Tag: Cannabinoids

Cannabinoids, Endocannabinoids, and Related Analogs in Inflammation

Sumner H. Burstein and Robert B. Zurier

The AAPS Journal, Vol. 11, No. 1, March 2009

DOI: 10.1208/s12248-009-9084-5

This review covers reports published in the last 5 years on the anti-inflammatory activities of all classes of cannabinoids, including phytocannabinoids such as tetrahydrocannabinol and cannabidiol, synthetic analogs such as ajulemic acid and nabilone, the endogenous cannabinoids anandamide and related compounds, namely, the elmiric acids, and finally, noncannabinoid components of Cannabis that show anti-inflammatory action. It is intended to be an update on the topic of the involvement of cannabinoids in the process of inflammation. A possible mechanism for these actions is suggested involving increased production of eicosanoids that promote the resolution of inflammation. This differentiates these cannabinoids from cyclooxygenase-2 inhibitors that suppress the synthesis of eicosanoids that promote the induction of the inflammatory process.

Abstract

Cannabinoid influences on palatability: microstructural analysis of sucrose drinking after Δ9-tetrahydrocannabinol, anandamide, 2-arachidonoyl glycerol and SR141716

Higgs, S., Williams, C. M., & Kirkham, T. C. 

Psychopharmacology, 165(4), 370–377. (2003)
 
doi: 10.1007/s00213-002-1263-3

Central cannabinoid systems have been implicated in appetite control through the respective hyperphagic and anorectic actions of CB1 agonists and antagonists. The motivational changes underlying these actions remain to be determined, but may involve alterations to food palatability. The mode of action of cannabinoids on ingestion was investigated by examining the effects of exogenous and endogenous agonists, and a selective CB1 receptor antagonist, on licking microstructure in rats ingesting a palatable sucrose solution.

Abstract

Cannabinoid Delivery Systems for Pain and Inflammation Treatment

Bruni, N., Della Pepa, C., Oliaro-Bosso, S., Pessione, E., Gastaldi, D., & Dosio, F. 

Molecules, 23(10), 2478. (2018).

doi: 10.3390/molecules23102478

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.

Abstract

A Systematic Review on the Pharmacokinetics of Cannabidiol in Humans

Sophie A. Millar, Nicole L. Stone, Andrew S. Yates, Saoirse E. O'Sullivan

Frontiers in Pharmacology, 9. 2018

doi: 10.3389/fphar.2018.01365

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.

Background

A Phase I, Randomized, Double‑Blind, Placebo‑Controlled, Single Ascending Dose, Multiple Dose, and Food Effect Trial of the Safety, Tolerability and Pharmacokinetics of Highly Purifed Cannabidiol in Healthy Subjects

Lesley Taylor, Barry Gidal, Graham Blakey, Bola Tayo, Gilmour Morrison

CNS Drugs (2018) 32:1053–1067

doi: 10.1007/s40263-018-0578-5

A formal single ascending and multiple dose pharmacokinetic (PK) trial of cannabidiol (CBD) oral solution was required to determine the safety and tolerability of CBD, the maximum tolerated dose, and to examine the effect of food on CBD PK parameters.

Abstract

Antibacterial Cannabinoids from Cannabis sativa: A Structure−Activity Study

Appendino, G., Gibbons, S., Giana, A., Pagani, A., Grassi, G., Stavri, M., Rahman M. M. 

Journal of Natural Product, 71(8), 1427–1430. (2008)
 
doi: 10.1021/np8002673

Marijuana (Cannabis satiVa) has long been known to contain antibacterial cannabinoids, whose potential to address antibiotic resistance has not yet been investigated. All five major cannabinoids (cannabidiol (1b), cannabichromene (2), cannabigerol (3b), ∆9-tetrahydrocannabinol (4b), and cannabinol (5)) showed potent activity against a variety of methicillin-resistant Staphylococcus aureus (MRSA) strains of current clinical relevance. Activity was remarkably tolerant to the nature of the prenyl moiety, to its relative position compared to the n-pentyl moiety (abnormal cannabinoids), and to carboxylation of the resorcinyl moiety (pre-cannabinoids). Conversely, methylation and acetylation of the phenolic hydroxyls, esterification of the carboxylic group of pre-cannabinoids, and introduction of a second prenyl moiety were all detrimental for antibacterial activity. Taken together, these observations suggest that the prenyl moiety of cannabinoids serves mainly as a modulator of lipid affinity for the olivetol core, a per se poorly active antibacterial pharmacophore, while their high potency definitely suggests a specific, but yet elusive, mechanism of activity.

Abstract

An Overview on Medicinal Chemistry of Synthetic and Natural Derivatives of Cannabidiol.

Morales, P., Reggio, P. H., & Jagerovic, N.

Frontiers in Pharmacology, 8. (2017) 

doi: 10.3389/fphar.2017.00422

Cannabidiol (CBD) has been traditionally used in Cannabis-based preparation, however historically, it has received far less interest as a single drug than the other components of Cannabis. Currently, CBD generates considerable interest due to its beneficial neuroprotective, antiepileptic, anxiolytic, antipsychotic, and anti-inflammatory properties. Therefore, the CBD scaffold becomes of increasing interest for medicinal chemists. This review provides an overview of the chemical structure of natural and synthetic CBD derivatives including the molecular targets associated with these compounds. A clear identification of their biological targets has been shown to be still very challenging.

Abstract

Yield and cannabinoids contents in different cannabis (Cannabis sativa L.) genotypes for medical use

Anežka Janatováa, Adéla Fraňkováb, Pavel Tlustošc, Karel Hamouza, Matěj Božikb,

Pavel Kloučekb,

Industrial Crops & Products 112 (2018) 363–367

Doi: 10.1016/j.indcrop.2017.12.006

In the last decades, there has been a significant increase in the number of lifestyle and auto-immune diseases, such as various cancers or multiple sclerosis. In countries where cannabis is decriminalized for medical purposes, it is most often prescribed for these diagnoses. Today, over 700 different cannabis genotypes are being bred, and it is very important to describe in detail their cultivation, potential yields, chemical profile and stability, to be recommended to a particular patient with a specific diagnosis. The aim of this study was to evaluate the in-florescence yields and the content of Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) of seven traditional genotypes of cannabis – Conspiracy Kush, Nurse Jackie, Jilly Bean, Nordle, Jack Cleaner 2, Jack Skellington and National Health Services. The plants were grown under controlled climatic conditions during six growing cycles at a density of 9 plants/m2. Dried inflorescences from each plant were homogenized and analyzed by gas chromatography with flame ionization detection. The average yield per plant was 21.02 ± 3.33 g and the highest yields showed genotype Nurse Jackie (24.74 ± 6.11 g). The lowest yields were shown by genotype Jack Skellington (15.41 ± 4.02 g). Average Δ9-THC levels for each variety in all 6 growing cycles ranged from 15.69 ± 2.6 % to 19.31 ± 2.47 % (w/w). The lowest contents of Δ9-THC were measured in the Nordle genotype and the highest values were found in the Jack Cleaner 2 and Jack Skellington genotypes. Average CBD levels in the plants ranged from 0.45 ± 0.1 % to 0.57 ± 0.08 % (w/w) over six individual cycles. This study shows that among genotypes studied, the best parameters – high yield and stable cannabinoids production – are shown by genotypes Nurse Jackie and Jilly Bean.

Abstract

Human Metabolites of Cannabidiol: A Review on Their Formation, Biological Activity, and Relevance in Therapy

Istvan Ujvary, and Lumır Hanus

Cannabis and Cannabinoid Research
Volume 1.1, 2016

DOI: 10.1089/can.2015.0012

Cannabidiol (CBD), the main nonpsychoactive constituent of Cannabis sativa, has shown a wide range of therapeutically promising pharmacological effects either as a sole drug or in combination with other drugs in adjunctive therapy. However, the targets involved in the therapeutic effects of CBD appear to be elusive. Furthermore, scarce information is available on the biological activity of its human metabolites which, when formed in pharmacologically relevant concentration, might contribute to or even account for the observed therapeutic effects. The present overview summarizes our current knowledge on the pharmacokinetics and metabolic fate of CBD in humans, reviews studies on the biological activity of CBD metabolites either in vitro or in vivo, and discusses relevant drug–drug interactions. To facilitate further research in the area, the reported syntheses of CBD metabolites are also catalogued.

Abstract