PMID- 32103958
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231113
IS  - 1176-6328 (Print)
IS  - 1178-2021 (Electronic)
IS  - 1176-6328 (Linking)
VI  - 16
DP  - 2020
TI  - Cannabinoids in the Treatment of Epilepsy: Current Status and Future Prospects.
PG  - 381-396
LID - 10.2147/NDT.S203782 [doi]
AB  - Cannabidiol (CBD) is one of the prominent phytocannabinoids found in Cannabis 
      sativa, differentiating from Delta(9)-tetrahydrocannabinol (THC) for its 
      non-intoxicating profile and its antianxiety/antipsychotic effects. CBD is a 
      multi-target drug whose anti-convulsant properties are supposed to be independent 
      of endocannabinoid receptor CB(1) and might be related to several underlying 
      mechanisms, such as antagonism on the orphan GPR55 receptor, regulation of 
      adenosine tone, activation of 5HT(1A) receptors and modulation of calcium 
      intracellular levels. CBD is a lipophilic compound with low oral bioavailability 
      (6%) due to poor intestinal absorption and high first-pass metabolism. Its 
      exposure parameters are greatly influenced by feeding status (ie, high 
      fat-containing meals). It is mainly metabolized by cytochrome P 450 (CYP) 3A4 and 
      2C19, which it strongly inhibits. A proprietary formulation of highly purified, 
      plant-derived CBD has been recently licensed as an adjunctive treatment for 
      Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS), while it is being 
      currently investigated in tuberous sclerosis complex. The regulatory agencies' 
      approval was granted based on four pivotal double-blind, placebo-controlled, 
      randomized clinical trials (RCTs) on overall 154 DS patients and 396 LGS ones, 
      receiving CBD 10 or 20 mg/kg/day BID as active treatment. The primary endpoint 
      (reduction in monthly seizure frequency) was met by both CBD doses. Most patients 
      reported adverse events (AEs), generally from mild to moderate and transient, 
      which mainly consisted of somnolence, sedation, decreased appetite, diarrhea and 
      elevation in aminotransferase levels, the last being documented only in subjects 
      on concomitant valproate therapy. The interaction between CBD and clobazam, 
      likely due to CYP2C19 inhibition, might contribute to some AEs, especially 
      somnolence, but also to CBD clinical effectiveness. Cannabidivarin (CBDV), the 
      propyl analogue of CBD, showed anti-convulsant properties in pre-clinical 
      studies, but a plant-derived, purified proprietary formulation of CBDV recently 
      failed the Phase II RCT in patients with uncontrolled focal seizures.
CI  - (c) 2020 Morano et al.
FAU - Morano, Alessandra
AU  - Morano A
AD  - Epilepsy Unit, Department of Human Neurosciences, "Sapienza" University of Rome, 
      Rome, Italy.
FAU - Fanella, Martina
AU  - Fanella M
AD  - Epilepsy Unit, Department of Human Neurosciences, "Sapienza" University of Rome, 
      Rome, Italy.
FAU - Albini, Mariarita
AU  - Albini M
AD  - Epilepsy Unit, Department of Human Neurosciences, "Sapienza" University of Rome, 
      Rome, Italy.
FAU - Cifelli, Pierangelo
AU  - Cifelli P
AD  - Department of Physiology and Pharmacology, Pasteur Institute-Cenci Bolognetti 
      Foundation, University of Rome Sapienza, Rome, Italy.
AD  - IRCCS "Neuromed", Pozzilli, IS, Italy.
FAU - Palma, Eleonora
AU  - Palma E
AD  - Department of Physiology and Pharmacology, Pasteur Institute-Cenci Bolognetti 
      Foundation, University of Rome Sapienza, Rome, Italy.
FAU - Giallonardo, Anna Teresa
AU  - Giallonardo AT
AD  - Epilepsy Unit, Department of Human Neurosciences, "Sapienza" University of Rome, 
      Rome, Italy.
FAU - Di Bonaventura, Carlo
AU  - Di Bonaventura C
AUID- ORCID: 0000-0003-1890-5409
AD  - Epilepsy Unit, Department of Human Neurosciences, "Sapienza" University of Rome, 
      Rome, Italy.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20200207
PL  - New Zealand
TA  - Neuropsychiatr Dis Treat
JT  - Neuropsychiatric disease and treatment
JID - 101240304
PMC - PMC7012327
OTO - NOTNLM
OT  - cannabidiol
OT  - cannabidivarin
OT  - drug-resistance
OT  - epileptic encephalopathies
OT  - phytocannabinoids
OT  - tuberous sclerosis complex
COIS- The authors have no conflicts of interest to report.
EDAT- 2020/02/28 06:00
MHDA- 2020/02/28 06:01
PMCR- 2020/02/07
CRDT- 2020/02/28 06:00
PHST- 2019/11/13 00:00 [received]
PHST- 2020/01/18 00:00 [accepted]
PHST- 2020/02/28 06:00 [entrez]
PHST- 2020/02/28 06:00 [pubmed]
PHST- 2020/02/28 06:01 [medline]
PHST- 2020/02/07 00:00 [pmc-release]
AID - 203782 [pii]
AID - 10.2147/NDT.S203782 [doi]
PST - epublish
SO  - Neuropsychiatr Dis Treat. 2020 Feb 7;16:381-396. doi: 10.2147/NDT.S203782. 
      eCollection 2020.