Accurate Education: Cannabidiol (CBD) – Drug Actions & Interactions

Cannabidiol (CBD) – Drug Actions & Interactions

Pharmacokinetics & Pharmacodynamics

 

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) has promise for many medical applications although they are not yet well defined nor are the mechanisms by which it works well understood.

 

This page is still incomplete and still being worked on for accuracy and completeness.

  

See:

Marijuana – Legislative Update for Louisiana

Medical Marijuana Use – Overview

“Medical Marijuana” – Getting Started

Marijuana vs Hemp

 

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:

CBD (Cannabidiol) – Introduction

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

 

Terpenes:

Terpenes – An Overview (coming soon)

    

Cannabimimetics:

Palmitoylethanolamide (PEA)

 

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 – Pharmacokinetics & Pharmacodynamics

Cannabidiol (CBD) – Pharmacokinetics & Pharmacodynamics

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 pharmacological effects observed with CBD may be attributed at least in part to its metabolites.

 

CBD: 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 down or 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 through their effect on drug transport systems, especially the P-glycoprotein (P- gp) system. The P-gp transporters transport medications and metabolites out of the central nervous system and brain through the blood-brain barrier into the blood. The activity of P-gp transporters can significantly impact the effect of drugs such as morphine, oxycodone and methaone 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.

See: Cannabinoids and Opioids

Smoking – Tobacco and Marijuana

Smoking marijuana and tobacco both induce CYP 1A2 through activation of the aromatic hydrocarbon receptors, and this effect between the two products is additive. As a result of this CYP 1A2 enzyme being induced, in other words more CYP 1A2 enzyme is manufactured, medications that are metabolized by CYP 1A2 will be broken down faster, blood levels will be decreased and the therapeutic effects of the drug will be reduced. CYP 1A2 is the enzyme responsible for metabolizing such drugs as caffeine, tizanidine (Zanaflex), duloxetine (Cymbalta), methadone, olanzapine (Zyprexa) and melatonin.

When one suddenly stops smoking either tobacco, marijuana or both, the induction effect is quickly reversed and the levels of CYP 1A2 enzyme rapidly return to previous levels (downregulation) over a few days. When this occurs in an individual chronically taking one of the medications metabolized by CYP 1A2, the blood levels of this medication may quickly rise leading to the potential for increased side effects and toxicity from the medication.

 

This is especially significant in medications that have a narrow therapeutic index such as tizanidine (Zanaflex), in which even small increases in blood levels may be associated with increased side effects. It is therefore important to reduce doses of these medications in the first few days after suddenly stopping smoking either tobacco, marijuana or both to avoid possible toxicity from the medication. Due to body size and gender-related variables, this reduction is especially warranted in small females.

While the CYP 1A2 enzyme is not a major enzyme in the metabolism of methadone, it has been reported that methadone levels can dangerously increase with smoking cessation. As a rule of thumb, it has been recommended that a stepwise daily methadone dose reduction of approximately 10% be engaged until the fourth day after smoking cessation.

 

Alcohol and Benzodiazepines

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

 

NSAIDS (Non-Steroid Anti-inflammatory Drugs)

It has been reported that NSAIDs such as ibuprofen and naproxen, particularly indomethacin, can partially antagonize the effects of THC, although the mechanism responsible is not fully understood.

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.

 

 

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 one study, potential drug–drug interactions of THC/CBD oro-mucosal spray (Sativex, nabiximols) in combination with 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.

Limited evidence also suggests that CBD may significantly inhibit CYP2C19, the enzyme  responsible for metabolizing many medications including:

  1. Anticoagulants such as clopidogrel (Plavix),
  2. Tricyclic antidepressants such as amitriptyline (Elavil)
  3. SSRI antidepressants including citalopram Celexa) and escitalopram (Lexapro)
  4. Proton pump inhibitors such as omeprazole (Prilosec) and pantoprazole (Protonix)
  5. Other drugs including indomethacin (Indocin), diazepam (Valium) and propranolol (Inderal).

 

As a result this may lead to elevated blood levels of these medications and their associated side effects.

 

CBD: Mechanism of Action

Pain

Scientific evidence shows that CBD has analgesic benefits for inflammatory and neuropathic pain but the explanation of how is not yet clear, although it may in part be attributed to the anxiolytic properties of CBD which may influence the impact of pain. CBD is an allosteric modulator of the mu- and delta-opioid receptors and has been noted to potentially enhance the analgesic effects of both endogenous and exogenous opioids.  CBD also behaves as an agonist of the TRPV1 (transient potential vanilloid receptor, type 1), the receptor associated with the analgesic benefit of capsaicin in neuropathic pain, suggesting another mechanism for its action against nerve pain.

 

  

Anxiety

Clinical studies have revealed definitive anxiolytic effects of CBD. CBD reverses anxiety brought on by THC and by a public-speaking simulation in patients with social phobia. Neuroimaging studies also show that CBD decreases activation of brain regions associated with anxiety, fear, and emotional processing, including the amygdala and the anterior and posterior cingulate cortex.

 

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, Xanax 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.

 

Inflammatory Bowel Disease

The reduction of intestinal inflammation through the control of neuroimmune axis exerted by CBD suggests this CBD may be a promising drug for the therapy of inflammatory bowel disease, especially Chrohn’s disease. CBD modulates inflammatory agents IL-12 and IL-10 and reduces activity of TNF-α, another inflammatory agent. CBD inhibits recruitment of inflammation-inducing mast cells and macrophages in the intestine, reducing intestinal damage principally mediated by peroxisome proliferator activated receptor-γ (PPAR-γ) receptor pathway. These findings may explain the significant reduction in disease activity for Crohn’s disease in a retrospective observational study of 30 patients treated with Δ9-THC and CBD. Lymphocytes are another key target of the immunomodulatory action of CBD. Specifically, CBD exhibited a generalized suppressive effect on T- cell functional activities in the gut.

 

Neurodegenerative Diseases

CBD has a role in inflammatory neurodegenerative diseases. CBD strongly inhibits the production of inflammatory cytokines, including IL-1β, IL-6, and interferon-β (IFN-β), in microglial cells. Microglia act as primary responding cells for infection and injury, but prolonged or excessive activation may result in pathological forms of inflammations that contribute to the progression of neurodegenerative disease including Parkinson’s and Alzheimer’s diseases, multiple sclerosis and HIV-associated dementia and brain trauma-related chronic traumatic encephelopathy. In this case the effects are not mediated via CB1 or CB2 receptors.

 

CBD is also thought to be neuroprotective by reducing oxidative stress, mitochondrial dysfunction and inflammatory changes. One mechanism of the neuroprotection provided by CBD is the up-regulation of the mRNA levels for Cu–Zn superoxide dismutase, resulting in increased activity of an important enzyme in endogenous defenses against oxidative stress and mitochondrial dysfunction.

 

Reward Deficiency Syndrome – Addiction

As an allosteric modulator of the dopamine D2 receptor, an essential element in the reward system of the brain, evidence suggests CBD offers benefit in addiction treatment. In preclinical studies, CBD reduces drug-motivated behavior, suppresses withdrawal symptoms and limits cravings.

 

Opioid Addiction – The majority of the addiction treatment effects of CBD have been investigated in the context of opiate drugs. CBD  normalizes opioid-induced impairments in the reward center (the nucleus accumbens – NAc), including AMPA and CB1 receptor levels. In a human clinical study it was demonstrated that CBD does not alter the subjective effects of fentanyl but reduces heroin cue-induced drug craving and anxiety. These results suggest that CBD reduces opioid-paired cue reactivity but has little effect on the acute reinforcing properties of opioids.

 

However, other research shows that the reward-facilitating effects of morphine are decreased by CBD, and these effects are associated with the 5-HT1A receptor.  CBD is an agonist of the 5-HT1A receptor and evidence suggests that 5-HT1A agonists reduce baseline serotonin and dopamine release in the NAc, suggesting a mechanism whereby CBD may reduce the acute reinforcing effects of morphine. The 5-HT1A receptor is also localized in dopamine terminal regions elsewhere in the brain reward circuitry such as the prefrontal cortex, amygdala, and hippocampus as well as the NAc.

 

Nicotine Addiction  – Preliminary findings indicate that CBD reduces cigarette smoking in smokers trying to quit. Although the mechanism for this effect has not been definitely identified, CBD may modulate nicotine reward through its ability to increase endocannabinoid tone by FAAH inhibition. It has been demonstrated that inhibiting FAAH blocks nicotine seeking and nicotine-induced dopamine release in the NAc reward center. It also reduces anxiety during nicotine withdrawal in animals.

 

Psychostimulant Addiction – In contrast to its effects on opioid-motivated behaviors, CBD has less  impact on psychostimulant reward and reinforcement. Administration of CBD fails to reduce cocaine-mediated decreases in self-stimulation thresholds or disrupt cocaine- and amphetamine-conditioned place preference.

 

Pharmacodynamics of CBD

As part of the endocannabinoid system, 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.

See: Endocannabinoid System

 

CB1 Receptor

Whereas THC acts primarily  on the CB1 receptor, CBD may modulate but does not seem to act directly at CB1 receptors but instead acts as a non-competitive negative allosteric modulator of CB1. While CBD is not a primary ligand of the CB1 receptor, it may influence CB1 receptor transmission by other indirect methods. CBD increases levels of the endogenous cannabinoid, anandamide (AEA), by blocking anandamide reuptake by inhibiting its transporters and by inhibiting its breakdown by fatty acid amide hydrolase (FAAH), the hydrolytic enzyme of AEA that breaks AEA down.

 

Apart from its known effects on the endocannabinoid system system, CBD exhibits pharmacological activity across a range of other receptors as noted above.  Another benefit 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. In addition, CBD inhibits adenosine uptake. 

 

Adenosine Receptors

CBD not only affects the central nervous system, but also the cardiovascular system. Adenosine receptors have been implicated in regulating coronary blood flow and oxygen consumption by cardiac muscle and they are also present in the brain. CBD inhibits the subsequent ventricular tachycardia following coronary artery occlusion in rats, demonstrating that CBD may have anti-arrhythmic effects, possibly mediated by the adenosine A1 receptor. In addition to effects on the A1 receptor, A2 receptor-mediated effects of CBD have also been reported  to mediate anti-inflammatory effects of CBD.  Studies have suggested that neuroprotective effects of CBD are mediated via adenosine A2 receptor modulation although this has also been contested and a clear link between the reported neuroprotective effects of CBD and adenosine A2 receptors has not yet been confirmed.

 

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Peroxisome Proliferator-activated Receptors

The peroxisome proliferator-activated receptor (PPAR) γ, otherwise known as the glitazone receptor, is thought to be responsible for lipid storage and glucose metabolism, and some anticancer effects of CBD are thought to by mediated through interaction with PPARγ. CBD has also been shown to inhibit tumor cell viability. These effects on tumor cells are not believed to be due to CBD action on CB1, CB2, or TRPV1 receptors.

 

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

 

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 – Pharmacodynamics

  1. Beyond the CB1 Receptor – Is Cannabidiol the Answer for Disorders of Motivation? – 2016
  2. Molecular Targets of Cannabidiol in Neurological Disorders – 2015

   

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
  4. Beyond the CB1 Receptor – Is Cannabidiol the Answer for Disorders of Motivation? – 2016
  5. Pharmacokinetic Drug Interactions with Tobacco, Cannabinoids and Smoking Cessation Products. – PubMed – NCBI – 2016
  6. The pharmacokinetics and the pharmacodynamics of cannabinoids. – PubMed – NCBI – 2018

  

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

 

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

 

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