Book ChapterDOI
Neuropharmacological Effects of the Main Phytocannabinoids: A Narrative Review.
TLDR
An overview of the main neurochemical mechanisms of action of the phytocannabinoids, especially THC and CBD is presented, which could be responsible for their wide therapeutic spectrum and "promiscuous" pharmacology.Abstract:
Cannabis can synthetize more than 400 compounds, including terpenes, flavonoids, and more than 100 phytocannabinoids. The main phytocannabinoids are Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Cannabis-based products are used as medicines in several countries. In this text, we present an overview of the main neurochemical mechanisms of action of the phytocannabinoids, especially THC and CBD. We also reviewed the indications and adverse effects of the main cannabis-based medicinal products. THC acts as a partial agonist at cannabinoid 1/2 receptors (CB1/2). It is responsible for the characteristic effects of cannabis, such as euphoria, relaxation, and changes in perceptions. THC can also produce dysphoria, anxiety, and psychotic symptoms. THC is used therapeutically in nausea and vomiting due to chemotherapy, as an appetite stimulant, and in chronic pain. CBD acts as a noncompetitive negative allosteric modulator of the CB1 receptor, as an inverse agonist of the CB2 receptor, and as an inhibitor of the reuptake of the endocannabinoid anandamide. Moreover, CBD also activates 5-HT1A serotonergic receptors and vanilloid receptors. Its use in treatment-resistant epilepsy syndromes is approved in some countries. CBD does not produce the typical effects associated with THC and has anxiolytic and antipsychotic effects. Some of the most common adverse effects of CBD are diarrhea, somnolence, nausea, and transaminase elevations (with concomitant use of antiepileptics). The mechanisms of action involved in both the therapeutic and adverse effects of the phytocannabinoids are not fully understood, involving not only the endocannabinoid system. This "promiscuous" pharmacology could be responsible for their wide therapeutic spectrum.read more
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Journal ArticleDOI
Public health monitoring of cannabis use in Europe: prevalence of use, cannabis potency, and treatment rates.
Jakob Manthey,Jakob Manthey,Jakob Manthey,Tom P. Freeman,Carolin Kilian,Hugo López-Pelayo,Jürgen Rehm +6 more
TL;DR: In this article, the authors describe the trends of key public health indicators in European Union (27 member states + UK, Norway and Turkey) for the period 2010 to 2019, their public health implications, and identify the steps required to improve current practice in monitoring of cannabis use and harm in Europe.
Journal ArticleDOI
Cannabinoids, the endocannabinoid system, and pain: a review of preclinical studies
David P. Finn,Simon Haroutounian,Andrea G. Hohmann,Elliot J. Krane,Nadia Soliman,Andrew S.C. Rice +5 more
TL;DR: In this paper, a companion systematic review and meta-analysis of preclinical studies in this area is presented, with specific relevance to animal models of pathological or injury-related persistent pain.
Journal ArticleDOI
Serious adverse effects of cannabidiol (CBD): a review of randomized controlled trials
Rafael G. dos Santos,Rafael G. dos Santos,Francisco S. Guimarães,Francisco S. Guimarães,José Alexandre de Souza Crippa,José Alexandre de Souza Crippa,Jaime Eduardo Cecílio Hallak,Jaime Eduardo Cecílio Hallak,Giordano Novak Rossi,Juliana Mendes Rocha,Antonio Waldo Zuardi,Antonio Waldo Zuardi +11 more
TL;DR: Evaluated SAEs related to CBD in RCT are mainly elevated transaminases, convulsion, sedation, lethargy, and upper respiratory tract infections that are related to concomitant clobazam use and should be monitored when using CBD concomitantly with these and other antiepileptic drugs.
Journal ArticleDOI
Serotonin receptors in epilepsy: Novel treatment targets?
Jo Sourbron,Lieven Lagae +1 more
TL;DR: There are divergent data demonstrating that modulation of distinct serotonin receptors subtypes could be beneficial in the treatment of epilepsy and its comorbidities, whereas only a few ASM, such as fenfluramine (FA), act via 5‐HT.
Journal ArticleDOI
Why Do Marijuana and Synthetic Cannabimimetics Induce Acute Myocardial Infarction in Healthy Young People?
Jolanta Weresa,Anna Pędzińska-Betiuk,Krzysztof Mińczuk,Barbara Malinowska,Eberhard Schlicker +4 more
TL;DR: Additional research is warranted to decipher the mechanisms involved, since cannabis use is being legalized increasingly and Δ9-tetrahydrocannabinol and its synthetic analogue nabilone are indicated for the treatment of various disease states.
References
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Journal ArticleDOI
Plastic and Neuroprotective Mechanisms Involved in the Therapeutic Effects of Cannabidiol in Psychiatric Disorders
Alline C. Campos,Manoela V. Fogaça,Franciele F. Scarante,Sâmia R.L. Joca,Amanda J. Sales,Felipe V. Gomes,Andreza Buzolin Sonego,Naielly S. Rodrigues,Ismael Galve-Roperh,Francisco Silveira Guimarães +9 more
TL;DR: It was found that CBD modulates cell fate regulatory pathways such as autophagy and others critical pathways for neuronal survival in Neurodegenerative experimental models, suggesting the potential benefit of CBD treatment for psychiatric/cognitive symptoms associated with neurodegeneration.
Journal ArticleDOI
Does Cannabis Composition Matter? Differential Effects of Delta-9-tetrahydrocannabinol and Cannabidiol on Human Cognition.
TL;DR: This article selectively reviews studies examining the distinctive effects of cannabinoids on human cognition, particularly those of delta-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), and it is unclear whether at specific concentrations CBD might outweigh any harmful effects of Δ9- THC on cognition.
Journal ArticleDOI
Δ9‐Tetrahydrocannabivarin suppresses in vitro epileptiform and in vivo seizure activity in adult rats
Andrew Hill,Samantha E. Weston,Nicholas A. Jones,Imogen Smith,Sarah A. Bevan,Elizabeth Williamson,Gary J. Stephens,Claire M. Williams,Benjamin J. Whalley +8 more
TL;DR: The anticonvulsant potential of the phytocannabinoid Δ9‐tetrahydrocannabivarin (Δ9‐THCV) is assessed by investigating its effects in an in vitro piriform cortex brain slice model of epileptiform activity, on cannabinoid CB1 receptor radioligand‐binding assays and in a generalized seizure model in rats.
Journal ArticleDOI
Abuse potential assessment of cannabidiol (CBD) in recreational polydrug users: A randomized, double-blind, controlled trial.
Kerri A. Schoedel,Isabella Szeto,Beatrice Setnik,Edward M. Sellers,Naama Levy-Cooperman,Catherine Mills,Tilden Etges,Kenneth W. Sommerville +7 more
TL;DR: Administration of a therapeutic dose of CBD (750 mg) showed significantly low abuse potential in a highly sensitive population of polydrug users.
Journal ArticleDOI
Therapeutic Effects of Prolonged Cannabidiol Treatment on Psychological Symptoms and Cognitive Function in Regular Cannabis Users: A Pragmatic Open-Label Clinical Trial.
Nadia Solowij,Samantha J. Broyd,Camilla Beale,Julie-Anne Prick,Lisa-Marie Greenwood,Hendrika H van Hell,Chao Suo,Peter Galettis,Nagesh B Pai,Shanlin Fu,Rodney J. Croft,Jennifer H. Martin,Murat Yücel +12 more
TL;DR: Prolonged CBD treatment appears to have promising therapeutic effects for improving psychological symptoms and cognition in regular cannabis users, and it is suggested that CBD may be a useful adjunct treatment for cannabis dependence.