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DOI (Digital Object Identifier) for Current Pain/Inflamation CBD Research

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 A collection of timely research (2016 to now) on Pain and Inflammation impacts of CBD

All citations are made by DOI with the abstract, authors and title. Some reprint rights apply for full text.

Cannabis Cannabinoid Res. 2018; 3(1): 282–290.

Published online 2018 Dec 26. doi: 10.1089/can.2018.0014

PMCID: PMC6308289 -- PMID: 30596146

The Anti-Inflammatory Properties of Terpenoids from Cannabis

Ruth Gallily,1,* Zhannah Yekhtin,1 and Lumír Ondřej Hanuš2

Abstract

Introduction: Cannabinoids are well known to have anti-inflammatory effects in mammalians; however, the Cannabis plant also contains other compounds such as terpenoids, whose biological effects have not yet been characterized. The aim of this study was to compare the anti-inflammatory properties of terpenoids with those of cannabidiol (CBD).

Materials and Methods: Essential oils prepared from three monoecious nonpsychoactive chemotypes of Cannabis were analyzed for their terpenoid content and subsequently studied pharmacologically for their anti-inflammatory properties in vitro and in vivo.

Results: In vitro, the three essential oils rich in terpenoids partly inhibited reactive oxygen intermediate and nitric oxide radical (NO•) production in RAW 264.7 stimulated macrophages. The three terpenoid-rich oils exerted moderate anti-inflammatory activities in an in vivo anti-inflammatory model without affecting tumor necrosis factor alpha (TNFα) serum levels.

Conclusions: The different Cannabis chemotypes showed distinct compositions of terpenoids. The terpenoid-rich essential oils exert anti-inflammatory and antinociceptive activities in vitro and in vivo, which vary according to their composition. Their effects seem to act independent of TNFα. None of the essential oils was as effective as purified CBD. In contrast to CBD that exerts prolonged immunosuppression and might be used in chronic inflammation, the terpenoids showed only a transient immunosuppression and might thus be used to relieve acute inflammation.

doi: 10.1089/can.2018.0014

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Molecules. 2018 Oct; 23(10): 2478.

Published online 2018 Sep 27. doi: 10.3390/molecules23102478

PMCID: PMC6222489 --- PMID: 30262735

Cannabinoid Delivery Systems for Pain and Inflammation Treatment

Natascia Bruni,1 Carlo Della Pepa,2 Simonetta Oliaro-Bosso,2 Enrica Pessione,3 Daniela Gastaldi,4 and Franco Dosio2,*

Abstract

There is a growing body of evidence to suggest that cannabinoids are beneficial for a range of clinical conditions, including pain, inflammation, epilepsy, sleep disorders, the symptoms of multiple sclerosis, anorexia, schizophrenia and other conditions. The transformation of cannabinoids from herbal preparations into highly regulated prescription drugs is therefore progressing rapidly. The development of such drugs requires well-controlled clinical trials to be carried out in order to objectively establish therapeutic efficacy, dose ranges and safety. The low oral bioavailability of cannabinoids has led to feasible methods of administration, such as the transdermal route, intranasal administration and transmucosal adsorption, being proposed. The highly lipophilic nature of cannabinoids means that they are seen as suitable candidates for advanced nanosized drug delivery systems, which can be applied via a range of routes. Nanotechnology-based drug delivery strategies have flourished in several therapeutic fields in recent years and numerous drugs have reached the market. This review explores the most recent developments, from preclinical to advanced clinical trials, in the cannabinoid delivery field, and focuses particularly on pain and inflammation treatment. Likely future directions are also considered and reported.

doi: 10.3390/molecules23102478

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Current Clincal Pharmacology. 2016;11(2):110-7.

Endocannabinoid System: A Multi-Facet Therapeutic Target.

Kaur R1, Ambwani SR, Singh S.

Volume 11, Number 2, May 2016, pp. 110-117(8) Publisher: Bentham Science Publishers

Department of Pharmacology, AIIMS, Jodhpur, Rajasthan, India. [email protected]

Abstract

Cannabis sativa is also popularly known as marijuana. It has been cultivated and used by man for recreational and medicinal purposes since many centuries. Study of cannabinoids was at bay for very long time and its therapeutic value could not be adequately harnessed due to its legal status as proscribed drug in most of the countries. The research of drugs acting on endocannabinoid system has seen many ups and downs in the recent past. Presently, it is known that endocannabinoids has role in pathology of many disorders and they also serve "protective role" in many medical conditions. Several diseases like emesis, pain, inflammation, multiple sclerosis, anorexia, epilepsy, glaucoma, schizophrenia, cardiovascular disorders, cancer, obesity, metabolic syndrome related diseases, Parkinson's disease, Huntington's disease, Alzheimer's disease and Tourette's syndrome could possibly be treated by drugs modulating endocannabinoid system. Presently, cannabinoid receptor agonists like nabilone and dronabinol are used for reducing the chemotherapy induced vomiting. Sativex (cannabidiol and THC combination) is approved in the UK, Spain and New Zealand to treat spasticity due to multiple sclerosis. In US it is under investigation for cancer pain, another drug Epidiolex (cannabidiol) is also under investigation in US for childhood seizures. Rimonabant, CB1 receptor antagonist appeared as a promising anti-obesity drug during clinical trials but it also exhibited remarkable psychiatric side effect profile. Due to which the US Food and Drug Administration did not approve Rimonabant in US. It sale was also suspended across the EU in 2008. Recent discontinuation of clinical trial related to FAAH inhibitor due to occurrence of serious adverse events in the participating subjects could be discouraging for the research fraternity. Despite some mishaps in clinical trials related to drugs acting on endocannabinoid system, still lot of research is being carried out to explore and establish the therapeutic targets for both cannabinoid receptor agonists and antagonists. One challenge is to develop drugs that target only cannabinoid receptors in a particular tissue and another is to invent drugs that act selectively on cannabinoid receptors located outside the blood brain barrier. Besides this, development of the suitable dosage forms with maximum efficacy and minimum adverse effects is also warranted. Another angle to be introspected for therapeutic abilities of this group of drugs is non-CB1 and non-CB2 receptor targets for cannabinoids. In order to successfully exploit the therapeutic potential of endocannabinoid system, it is imperative to further characterize the endocannabinoid system in terms of identification of the exact cellular location of cannabinoid receptors and their role as "protective" and "disease inducing substance", time-dependent changes in the expression of cannabinoid receptors.

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European Journal of Pain

Current evidence of cannabinoid‐based analgesia obtained in preclinical and human experimental settings

J. Lötsch -- I. Weyer‐Menkhoff -- I. Tegeder

First published: 21 November 2017 - https://doi.org/10.1002/ejp.1148

Abstract

Cannabinoids have a long record of recreational and medical use and become increasingly approved for pain therapy. This development is based on preclinical and human experimental research summarized in this review. Cannabinoid CB1 receptors are widely expressed throughout the nociceptive system. Their activation by endogenous or exogenous cannabinoids modulates the release of neurotransmitters. This is reflected in antinociceptive effects of cannabinoids in preclinical models of inflammatory, cancer and neuropathic pain, and by nociceptive hypersensitivity of cannabinoid receptor‐deficient mice. Cannabis‐based medications available for humans mainly comprise Δ9‐tetrahydrocannabinol (THC), cannabidiol (CBD) and nabilone. During the last 10 years, six controlled studies assessing analgesic effects of cannabinoid‐based drugs in human experimental settings were reported. An effect on nociceptive processing could be translated to the human setting in functional magnetic resonance imaging studies that pointed at a reduced connectivity within the pain matrix of the brain. However, cannabinoid‐based drugs heterogeneously influenced the perception of experimentally induced pain including a reduction in only the affective but not the sensory perception of pain, only moderate analgesic effects, or occasional hyperalgesic effects. This extends to the clinical setting. While controlled studies showed a lack of robust analgesic effects, cannabis was nearly always associated with analgesia in open‐label or retrospective reports, possibly indicating an effect on well‐being or mood, rather than on sensory pain. Thus, while preclinical evidence supports cannabinoid‐based analgesics, human evidence presently provides only reluctant support for a broad clinical use of cannabinoid‐based medications in pain therapy.

Significance:   Cannabinoids consistently produced antinociceptive effects in preclinical models, whereas they heterogeneously influenced the perception of experimentally induced pain in humans and did not provide robust clinical analgesia, which jeopardizes the translation of preclinical research on cannabinoid‐mediated antinociception into the human setting.

https://doi.org/10.1002/ejp.1148

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Pain. 2017 Dec;158(12):2442-2451. doi: 10.1097/j.pain.0000000000001052.

Attenuation of early phase inflammation by cannabidiol prevents pain and nerve damage in rat osteoarthritis.

Philpott HT1, OʼBrien M, McDougall JJ. Departments of Pharmacology and Anaesthesia, Pain Management and Perioperative Medicine, Dalhousie University, Halifax, NS, Canada.

Abstract

Osteoarthritis (OA) is a multifactorial joint disease, which includes joint degeneration, intermittent inflammation, and peripheral neuropathy. Cannabidiol (CBD) is a noneuphoria producing constituent of cannabis that has the potential to relieve pain. The aim of this study was to determine whether CBD is anti-nociceptive in OA, and whether inhibition of inflammation by CBD could prevent the development of OA pain and joint neuropathy. Osteoarthritis was induced in male Wistar rats (150-175 g) by intra-articular injection of sodium monoiodoacetate (MIA; 3 mg). On day 14 (end-stage OA), joint afferent mechanosensitivity was assessed using in vivo electrophysiology, whereas pain behaviour was measured by von Frey hair algesiometry and dynamic incapacitance. To investigate acute joint inflammation, blood flow and leukocyte trafficking were measured on day 1 after MIA. Joint nerve myelination was calculated by G-ratio analysis. The therapeutic and prophylactic effects of peripheral CBD (100-300 μg) were assessed. In end-stage OA, CBD dose-dependently decreased joint afferent firing rate, and increased withdrawal threshold and weight bearing (P < 0.0001; n = 8). Acute, transient joint inflammation was reduced by local CBD treatment (P < 0.0001; n = 6). Prophylactic administration of CBD prevented the development of MIA-induced joint pain at later time points (P < 0.0001; n = 8), and was also found to be neuroprotective (P < 0.05; n = 6-8). The data presented here indicate that local administration of CBD blocked OA pain. Prophylactic CBD treatment prevented the later development of pain and nerve damage in these OA joints. These findings suggest that CBD may be a safe, useful therapeutic for treating OA joint neuropathic pain.

[Indexed for MEDLINE] Free PMC Article  -PMID: 28885454 PMCID: PMC5690292

DOI: 10.1097/j.pain.0000000000001052

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J Clin Pharmacol. 2002 Nov;42(S1):11S-19S.

Cannabidiol: an overview of some pharmacological aspects.

Mechoulam R1, Parker LA, Gallily R.  -- Department of Medicinal Chemistry and Natural Products, Hebrew University of Jerusalem, Israel.

Abstract

Over the past few years, considerable attention has focused on cannabidiol (CBD), a major nonpsychotropic constituent of cannabis. The authors present a review on the chemistry of CBD and discuss the anticonvulsive, antianxiety, antipsychotic, antinausea, and antirheumatoid arthritic properties of CBD. CBD does not bind to the known cannabinoid receptors, and its mechanism of action is yet unknown. It is possible that, in part at least, its effects are due to its recently discovered inhibition of anandamide uptake and hydrolysis and to its antioxidative effect.

PMID:   12412831

Front Pharmacol. 2018 Nov 26;9:1365. doi: 10.3389/fphar.2018.01365. eCollection 2018.

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A Systematic Review on the Pharmacokinetics of Cannabidiol in Humans.

Millar SA1, Stone NL1, Yates AS2, O'Sullivan SE1. 1

Division of Medical Sciences and Graduate Entry Medicine, School of Medicine, University of Nottingham, Royal Derby Hospital, Derby, United Kingdom.

2 -- Artelo Biosciences, San Diego, CA, United States.

Abstract

Background: Cannabidiol is being pursued as a therapeutic treatment for multiple conditions, usually by oral delivery. Animal studies suggest oral bioavailability is low, but literature in humans is not sufficient. The aim of this review was to collate published data in this area. Methods: A systematic search of PubMed and EMBASE (including MEDLINE) was conducted to retrieve all articles reporting pharmacokinetic data of CBD in humans. Results: Of 792 articles retireved, 24 included pharmacokinetic parameters in humans. The half-life of cannabidiol was reported between 1.4 and 10.9 h after oromucosal spray, 2-5 days after chronic oral administration, 24 h after i.v., and 31 h after smoking. Bioavailability following smoking was 31% however no other studies attempted to report the absolute bioavailability of CBD following other routes in humans, despite i.v formulations being available. The area-under-the-curve and Cmax increase in dose-dependent manners and are reached quicker following smoking/inhalation compared to oral/oromucosal routes. Cmax is increased during fed states and in lipid formulations. Tmax is reached between 0 and 4 h. Conclusions: This review highlights the paucity in data and some discrepancy in the pharmacokinetics of cannabidiol, despite its widespread use in humans. Analysis and understanding of properties such as bioavailability and half-life is critical to future therapeutic success, and robust data from a variety of formulations is required.

KEYWORDS:

CMAX; TMAX; bioavailability; endocannabinoid system; half life; pharmacokinetics; plasma clearance; volume of distribution

PMID:  30534073   ---   PMCID:  PMC6275223

DOI:    10.3389/fphar.2018.01365 

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Neuropsychiatric effects of marijuana

Volume 3 Issue 2 - 2017

Edward Wadieh, 1 Lisa Adams, 1,2 Tony L

Brown     College of Medicine, University of Science, Arts & Technology, Major General Hugh G Robinson Center

for Medical Studies,Harvard University, USA

Abstract

Background:

Cannabis (Marijuana) is one of the most widely used illicit drugs around the world. In the United States, it is the most commonly-used illicit drug. While there have been increasing numbers of arguments about legalizing marijuana primarily for its medicinal and recreational use, there remain concerns about its impact on the brain: neuropsychiatric problems, in particular, from its chronic use.

Purpose & Method:

To highlight recent knowledge, understanding and research of marijuana, its potency, mechanism of action, effects on psychomotor and cognitive

performance and other neuropsychiatric function are explored; paying particular attention to the long term effects of Marijuana usage. Marijuana interacts with endogenous cannabinoid (CB) systems in the body. Actions on specific brain receptors are reflected in CB dose-related impairments of psychomotor performance. Further effects relating to psychosis, memory problems, and depression, are also experienced;primarily as a result of cortex degeneration.

Conclusion:

Marijuana significantly impacts the brain, specifically, the brain’s structure, function and connectivity. Although marijuana use is linked to many

neurological and psychiatric effects from long term use, it is often perceived in society'