Beyond THC and Endocannabinoids

Pacher, Pál; Kogan, Natalya M.; Mechoulam, Raphael

doi:10.1146/annurev-pharmtox-010818-021441

Cited by 126 publications

(109 citation statements)

References 166 publications

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“…It has a broad therapeutic potential resulting from its anti-inflammatory, antioxidant, anticonvulsant, antipsychotic, anxiolytic and antiproliferative properties. It is approved by the US Food and Drug Administration for the treatment of resistant epilepsy, and it is indicated in the therapy of neuropathic pain in multiple sclerosis and other diseases [ 2 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

Cannabidiol Ameliorates Monocrotaline-Induced Pulmonary Hypertension in Rats

Sadowska

Baranowska-Kuczko

Gromotowicz-Popławska

et al. 2020

IJMS

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Cannabidiol (CBD) is known for its vasorelaxant (including in the human pulmonary artery), anti-proliferative and anti-inflammatory properties. The aim of our study was to examine the potential preventive effect of chronic CBD administration (10 mg/kg/day for three weeks) on monocrotaline (MCT)-induced pulmonary hypertension (PH) rats. PH was connected with elevation of right ventricular systolic pressure; right ventricle hypertrophy; lung edema; pulmonary artery remodeling; enhancement of the vasoconstrictor and decreasing vasodilatory responses; increases in plasma concentrations of tissue plasminogen activator, plasminogen activator inhibitor type 1 and leukocyte count; and a decrease in blood oxygen saturation. CBD improved all abovementioned changes induced by PH except right ventricle hypertrophy and lung edema. In addition, CBD increased lung levels of some endocannabinoids (anandamide, N-arachidonoyl glycine, linolenoyl ethanolamide, palmitoleoyl ethanolamide and eicosapentaenoyl ethanolamide but not 2-arachidonoylglycerol). CBD did not affect the cardiopulmonary system of control rats or other parameters of blood morphology in PH. Our data suggest that CBD ameliorates MCT-induced PH in rats by improving endothelial efficiency and function, normalization of hemostatic alterations and reduction of enhanced leukocyte count determined in PH. In conclusion, CBD may be a safe, promising therapeutic or adjuvant therapy agent for the treatment of human pulmonary artery hypertension.

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Section: Introductionmentioning

confidence: 99%

Cannabidiol Ameliorates Monocrotaline-Induced Pulmonary Hypertension in Rats

Sadowska

Baranowska-Kuczko

Gromotowicz-Popławska

et al. 2020

IJMS

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“…THC and synthetic cannabinoids have affinity for the cannabinoid receptors. CBD does not have affinity for the cannabinoid 1 receptor (CB1R) and the cannabinoid 2 receptor (CB2R) and there is animal model evidence to show it modulates the adverse effects of ischemic stroke and likely acts on the sigma-1 receptor [5][6][7]. Additionally, CBD, in laboratory animal models, has been shown to be a beneficial treatment in substance use disorder including protection of the liver from alcohol damage [8,9].…”

Section: Introductionmentioning

confidence: 99%

Safety Assessment of a Hemp Extract using Genotoxicity and Oral Repeat-Dose Toxicity Studies in Sprague-Dawley Rats

Dziwenka¹,

Coppock²,

Alexander³

et al. 2020

Toxicology Reports

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Keywords:Cannabis sativa cannabinoids cannabidiol CBD toxicology olive oil hemp extract CYP liver mutagenicity CW hemp Charlotte's Web, Inc. A B S T R A C TCannabinoids are extracted from Cannabis sativa L. and are used for a variety of medicinal purposes. Recently, there has been a focus on the cannabinoid Cannabidiol (CBD) and its potential benefits. This study investigated the safety of a proprietary extract of C. sativa, consisting of 9% hemp extract (of which 6.27% is CBD) and 91% olive oil. The mutagenic potential of the hemp extract was evaluated with the AMES assay inclusive of a hepatic drug metabolizing mix (S9) rich in CYP enzymes. The test article did not elicit evidence of bacterial mutagenicity. GLP compliant 14-day and a 90-day toxicity study were conducted. Olive oil was used as a control. The 90-day study had a 28-day recovery period. Treatments for the 14-day non-recovery range-finding study were 0, 1000, 2000 and 4000 mg test article/kg body weight (bw)/day for 14 days. There was a non-statistically significant (p > 0.05) decrease in body weights for the male and female rats receiving the test article. Hypoactivity, hyperactivity, reduced food consumption and piloerection were observed in the rats receiving 4000 mg test article/kg bw. Histopathology showed an increase in the size of liver cells (hypertrophy) around the central vein (centrilobular) in Groups 3 (3/10) and 4 (5/10) that correlated with increased liver weights. In the 90-day study, 8 groups of rats were dosed with 0, 200, 400 and 800 mg test article/kg bw/day. Groups 5 to 8 had a 28-day recovery. There were no test article-linked changes in clinical observations, physical examinations, Functional Observation Battery, ophthalmology, Motor Activity Assessment, hematology, clinical chemistries and macropathology (all groups). With the exception of the liver and adrenal gland, no test article-linked pathology was observed. For all rats receiving the test article, histopathology showed hypertrophy of liver cells around the central vein. The increase of liver weight is most likely caused by hypertrophy due to up-regulation of the hepatic drug metabolizing enzymes. The hepatocellular hypertrophy was completely reversed in 28 days and was not considered to be an adverse effect. Vacuolization of the adrenal zona fasciculata was observed in the control and 800 mg test article/kg bw groups. The vacuolization of the zona fasciculata was of the same incidence and severity in treatment and control male rats and correlated with an increased in the weights of the adrenal glands. In addition, a statistically significant increase (p < 0.05) in adrenal-to-body weight ratios was observed for females receiving 800 mg test article/kg bw. This increase in adrenal-to-body weight ratio did not correlate with any of the pathology findings. The NOAEL for the test article is 800 mg/kg bw/day for female and 400 mg/kg bw/day for male Sprague Dawley rats.

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“…Sobre este aspecto, o CBD poderia atuar através de várias vias, incluindo os receptores 5-HT 1A e CB2, sobre os níveis de serotonina e glutamato e sobre outros fatores, como o BNDF ou mTOR (CAMPOS et al, 2017;PACHER et al, 2019). É um transtorno recorrente, uma vez que três quartos dos pacientes depressivos sofrem mais de um episódio (BOLAND;KELLER, 2009) e com índice de remissão em torno de 40% em resposta a um primeiro tratamento (RUSH et al, 2006).…”

Section: Efeito Antidepressivo Do Cbdunclassified

“…Estes efeitos podem estar associados à atuação direta ou indireta do CBD sobre múltiplas vias. A facilitação da neurogenese hipocampal e os efeitos neuroprotetores, anti-oxidativos e antiinflamatórios do CBD também estão associados ao seu efeito antidepressivo (HAMPSON et al, 1998;CAMPOS et al, 2017;CRIPPA et al, 2018;PACHER et al, 2019…”

Section: Canabidiol No Contexto Da Depressão Maiorunclassified

“…Assim, a investigação da dosagem plasmática do CBD se dos receptores CB1 em estudos pré-clínicos(BITENCOURT et al, 2008;CASAROTTO et al, 2010;CAMPOS et al, 2013). Outros efeitos do CBD, como a facilitação da neurogenese hipocampal e seu efeito anti-inflamatório, com a possível participação dos receptores CB2 (via 2-AG)(CAMPOS et al, 2017;PACHER et al, 2019), também poderiam contribuir para seu potencial antidepressivo (DUMAN et al, 2016; FOGAÇA; DUMAN, 2019). Apesar das evidências, as associações entre a ativação do sistema eCBD com os seus potenciais efeitos devem ser refletidas com cautela, uma vez os possíveis efeitos que seriam produzidos pela administração dos eCB nunca foram avaliados em humanos (PACHER et al, 2019) e a ativação destes receptores através de um único ligante Em vários estudos anteriores, o CBD apresentou efeito ansiolítico, avaliado por meio da escala VAMS.…”

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Efeitos agudos centrais do canabidiol por meio de neuroimagem funcional e sobre o reconhecimento de emoções faciais em pacientes com transtorno depressivo maior

Zamarrenho¹

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Beyond THC and Endocannabinoids

Cited by 126 publications

References 166 publications

Cannabidiol Ameliorates Monocrotaline-Induced Pulmonary Hypertension in Rats

Cannabidiol Ameliorates Monocrotaline-Induced Pulmonary Hypertension in Rats

Safety Assessment of a Hemp Extract using Genotoxicity and Oral Repeat-Dose Toxicity Studies in Sprague-Dawley Rats

Efeitos agudos centrais do canabidiol por meio de neuroimagem funcional e sobre o reconhecimento de emoções faciais em pacientes com transtorno depressivo maior

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