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Cannabinoids in Cannabis: Chemistry, Pharmacology and Real World Evidence
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Cannabinoids in Cannabis: Chemistry, Pharmacology and Real World Evidence

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Natural Products Chemistry".

Deadline for manuscript submissions: closed (31 July 2020) | Viewed by 29825

Special Issue Editor

Prof. Dr. Lakshmi Kotra

E-Mail Website
Guest Editor
Leslie Dan Faculty of Pharmacy, University of Toronto, and Krembil Research Institute, University Health Network, Toronto, ON, Canada
Interests: drug discovery; enzyme inhibitors; cannabinoids; psychoactive molecules; multiple sclerosis; inflammatory disorders; mental health
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cannabinoids, viz. endocannabinoids and phytocannabinoids, play an important role in a number of diseases spanning immunological, neurological and neuroimmunological conditions. These compounds interestingly act as ligands to a number of receptors and ion channels, such as CB1, CB2, GPR55, 5HT1A, and TRPV channels, among others. In recent years, there has been a renewed interest in almost all aspects of cannabinoids and the endocannabinoid system (ECS) due to the relaxation of regulations around the globe. This is permitting us to answer many questions that could not be answered until now, in the context of chemical modifications to cannabinoids, effects of cannabinoids on receptors, pharmacology and physiology, and associated clinical evidence. Chemical modifications to endocannabinoids and phytocannabinoids are important to probe the in vitro and in vivo pharmacology. Cannabinoids, in the form of various cannabis-derived products, are available in many countries, and research on these products and their effects on receptors—in animal models and in humans—are also very much relevant to health.

This Special Issue aims to bring together high-quality publications that appreciate and investigate the diversity of cannabinoid chemistry, the chemical complexity of cannabis, in vitro and in vivo studies involving cannabinoids and/or cannabis products, and real-world evidence on chemically defined cannabis products.

 

Prof. Lakshmi P. Kotra
Guest Editor

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Keywords

  • Cannabinoids
  • Endocannabinoid system
  • Cannabinoid receptors
  • GPR55
  • 5HT1A
  • TRPV1
  • Real world evidence
  • Immune modulation
  • Neuromodulation
  • In vitro studies
  • In vivo studies
  • Structure-activity relationship

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Published Papers (3 papers)

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Research

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13 pages, 1466 KiB  
Communication
Understanding the Medical Chemistry of the Cannabis Plant is Critical to Guiding Real World Clinical Evidence
by Karim S. Ladha, Prabjit Ajrawat, Yi Yang and Hance Clarke
Molecules 2020, 25(18), 4042; https://doi.org/10.3390/molecules25184042 - 4 Sep 2020
Cited by 25 | Viewed by 5281
Abstract
While cannabis has been consumed for thousands of years, the medical-legal landscape surrounding its use has dramatically evolved over the past decades. Patients are turning to cannabis as a therapeutic option for several medical conditions. Given the surge in interest over the past [...] Read more.
While cannabis has been consumed for thousands of years, the medical-legal landscape surrounding its use has dramatically evolved over the past decades. Patients are turning to cannabis as a therapeutic option for several medical conditions. Given the surge in interest over the past decades there exists a major gap in the literature with respect to understanding the products that are currently being consumed by patients. The current perspective highlights the lack of relevance within the current literature towards understanding the medical chemistry of the products being consumed. The cannabis industry must rigorously invest into understanding what people are consuming from a chemical composition standpoint. This will inform what compounds in addition to Δ9-tetrahydrocannabinol and cannabidiol may be producing physiologic/therapeutic effects from plant based extracts. Only through real-world evidence and a formalized, granular data collection process within which we know the chemical inputs for patients already using or beginning to use medical cannabis, we can come closer to the ability to provide targeted clinical decision making and design future appropriate randomized controlled trials. Full article
(This article belongs to the Special Issue Cannabinoids in Cannabis: Chemistry, Pharmacology and Real World Evidence)
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17 pages, 649 KiB  
Article
Bioactive Chemical Composition of Cannabis Extracts and Cannabinoid Receptors
by Yi Yang, Rupali Vyawahare, Melissa Lewis-Bakker, Hance A. Clarke, Albert H. C. Wong and Lakshmi P. Kotra
Molecules 2020, 25(15), 3466; https://doi.org/10.3390/molecules25153466 - 30 Jul 2020
Cited by 14 | Viewed by 7056
Abstract
Cannabis is widely used as a therapeutic drug, especially by patients suffering from psychiatric and neurodegenerative diseases. However, the complex interplay between phytocannabinoids and their targets in the human receptome remains largely a mystery, and there have been few investigations into the relationship [...] Read more.
Cannabis is widely used as a therapeutic drug, especially by patients suffering from psychiatric and neurodegenerative diseases. However, the complex interplay between phytocannabinoids and their targets in the human receptome remains largely a mystery, and there have been few investigations into the relationship between the chemical composition of medical cannabis and the corresponding biological activity. In this study, we investigated 59 cannabis samples used by patients for medical reasons. The samples were subjected to extraction (microwave and supercritical carbon dioxide) and chemical analyses, and the resulting extracts were assayed in vitro using the CB1 and CB2 receptors. Using a partial least squares regression analysis, the chemical compositions of the extracts were then correlated to their corresponding cannabinoid receptor activities, thus generating predictive models that describe the receptor potency as a function of major phytocannabinoid content. Using the current dataset, meaningful models for CB1 and CB2 receptor agonism were obtained, and these reveal the insignificant relationships between the major phytocannabinoid content and receptor affinity for CB1 but good correlations between the two at CB2 receptors. These results also explain the anomalies between the receptor activities of pure phytocannabinoids and cannabis extracts. Furthermore, the models for CB1 and CB2 agonism in cannabis extracts predict the cannabinoid receptor activities of individual phytocannabinoids with reasonable accuracy. Here for the first time, we disclose a method to predict the relationship between the chemical composition, including phytocannabinoids, of cannabis extracts and cannabinoid receptor responses. Full article
(This article belongs to the Special Issue Cannabinoids in Cannabis: Chemistry, Pharmacology and Real World Evidence)
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Review

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24 pages, 1387 KiB  
Review
It Is Our Turn to Get Cannabis High: Put Cannabinoids in Food and Health Baskets
by Seyed Alireza Salami, Federico Martinelli, Antonio Giovino, Ava Bachari, Neda Arad and Nitin Mantri
Molecules 2020, 25(18), 4036; https://doi.org/10.3390/molecules25184036 - 4 Sep 2020
Cited by 68 | Viewed by 16490
Abstract
Cannabis is an annual plant with a long history of use as food, feed, fiber, oil, medicine, and narcotics. Despite realizing its true value, it has not yet found its true place. Cannabis has had a long history with many ups and downs, [...] Read more.
Cannabis is an annual plant with a long history of use as food, feed, fiber, oil, medicine, and narcotics. Despite realizing its true value, it has not yet found its true place. Cannabis has had a long history with many ups and downs, and now it is our turn to promote it. Cannabis contains approximately 600 identified and many yet unidentified potentially useful compounds. Cannabinoids, phenolic compounds, terpenoids, and alkaloids are some of the secondary metabolites present in cannabis. However, among a plethora of unique chemical compounds found in this plant, the most important ones are phytocannabinoids (PCs). Over hundreds of 21-22-carbon compounds exclusively produce in cannabis glandular hairs through either polyketide and or deoxyxylulose phosphate/methylerythritol phosphate (DOXP/MEP) pathways. Trans-Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) are those that first come to mind while talking about cannabis. Nevertheless, despite the low concentration, cannabinol (CBN), cannabigerol (CBG), cannabichromene (CBC), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabinodiol (CBND), and cannabinidiol (CBDL) may have potentially some medical effects. PCs and endocannabinoids (ECs) mediate their effects mainly through CB1 and CB2 receptors. Despite all concerns regarding cannabis, nobody can ignore the use of cannabinoids as promising tonic, analgesic, antipyretic, antiemetic, anti-inflammatory, anti-epileptic, anticancer agents, which are effective for pain relief, depression, anxiety, sleep disorders, nausea and vomiting, multiple sclerosis, cardiovascular disorders, and appetite stimulation. The scientific community and public society have now increasingly accepted cannabis specifically hemp as much more than a recreational drug. There are growing demands for cannabinoids, mainly CBD, with many diverse therapeutic and nutritional properties in veterinary or human medicine. The main objective of this review article is to historically summarize findings concerning cannabinoids, mainly THC and CBD, towards putting these valuable compounds into food, feed and health baskets and current and future trends in the consumption of products derived from cannabis. Full article
(This article belongs to the Special Issue Cannabinoids in Cannabis: Chemistry, Pharmacology and Real World Evidence)
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