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

Cannabidiol (CBD)


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 prevalent 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. 



Marijuana – Legislative Update for Louisiana

Marijuana – Medical Use Overview

“Medical Marijuana” – Getting Started

Cannabis-Based Medications:

Over-the-Counter Cannabinoid Medications:

Marijuana – Cannabidiol (CBD)


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 – Fibromyalgia

Cannabis – Headaches (coming soon)

Cannabis – Inflammatory Bowel Disease (coming soon)

Cannabis – Neuroinflammation (coming soon)

Cannabis – Pain (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)


Marijuana – Cannabidiol (CBD)


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)

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, however, it has been reported that 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.”


Types of CBD Oil Products

There are three basic types of CBD oil products:  Full Spectrum, Broad Spectrum and Isolate. They differ in how the CBD oil is extracted from cannabis and the presence of other constituents. Sometimes products are  as “Whole Plant,” “Derived from Aerial Plant Parts” (including all plant parts above ground) or “Pure CBD.” These are the differences:


Full Spectrum CBD Oil

“Full Spectrum” generally refers to CBD oil products that are extracted from the cannabis plant and not only contain CBD, but also contain some terpenes and other cannabinoids such as CBG, CBN and even some THC. The concentration and ratios will vary based on the plant and specific strain. Sometimes individual constituents 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%), they can still trigger positive urine drug tests.


The possibe advantage of Full Spectrum CBD oil products is due to the “Entourage Effect,” in which the other cannabinoids and terpenes work together in synergy, providing additional therapeutic benefits that the CBD alone. See below for more information regarding the Entourage Effect.


Broad Spectrum CBD Oil

“Broad Spectrum” CBD oil products typically contain cannabinoids and terpenes like “Full Spectrum products but they have zero THC as established by the manufacturer’s lab testing. Third party lab reports should be readily available from reputable companies which identify which cannabinoids and terpenes are in the product and at what levels.


Broad Spectrum products generally go through additional processing to remove as much THC as possible while still maintaining the other cannabinoids and terpenes. In some cases additional cannabinoids and terpenes are added in.


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 ant isolate, it is important to verify the purity. Beware of disreputable sources and avoid purchasing from gas stations. As noted above, due to the absence of other potentially pharmacologically acitve cannabis constituents, CBD isolates may be less effective.


There are also products out there called terpsolates, wheere the CBD oil is infused with terpenes to enhance their scent and possible enhance their effects.


CBD – Therapeutic Benefits

The clinical benefits from marijuana are derived from the many constituents found in the plant, including more than 100 pharmacologically active cannabinoids. In addition to the  cannabinoids, there are eighteen different classes of chemicals, including nitrogenous compounds, amino acids, hydrocarbons, carbohydrates, terpenes (and related terpenoids), and fatty acids, that contribute to the known pharmacological and toxicological properties of cannabis.. The two best understood and most common of these cannabinoids are THC (tetrahydrocannabinol) and CBD (cannabidiol). There is very limited scientific information on the pharmacology and toxicology of the other cannabinoids and pharmacologially active constituents found in cannabis.


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 final effects. There is a wide range of differences in both the number, amounts and ratios of different constituents in different cannabis plants.


The strength and ratio of the two major cannabinoids, THC and CBD, plays a large, possibly dominating, role in the clinical effects of marijuana. 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.


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 if the THC–CBD combination.


In addition to cannabinoids there are many other pharmacologically active chemical constituents such as terpenes believed to impact clinic effects of marijuana and to be included in the entourage effext.


Four basic mechanisms of synergy have been proposed: (i) multi-target effects; (ii) pharmacokinetic effects such as improved solubility or bioavailability; (iii) agent interactions affecting bacterial resistance; and (iv) modulation of adverse events.


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 mimic the effects of marijuana while it may nevertheless offer its own specific therapeutic benefits. As a brief overview, the following clinical effects are associated with THC and CBD:


THC (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.


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.



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.


CBD – Potential Conditions Responsive to CBD

Because CBD has become commonly available in pure, THC-free formulations, it is important to evaluate what therapeutic benefits may be obtained with its use. The FDA did, however, recently approve one pharmaceutical prescription form of cannabis plant-derived CBD, an oral solution called Epidiolex. It is FDA-approved for the treatment of certain rare pediatric epilepsy conditions (see: Epidiolex, below). Aside from these pediatric epiplepsy conditions, specific definitive therapeutic benefits of CBD still lack good quality scientific evidence. The following is a list of conditions that may respond to CBD:


  1. Anxiety
  2. Pain
  3. Muscle Spasticity in Multiple Sclerosisi
  4. Seizures (see Epidiolex, below)



The first human study of CBD’s anxiolytic effects was published in 1982 when it was identified that the increased anxiety that followed the use of THC was significantly reduced with the simultaneous use of CBD. Since then a number of publications support the belief that CBD reduces the side effect of anxiety that is associated with the use of THC. A review article published in 2012 looked at the animal and human volunteer-based literature published in English, Portuguese and Spanish that included review articles and book chapters identified an anxiolytic-like effect of CBD. In most of these studies an oral dose of CBD between 300-600 mg was employed. It has been reported that CBD is safe and well- tolerated in doses up to 1,500 mg/day.


Social Anxiety Disorder (SAD)

Early evidence came from the investigation of CBD in experimentally induced anxiety in healthy volunteers using a model of simulated public speaking (SPS). Self-rated scales and physiological measures of anxiety (heart rate, blood pressure, sweating) after a 300mg dose of CBD revealed the effectiveness of CBD. The SPS test is a good model of anxiety for assessing social anxiety disorder (SAD), because the fear of speaking in public is considered a central feature in SAD. CBD has been shown to reduce anxiety in patients with social anxiety disorder. A small study published in 2011 using a dose of 600mg CBD in patients with SAD revealed CBD to be helpful in reducing anxiety.


Panic Disorder

A 2017 publication presented CBD as a promising drug for the treatment of panic disorder. However, they noted that additional research is clearly needed to clarify the specific mechanism of action of CBD and identify the ideal safe therapeutic doses.


Post-Traumatic Stress Disorder (PTSD)

Experimental evidence supports the benefit of cannabis and of CBD for PTSD. CBD helps to regulate the negative emotional memory associated with PTSD by reducing fear-associated memory acquisition. CBD also stops anxiety-induced REM sleep suppression, although it has little effect on the alteration of NREM sleep, possibly due to its anxiolytic effect, rather than through a direct regulation of sleep mechanisms. This is significant in PTSD patients who often complain of having sleep disturbances, including nightmares (associated with REM) and insomnia.



CBD Mechanism of Action in Anxiety

While the mechanism by which CBD may reduce anxiety is not clear, there is strong evidence that the serotonergic system is involved in the anxiolytic action of CBD. 5-HT1A is a member of the family of 5-HT receptors, which are activated by the neurotransmitter serotonin. Found in both the central and peripheral nervous systems, 5-HT receptors trigger various intracellular cascades of chemical messages to produce either an excitatory or inhibitory response, depending on the chemical context of the message. At high concentrations, CBD directly activates the 5-HT1A (hydroxytryptamine) serotonin receptor, which confers an anti-anxiety effect. This G-coupled protein receptor is implicated in a range of biological and neurological processes, including  anxiety, addiction, appetite, sleep, pain perception, nausea and vomiting.

The serotonergic system in the brain is the site of action of the prominent classes of anxiolytic medications, the Selective Serotonin Reuptake Inhibitors (SSRIs – Prozac, Paxil, Zoloft, Celexa etc.) and the Serotonin Norepinephrine Reuptake Inhibitors (SNRIs – Cymbalta and Effexor). It is likely that CBD also acts on the endocannabinoid system by direct or indirect stimulation of cannabinoid receptors in ways that effect emotion and emotional memory.


CBD also acts as a “positive allosteric modulator” of the GABA-A receptor. An allosteric modulator is an agent that modulates, or changes, the shape of a receptor. A “negative” modulator changes the shape in such a way as to weaken or reduce the ability of the receptor to interact with another molecule, whereas a “positive” modulator changes the shape in such a was as to enhance the ability of the receptor to interact with another molecule. In other words, CBD interacts with the GABA-A receptor in a way that enhances the receptor’s binding affinity for its principal endogenous agonist, gamma-Aminobutyric acid  (GABA), which is the main inhibitory neurotransmitter in the central nervous system. The sedating effects of Valium, Xanaz and other benzodiazepines are mediated by GABA receptor transmission. CBD reduces anxiety by changing the shape of the GABA-A receptor in a way that amplifies the natural calming effect of GABA.



Research shows that CBD may have analgesic effects but the explanation of how it does is not yet clear. Studies show that cannabinoid benefits for pain are only marginally superior to placebo in terms of effectiveness but actually inferior to placebo in terms of tolerability/side effects.


Other Possible Therapeutic Benefits

There are many conditions for which CBD has been suggested to be effective, consistent with CBD’s neuroprotective, antiepileptic, hypoxia-ischemia, anxiolytic, antipsychotic, analgesic, anti-inflammatory, anti-asthmatic, and antitumor properties. Some of these conditions include inflammatory and neurodegenerative diseases (Alzheimers, Parkinsons Disease), epilepsy, autoimmune disorders like multiple sclerosis, arthritis, schizophrenia and cancer. The reduction of intestinal inflammation through the control of the neuroimmune axis suggests CBD may be a promising drug for the therapy of inflammatory bowel disease, especially Chrohn’s disease.


Another mechanism of neuro-protection provided by CBD is the up-regulation of the mRNA levels for Cu–Zn superoxide dismutase, an important enzyme in endogenous defenses against oxidative stress and mitochondrial dysfunction.


One possible therapeutic application for CBD is to treat drug addiction. A recent systematic review concluded that a limited number of preclinical studies suggest that CBD may have therapeutic properties on opioid, cocaine, and psychostimulant addiction, and that it may be beneficial in cannabis and tobacco addiction. However, considerably more research is required to evaluate CBD as a potential treatment.


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 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 (maybe 10mg at the most), depending on the product and method of use. A typical starting CBD dose for most people would be a total of 12 mg of CBD a 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.


Bioavailability and Tissue Distribution of CBD

Oral bioavailability of CBD is estimated to be only 6-19% due to significant first-pass metabolism in the liver. Aerosolized CBD provides rapid high peak plasma concentrations in 5–10 minutes with higher bioavailability than oral use. Like THC, CBD is rapidly distributed into tissues with a high volume of distribution CBD and preferentially accumulates in adipose (fat) tissues due to its high lipophilicity.


Metabolism of CBD

CBD is extensively metabolised in the liver, primarily to 7-OH-CBD which is then metabolised further into as many as 100 metabolites that are excreted in feces and urine. Seven CYP enzymes have been identified as metabolising CBD: CYP1A1, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5, but the two main ones are CYP3A4 and CYP2C19.


Although research is lacking, the metabolites formed from CBD are believed to be present in the body at pharmacologically significant concentrations. Pharmacological studies of CBD metabolites are scarce but suggest biological activities not directly related to CB receptors. The question has been asked if any of the pharmacological effects observed with CBD may be attributed to its metabolites.


CBD Drug-Metabolic Interactions

The major cannabanoids, THC and CBD are both metabolized in the liver by the CYP450 enzymes 2C19 and 3A4. Drugs that inhibit these enzymes may enhance or prolong the effects of THC and CBD. Whether people with genetic variants of these enzymes may experience altered effects from cannabinoids is not known. In a study with healthy male subjects, potential drug–drug interactions of THC/CBD oro-mucosal spray (Sativex, nabiximols) in combination of CYP450 inducers and inhibitors were assessed using various dose regimens. The antibiotic rifampicin, an inducer of CYP3A4, significantly reduced the peak plasma concentration of CBD, while the antifungal ketoconazole, a CYP3A4 inhibitor, nearly doubled the peak plasma concentration of CBD.  However, the moderate CYP2C19 inhibitor omeprazole (Prilosec), a proton-pump inhibitor used to treat gastroesophageal reflux disease (GERD), did not significantly alter the pharmacokinetics of CBD.


CBD has been identified as a potent inhibitor of CYP2D6 which may have significant impact on the metabolism of medications that are broken down by CYP2D6, including hydrocodone (Norc0, Vicodin, Zohydro, Hysingla). As such, use of CBD especially at high doses with tramadol, codeine or hydrocodone may significantly reduce the analgesic effectiveness of these opioids.


Cannabidiol – Prescription CBD Products


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.


Cannabidiol – Commercial CBD Products

Quality Control

The quality of over-the-counter (OTC) CBD oil available on the market and over the internet varies and may not be as advertised and many are not THC-free. ( See: News Item March 2018). One study found that 70% of products did not contain what their labels indicated. It is best to buy from reputable businesses and gas stations are probably not to be recommended. There is no governmental oversight or regulation to oversee the quality of production of CBD products to assure the consumer regarding the product’s actual content.


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.


Cannabis Source of CBD

 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). Furthermore, since the extraction is low in total cannabinoid content and likely low in terpenes as well, this extraction does not provide for the “Entourage Effect” in which the therapeutic benefit of CBD is believed to be enhanced by the presence of other plant-based cannabinoids and terpenes (see Terpenes).


Therefore, the legal OTC CBD oil that lacks the potential benefit of the Entourage Effect may be less effective than a CBD product legally obtained as “medical marijuana,” prescribed by a licensed physician in LA and obtained from one of the nine pharmacies located in the state licensed for distribution of medical marijuana products.


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



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.


Cannabinoid Drug Interactions

Cannabinoids and Opioids

There appears to be a synergistic analgesic (pain-relieving) benefit when cannabinoids are added to opioid treatment for pain in which there is a greater-than-additive benefical effect with the addition of cannabinoids. Studies indicate a trend towards reduced use of opioids when patients taking opioids add cannabinoids to their regimen. It is not uncommon for patients started on cannabinoids to be able to taper off opioids.


Interestingly, animal studies suggest that cannabinoids may reduce the development of tolerance to the analgesic benefits of opioids, resulting in less need for opioid dose escalation.


There is no enhancement of cardiorespiratory suppression from opioids with the addition of cannabinoids due to the very low density of cannabinoid (CB) receptors in brainstem cardiorespiratory centers. There does not appear to be any significant interactions with opioids regarding a cannabinoid effect on the metabolism of most opioids. However, there is research showing that CBD may inhibit CYP2D6, one of the liver enzymes responsible for metabolizing tramadol and codeine. Because the analgesic benefits from tramadol and codeine come from their active metabolites resulting from CYP2D6 metabolism, these two opioids may be less effective if taken with CBD.


Another way in which medications may interact with one another is throught their effect on drug transport systems, especially the P-glycoprotein (P- gp) system. The Pgp transporters transport medications and metabolites out of the central nervous system and brain through the blood-brain barrier into the blood. The activity of Pgp transporters can significantly impact the effect of drugs such as morphine on the brain by reducing their levels in the brain. Early findings indicate that CBD significantly inhibits P-gp-mediated drug transport, suggesting CBD could potentially increase brain levels of morphine and other opioids that are P-gp substrates thus enhancing their impact. CBD may also influence the absorption and disposition of other coadministered compounds that are P-gp substrates.


Alcohol and Benzodiazepines

The combination of cannabinoids with alcohol and benzodiazepines may increase sedation and cognitive impairment.


NSAIDS (Non-Steroid Anti-inflammatory Drugs)

NSAIDs such as ibuprofen and naproxen, particularly indomethacin, can partially antagonize the effects of THC.


 Anticholinergic drugs (Tricyclic antidepressants (TCAs) and some muslce relatxers)

Medications with anticholinergic activity such as amitriptyline (Elavil) and doxepin, and muscle relaxers such as cyclobenzaprine (Flexeril) may increase the psychoactive side effccts of cannabinoids.


Pharmacodynamics of CBD

There are two main cannabinoid (CB) receptors, CB1 which is primarily located in the central nervous system with small amounts found in peripheral tissues and CB2 receptors, which are found mostly in the periphery,  with low amounts in the central nervous system.CB2 receptors are primarily found on cells and organs associated with the immune system and in the gastrointestinal tract.


CBD may modulate but does not seem to act directly at CB1 receptors, whereas THC does primarily act on the CB1 receptor. In the presence of THC, CBD is able to antagonize CB1 receptors because CBD is an inverse agonist at the CB2 receptor (with low affinity), which may be why CBD  has anti-inflammatory effects. CB2 inverse agonism can block migration of immune cells and thereby decrease inflammation.


Other mechanisms of CBD’s activity are not clearly understood. CBD may also interact with the endocannabinoid system through indirect mechanisms such as acting on the endogenous cannabinoid, anandamide, by blocking anandamide reuptake and the inhibition of its breakdown thus increasing anandamide effects.


CBD also behaves as an agonist of the TRPV1 (transient potential vanilloid receptor, type 1), suggesting another mechanism for its action against nerve pain similar to capsaicin, but without noxious effects. In addition, CBD binds as an agonist to the serotonin receptor 5-HT1A  which may contribute to CBD’s benefit for anxiety. Also, another mechanism of neuroprotection provided by CBD is the up-regulation of the mRNA levels for Cu–Zn superoxide dismutase, an important enzyme in endogenous defenses against oxidative stress.



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:





Epidiolex (cannabidiol)

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

Marinol (dronabinol)

  1. Marinol – dronabinol



Medical Marijuana – Federal Law

  1. The legal status of cannabis (marijuana) and cannabidiol (CBD) under U.S. law – 2017

Medical Marijuana – Louisiana Law

  1. Louisiana-2016-SB180-Chaptered
  2. HOUSE BILL NO. 225 – 2017 Regular Session
  3. Louisiana medical marijuana expansion bill signed into law – May 20, 2016
  4. Now in Effect, Louisiana Medical Marijuana Law Shields Patients and Caregivers from Prosecution – Aug 5, 2016
  5. Louisiana-2016-SB180-Chaptered

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


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


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



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


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

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. The Cannabinoid Content of Legal Cannabis in Washington State Varies Systematically Across Testing Facilities and Popular Consumer Products – 2018
  2. 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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