDV, for example. We’ve also included a few PubMed studies that illuminate various aspects of the endocannabinoid system without focusing on CBD.

Below is a partial list of conditions that may respond favorably to CBD-rich remedies.

 

Clinical applications

Antimicrobial action

CBD absorbed transcutaneously may attenuate the increased sebum production at the root of acne, according to an untested hypothesis.[7]

Neurological effects

A 2010 study found that strains of cannabis containing higher concentrations of cannabidiol did not produce short-term memory impairment vs. strains with similar concentrations of THC, but lower concentrations of CBD. The researchers attributed this attenuation of memory effects to CBD’s role as a CB1 antagonist. Transdermal CBD is neuroprotective in animals.[8]

Cannabidiol’s strong antioxidant properties have been shown to play a role in the compound’s neuroprotective and anti-ischemic effects.[9]

Psychotropic effect

CBD has anti-psychotic effects and may counteract the potential psychotomimetic effects of THC on individuals with latent schizophrenia;[5] some reports show it to be an alternative treatment for schizophrenia that is safe and well-tolerated.[10] Studies have shown CBD may reduce schizophrenic symptoms due to its apparent ability to stabilize disrupted or disabled NMDA receptor pathways in the brain, which are shared and sometimes contested by norepinephrine and GABA.[10][11] Leweke et al. performed a double blind, 4 week, explorative controlled clinical trial to compare the effects of purified cannabidiol and the atypical antipsychotic amisulpride on improving the symptoms of schizophrenia in 42 patients with acute paranoid schizophrenia. Both treatments were associated with a significant decrease of psychotic symptoms after 2 and 4 weeks as assessed by Brief Psychiatric Rating Scale and Positive and Negative Syndrome Scale. While there was no statistical difference between the two treatment groups, cannabidiol induced significantly fewer side effects (extrapyramidal symptoms, increase in prolactin, weight gain) when compared to amisulpride.[12]

Studies have shown cannabidiol decreases activity of the limbic system[13] and decreases social isolation induced by THC.[14] Cannabidiol has also been shown to reduce anxiety in social anxiety disorder.[15][16]

Chronic cannabidiol administration in rats was found to produce anxiogenic-like effects, indicating that prolonged treatment with cannabidiol might incite anxiogenic effects.[17] Those results have been contested by,[18] and contradict [19] whose experimentation cover the same duration.

Cannabidiol has demonstrated antidepressant-like effects in animal models of depression.[20][21][22]

Dravet syndrome

Dravet syndrome is a rare form of epilepsy that is difficult to treat. Dravet syndrome, also known as Severe Myoclonic Epilepsy of Infancy (SMEI), is a rare and catastrophic form of intractable epilepsy that begins in infancy. Initial seizures are most often prolonged events and in the second year of life other seizure types begin to emerge.[23] While high profile and anecdotal reports of results from high-CBD/low-THC preparations have sparked interest in treatment with cannabinoids,[24] there is insufficient medical evidence to draw conclusions about their safety or efficacy.[24][25]

Pharmacology

Pharmacodynamics

Cannabidiol has a very low affinity for CB1 and CB2 receptors but acts as an indirect antagonist of their agonists.[9] While one would assume that this would cause cannabidiol to reduce the effects of THC, it may potentiate THC’s effects by increasing CB1 receptor density or through another CB1-related mechanism.[32] It is also an inverse agonist of CB2 receptors.[9][33] Recently, it was found to be an antagonist at the putative new cannabinoid receptor, GPR55, a GPCR expressed in the caudate nucleus and putamen.[34]Cannabidiol has also been shown to act as a 5-HT1A receptor agonist,[35] an action which is involved in its antidepressant,[20][36] anxiolytic,[36][37] and neuroprotective[38][39] effects. Cannabidiol is an allosteric modulator of μ and δ-opioid receptors.[40] Cannabidiol’s pharmacological effects have also been attributed to PPAR-γ receptor agonism and intracellular calcium release.[5]