CBD 101

What Is CBD?

CBD is an abbreviation for Cannabidiol, a chemical compound found naturally in the cannabis plant. It is not mind altering like marijuana. CBD will not make you high. Over the past 40 years, there have been numerous studies that highlight the potential benefits of CBD and how it can support the Endocannabinoid System (ECS).

Every mammal has an endocannabinoid system (ECS) with receptors throughout their bodies.  This system is involved in almost all brain and body functions, from our ability to handle pain, stress and anxiety to our mobility and muscle health.  

Sublingual CBD Oils are the most popular CBD products, thanks to their high bioavailability and ease of use. Other popular routes of administration include topical salves and patches.

Importantly, CBD has been found to be well-tolerated and absent of adverse effects at doses up to 600 MG/day. It was also comparable to placebo in producing no physiological effects at these relatively high doses.

Reference: https://www.ncbi.nlm.nih.gov/pubmed/22716148

What Is Industrial Hemp?

Hemp Derived CBD  Is NOT Medical Marijuana

Industrial hemp – defined as any cannabis plant with “less than 0.3 percent THC by dry weight” – is NOT marijuana.

Section 7606 of the Agricultural Act of 2014 – which preempts the Controlled Substances Act (CSA) – specifically excludes industrial hemp and any derivatives thereof from the definition of “marijuana” as found in the CSA. Although “industrial hemp” is the legal name, any reference to hemp in general can typically be assumed to mean industrial hemp. Since hemp is non-psychoactive by definition, it is subject to entirely different regulations than recreational or medical marijuana, which contain high levels of THC.

Like any substance intended for human ingestion, there are regulations and standards that govern the hemp-derived CBD industry.

The Farm Bill of 2014 created a federal legal framework through which individual states can initiate research pilot programs under either the state department of agriculture or a state university school of agriculture. Any hemp plant or hemp-derived product produced in compliance with applicable state law is an agricultural commodity as opposed to a controlled substance.
This includes hemp-derived CBD products. The DEA has been very clear that “the mere presence of cannabinoids is not itself dispositive as to whether a substance is within the scope of the [Controlled Substances Act]”, referencing the fact that cannabinoids produced by plants which produce less than 0.3% THC are not considered marijuana, but are in fact hemp plants.


MANY COMMON CONDITIONS ARE RELATED TO ENDOCANNABINOID SYSTEM DEFICIENCY

Neurodegenerative Disorders

Neuroprotective mechanisms promote neurogenesis, and reduce neuro-inflammation and oxidative stress.

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Osteoarthritis & Rheumatoid Arthritis

Inhibition of the anti-inflammatory cascade and modulation of PPARγ limits the progression of arthritic disease.

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Depression, Anxiety & PTSD

5-HT1a receptor agonism and induction of endocannabinoid receptors has shown efficacy in several mental health models.

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Insomnia

Balance within the endocannabinoid system helps maintains a multitude of variables relating to homeostasis and our circadian rhythm.

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Side Effects of Chemotherapy

Chemotherapy harms good cells as well as bad cells. Endocannabinoid regulation protects healthy cells and promotes apoptosis of diseased cells.

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Acne & Comedo Formation

Most acne treatments aim to kill surface bacteria. Regulation of sebocyte activity prevents comedogenesis caused by excessive sebum production.

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Acute & Chronic Inflammation

PPARγ receptor modulation reduces proinflammatory markers and lymphocyte activation, while inhibition of COX enzymes limits prostaglandin production.

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Epilepsy & Seizure Disorders

Endocannabinoid activity reduces seizure frequency and excess excitability by stabilizing glutamatergic and GABAergic signaling.

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Chronic Pain & Fibromyalgia

The ECS regulates pain sensitivity in the periphery and receptivity centrally; induction of the ECS promotes an increased threshold for pain.

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How Does CBD Work?

CBD is a negative allosteric modulator of CB1 and CB2 cannabinoid receptors.

This has several implications.

  1. Firstly, negative modulation of CB1 receptors reduces the perceived effects of cannabinoid agonists, like THC.
  2. Secondly, it causes upregulation of the same CB1 receptors, which improves signaling and reduces the likelihood of endocannabinoid deficiency [1] [2].

What is the role of cannabinoid receptors?

Cannabinoid receptors are the most widely expressed G protein-coupled receptors in humans: they’re more numerous than all other GPCRs combined.

This well-established fact of human biology has been overlooked for years, thanks in part to the stigma against the only known agonist of these receptors, marijuana. Nonetheless, CB1 receptors specifically are immensely important in the regulation of neurotransmission patterns, especially inhibitory GABAergic transmission in the cortex, hippocampus, and amygdala.

Depolarization-Induced Suppression of Inhibition

The functional role of cannabinoid receptors in the brain is to facilitate depolarization-induced suppression of inhibition. Also known as agonist-induced disinhibition, this phenomenon occurs when a presynaptic action potentially causes the retrograde release of endocannabinoids from the postsynaptic dendrite which activate inhibitory CB1 receptors found on the inhibitory basket cells serving to tonically inhibit the activity of neuron A.

In other words, when neuron A signals Glutamate to neuron B, neuron B releases endocannabinoids which inhibit the basket cells serving to inhibit neuron A, with the ultimate effect of increasing the likelihood that neuron A will generate another action potential.

Because the endocannabinoid system (ECS) regulates the activity of several other neurotransmitter systems, ECS dysregulation can have far-reaching implications that are equally difficult to elucidate. On the other hand, many common conditions from Acne to Alzheimer’s disease have unknown pathogenesis but affect areas of the body known to express cannabinoid receptors. Taken together, these facts suggest that the endocannabinoid system could be a novel and highly-effective target in the treatment of diverse disorders of the central and peripheral nervous systems.

References:

[1] https://www.ncbi.nlm.nih.gov/pubmed/26218440
[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4621983

CBD demonstrates dose-dependent in vivo inhibition of key pro-inflammatory factors including iNOS and IL-1β.

The anti-inflammatory properties of CBD are different from NSAIDs or steroids in that CBD chemically alters the proinflammatory process, as opposed to blocking a single step in the inflammatory pathway.

Moreover, CBD also reduces inflammatory responses through direct involvement with PPARγ nuclear receptors [1]. Certain tonic cellular processes produce highly reactive oxygen species which, over time, alter the inflammatory response to become pathologically sensitive to ROS stimuli. CBD reduces this sensitivity without eradicating the immune response to protect against ROS damage.

In addition, CBD potently reduces sebocyte activity and inflammation, which are key processes in the pathogenesis of acne [2] [3] [4].

References:

[1] http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0028668
[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4151231
[3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2189818
[4] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3232190

CBD is an inhibitor of tryptophan degradation, which leads to increased levels of brain serotonin.

Serotonin is one of the most ubiquitous signaling molecules in mammals. It is intricately involved in both mood and cognition, and immune system signaling.

  • The limiting factor in serotonin (5-hydroxytryptamine) synthesis in humans is the synthesis of serotonin’s immediate precursor, 5-hydroxytryptophan (5-HTP), from the amino acid tryptophan. When this process is limited, or tryptophan follows a metabolic pathway other than [tryptophan → 5-HTP → serotonin], serotonin levels will fall, causing mood to become dysregulated and inflammation to become disinhibited.
  • Regulation of the serotonin system is one of the primary roles of the endocannabinoid system (ECS), and when the ECS fails to maintain serotonin homeostasis, CBD can help to reinstate balance within the ECS, which indirectly improves the condition of the serotonin system.

Furthermore, CBD acts as a partial agonist of serotonin 5-HT1a receptors [1] [2].

References:

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2697769/
[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4033942/

CBD also acts as an antioxidant with similar efficacy to α-tocopherol, preventing glutamate-induced neurotoxicity and ROS-induced cell death in vivo.

Thanks to the presence of two phenolic hydroxyl groups, CBD is a potent antioxidant comparable to Vitamins C and E in terms of reduction of oxidative free radicals in vivo and in vitro. This contributes to anti-inflammatory and neuroprotective properties of CBD as well as to its antifungal and antibacterial effects.

The property of CBD which has garnered the greatest degree of publicity has been its ineffable anti-seizure activity.

Through several different mechanisms, CBD is able to relieve intractable seizures when more than 6 traditional AEDs have been ineffective (Δ seizure frequency ≤ 5%).

CBD is biphasic and has multiple biological targets as well as several interactive endogenous compounds that contribute to a unique spectrum of activity in the pathological human system. The class of disorders for which CBD is most effective appears to be epileptic and non-epileptic seizure disorders. Through agonism of 5-HT1a, as well as negative modulation of “disinhibitory” cannabinoid receptors, CBD is able to reduce the frequency and severity of many types of seizure, because it stabilizes neuronal excitability as well as reducing excitatory transmission.

 

CBD Supplements Our Own Endocannabinoid System (ECS)

The ECS is a system of G protein-coupled receptors, their several lipid signaling ligands, and the anabolic and catabolic enzymes which produce and degrade the signaling molecules. Activation of cannabinoid receptors initiates a second messenger cascade which, in immune cells, inhibits proinflammatory processes, and in neurons, causes polarization and subsequently, reduced likelihood of neurotransmitter release.

 

*The statements regarding these products have not been completely evaluated by the Food and Drug Administration. This Product is not intended to diagnose, treat, cure or prevent any disease. Individual results from product usage may vary.

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