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Emerging Clinical and Mechanistic Support for CBD Treatment of Autism Spectrum Disorder
Published in Betty Wedman-St Louis, Cannabis as Medicine, 2019
Kaylee Martig, Keelee Reid, Joshua S. Kaplan
These early-stage clinical trials have paved the way for larger clinical trials currently underway using CBD-rich cannabis72 or another cannabinoid, cannabidivarin,73 which, like CBD, is gaining recognition for its therapeutic potential in several clinical indications including epilepsy and Rett Syndrome by elevating inhibitory signaling.74–77
Cannabis and Cannabinoids
Published in Dilip Ghosh, Pulok K. Mukherjee, Natural Medicines, 2019
The Cannabis plant, which may be of different species (principally Cannabis sativa and Cannabis indica) or variants of the same species, is a dioecious entity that contains a number of unique resorcinol metabolites (van Bakel et al. 2011), although the estimated number may vary from 60–110. The most recognisable cannabinoid metabolite is Δ9-tetrahydrocannabinol (THC). Recent published data described the pharmacology of two of these agents, cannabidiol (CBD) and Δ9-tetrahydrocannabivarin (THCV) and concluded that these compounds exhibited complex interactions with the human endocannabinoid system. Apart from these three compounds, other cannabinoids showing pharmacological affects include cannabigerol, cannabidivarin, cannabidiolic acid and cannabichromene.
Medical cannabis in mental health–substance use
Published in David B Cooper, Ethics in Mental Health–Substance Use, 2017
Kevin Reel, Jean-François Crépault, Gavin S MacKenzie, Bernard Le Foll
The cannabinoid receptors are most extensive in the brain and widely present in the peripheral nervous system. Therefore, it is not surprising that exposure to cannabis will lead to pharmacological modulation of this endogenous system, which could lead to some therapeutic effects. In addition to the delta 9-Tetrahydrocannabinol (THC) that acts on the CB1 receptors and on the CB2 receptors as a partial agonist, some other components of cannabis may have some potential therapeutic utility. The most studied is canna bidiol, but a series of cannabinoid ligands (ex cannabidivarin, cannabinol …) have been also identified in cannabis. Their function still remains to be fully understood (Yücel et al. 2015).
Cannabinoids and drug metabolizing enzymes: potential for drug-drug interactions and implications for drug safety and efficacy
Published in Expert Review of Clinical Pharmacology, 2022
Keti Bardhi, Shelby Coates, Christy J.W. Watson, Philip Lazarus
In the plant, the precursors Δ9-tetrahydrocannabinol acid (THCA) and cannabidiolic acid (CBDA) are decarboxylated via light and high temperature to produce THC and CBD [46,48]. In addition to the major cannabinoids, cannabis contains other minor phytocannabinoids such as cannabigerol (CBG), cannabichromene (CBC), and cannabidivarin (CBDV), as well as other minor constituents [46,49]. Another important cannabinoid is Δ8-THC, which is similar to Δ9-THC but has greater stability and fewer intoxicating effects [50], and whose recreational usage has grown in recent years [51]. Δ8-THC is present in minimal amounts in the cannabis plant, but it can be synthesized from CBD extracted from hemp using a strong acid and heat [51]. All phytocannabinoids undergo hepatic and extra-hepatic metabolism upon human consumption, and some of their metabolites retain significant affinity towards cannabinoid receptors.
Investigational small molecules in phase II clinical trials for the treatment of epilepsy
Published in Expert Opinion on Investigational Drugs, 2018
Marco Greco, Gaia Varriale, Giangennaro Coppola, Francesca Operto, Alberto Verrotti, Maria Laura Iezzi
Possible role of cannabinoids in control of seizures attracted much interest in the last decade, results of preclinical investigations favored cannabidivarin as efficient anticonvulsant, which then entered clinical trials [28,29]. The ultimate objective should be investigation of full antiepileptic potential of all investigational cannabinoids. As the first step in achievement of this goal, further clinical trials with cannabidivarin in other types of treatment-resistant seizures are necessary. However, while it is reasonable to expect results of pre-clinical testing soon, quite a time would be necessary to conduct clinical trials, as patients with treatment-resistant seizures comprise a heterogenic group, and actually a number of parallel clinical trials with difficult-to-recruit patients would be necessary to get the whole picture. The first what we could expect in near future are results of current phase II clinical trials of cannabidivarin in patients with inadequately controlled focal seizures [19,30,31]. If they are beneficial, larger phase III clinical trials would probably be undertaken in the same patient population.
Emerging drugs for focal epilepsy
Published in Expert Opinion on Emerging Drugs, 2018
The biological activity of cannabinoids is mediated by cannabinoids receptors type 1 (CB1) and type 2 (CB2) which belong to a family of Gi/0-coupled receptors widely distributed in the central nervous system (CNS) with CB1 mainly in neurons while CB2 in the microglia and in the immune system [12]. CB1 receptors are mainly expressed pre-synaptically in GABAergic and glutamatergic neurons and the activation of these receptors result in inhibition of synaptic neurotransmission [15]. The well-known psychoactive effect of tetrahydrocannabinol (THC) seems to be mostly mediated by CB1 receptors which seem also to mediate some of the anti-seizure effects [15]. However, the psychotropic effect of THC has always been a barrier to a potential use in epilepsy and, for this reason, modern cannabinoid research focused only on non-psychoactive agents and two specific compounds, namely cannabidiol (CBD) and cannabidivarin (CBDV), are currently under development [12].