Cannabidiol (CBD)

Clinical Use Overview

 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 Vitamin 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.

 

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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.

 

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Cannabidiol (CBD) – Clinical Use Overview

Contrary to popular belief, THC is not the most relevant cannabinoid for medical application, cannabidiol  (CBD) is. CBD was first isolated in 1934 and first synthesized in 1967. While the clinical benefits obtained from marijuana (cannabis) are derived from the many constituents found in the plant, the two cannabinoids, THC (delta-9 tetrahydrocannabinol) and CBD (cannabidiol), together are responsible for the majority of the medical benefits. CBD has the advantage over THC in that it is associated with fewer side effects; notably it lacks the euphoric effect or high that impairs thought processing. Furthermore, CBD is now legally available over-the-counter in Louisiana and offers a new and accessible alternative means of treating a number of symptoms and conditions including chronic pain.

For more information regarding CBD products, See:Cannabidiol (CBD) – Introduction

In a quick overview, current research on CBD suggests it has the potential to be an effective anti-anxiety and antipsychotic drug. It is also considered to be a possibly useful drug for cancer, diabetes, inflammatory and neurodegenerative disorders. CBD is known to have anticonvulsant effects and to be neuroprotective. It is a strong antioxidant and may offer benefit for oxidative stress, the underlying process behind many diseases of aging. CBD has anti-nausea and analgesic effects, possibly reducing the exaggerated and physiologically inappropriate responses to pain frequently found in conditions such as migraine headaches and fibromyalgia.  Furthermore, CBD shows toxicity to breast tumor cells and helps preserve normal cells. Also, CBD shows potent antibacterial effects against methicillin-resistant Staphylococcus aureus (MRSA), the bacteria responsible for many serious infections currently resistant to commonly used antibiotics. Finally, CBD may reduce stroke risk and offer protection against heart attacks.

While the above general benefits are commonly attributed to CBD, quality research is still lacking as to identifying specific benefits associated with specific medical conditions, definitive dosing and which cannabis-based constituent combinations are the most effective.

There is some evidence that CBD may actually interfere with the therapeutic benefits of THC and certain terpenes (see “Chemovars” below).

 

Conditions Potentially Responsive to CBD

FDA-approved

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.

 

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 (Alzheimer’s, Parkinsons Disease and Chronic Traumatic Encephalopathy (CTE) associated with brain trauma), 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 Crohn’s disease and Ulcerative Colitis.

The following is a list of conditions that may respond to CBD:

    1. Pain
    2. Anxiety
    3. Addiction
    4. Dental Disease
    5. Inflammatory Bowel Disease (Crohn’s & Ulcerative Colitis)
    6. Muscle Spasticity (in Multiple Sclerosis)
    7. Neurodegenerative Disorders (Alzheimers & Parkinsons Diseases
    8. Seizures
    9. Traumatic Brain Injury & Chronic Traumatic Encephalopathy

 

Pain

While use of cannabis and various cannabis-based products have been shown to provide pain relief and reduce pain unpleasantness, the effect of CBD alone on acute or chronic pain is still not well understood.  A few animal studies suggest that CBD can be used to control inflammatory and neuropathic pain. In rat models, it has been shown that CBD exerts anti-hyperalgesic effects on neuropathic and inflammatory pain. However, some 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.

 

2018 Review

A 2018 narrative review summarized the literature regarding the use of cannabinoids for the treatment of neuropathic pain. Like THC, cannabidiol has been shown to reduce the pain associated with various neuropathic pain models in pre-clinical animal studies. However, it has been suggested that CBD has a maximal analgesic effect (efficacy) that is oly half of that observed for THC. Unlike THC however, CBD does not produce cannabis-like side effects even at high doses, which suggests that cannabidiol has a very wide therapeutic window, compared to THC which has a therapeutic index of only 5-6. This means that it produces analgesia with a dose 5–6 times lower than that at which it produces side-effects.

It has been noted that some studies show that the analgesic efficacy of CBD improves with chronic treatment. Thus, while CBD offers a potential alternative therapy for pain, to date (2018), there are no major human clinical studies on the effectiveness of CBD for the treatment of (neuropathic) pain.

 

2024 Review

A 2024 study reported significant concerns regarding the disparity between claims made for CBD’s health benefits, predominantly pain, and the research to support the claims. Furthermore, the study also emphasized that potentially harmful chemicals are often included in over the counter CBD products. 

A 2021 International Association for the Study of Pain task force examined the evidence for cannabinoids and pain but found no trials of CBD. The 2024 study noted that sixteen CBD randomized trials using pharmaceutical-supplied CBD with pain as an outcome have been published subsequently. The trials were conducted in 12 different pain states, using 3 oral, topical, and buccal/sublingual administration, with CBD doses between 6 and 1,600 mg, and durations of treatment between a single dose and 12 weeks.

Fifteen of the 16 showed no benefit of CBD over placebo. Small clinical trials using verified CBD suggest the drug to be largely benign; while large-scale evidence of safety is lacking, there is growing evidence linking CBD to increased rates of serious adverse events and hepatotoxicity. In January 2023, the Food and Drug Administration (FDA) announced that a new regulatory pathway for CBD was needed. Consumers and health care providers were advised to rely on evidence-based sources of information on CBD, not just advertisements.

The study concluded that current evidence is that CBD for pain is expensive, ineffective, and possibly harmful,  stating “There is no good reason for thinking that CBD relieves pain, but there are good reasons for doubting the contents of CBD products in terms of CBD content and purity.”

 

Preclinical Study Evaluating Synergy Between Morphine and a CB-2 Agonist

A 2017 preclinical study showed for the first time that morphine and a CB2 agonist, JWH015 (like CBD) interact synergistically to suppress inflammatory, post-operative, and neuropathic pain. Furthermore, the synergy extends to preventing opioid-induced reward behaviors in animals, suggesting that CBD may reduce abuse risk when taken with opioids. Additionally, the combination of morphine with the CB2 agonist reduces constipation associated with morphine. The authors conclude that their data support the use of opioid-CB2 combination therapy in treating chronic pain while limiting abuse liability.

 

Topical CBD for Pain

CBD may be used effectively as a topical salve for pain, including arthritis pain, pain due to peripheral neuropathy and muscle pain related to spasm.

 

Peripheral Neuropathy

There has been an increasing evidence for the benefits of cannabinoids in the treatment of chronic, neuropathic pain.  A 2020 study evaluated the effectiveness of topical cannabidiol (CBD) oil in the management of neuropathic pain associated with peripheral neuropathy. The 29 test subjects with a mean age of 68 year had at least one of the following underlying conditions that caused the peripheral neuropathy: type 1 or type 2 diabetes, alcoholic neuropathy, idiopathic neuropathy, congenital hypomyelinating neuropathy or neuropathy as a result of syphilis or leprosy. Subjects were studied in a four-week, randomized crossover and placebo-controlled trial with treatment including the use of a product containing 250 mg CBD/3 fl. oz.

Results showed a statistically significant reduction in intensity of pain, cold and itchy sensations in the CBD group when compared to the placebo group. The treatment product was well tolerated with no adverse events reported.

Topical CBD Formulations

A 2020 study investigated the topical administration of CBD focusing on different compounds as vehicles to enhance skin permeation. The authors concluded that a hydrophilic gel, mostly consisting of propylene glycol (79%, w/w), can be an optimal choice for the topical administration of CBD.

An interesting 2019 study evaluated a commercial brand of CBD oil (Charlotte’s Web Hemp Extract Oil) blended with cholesterol ointment (20% CBD oil) applied topically to the masseter muscles in patients with TMJ pain. When the compound was applied twice a day for two weeks, patients experienced less pain and measurements indicated less spasm of the masseter muscles.

 

Topical CBD with β-Caryophyllene

β-Caryophyllene, with its anti-inflammatory and analgesic properties, is a synergistic combination that is effective in topical formulations with CBD. Anecdotal evidence demonstrates this topical combination to be useful in managing joint pain associated with different types of arthritis, muscle pain and also peripheral neuropathies of different etiologies. 

 

 

Anxiety

CBD is known to provide excellent benefits for anxiety while it does not produce the mind-altering effects such as euphoria that is associated with THC. In fact, CBD in combination with THC may reduce THC-induced anxiety.

See: Cannabidiol (CBD) – Treatment of Anxiety

 

Addiction

Drug addiction, currently defined as substance use disorders (SUD), are chronic relapsing disorders characterized by a compulsive desire to seek and use drugs or continue behaviors. Additionally, there is impaired control over the substance use or behavior resulting in the persistence of use despite negative consequences.

CBD has potential for treating SUD by improving impaired impulse control and reducing relapse risk by suppressing:

  • Craving induced by drug contexts
  • Susceptibility to stress
  • Anxiety
 
See:Cannabidiol (CBD) – Treatment of Addiction

 

 

Dental Disease

CBD is known to have anti-inflammatory, anti-anxiety, analgesic, anti-microbial and anti-cancer effects that may have therapeutic potential for oral and dental conditions.

 

 

Inflammatory Bowel Disease (IBD) – Crohn’s & Ulcerative Colitis

The inflammatory bowel diseases (IBD) include chronic immune-mediated inflammatory diseases of the intestinal tract, typified by Crohn’s disease (CD) and ulcerative colitis (UC). Their development is complex and involves genetic and environmental factors, among which diet and the intestinal microbiota are common targets for prevention and treatment. Some of the most common symptoms of IBD are abdominal pain, diarrhea, and weight loss. However, one of the major challenges in management of IBD is to reduce and/or reverse the underlying intestinal inflammation characteristic of these diseases.

Enteric Glial Cells (EGC)

Both the acute and chronic inflammation in the gut associated with IBD is related to immune cells called glial cells. The enteric glial cells (EGC) located in the gut are functionally similar to those found in the central and peripheral nervous system. They function to maintain balance in nerve and neurotransmitter activity, providing support and protection for enteric nerve cells. EGC play a fundamental role in the maintenance of gut homeostasis where they are the first defensive line against infection by supplying nutrients and oxygen to aid in the repair of damaged cells.

As with the process of neuroinflammation related to chronic nerve pain (See: Neuropathic Pain) and neurodegenerative brain diseases, EGC may also proliferate and become perpetually activated leading to the chronic inflammation associated with IBD. This is characterized by the ongoing release of multiple pro-inflammatory chemicals as well as stimulating the infiltration of other immune cells such as macrophages, neutrophils and mast cells.

Research indicates that CBD is a potent compound that may suppress enteroglial-mediated inflammation, leading to reduction of intestinal damage associated with acute and chronic intestinal gut inflammation. While the exact mechanisms responsible for the effects of CBD still remain unclear, CBD is  regarded as a promising therapeutic agent in the treatment of inflammatory bowel disorders. Clinical studies are needed to confirm the effectiveness of CBD.
See also:Palmitoylethanolamide (PEA)and NRF2 activators.

Despite extensive pre-clinical evidence, only two studies have assessed the effectiveness of CBD. The only study assessing the efficacy of CBD in Crohn’s Disease (CD) was negative, with no improvement in disease activity as measured by a CD Activity Index (CDAI), as well as several laboratory parameters. Of note, however, the treatment was safe, and the negative results nay have been due to the small number of cases and the very low dose tested (10 mg, orally) as well as the lack of synergism with other cannabinoids. Another study addressed the effects of a CBD-rich botanical extract in Ulcerative Colitis (UC). This study found a lack of benefit and a lack of tolerability of the botanical extract. However, there was a trend toward improved quality of life scores suggesting that the CBD-rich botanical extract may have provided therapeutic benefit to those patients who tolerated it.

A recent meta-analysis that reviewed the evidence of cannabis and CBD on UC and CD was unable to make any definitive conclusions on their safety or effectiveness in IBD. It was concluded that further studies with a larger number of patients, different doses and routes of administration are still necessary and the use of CBD and other phytocannabinoids should be considered for clinical studies.

 

 

Neurodegenerative Disorders

Alzheimer Dementia (AD)

Alzheimer’s dementia (AD) is a type of dementia in which deposits of “senile” plaques form in the brain. These plaques consist of a neurotoxic substance called beta-amyloid peptide (Aβ) and they contribute to inflammation and oxidative stress, both crucial components of AD. Microglia are immune cells found in the nervous system that when activated under certain condions produce pro-inflammatory chemicals (cytokines ) that increase Aβ production by nerve cells.

The role of Aβ in inflicting nerve damage and neuroinflammation in AD is well established. Numerous studies exploring CBD in neurotoxicity have shown CBD to exhibit beneficial effects against the neuroinflammation and damaging action induced by Aβ due to CBD’s combination of antioxidant and anti-inflammatory properties, mechanisms not shared by classic antioxidant drugs. CBD exhibits beneficial effects in animal models of neuroinflammation by reducing mictoglia activation and their production of pro-inflammatory compounds.

 

Parkinson’s Disease (PD)

Parkinson’s disease (PD) is a motor neurodegenerative disorder, in which the main feature is a progressive death of dopaminergic neurons, resulting in slowing of movement (bradykinesia), rigidity and tremor. There is substantial growing evidence for a role for CBD as a potential pharmacological approach to PD. Animal studies have been encouraging but only a few small trials have been conducted on Parkinson’s disease patients.

 

Traumatic Brain Injury (TBI) & Chronic Traumatic Encephalopathy (CTE)

Traumatic brain injury (TBI) is a growing health concern that affects millions of individuals. TBI can lead to a debilitating condition called Chronic Traumatic Encephalopathy (CTE), a neurodegenerative disease thought to be associated with a history of repetitive head impacts, such as those sustained through contact sports or military combat. CTE develops symptoms slowly, often developing over years, and is often unrecognized and undiagnosed. 

Like AD, CTE is associated with abnormal development of beta-amyloid peptide (Aβ) and also a protein called “tau” which are believed to underly the functional brain impairment associated with the condition. Encouraging research regarding CBD and another agent, palmitoylethanolamide (PEA), indicates they work synergistally in protecting against the development of CTE.

See also:Traumatic Brain Injury (TBI),Palmitoylethanolamide (PEA)and NRF2 activators.

 

So far, no treatment has been shown to cure AD, PD or CTE and no treatment has been FDA-approved to slow or reverse the neurodegenerative processes of these diseases. While it is much too early to make therapeutic claims for CBD in these conditions, given the benefits of CBD as an anti-inflammatory, neuroprotective, immune-modulating agent and considering its safety record, CBD represents an attractive  potential therapeutic alternative for these patients.

 

 

Weight Loss

CBD is not an appetite stimulant like THC and is has been reported to promote weight loss and decrease the appetite stimulating effect of THC.  CBD may facilitate the conversion of white fat cells to brown fat cells, which are considered to be healthier, non-inflammatory fat. 


 

Anti-Diabetic

CBD also shows increased anti-diabetic properties. This may be in part due to its ability to convert white fat cells to healthier brown fat cells. CBD was shown to significantly lower the incidence of diabetes in pre-clinical trials. CBD has the unique ability to protect the heart from diabetic cardiomyopathy  

 

What can be learned about constituent combinations from studies of chemovars

Preliminary research into predicting therapeutic benefits based on chemovars has provided some insights although reports are often inconsistent. A 2023 study was directed at indexing Cannabis flower strains based on the plant’s primary and secondary terpene concentrations and absolute THC and CBD potency levels in context of patient symptom relief for chronic pain, depression, and anxiety.

Of the five most frequent chemovars identified in the study, four of the five  chemovars containing myrcene as the primary or secondary terpene, all the chemovars had THC levels that ranged between 15 and 25%, and all but one had less than 1% CBD.

Significant group differences in symptom relief were found across the chemovars as well as for patients treating only pain and for patients treating anxiety or depression. The chemovars with slightly higher-than-average levels (between 0.50 and 1.0%) of myrcene and terpinolene and no CBD appeared to be associated with reliably stronger therapeutic effects and the least likelihood of experiencing negative side effects.

 

Apparent anti-therapeutic effect of CBD

Chemovars with the lowest terpene levels and any detectable amounts of CBD were associated with the least likelihood of experiencing positive benefits and the greatest likelihood of experiencing negative side effects. Additionally, chemovars with any identifiable amounts of CBD provided less symptom relief than those without CBD. This appears to contradict common reports of CBD providing synergistic benefits when accompanying THC both in enhanced benefits and reduced side effects such as anxiety.

 

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
  4. A systematic review of cannabidiol dosing in clinical populations – 2019
  5. Applications of Cannabis Sativa L. in Food and Its Therapeutic Potential – From a Prohibited Drug to a Nutritional Supplement – 2021
  6. Cannabidiol (CBD) Products for Pain Ineffective, Expensive, and With Potential Harms – PubMed 2024
  7. Health Claims About Cannabidiol Products- A Retrospective Analysis of U.S. Food and Drug Administration Warning Letters from 2015 to 2019 – 2021

 

 

CBD – Addiction

  1. Cannabidiol as an Intervention for Addictive Behaviors – A Systematic Review of the Evidence -2015
  2. Unique treatment potential of cannabidiol for the prevention of relapse to drug use – preclinical proof of principle – 2018
  3. Pharmacokinetics, efficacy, and safety of cannabidiol in dogs an update of current knowledge – 2023
  4. Effect of Pharmacological Modulation of the Endocannabinoid System on Opiate Withdrawal: A Review of the Preclinical Animal Literature – 2016

CBD – Animals

  1. Pharmacokinetics, efficacy, and safety of cannabidiol in dogs an update of current knowledge – 2023

 

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
  11. Beyond the CB1 Receptor – Is Cannabidiol the Answer for Disorders of Motivation? – 2016
  12. Cannabis Therapeutics and the Future of Neurology – 2018
  13. Cannabidiol in Anxiety and Sleep – A Large Case Series – 2019
  14. Cannabidiol modulates serotonergic transmission and reverses both allodynia and anxiety-like behavior in a model of neuropathic pain – 2019
  15. A systematic review of cannabidiol dosing in clinical populations – 2019
  16. Medicinal cannabis for psychiatric disorders – a clinically-focused systematic review – 2020
  17. THC, CBD, and Anxiety- A review of recent findings on the anxiolytic and anxiogenic effects of cannabis’ primary cannabinoids – 2022

 

CBD – Dental

  1. The Current and Potential Application of Medicinal Cannabis Products in Dentistry – 2021

 

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. Impact of cannabidiol on the acute memory and psychotomimetic effects of smoked cannabis – 2010

 

 

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

 

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
  6. Synergistic attenuation of chronic pain using mu opioid and cannabinoid receptor 2 agonists – 2017
  7. Effects of Cannabidiol and a Novel Cannabidiol Analog against Tactile Allodynia in a Murine Model of Cisplatin-Induced Neuropathy – Enhanced Effects of Sub-Analgesic Doses of Morphine – 2018
  8. Plant-Based Cannabinoids for the Treatment of Chronic Neuropathic Pain – 2018
  9. The Effectiveness of Topical Cannabidiol Oil in Symptomatic Relief of Peripheral Neuropathy of the Lower Extremities – 2020
  10. Cannabidiol (CBD) Products for Pain Ineffective, Expensive, and With Potential Harms – PubMed 2024

 

CBD – PEA (Palmitoylethanolamide)

  1. The Endocannabinoid System and PPARs – Focus on Their Signalling Crosstalk, Action and Transcriptional Regulation – 2021
  2. The Current and Potential Application of Medicinal Cannabis Products in Dentistry – 2021
  3. The Therapeutic Potential of Cannabis in Counteracting Oxidative Stress and Inflammation – 2021
  4. Cannabis and Canabidinoids on the Inflammatory Bowel Diseases – Going Beyond Misuse – 2020
  5. Endocannabinoid System and Its Regulation by Polyunsaturated Fatty Acids and Full Spectrum Hemp Oils – 2021
  6. CB2 Receptor in Microglia – The Guardian of Self-Control – 2021
  7. Therapeutic Potential of Cannabidiol (CBD) for Skin Health and Disorders – 2020
  8. Mast cell–glia axis in neuroinflammation and therapeutic potential of the anandamide congener palmitoylethanolamide – 2012
  9. The Role of the Brain’s Endocannabinoid System in Pain and Its Modulation by Stress – 2015
  10. Cannabinoid‐based therapy as a future for joint degeneration. Focus on the role of CB2 receptor in the arthritis progression and pain – an updated review – 2021
  11. Manipulation of the endocannabinoid system in colitis – A comprehensive review – 2017
  12. Fibromyalgia – Recent Advances in Diagnosis, Classification, Pharmacotherapy and Alternative Remedies – 2020
  13. Cannabinoid Receptor-2 Ameliorates Inflammation in Murine Model of Crohn’s Disease – 2017
  14. Cannabinoids for treating inflammatory bowel diseases – where are we and where do we go? – 2017
  15. Relevance of Peroxisome Proliferator Activated Receptors in Multitarget Paradigm Associated with theEndocannabinoid System – 2021
  16. Palmitoylethanolamide and Cannabidiol Prevent Inflammation- induced Hyperpermeability of the Human Gut In Vitro and In Vivo—A Randomized, Placebo-controlled, Double-blind Controlled Trial. – 2018
  17. Synergistic attenuation of chronic pain using mu opioid and cannabinoid receptor 2 agonists – 2016
  18. Short-term efficacy of a fixed association of Palmitoylethanolamide and other phytochemicals as add-on therapy in the management of chronic pain in elderly patients – 2018
  19. Efficacy of a Combination of N-Palmitoylethanolamide, Beta-Caryophyllene, Carnosic Acid, and Myrrh Extract on Chronic Neuropathic Pain – A Preclinical Study – 2019
  20. Cannabimimetic phytochemicals in the diet – an evolutionary link to food selection and metabolic stress adaptation? – 2016
  21. Fatty Acid Amide Hydrolase – an overview | ScienceDirect Topics – 2009
  22. The Endogenous Cannabinoid System – A Budding Source of Targets for Treating Inflammatory and Neuropathic Pain- 2018
  23. Cannabis sativa L. as a Natural Drug Meeting the Criteria of a Multitarget Approach to Treatment – 2021
  24. The ‘Entourage Effect’- How THC can team up with PEA to treat symptoms of Tourette syndrome – 2017
  25. A novel composite formulation of palmitoylethanolamide and quercetin decreases inflammation and relieves pain in inflammatory and osteoarthritic pain models – 2013
  26. Effect of Ultra-Micronized-Palmitoylethanolamide and Acetyl-l-Carnitine on Experimental Model of Inflammatory Pain – 2021
  27. Palmitoylethanolamide and hemp oil extract exert synergistic anti-nociceptive effects in mouse models of acute and chronic pain – PubMed 2021

 

CBD – Topical

  1. Transdermal cannabidiol reduces inflammation and pain-related behaviours in a rat model of arthritis – 2015
  2. Myorelaxant Effect of Transdermal Cannabidiol Application in Patients with TMD – A Randomized, Double-Blind Trial – 2019
  3. The Cannabinoids Δ8THC, CBD, and HU-308 Act via Distinct Receptors to Reduce Corneal Pain and Inflammation – 2018
  4. Therapeutic Potential of Cannabidiol (CBD) for Skin Health and Disorders – 2020
  5. Topical Administration of Cannabidiol – Influence of Vehicle-Related Aspects on Skin Permeation Process – 2020
  6. The Effectiveness of Topical Cannabidiol Oil in Symptomatic Relief of Peripheral Neuropathy of the Lower Extremities – 2020
  7. The Skin and Natural Cannabinoids–Topical and Transdermal Applications – 2023
  8. Topical cannabidiol (CBD) in skin pathology – A comprehensive review and prospects for new therapeutic opportunities – 2022

  

 

CBD – Pharmacokinetics

  1. Human Cannabinoid Pharmacokinetics – 2007
  2. A tale of two cannabinoids: the therapeutic rationale for combining tetrahydrocannabinol and cannabidiol. – PubMed – NCBI
  3. Human Metabolites of Cannabidiol – A Review on Their Formation, Biological Activity, and Relevance in Therapy 2016
  4.  A Comprehensive Review on Pharmacotherapeutics of Herbal Bioenhancers – 2012
  5. The effects of black pepper on the intestinal absorption and hepatic metabolism of drugs. – PubMed – NCBI – 2011
  6. Piperine-pro-nanolipospheres as a novel oral delivery system of cannabinoids: Pharmacokinetic evaluation in healthy volunteers in comparison to buc… – PubMed – NCBI – 2017
  7. A Systematic Review on the Pharmacokinetics of Cannabidiol in Humans

 

CBD – Inflammatory Bowel Disease

  1. Cannabidiol Reduces Intestinal Inflammation through the Control of Neuroimmune Axis – 2011
  2. Cannabidiol and Other Non-Psychoactive Cannabinoids for Prevention and Treatment of Gastrointestinal Disorders – Useful Nutraceuticals? – 2020
  3. Manipulation of the endocannabinoid system in colitis – A comprehensive review – 2017
  4. Cannabinoids and Inflammations of the Gut-Lung-Skin Barrier – 2021

  

CBD – Neurologic Disorders: Overviews

  1. Molecular Targets of Cannabidiol in Neurological Disorders – 2015

 

CBD – Neurodegenerative Disorders: Traumatic Brain Injury and CTE

  1. Molecular Targets of Cannabidiol in Neurological Disorders – 2015
  2. Endocannabinoids and traumatic brain injury – 2011
  3. Endocannabinoids – A Promising Impact for Traumatic Brain Injury. – 2017
  4. Natural cannabinoids improve dopamine neurotransmission and tau and amyloid pathology in a mouse model of tauopathy. – PubMed – NCBI
  5. Preventive Effects of Resveratrol on Endocannabinoid System and Synaptic Protein Modifications in Rat Cerebral Cortex Challenged by Bilateral Common Carotid Artery Occlusion and Reperfusion – 2018
  6. Cannabidiol Reduces Aβ-Induced Neuroinflammation and Promotes Hippocampal Neurogenesis through PPARγ Involvement – 2011
  7. Critical role of mast cells and peroxisome proliferator-activated receptor gamma (PPARγ) in the induction of myeloid-derived suppressor cells by marijuana cannabidiol in vivo – 2015
  8. Endocannabinoid Degradation Inhibition Improves Neurobehavioral Function, Blood–Brain Barrier Integrity, and Neuroinflammation following Mild Traumatic Brain Injury – 2015
  9. Palmitoylethanolamide Reduces Neuropsychiatric Behaviors by Restoring Cortical Electrophysiological Activity in a Mouse Model of Mild Traumatic Brain Injury – 2017
  10. Cannabidiol for neurodegenerative disorders – important new clinical applications for this phytocannabinoid? – 2013
  11. Modulation of Astrocyte Activity by Cannabidiol, a Nonpsychoactive Cannabinoid – 2017

 

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 recommendations – Canadian 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
  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. Cannabidiol enhances morphine antinociception, diminishes NMDA-mediated seizures and reduces stroke damage via the sigma 1 receptor – 2018

 

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
  25. Cannabis sativa L. as a Natural Drug Meeting the Criteria of a Multitarget Approach to Treatment – 2021

 

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.

Accurate Supplement Prices

 

 

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