Accurate Education – Marijuana (Cannabis): Cannabidiol (CBD) – Introduction

Cannabidiol (CBD) – Introduction

 

The medical information on this site is provided as a resource for information only, and is not to be used or relied upon for any diagnostic or treatment purposes and is not intended to create any patient-physician relationship.  Readers are advised to seek professional guidance regarding the diagnosis and treatment of their medical concerns.

 

Cannabidiol (CBD), the second most abundant cannabinoid in marijuana, has medicinal properties differing from THC and, most importantly, it does not provide the euphoria, or “high” that is associated with THC. Currently, cannabidiol products are legal in the U.S. including Louisiana but only if derived from industrial hemp seeds and stalks but not flowers or leaves, not synthetic, and they must be 100% free of THC. 

  

See:

Marijuana – Legislative Update for Louisiana

Marijuana – Medical Use Overview

“Medical Marijuana” – Getting Started

 

Cannabis-Based Medications:

Over-the-Counter Cannabinoid Medications:

Cannabidiol (CBD)

Cannabidiol (CBD) – Introduction

Cannabidiol (CBD) – Clinical Use

Cannabidiol (CBD) – Drug Actions & Interactions

 

Prescription Cannabis-Based Medications:

FDA-Approved Prescription Cannabis-Based Medications

Louisiana Prescription Cannabis-Based Products – “Medical Marijuana”

 

Clinical Applications of Cannabis:

Cannabis – Anxiety (coming soon)

Cannabis – Chronic Pain Overview

Cannabis – Fibromyalgia

Cannabis – Headaches (coming soon)

Cannabis – Inflammatory Bowel Disease (coming soon)

Cannabis – Neuroinflammation (coming soon)

Cannabis – Sleep (coming soon)

 

The Medical Science of Cannabis:

The Endocannabinoid System

Marijuana – Botanical

Marijuana – Pharmacokinetics

Marijuana – Inhaled (Smoked and Vaporized)

Marijuana – Cannabinoids and Opioids

 

Cannabinoids and Terpenes:

Cannabinoids & Terpenes – An Overview (coming soon)

“Entourage Effect” (coming soon)

 

Cannabinoids:

Cannabidiol (CBD) – Introduction

Cannabidiol (CBD) – Clinical Use

Cannabidiol (CBD) – Drug Actions & Interactions

THC (Delta-9 Tetrahydrocannabinol or ∆9 THC) (coming soon)

 

Terpenes:

Terpenes – An Overview (coming soon)

   

See also:

Marijuana – Discontinuing Use

Marijuana Addiction – Cannabis Use Disorder (CUD)

 

Key to Links:

Grey text – handout

Red text – another page on this website

Blue text – Journal publication

Cannabidiol Oil

Cannabidiol (CBD) – Introduction

CBD, not considered a drug of abuse, is at the same time legal but not regulated. This has caused the development of a market of CBD-based products for medical purpose, such as CBD oil, tinctures and vapors that has rapidly expanded in a no man’s land of scientific ignorance relative to specific therapeutic benefits and applicable doses. The lack of regulation of CBD products does not allow for knowledge of the quality of CBD products including their purity and their absence of chemical or microbiological contaminations that is fundamental for predicting its therapeutic effectiveness and safety. It is therefore important for the consumer/patient to inform themselves prior to embarking on self-treatment with CBD.

The clinical benefits obtained from marijuana (cannabis) are derived from the many constituents found in the plant, including more than 100 pharmacologically active compounds called cannabinoids. The two best understood and most common of the cannabinoids are THC (delta-9 tetrahydrocannabinol) and CBD (cannabidiol) which together are likely responsible for the majority of the medical benefits associated with cannabis use, as briefly summarized below:

 

THC (∆-9 tetrahydrocannabinol)

THC has analgesic, anti-spasmodic, anti-tremor, anti-inflammatory, appetite stimulant and anti-emetic properties, but also mind-altering effects (euphoria). It has 20 times the anti- inflammatory power of aspirin and twice that of hydrocortisone. THC and its active metabolite, 11-Hydroxy-THC. are responsible for the “high” associated with use of marijuana.

For more information regarding the clinical use of CBD: THC – Introduction (coming soon)

 

CBD (Cannabidiol)

CBD has anti-inflammatory, anti-convulsant, anti-psychotic, anti-oxidant, neuroprotective and immunomodulatory effects but does not produce mind-altering effects like euphoria. CBD is a neuroprotective antioxidant more potent than Vitemin C (ascorbate) or Vitamin E (tocopherol). CBD is also thought to support sleep and reduce nausea, particularly related to chemotherapy. CBD, in combination with THC, modulates some of the side effects of THC, including reducing THC-induced anxiety and euphoria.

For more information regarding the clinical use of CBD: Cannabidiol (CBD) – Clinical Use

 

Other Cannabis-based Compounds

In addition to the cannabinoids, another major family of compounds is the terpenes (and related terpenoids) which are responsible for the distinct aromas associated with cannabis. The terpenes may also contribute to therapeutic benefits although less is known about the terpenes compared to THC and CBD. Besides the cannabinoids and terpenes, there at least fifteen different classes of compounds, including nitrogenous compounds, amino acids, hydrocarbons, carbohydrates, and fatty acids, all of which may contribute to the pharmacological and toxicological properties of cannabis. There is very limited scientific information available on the pharmacology and toxicology of the constituents found in cannabis.

 

Marijuana (Cannabis) vs. Cannabis-based Commercial Products

This underscores the importance of pharmaceutical medical marijuana in which pharmacologic agents are manufactured with specific doses and ratios which allow for safer titration of dosing to achieve desired clinical benefits. It also underscores the fact that the use of CBD only as an isolated constituent of marijuana will not reproduce the effects of marijuana while it may nevertheless offer its own specific therapeutic benefits.

 

CBD – Legal Status

The conflict between federal and state laws on the medical use of cannabis products, the lack of consistency among state laws, and the availability of artisanal cannabis and CBD products in dispensaries and online has caused significant confusion for researchers, practitioners, and patients and their caregivers, particularly with regard to CBD products.

 

Federal Law

The DEA’s most recent denial of two marijuana rescheduling petitions means that marijuana and its constituent cannabinoids, including CBD from any source, including hemp, will currently remain in Schedule I and therefore, based on federal law, CBD is illegal in all states regardless of source. This conclusion is based on a recent legal review article published in 2017 and considered accurate through August, 2016, However, while the DEA maintains that CBD is definitely still illegal, in November 2017, a spokesperson for the agency stated that while those who violate federal drug laws could run the “risk of arrest and prosecution,”  the DEA is not going after individuals who have benefited from CBD oil.

 

Louisiana Law

Currently, CBD (cannabidiol) products are legal in Louisiana but only if derived from industrial hemp seeds and/stalks but not flowers or leaves, not synthetic and they must be 100% free of THC (See: House Bill 225 – 2017). Practically speaking, it appears that if the THC content is less than 0.3%, it is considered “THC-free.”

See:  Marijuana -Legislative Update for Louisiana

 

Cannabidiol – Prescription CBD Products

Currently, there is only one prescription CBD-only medication (Epidiolex) available and one medication (Sativex) that contains both THC and CBD. They are available by prescription but are very expensive and insurance is likely to pay for them only for FDA-approved conditions.

See: FDA-Approved Prescription Cannabis-Based Medications

 

Epidiolex

Epidiolex (cannabidiol) is an oral solution of cannabidiol (CBD), FDA-approved for the treatment of only four medical conditions: the pediatric epilepsy conditions – Dravet syndrome, Lennox-Gastaut syndrome (LGS) and Tuberous Sclerosis Complex – and infantile spasms, a specific type of seizure seen in  infancy and childhood that is characterized by developmental regression and spasms that tend to occur upon awakening or after feeding, and often occur in clusters of up to 100 spasms at a time. 

 

Epidiolex is the first prescription, plant-derived FDA-approved cannabinoid medicine in the United States and the first in the new class of cannabinoid anti-epileptic medications. Despite FDA approval, however, the DEA continues to classify it as a Schedule I drug and therefore is not generally available for prescription by physicians without a special license for prescribing it.  Schedule I drugs, substances or chemicals are defined as “drugs with no currently accepted medical use and a high potential for abuse.” Unfortunately, use of Epidiolex for conditions other than those mentioned above would be considered “off-label” and would not likely be covered by insurance.

 

Sativex

Sativex (a combination of THC and CBD in a 1:1 ratio) is a prescription cannabinoid available in Canada and Europe but not yet FDA-approved or available in the U.S.  Some of the most informative research into medical uses of marijuana has come from studies evaluating Sativex because it is plant-base and contains both THC and CBD as well as other pharmacologicaly significant cannabis plant constituents including some terpenes.

 

Cannabidiol – Over-the-Counter (OTC) CBD Products

There are three basic types of over-the-counter (OTC) CBD products:  Isolate, Broad Spectrum and Full Spectrum. They differ in  the presence of other cannabis-based constituents than CBD. Sometimes products are described as “Whole Plant,” “Derived from Aerial Plant Parts” (including all plant parts above ground) or “Pure CBD.” In addition to different types of CBD products, there are also different formulations of CBD products. Because CBD oil is very poorly soluble in water and is not absorbed well with oral ingestion, special formulations are being introduced to the commercial marked designed to enhance absorption and improve effectiveness (See “Commercial Products” below, at the bottom of this page). These are the different CBD types:

 

CBD Isolates

A CBD oil “Isolate” is 99+% pure CBD, with no other cannabinoids such as THC and no terpenes. CBD oil isolate products are legal without a prescription in Louisiana, and are the product of choice for those who get drug tested. When seeking an isolate, it is important to verify the purity. There are also products out there called terpsolates, where the CBD isolate is infused with terpenes to enhance their scent and possibly enhance their effects. As noted above, in Louisiana legal OTC CBD products  must be extracted from industrial hemp stalk fiber or seed – the law does not allow for leaf or flower source. It is unclear if this distinction is enforced as long as the THC content is less than 0.3%.

 

Compared to whole plant CBD-rich cannabis, industrial hemp grown for fiber or seed is typically low in cannabinoid content. A huge amount of fiber hemp is required to extract a small amount of CBD, which raises the risk of contaminants because hemp, a bioaccumulator, draws toxins from the soil. CBD oil obtained in this product may be labeled “isolate” as opposed to “whole -plant derived” or derived from “aerial parts” (all plant parts above the ground, excluding roots).This is one important reason why it is stressed to obtain a “Certificate of Analysis” of any CBD product before purchase.

 

A “Certificate of Analysis” is a third party lab report that analyzes the chemical content of the CBD product and identifies the presence of toxins that should not be there, including heavy metals such as arsenic, lead and mercury as well as solvents such as acetone and pesticides.  A “Certificate of Analysis,” which should be readily available from reputable manufacturers also identifies which cannabinoids and terpenes are present in the product and at what concentrations.

 

Furthermore, since the extraction is low in total cannabinoid content and likely low in terpenes as well, CBD Isolates do not allow for the “Entourage Effect” (see below) in which the therapeutic benefit of CBD is believed to be enhanced by the presence of other plant-based cannabinoids and terpenes. Based on this argument, “Broad Spectrum” and “Full Spectrum” CBD products may provide greater effectiveness.

 

Broad Spectrum CBD Oil

“Broad Spectrum” products are processed to maintain the presence of CBD and other cannabinoids and terpenes but remove THC so they have zero THC. The concentration and ratios of these compounds in the “Broad Spectrum” product will vary based on the specific strain of the plant(s) from which the CBD was extracted as well as the growing conditions and extraction techniques. Sometimes individual cannabinoids and terpenes are also added back into CBD oil products to raise the potency of the product. Third party lab reports or “Certificates of Analysis” should be readily available from reputable manufacturers that identify which cannabinoids and terpenes are present in the product and at what concentrations.

 

Full Spectrum CBD Oil

Like “Broad Spectrum” CBD, “Full Spectrum” refers to CBD oil products that are extracted from the cannabis plant and contain not only CBD, but also terpenes, other cannabinoids and even some THC. The concentration and ratios of these compounds in the product will vary based on the specific strain of the plant(s) from which the CBD was extracted as well as the growing conditions and extraction techniques. Sometimes individual cannabinoids and terpenes are also added back into CBD oil products to raise the potency of the product. Full Spectrum CBD products may also contain small amounts of THC and although minimal (less than 0.3%) and unlikely to contribute significant effects, they can still trigger positive urine drug tests. As with Broad Spectrum products, third party lab “Certificates of Analysis” should be readily available from reputable manufacturers that identify which cannabinoids and terpenes are present in the product and at what concentrations.

 

Possibe Advantages of Broad Spectrum and Full Spectrum CBD Compared Isolates

The possibe advantages of Broad Spectrum and Full Spectrum CBD oil products are due to the “Entourage Effect,” in which cannabinoids and terpenes work together in synergy, providing supplemental therapeutic benefits in addition to those of CBD alone (See below).

   

Entourage Effect

The pharmacologic effects of cannabis depend on the combined effects of all the pharmacologically active constituents present. The interplay of the different constituents that determine both the therapeutic benefits as well as the adverse effects is known as the “Entourage Effect,” which simply underscores the idea that it is not just one constituent but the combined effects of all the constituents that determine the ultimate therapeutic and side effects. There is a wide range of differences in both the number, amounts and ratios of different constituents in different cannabis plants leading to an equally wide range of therapeutic benefits and side effects obtained from cannabis-based products.

 

Different mechanisms of synergy have been proposed to explain the Entourage Effect: (i) multi-target effects; (ii) pharmacokinetic effects such as improved solubility or bioavailability; (iii) agent interactions; and (iv) modulation of adverse events. For more in-depth information regarding the Entourage Effects and synergy between cannabis-based constituents, see: Cannabis – The Entourage Effect.

 

Entourage Effect – CBD & THC

The strength and ratio of the two major cannabinoids, THC and CBD, play a dominate role in the clinical effects of cannabis. A synergy, or “entourage effect,” exists between these two components in which their combination produces effects that are uniquely determined by the amount and ratios of these two constituents. At low concentrations CBD antagonizes the effects of THC, regulating THC-related adverse effects like rapid heart rate, anxiety, sedation and hunger.

 

In one study, CBD proved to be a critical factor in the ability of Sativex (nabiximols oromucosal extract consisting of a 1:1 ratio combination of THC and CBD) in successfully treating intractable cancer pain patients unresponsive to opioids (30% reduction in pain from baseline). In this study a high-THC extract devoid of CBD failed to distinguish from placebo. This may represent true synergy of the THC–CBD combination.

 

Therefore, the legal OTC CBD products may lack the potential benefit of the Entourage Effect contributed by the THC, they may be less effective than a cannabis-based product legally obtained as “medical marijuana.”  Cannabis-based products containing more than 0.3% THC must be prescribed by a licensed physician in LA and obtained from one of the nine pharmacies located in the state that are licensed for distribution of medical marijuana products.

For a list of these nine pharmacies, See: Marijuana – Legislative Update for Louisiana

 

Entourage Effect – CBD & Other Cannabinoids and Terpenes

In addition to CBD & THC, the other cannabinoids and terpenes are believed to impact the clinic effects of cannabis and contribute to the entourage effect. For this reason, the Broad Spectrum and Full Spectrum CBD products are purported to offer potentially greater clinical benefits compared with the CBD Isolates. While the theory is sound, there does not appear to be any research to support specific constituent combinations or doses nor specific therapeutic benefits as related to CBD products. Furthermore, it appears to be difficult to even clearly identify the content of cannabinoids and terpenes available in the multitude of CBD products on the market. As the industry grows and research begins to catch up, it may be possible to select specific Broad Spectrum and Full Spectrum products to match specific desired therapeutic benefits.

 

In the meantime, one can explore what is known about the therapeutic effects of specific cannabinoids and terpenes and look for CBD products which could likely target desired therapeutic benefits. Careful attention to Certificates of Analysis can guide one to better product choices.

See: Cannabinoids – An Overview and Terpenes – An Overview

 

Entourage Effect – CBD & Palmitoylethnolamide (PEA)

Palmitoylethnolamide (PEA) is a potent nutraceutical that is naturally produced in many plant and animal food sources, as well as in cells and tissues of mammals.  PEA has important neuroprotective, anti- inflammatory and analgesic actions both in the central and the peripheral nervous system. There are multiple mechanisms of action of PEA responsible for its therapeutic benefits, some that involve the endocannabinoid system (ECS) which is the basis of its proposed synergistic action with CBD, THC and other cannabinoids.

 

PEA produces indirect receptor-mediated effects within the ECS. PEA inhibits FAAH, the enzyme that breaks down endogenous (natural) cannabinoids (or endocannabinoids) such as anandamide (AEA), and plant cannaabinoids (phyhtocannabinoids) like CBD and THC, that directly or indirectly activate CB2 and CB1 receptors. Likewise, PEA can indirectly activate the transient receptor potential vanilloid receptor type 1 (TRPV1) channels, which are also targets for the endocannabinoids. In addition, PEA is also able to increase AEA- or 2-AG-induced TRPV1 activation and desensitization . More recently, it has also been demonstrated that PEA can activate TRPV1 channels or increase the expression of CB2 receptors via PPAR-α receptors.

 

Quality Control – A Cautionary Note on Purchasing CBD Products

Because there are no regulatory agencies that oversee CBD manufacturing processes or product quality and no universal standards for laboratory testing protocols currently exist, there are many products on the market, especially on the internet, that are not as advertised and many are not THC-free ( See: News Item March 2018). One study found that 70% of CBD products sold onb the intenet did not contain what their labels indicated (See: Label Accuracy by Cannabidiol Extract Type). It is best to buy from reputable businesses and gas stations are probably not to be recommended.

 

Look for products with labels clearly showing the quantity and concentration, a manufacturing date, and a batch number (for quality control). Choose products without corn syrup, transfats, GMOs, artificial additives, thinning agents or preservatives. Look to see if they have been lab tested for product consistency and verified as being free of mold, bacteria, pesticides, solvent residues, and other contaminants. Avoid CBD products extracted with toxic solvents like BHO, propane, hexane or other hydrocarbons. Instead, select products utilizing safer extraction methods such as supercritical CO2 or food-grade ethanol.

 

It is recommended that one obtain a “Certificate of Analysis” from an independent laboratory prior to purchasing a CBD product. A reputable dealer should be able to provide such a certificate on demand. The purpose of obtaining this certificate is to both provide an accurate breakdown of the compounds present in the product including cannabinoids and terpenes, but also to confirm the absence of toxic compounds introduced during the manufacturing process such as heavy metals, solvents and pesticides.

  

Dosing of CBD

Specific dosing of CBD needs to be guided individually, taking into account desired therapeutic benefits related to specific symptoms and disease processes as well as the potential for drug-drug interactions with other prescribed medications. Dosing should be guided by a physician knowledgeable about cannabis and cannabis-based products.

 

CBD can be effective at very wide range of dosages. It has been noted that very low doses can have a very profound impact, from as little as 2.5 mg of CBD daily depending on method of delivery. Doses up to hundreds of milligrams have been used safely and effectively. In a study that evaluated daily oral doses of 700mg, CBD was found to be nontoxic and other studies have reported CBD doses up to 1500mg/day to be safe. It has also been reported that cannabinoids may have a biphasic or triphasic effect, in that a low dose may provide a certain effect, but higher doses may provide different or opposite effects.

 

A very high dose may also not provide additional benefit over a low dose, so it’s best to start with a low dose: 2.5-5 mg of CBD initially (maybe 10 mg at the most), depending on the product and method of use. A typical starting CBD dose for most people would be a total of 10-12 mg of CBD a day, divided into 3 daily doses. If the desired effect is not achieved at a low dose, then higher doses can gradually be introduced until the therapeutic goal is achieved or side effects deter further increased dosing.

 

The use of tinctures sublingually will be expected to provide a more rapid onset of effect but may not last as long as an oral dose. Orally administered CBD oil can last for four hours or more, but the onset of effects is much slower (30-90 minutes) than a tincture administered sublingually (under the tongue). Tincture dosing is generally performed with a 1 ml dropper which provides about 20 drops/ml.

 

Safety

CBD has been determined to be safe, with no fatal overdoses on record and is generally well tolerated with minimal or mild side effects. CBD does not affect motor function or memory and does not appear to have the potential for physical dependence (e.g. withdrawal and tolerance), nor is it associated with abuse or addiction. The side effects of CBD are mild and include low blood pressure, dry mouth, light-headedness, sedation and drowsiness.

 

  

Dosing of CBD

CBD can be effective at very wide range of dosages. It has been noted that very low doses can have a very profound impact, from as little as 2.5 mg of CBD per dose and up to hundreds of milligrams per dose, depending on method of delivery. In a study that evaluated daily oral doses of 700mg,  CBD was found to be nontoxic. Other studies have reported CBD doses up to 1500mg/day to be safe. It has also been reported that cannabinoids in general, CBD specifically, may have a biphasic effect, actually more like a triphasic effect, in thata  low dose may provide a certain effect, a high dose may provide a different or opposite effect.

 

A very high dose may also not provide additional benefit over a low dose, so it’s best to start with a low dose: 2.5-5 mg of CBD initially, depending on the product and method of use. A typical starting CBD dose for most people would be a total of up to 12-30 mg of CBD per day, divided into 3 daily doses. If the desired effect is not achieved at a low dose, then gradually higher doses can be introduced until the therapeutic goal is achieved or side effects deter further increased dosing.

 

The use of tinctures sublingually will be expected to provide a more rapid onset of effect but may not last as long. Orally administered CBD oil can last for four hours or more, but the onset of effects is much slower (30-90 minutes). Tincture dosing is generally performed with a 1 ml dropper which provides about 20 drops/ml.

 

Commercial CBD Formulations

Because CBD oil is very poorly soluble in water it is not absorbed well with oral ingestion (80% or more of ingested CBD is not absorbed. Because of its poor solubility in water, only a small fraction – less than 10% – of orally ingested CBD  actually enter a cells where they exert their medical properties (true also for other cannabinoids and terpenes in marijuana).  Instead, CBD remains in the blood until it passes through the liver and is metabolized. New formulations of CBD are appearing on the market that offer enhanced water solubility and absorption. These products include liposomal CBD and nano-CBD.

 

Liposomal CBD

Liposomal technology provides a method used to enable medications to be better absorbed from the gut and into cells. It is a technology commonly used in nutriceutical supplements, including products described elsewhere on this website (See Meriva and Siliphos). Liposomes are small sacs with membranes made of phospholipids – the same type of membrane that encloses every cell in our bodies. Liposomal formulations involves enclosing individual drug molecules like CBD inside liposomes, which facilitates their entry into cells in the same way the body transports its own substances into and out of cells. Thus, liposomal CBD is more efficiently used by the body.

 

Advantages of Liposomal CBDs

  1. Encapsulates the active ingredients and delivers them directly into the cell;
  2. Reduces the breakdown of the CBD (avoids first pass metabolism by the liver); and 
  3. It improves the percentage of bioavailable CBD, as the full concentration can be absorbed

 

Nano-CBD

In general, cells can absorb particles only up to 50 nanometers (billionths of a meter) in diameter. Because CBD is hydrophobic and fatty, it binds with itself to a certain extent, creating chains of CBD that are too large to be absorbed by cells. Recent technology sometimes referred to as nano-amplification allows for the separation of CBD molecules  from each other.  Individually, CBD molecules are about 10-15 nanometers in diameter so that nano-forms of CBD are better absorbed by cells with less wastage.

 

  

Resources:

National Academy of Sciences

The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research

 

These lay-person websites appear to be good resources for exploring medical marijuana:

  1. www.GreenCamp.com
  2. www.Healer.com
  3. www.MedicalJane.com
  4. www.ProjectCBD.org

 

 

References:

Epidiolex (cannabidiol)

  1. FDA approves CBD drug – Epidiolex – The Washington Post

Marinol (dronabinol)

  1. Marinol – dronabinol

  

Cannabidiol (CBD)- Overviews

  1. CANNABIDIOL (CBD) Pre-Review Report WHO 2017
  2. Cannabidiol – State of the art and new challenges for therapeutic applications. – 2017 PubMed – NCBI
  3. Molecular Targets of Cannabidiol in Neurological Disorders – 2015

 

CBD – Anxiety

  1. Overlapping Mechanisms of Stress-Induced Relapse to Opioid Use Disorder and Chronic Pain – Clinical Implications – 2016
  2. Cannabidiol Modulates Fear Memory Formation Through Interactions with Serotonergic Transmission in the Mesolimbic System – 2016
  3. Cannabidiol regulation of emotion and emotional memory processing: relevance for treating anxiety-related and substance abuse disorders. – PubMed – NCBI
  4. Review of the neurological benefits of phytocannabinoids – 2018
  5. Plastic and Neuroprotective Mechanisms Involved in the Therapeutic Effects of Cannabidiol in Psychiatric Disorders – 2017
  6. Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report. – PubMed – NCBI
  7. Evidences for the Anti-panic Actions of Cannabidiol – 2017
  8. Cannabidiol, a Cannabis sativa constituent, as an anxiolytic drug – 2012
  9. Cannabidiol Reduces the Anxiety Induced by Simulated Public Speaking in Treatment-Naïve Social Phobia Patients – 2011
  10. The non-psychoactive cannabis constituent cannabidiol is an orally effective therapeutic agent in rat chronic inflammatory and neuropathic pain. – PubMed – NCBI 2007

 

CBD – Interaction with THC

  1. Cannabidiol: a promising drug for neurodegenerative disorders? – PubMed – NCBI
  2. Oral Cannabidiol does not Alter the Subjective, Reinforcing or Cardiovascular Effects of Smoked Cannabis – 2015
  3. Taming THC – potential cannabis synergy and phytocannabinoid-terpenoid entourage effects – 2011
  4. A tale of two cannabinoids: the therapeutic rationale for combining tetrahydrocannabinol and cannabidiol. – PubMed – NCBI
  5. Clinical and Preclinical Evidence for Functional Interactions of Cannabidiol and Δ9-Tetrahydrocannabinol. 2018 – PubMed – NCBI
  6. Does Cannabis Composition Matter? Differential Effects of Delta-9-tetrahydrocannabinol and Cannabidiol on Human Cognition – 2017

 

 

CBD – Metabolites

  1. Human Metabolites of Cannabidiol – A Review on Their Formation, Biological Activity, and Relevance in Therapy – 2016

 

CBD – Drug-Metabolic Interactions

  1. Cannabidiol, a Major Phytocannabinoid, As a Potent Atypical Inhibitor for CYP2D6 – 2011
  2. The Effect of CYP2D6 Drug-Drug Interactions on Hydrocodone Effectiveness – 2014 
  3. Characterization of P-glycoprotein Inhibition by Major Cannabinoids from Marijuana – 2006

Medical Marijuana – Prescribing Guidelines

  1. Simplified guideline for prescribing medical cannabinoids in primary care – Canadian Family Physician – 2018
  2. Physician Recommendation of Medical Cannabis Guidelines Calif Medical Assoc – 2011
  3. Prescribing smoked cannabis for chronic noncancer pain. Preliminary recommendationsCanadian Family Physician – 2014

 

CBD – Pain

  1. The non-psychoactive cannabis constituent cannabidiol is an orally effective therapeutic agent in rat chronic inflammatory and neuropathic pain. – PubMed – NCBI 2007
  2. Molecular Targets of Cannabidiol in Neurological Disorders – 2015
  3. Cannabidiol Modulates Fear Memory Formation Through Interactions with Serotonergic Transmission in the Mesolimbic System – 2016
  4. Cannabidiol enhances morphine antinociception, diminishes NMDA-mediated seizures and reduces stroke damage via the sigma 1 receptor – 2018
  5. Cannabidiol modulates serotonergic transmission and reverses both allodynia and anxiety-like behavior in a model of neuropathic pain. – PubMed – NCBI – 2018

 

Medical Marijuana – Pain

  1. Use-of-Prescription-Pain-Medications-Among-Medical-Cannabis-Patients
  2. It is premature to expand access to medicinal cannabis in hopes of solving the US opioid crisis – 2018
  3. Patterns of medicinal cannabis use, strain analysis, and substitution effect among patients with migraine, headache, arthritis, and chronic pain in a medicinal cannabis cohort – 2018
  4. Patterns and correlates of medical cannabis use for pain among patients prescribed long-term opioid therapy. – PubMed – NCBI
  5. Associations between medical cannabis and prescription opioid use in chronic pain patients – A preliminary cohort study – 2017
  6. Medical Marijuana for Treatment of Chronic Pain and Other Medical and Psychiatric Problems – A Clinical Review – 2015

 

Medical Marijuana – Opioids

  1. Use-of-Prescription-Pain-Medications-Among-Medical-Cannabis-Patients
  2. It is premature to expand access to medicinal cannabis in hopes of solving the US opioid crisis – 2018
  3. Patterns of medicinal cannabis use, strain analysis, and substitution effect among patients with migraine, headache, arthritis, and chronic pain in a medicinal cannabis cohort – 2018
  4. Patterns and correlates of medical cannabis use for pain among patients prescribed long-term opioid therapy. – PubMed – NCBI
  5. Associations between medical cannabis and prescription opioid use in chronic pain patients – A preliminary cohort study – 2017
  6. The prevalence and significance of cannabis use in patients prescribed chronic opioid therapy: a review of the extant literature. – PubMed – NCBI
  7. The use of cannabis in response to the opioid crisis: A review of the literature. – PubMed – NCBI
  8. Medical Cannabis Laws and Opioid Analgesic Overdose Mortality in the United States, 1999–2010 – 2014
  9. Rationale for cannabis-based interventions in the opioid overdose crisis – 2017
  10. Cannabis and the Opioid Crisis – 2018
  11. Impact of co-administration of oxycodone and smoked cannabis on analgesia and abuse liability. – PubMed – NCBI
  12. Cannabinoid–Opioid Interaction in Chronic Pain
  13. Synergistic interactions between cannabinoid and opioid analgesics. – PubMed – NCBI
  14. FDA approves CBD drug – Epidiolex – The Washington Post
  15. Opioid transport by ATP-binding cassette transporters at the blood-brain barrier: implications for neuropsychopharmacology. – PubMed – NCBI – 2011
  16. Opioids and the Blood-Brain Barrier – A Dynamic Interaction with Consequences on Drug Disposition in Brain – 2017
  17. The pharmacokinetics and the pharmacodynamics of cannabinoids. – PubMed – NCBI – 2018
  18. Cannabinoids and Cytochrome P450 Interactions. – PubMed – NCBI – 2016
  19. Pharmacogenetics of Cannabinoids – 2017 Enhanced Brain Disposition and Effects of Δ9-Tetrahydrocannabinol in P-Glycoprotein and Breast Cancer Resistance Protein Knockout Mice. 2012
  20. Pharmacogenomics of methadone maintenance treatment. – PubMed – NCBI
  21. Relationship between ABCB1 polymorphisms and serum methadone concentration in patients undergoing methadone maintenance therapy (MMT). – PubMed – NCBI- 2016
  22. Impact of ABCB1 and CYP2B6 Genetic Polymorphisms on Methadone Metabolism, Dose and Treatment Response in Patients with Opioid Addiction – A Systematic Review and Meta-Analysis – 2014
  23. ABCB1 haplotype and OPRM1 118A > G genotype interaction in methadone maintenance treatment pharmacogenetics – 2012
  24. The opioid epidemic – a central role for the blood brain barrier in opioid analgesia and abuse – 2017
  25. Morphine and the blood-brain barrier – diffusion, uptake, or efflux? – 2017
  26. Cyclosporine-inhibitable Blood-Brain Barrier Drug Transport Influences Clinical Morphine Pharmacodynamics – 2013
  27. Methadone Treatment for Pain States – 2005
  28. Cyclosporine-inhibitable Cerebral Drug Transport Does not Influence Clinical Methadone Pharmacodynamics – 2014
  29. Targeting blood–brain barrier changes during inflammatory pain – an opportunity for optimizing CNS drug delivery – 2011
  30. Targeting Transporters – Promoting Blood-Brain Barrier Repair in Response to Oxidative Stress Injury – 2015
  31. The non-psychoactive cannabis constituent cannabidiol is an orally effective therapeutic agent in rat chronic inflammatory and neuropathic pain. – PubMed – NCBI 2007

Medical Marijuana –Misc

  1. A tale of two cannabinoids: the therapeutic rationale for combining tetrahydrocannabinol and cannabidiol. – PubMed – NCBI
  2. Cannabis and cannabis extracts – greater than the sum of their parts? – 2001
  3. Medical cannabis and mental health: A guided systematic review. 2016 – PubMed – NCBI
  4. Epidemiological characteristics, safety and efficacy of medical cannabis in the elderly. – PubMed – NCBI
  5. Cannabis-conclusions – 2017 National Academy of Sciences
  6. Cannabis-chapter-highlights – 2017 National Academy of Sciences
  7. Cannabis-report-highlights – 2017 National Academy of Sciences
  8. Clinical Endocannabinoid Deficiency (CECD): Can this Concept Explain Therapeutic Bene ts of Cannabis in Migraine, Fibromyalgia, Irritable Bowel Syndrome and other Treatment-Resistant Conditions?-2004
  9. Marijuana use and the risk of lung and upper aerodigestive tract cancers: results of a population-based case-control study. – PubMed – NCBI
  10. Cannabis use and cognitive function: 8-year trajectory in a young adult cohort. – PubMed – NCBI
  11. Cannabinoids for Medical Use: A Systematic Review and Meta-analysis. – PubMed – NCBI
  12. Cannabinoids and Cytochrome P450 Interactions. – PubMed – NCBI Pharmacogenetics of Cannabinoids – 2018
  13. Systematic review of systematic reviews for medical cannabinoids – 2018
  14. Adverse effects of medical cannabinoids – a systematic review – 2008
  15. Cannabimimetic effects modulated by cholinergic compounds. – PubMed – NCBI
  16. Antagonism of marihuana effects by indomethacin in humans. – PubMed – NCBI
  17. Pharmacokinetics and pharmacodynamics of cannabinoids. – PubMed – NCBI
  18. Clinical Pharmacodynamics of Cannabinoids – 2004
  19. Affinity and Efficacy Studies of Tetrahydrocannabinolic Acid A at Cannabinoid Receptor Types One and Two. – 2017
  20. Quality Control of Traditional Cannabis Tinctures – Pattern, Markers, and Stability – 2016
  21. Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review. – PubMed – NCBI
  22. Pharmacology of Cannabinoids
  23. Current-status-and-future-of-cannabis-research-Clin-Researcher-2015
  24. Medical Marijuana for Treatment of Chronic Pain and Other Medical and Psychiatric Problems – A Clinical Review – 2015

 

Medical Marijuana – Product Evaluation

  1. Labeling Accuracy of Cannabidiol Extracts Sold Online – 2017
  2. Public Health Focus > Warning Letters and Test Results for Cannabidiol-Related Products – 2017
  3. The Cannabinoid Content of Legal Cannabis in Washington State Varies Systematically Across Testing Facilities and Popular Consumer Products – 2018
  4. Quality Control of Traditional Cannabis Tinctures – Pattern, Markers, and Stability – 2016

Emphasis on Education

 

Accurate Clinic promotes patient education as the foundation of it’s medical care. In Dr. Ehlenberger’s integrative approach to patient care, including conventional and complementary and alternative medical (CAM) treatments, he may encourage or provide advice about the use of supplements. However, the specifics of choice of supplement, dosing and duration of treatment should be individualized through discussion with Dr. Ehlenberger. The following information and reference articles are presented to provide the reader with some of the latest research to facilitate evidence-based, informed decisions regarding the use of conventional as well as CAM treatments.

 

For medical-legal reasons, access to these links is limited to patients enrolled in an Accurate Clinic medical program.

 

Should you wish more information regarding any of the subjects listed – or not listed –  here, please contact Dr. Ehlenberger. He has literally thousands of published articles to share on hundreds of topics associated with pain management, weight loss, nutrition, addiction recovery and emergency medicine. It would take years for you to read them, as it did him.

 

For more information, please contact Accurate Clinic.

 

Supplements recommended by Dr. Ehlenberger may be purchased commercially online or at Accurate Clinic.

Please read about our statement regarding the sale of products recommended by Dr. Ehlenberger.

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