“Cannabidiol (CBD) is a phytocannabinoid with multiple pharmacological effects and several potential therapeutic properties. Its low oral bioavailability, however, can limit its clinical use. Preliminary results indicate that fluorination of the CBD molecule increases its pharmacological potency. Here, we investigated whether HUF-101 (3, 10, and 30mg/kg), a fluorinated CBD analogue, would induce antinociceptive effects. These findings show that HUF-101 produced antinociceptive effects at lower doses than CBD, indicating that the addition of fluoride improved its pharmacological profile. Furthermore, some of the antinociceptive effects of CBD and HUF-101 effects seem to involve the activation of CB1 and CB2 receptors.” https://www.ncbi.nlm.nih.gov/pubmed/28720466 http://www.sciencedirect.com/science/article/pii/S0278584617302233]]>
Tag Archives: phytocannabinoids
Cannabidiol Is a Potential Therapeutic for the Affective-Motivational Dimension of Incision Pain in Rats.
“Drugs that interfere with the endocannabinoid system are alternatives for the management of clinical pain. Cannabidiol (CBD), a phytocannabinoid found in Cannabis sativa, has been utilized in preclinical and clinical studies for the treatment of pain. Herein, we evaluate the effects of CBD. The study provides evidence that CBD influences different dimensions of the response of rats to a surgical incision, and the results establish the rostral anterior cingulate cortex (rACC) as a brain area from which CBD evokes antinociceptive effects in a manner similar to the systemic administration of CBD. The present study has shown for the first time that CBD injected either systemically or into the rACC induces a long-lasting anti-allodynic effect with a bell-shaped dose-response curve in a rat model of incision pain.” https://www.ncbi.nlm.nih.gov/pubmed/28680401
Assessing the role of serotonergic receptors in cannabidiol's anticonvulsant efficacy.
“Cannabidiol (CBD) is a phytocannabinoid that has demonstrated anticonvulsant efficacy in several animal models of seizure. The current experiment validated CBD’s anticonvulsant effect using the acute pentylenetetrazol (PTZ) model. While this work further confirms the anticonvulsant efficacy of CBD and supports its application in the treatment of human seizure disorders, additional research on CBD’s mechanism of action must be conducted.” https://www.ncbi.nlm.nih.gov/pubmed/28624721 http://www.epilepsybehavior.com/article/S1525-5050(17)30122-1/fulltext]]>
Assessing the role of serotonergic receptors in cannabidiol’s anticonvulsant efficacy.
“Cannabidiol (CBD) is a phytocannabinoid that has demonstrated anticonvulsant efficacy in several animal models of seizure. The current experiment validated CBD’s anticonvulsant effect using the acute pentylenetetrazol (PTZ) model.
While this work further confirms the anticonvulsant efficacy of CBD and supports its application in the treatment of human seizure disorders, additional research on CBD’s mechanism of action must be conducted.”
https://www.ncbi.nlm.nih.gov/pubmed/28624721
http://www.epilepsybehavior.com/article/S1525-5050(17)30122-1/fulltext
Endocannabinoid System in Neurodegenerative Disorders.
“Most neurodegenerative disorders (NDDs) are characterized by cognitive impairment and other neurological defects. The definite cause of and pathways underlying the progression of these NDDs are not well defined. Several mechanisms have been proposed to contribute to the development of NDDs. These mechanisms may proceed concurrently or successively, and they differ among cell types at different developmental stages in distinct brain regions. The endocannabinoid system, which involves cannabinoid receptors type 1 (CB1R) and type 2 (CB2R), endogenous cannabinoids and the enzymes that catabolize these compounds, has been shown to contribute to the development of NDDs in several animal models and human studies. In this review, we discuss the functions of the endocannabinoid (EC) system in NDDs and converse the therapeutic efficacy of targeting the endocannabinoid system to rescue NDDs.” https://www.ncbi.nlm.nih.gov/pubmed/28608560 http://onlinelibrary.wiley.com/doi/10.1111/jnc.14098/abstract]]>
A single dose of cannabidiol reduces blood pressure in healthy volunteers in a randomized crossover study.
“Cannabidiol (CBD) is a nonpsychoactive phytocannabinoid used in multiple sclerosis and intractable epilepsies. Preclinical studies show CBD has numerous cardiovascular benefits, including a reduced blood pressure (BP) response to stress. The aim of this study was to investigate if CBD reduces BP in humans.
CONCLUSIONS:
This data shows that acute administration of CBD reduces resting BP and the BP increase to stress in humans, associated with increased HR. These hemodynamic changes should be considered for people taking CBD. Further research is required to establish whether CBD has a role in the treatment of cardiovascular disorders.” https://www.ncbi.nlm.nih.gov/pubmed/28614793 “Our data show that a single dose of CBD reduces resting blood pressure and the blood pressure response to stress. This may reflect the anxiolytic and analgesic effects of CBD, as well as any potential direct cardiovascular effects. CBD has multiple desirable effects on the cardiovascular system” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5470879/ https://insight.jci.org/articles/view/93760]]>GPR3 and GPR6, novel molecular targets for cannabidiol.
“GPR3 and GPR6 are members of a family of constitutively active, Gs protein-coupled receptors. Previously, it has been reported that GPR3 is involved in Alzheimer’s disease whereas GPR6 plays potential roles in Parkinson’s disease. GPR3 and GPR6 are considered orphan receptors because there are no confirmed endogenous agonists for them. However, GPR3 and GPR6 are phylogenetically related to the cannabinoid receptors. In this study, the activities of endocannabinoids and phytocannabinoids were tested on GPR3 and GPR6 using a β-arrestin2 recruitment assay. Among the variety of cannabinoids tested, cannabidiol (CBD), the major non-psychoactive component of marijuana, significantly reduced β-arrestin2 recruitment to both GPR3 and GPR6. In addition, the inhibitory effects of CBD on β-arrestin2 recruitment were concentration-dependent for both GPR3 and GPR6, with a higher potency for GPR6. These data show that CBD acts as an inverse agonist at both GPR3 and GPR6 receptors. These results demonstrate for the first time that both GPR3 and GPR6 are novel molecular targets for CBD. Our discovery that CBD acts as a novel inverse agonist on both GPR3 and GPR6 indicates that some of the potential therapeutic effects of CBD (e.g. treatment of Alzheimer’s disease and Parkinson’s disease) may be mediated through these important receptors.” https://www.ncbi.nlm.nih.gov/pubmed/28571738 http://www.sciencedirect.com/science/article/pii/S0006291X17310744]]>
Anticancer effects of phytocannabinoids used with chemotherapy in leukaemia cells can be improved by altering the sequence of their administration.
“Phytocannabinoids possess anticancer activity when used alone, and a number have also been shown to combine favourably with each other in vitro in leukaemia cells to generate improved activity.
We have investigated the effect of pairing cannabinoids and assessed their anticancer activity in cell line models. Those most effective were then used with the common anti-leukaemia drugs cytarabine and vincristine, and the effects of this combination therapy on cell death studied in vitro.
Results show a number of cannabinoids could be paired together to generate an effect superior to that achieved if the components were used individually.
For example, in HL60 cells, the IC50 values at 48 h for cannabidiol (CBD) and tetrahydrocannabinol (THC) when used alone were 8 and 13 µM, respectively; however, if used together, it was 4 µM. Median-effect analysis confirmed the benefit of using cannabinoids in pairs, with calculated combination indices being <1 in a number of cases.
The most efficacious cannabinoid-pairs subsequently synergised further when combined with the chemotherapy agents, and were also able to sensitise leukaemia cells to their cytotoxic effects.
The sequence of administration of these drugs was important though; using cannabinoids after chemotherapy resulted in greater induction of apoptosis, whilst this was the opposite when the schedule of administration was reversed.
Our results suggest that when certain cannabinoids are paired together, the resulting product can be combined synergistically with common anti-leukaemia drugs allowing the dose of the cytotoxic agents to be dramatically reduced yet still remain efficacious. Nevertheless, the sequence of drug administration is crucial to the success of these triple combinations and should be considered when planning such treatments.”