Tag Archives: cannabidiol

Cannabidiol reduces seizures following CNS infection with Theiler’s murine encephalomyelitis virus.

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Publication cover image“C57BL/6J mice infected with Theiler’s murine encephalomyelitis virus (TMEV) develop acute behavioral seizures in the first week of infection and later develop chronic epilepsy. The TMEV model provides a useful platform to test novel antiseizure therapeutics.

The present study was designed to test the efficacy of cannabidiol (CBD) in reducing acute seizures induced by viral infection.

RESULTS:

Cannabidiol (180 mg/kg; 360 mg/kg/day) decreased both the frequency and severity of acute behavioral seizures following TMEV infection, but 150 mg/kg of CBD did not improve overall seizure outcome. The time to peak effect (TPE) of CBD in the 6 Hz 32 mA psychomotor seizure test using C57BL/6J mice was observed at 2 hours post-CBD treatment. Interestingly, CBD (150 mg/kg) significantly reduced frequency and severity of TMEV-induced acute seizures at 2 hours post-CBD treatment. These results suggest that CBD could be effective in decreasing TMEV-induced acute seizures when the seizure test is conducted at the TPE of CBD.

SIGNIFICANCE:

Cannabinoids are increasingly studied for their potential antiseizure effects. Several preclinical and clinical studies provide evidence that CBD could be an effective therapy for intractable epilepsies. The present study corroborates those previous findings and provides an opportunity to investigate pharmacokinetics, pharmacodynamics, and mechanism(s) of antiseizure effects of CBD in the TMEV model, which may help to design future clinical studies more effectively.”

https://www.ncbi.nlm.nih.gov/pubmed/31440724

https://onlinelibrary.wiley.com/doi/full/10.1002/epi4.12351

Cannabidiol differentially regulates basal and LPS-induced inflammatory responses in macrophages, lung epithelial cells, and fibroblasts.

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Toxicology and Applied Pharmacology“Cannabidiol (CBD) containing products are available in a plethora of flavors including oral, sublingual, and inhalable forms. Immunotoxicological effects of CBD containing liquids were assessed by hypothesizing that CBD regulates oxidative stress and lipopolysaccharide (LPS) induced inflammatory responses in macrophages, epithelial cells, and fibroblasts.

RESULTS:

CBD showed differential effects on IL-8 and MCP-1, and acellular and cellular ROS levels. CBD significantly attenuated LPS-induced NF-κB activity and IL-8 and MCP-1 release from macrophages. Cytokine array data depicted a differential cytokine response due to CBD. Inflammatory mediators, IL-8, serpin E1, CXCL1, IL-6, MIF, IFN-γ, MCP-1, RANTES, and TNF-α were induced, whereas MCP-1/CCL2, CCL5, eotaxin, IL-1ra, and IL-2 were reduced. CBD and dexamethasone treatments reduced the IL-8 level induced by LPS when the cells were treated individually, but showed antagonistic effects when used in combination via MCPIP (monocytic chemotactic protein-induced protein).

CONCLUSION:

CBD differentially regulated basal pro-inflammatory response and attenuated both LPS-induced cytokine release and NF-κB activity in monocytes, similar to dexamethasone. Thus, CBD has a differential inflammatory response and acts as an anti-inflammatory agent in pro-inflammatory conditions but acts as an antagonist with steroids, overriding the anti-inflammatory potential of steroids when used in combination.”

https://www.ncbi.nlm.nih.gov/pubmed/31437494

https://www.sciencedirect.com/science/article/pii/S0041008X19303217?via%3Dihub

Cannabidiol attenuates the rewarding effects of cocaine in rats by CB2, 5-TH1A and TRPV1 receptor mechanisms.

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Neuropharmacology“Cocaine abuse continues to be a serious health problem worldwide. Despite intense research there is currently no FDA-approved medication to treat cocaine use disorder. The recent search has been focused on agents targeting primarily the dopamine system, while limited success has been achieved at the clinical level.

Cannabidiol (CBD) is a U.S. FDA-approved cannabinoid for the treatment of epilepsy and recently was reported to have therapeutic potential for other disorders. Here we systemically evaluated its potential utility for the treatment of cocaine addiction and explored the underlying receptor mechanisms in experimental animals.

These findings suggest that CBD may have certain therapeutic utility by blunting the acute rewarding effects of cocaine via a DA-dependent mechanism.”

https://www.ncbi.nlm.nih.gov/pubmed/31437433

https://www.sciencedirect.com/science/article/pii/S0028390819302990?via%3Dihub

Cannabidiol and the Remainder of the Plant Extract Modulate the Effects of Δ9-Tetrahydrocannabinol on Fear Memory Reconsolidation.

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Image result for frontiers in behavioral neuroscience “Δ9-Tetrahydrocannabinol (THC, a CB1 receptor agonist) and Cannabidiol (CBD, a non-competitive antagonist of endogenous CB1 and CB2 ligands) are two primary components of Cannabis species, and may modulate fear learning in mammals.

The CB1 receptor is widely distributed throughout the cortex and some limbic regions typically associated with fear learning. Humans with posttraumatic disorder (PTSD) have widespread upregulation of CB1 receptor density and reduced availability of endogenous cannabinoid anandamide, suggesting a role for the endocannabinoid system in PTSD.

Pharmacological blockade of memory reconsolidation following recall of a conditioned response modulates the expression of learned fear and may represent a viable target for the development of new treatments for PTSD.

In this study, we focused on assessing the impact of the key compounds of the marijuana plant both singly and, more importantly, in concert on attenuation of learned fear. Specifically, we assessed the impact of THC, CBD, and/or the remaining plant materials (post-extraction; background material), on reconsolidation of learned fear.

Results: CBD alone, but not THC alone, significantly attenuated fear memory reconsolidation when administered immediately after recall. The effect persisted for at least 7 days. A combination of CBD and THC also attenuated the fear response. Plant BM also significantly attenuated reconsolidation of learned fear both on its own and in combination with THC and CBD. Finally, THC attenuated reconsolidation of learned fear only when co-administered with CBD or plant BM.

Conclusion: CBD may provide a novel treatment strategy for targeting fear-memories. Furthermore, plant BM also significantly attenuated the fear response. However, whereas THC alone had no significant effects, its effects were modulated by the addition of other compounds. Future research should investigate some of the other components present in the plant BM (such as terpenes) for their effects alone, or in combination with isolated pure cannabinoids, on fear learning.”

https://www.ncbi.nlm.nih.gov/pubmed/31417379

https://www.frontiersin.org/articles/10.3389/fnbeh.2019.00174/full

Emerging role of cannabinoids and synthetic cannabinoid receptor 1/cannabinoid receptor 2 receptor agonists in cancer treatment and chemotherapy-associated cancer management

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Journal of Cancer Research and Therapeutics“Cannabis was extensively utilized for its medicinal properties till the 19th century. A steep decline in its medicinal usage was observed later due to its emergence as an illegal recreational drug.

Advances in technology and scientific findings led to the discovery of delta-9-tetrahydrocannabinol (THC), the primary psychoactive compound of cannabis, that further led to the discovery of endogenous cannabinoids system consisting of G-protein-coupled receptors – cannabinoid receptor 1 and cannabinoid receptor 2 along with their ligands, mainly anandamide and 2-arachidonoylglycerol.  Endocannabinoid (EC) is shown to be a modulator not only for physiological functions but also for the immune system, endocrine network, and central nervous system.

Medicinal research and meta-data analysis over the last few decades have shown a significant potential for both THC and cannabidiol (CBD) to exert palliative effects. People suffering from many forms of advanced stages of cancers undergo chemotherapy-induced nausea and vomiting followed by severe and chronic neuropathic pain and weight loss.

THC and CBD exhibit effective analgesic, anxiolytic, and appetite-stimulating effect on patients suffering from cancer. Drugs currently available in the market to treat such chemotherapy-induced cancer-related ailments are Sativex (GW Pharmaceutical), Dronabinol (Unimed Pharmaceuticals), and Nabilone (Valeant Pharmaceuticals).

Apart from exerting palliative effects, THC also shows promising role in the treatment of cancer growth, neurodegenerative diseases (multiple sclerosis and Alzheimer’s disease), and alcohol addiction and hence should be exploited for potential benefits.

The current review discusses the nature and role of CB receptors, specific applications of cannabinoids, and major studies that have assessed the role of cannabinoids in cancer management.

Specific targeting of cannabinoid receptors can be used to manage severe side effects during chemotherapy, palliative care, and overall cancer management. Furthermore, research evidences on cannabinoids have suggested tumor inhibiting and suppressing properties which warrant reconsidering legality of the substance.

Studies on CB1 and CB2 receptors, in case of cancers, have demonstrated the psychoactive constituents of cannabinoids to be potent against tumor growth.

Interestingly, studies have also shown that activation of CB1 and CB2 cannabinoid receptors by their respective synthetic agonists tends to limit human cancer cell growth, suggesting the role of the endocannabinoid system as a novel target for treatment of cancers.

Further explorations are required to exploit cannabinoids for an effective cancer management.”

http://www.cancerjournal.net/preprintarticle.asp?id=263538

“Could Cannabis Kill Cancer Cells? A New Study Looks Promising”  https://www.portlandmercury.com/blogtown/2019/08/15/26977361/could-cannabis-kill-cancer-cells-a-new-study-looks-promising

“Study Reviews How Marijuana Compounds Inhibit Tumor Growth And Kill Cancer Cells” https://www.marijuanamoment.net/study-reviews-how-marijuana-compounds-inhibit-tumor-growth-and-kill-cancer-cells/

Cannabinoids and inflammation: Implications for People Living with HIV.

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Image result for wolters kluwer “Thanks to the success of modern antiretroviral therapy (ART), people living with HIV (PLWH) have life expectancies which approach that of persons in the general population. However, despite the ability of ART to suppress viral replication, PLWH have high levels of chronic systemic inflammation which drives the development of comorbidities such as cardiovascular disease, diabetes and non-AIDS associated malignancies.

Historically, cannabis has played an important role in alleviating many symptoms experienced by persons with advanced HIV infection in the pre-ART era and continues to be used by many PLWH in the ART era, though for different reasons.

Δ-tetrahydrocannabinol (Δ-THC) and cannabidiol (CBD) are the phytocannabinoids which have received most attention for their medicinal properties. Due to their ability to suppress lymphocyte proliferation and inflammatory cytokine production, there is interest in examining their therapeutic potential as immunomodulators.

CB2 receptor activation has been shown in vitro to reduce CD4 T-cell infection by CXCR4-tropic HIV and to reduce HIV replication.

Studies involving SIV-infected macaques have shown that Δ-THC can reduce morbidity and mortality and has favourable effects on the gut mucosal immunity. Furthermore, ΔTHC administration was associated with reduced lymph node fibrosis and diminished levels of SIV proviral DNA in spleens of rhesus macaques compared with placebo-treated macaques.

In humans, cannabis use does not induce a reduction in peripheral CD4 T-cell count or loss of HIV virological control in cross-sectional studies. Rather, cannabis use in ART-treated PLWH was associated with decreased levels of T-cell activation, inflammatory monocytes and pro-inflammatory cytokines secretion, all of which are related to HIV disease progression and co-morbidities.

Randomized clinical trials should provide further insights into the ability of cannabis and cannabinoid-based medicines to attenuate HIV-associated inflammation. In turn, these findings may provide a novel means to reduce morbidity and mortality in PLWH as adjunctive agents to ART.”

https://www.ncbi.nlm.nih.gov/pubmed/31408029

https://insights.ovid.com/crossref?an=00002030-900000000-96855

Bones and Joints: The Effects of Cannabinoids on the Skeleton.

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Image result for j clin endocrinol metab“This paper reviews the endocannabinoid system and focuses on the role of endocannabinoids in bone metabolism and their potential use in the management of conditions associated with bone loss.

CONTEXT:

The endocannabinoid system uses tissue-specific lipid ligands and G protein-coupled transmembrane receptors to regulate neurological, metabolic, and immune responses. Recent studies demonstrate that the endocannabinoid system influences bone metabolism. With the increasing use of endocannabinoid mimetics, e.g. tetrahydrocannabinol (THC) and cannabidiol (CBD), endocannabinoids’ involvement in bone growth and remodeling has become clinically relevant.

EVIDENCE ACQUISITION:

This literature review is based upon a search of Pubmed and Google Scholar databases, as of June 2019, for all English-language publications relating to cannabinoids and bone. We evaluated retrieved articles for relevance, experimental design, data acquisition, statistical analysis, and conclusions.

EVIDENCE SYNTHESIS:

Preclinical studies establish a role for endocannabinoids in bone metabolism. These studies yield complex and often contradictory results attributed to differences in the specific experimental model examined. Studies using human cells or subjects are limited.

CONCLUSIONS:

In vitro and animal models document that endocannabinoids participate in bone biology. The relevance of these observations to humans is not clear. The increasing chronic use of medical and recreational cannabis underscores the need to better understand the role of endocannabinoids in human bone metabolism. Moreover, it is important to evaluate the role of endocannabinoids as a therapeutic target to prevent and treat disorders associated with bone loss.”

https://www.ncbi.nlm.nih.gov/pubmed/31393556

“[The endocannabinoid system and bone].”  https://www.ncbi.nlm.nih.gov/pubmed/27734700

“Joint problems arising from lack of repair mechanisms: can cannabinoids help?”  https://www.ncbi.nlm.nih.gov/pubmed/29574720

“Cannabinoids and bone regeneration.”  https://www.ncbi.nlm.nih.gov/pubmed/30702341

“Cannabinoids and the skeleton: from marijuana to reversal of bone loss.”  https://www.ncbi.nlm.nih.gov/pubmed/19634029

The safety, tolerability, and effectiveness of PTL-101, an oral cannabidiol formulation, in pediatric intractable epilepsy: A phase II, open-label, single-center study.

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“Several works have reported on the antiepileptic impact of cannabis-based preparations in patients with treatment-resistant epilepsy (TRE). However, current formulations suffer from low bioavailability and side effects. PTL-101, an oral formulation containing highly purified cannabidiol (CBD) embedded in seamless gelatin matrix beadlets was designed to enhance bioavailability and maintain a constant gastrointestinal transit time.

RESULTS:

Sixteen patients (age: 9.1±3.4) enrolled in the study; 11 completed the full treatment program. The average maintenance dose was 13.6±4.2mg/kg. Patient adherence to treatment regimens was 96.3±9.9%. By the end of the treatment period, 81.9% and 73.4±24.6% (p<0.05) reductions from baseline median seizure count and monthly seizure frequency, respectively, were recorded. Responders’ rate was 56%; two patients became fully seizure-free. By study end, 8 (73%) caregivers reported an improved/very much improved condition, and 9 (82%) reported reduced/very much reduced seizure severity. Most commonly reported treatment-related adverse effects were sleep disturbance/insomnia, (4 (25.0%) patients), followed by somnolence, increased seizure frequency, and restlessness (3 patients each (18.8%)). None were serious or severe, and all resolved.

CONCLUSIONS:

PTL-101 was safe and tolerable for use and demonstrated a potent seizure-reducing effect among pediatric patients with TRE.”

https://www.ncbi.nlm.nih.gov/pubmed/31394352

https://www.epilepsybehavior.com/article/S1525-5050(19)30305-1/fulltext

Application device for THC:CBD oromucosal spray in the management of resistant spasticity: pre-production testing.

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 Publication Cover“Patients with multiple sclerosis spasticity (MSS) and upper limb/hand impairment who are taking 9-delta-tetrahydrocannabinol:cannabidiol (THC:CBD) oromucosal spray (Sativex®) may have difficulty self-administering their medication, possibly limiting adherence and treatment effectiveness.

A Class I EU device is available to support administration of THC:CBD spray. Pre-production testing was undertaken in a patient sample.

Results: Fifteen patients participated. Mean treatment time with THC:CBD spray was 4 (range: 0.1-6.1) years. 87% of participants ‘always’, ‘often’ or ‘sometimes’ had hand impairment, and 53% reported difficulty administering THC:CBD spray. Participants reported better application using the device (73%), with less strength required (54%). Most participants (93%) considered the instruction leaflet to be clear and many (66%) expressed interest in using the device. Most HCPs (93%) did not foresee any difficulties in use of the device.

Conclusion: The proposed adherence device was useful to address self-application difficulties with THC:CBD spray in our sample. Providing the device to MSS patients with upper limb/hand spasticity impairment may restore autonomy and support adherence to THC:CBD spray.”

https://www.ncbi.nlm.nih.gov/pubmed/31393179

https://www.tandfonline.com/doi/abs/10.1080/17434440.2019.1653182?journalCode=ierd20

Cannabis and Epilepsy.

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 Publication Cover“In recent years, the use of cannabidiol in the treatment of refractory epilepsy has been increasingly investigated and has been gaining public support as a novel way to treat these disorders.

Marijuana has been used for medical purposes for thousands of years, and a lot of research has been conducted over the last several decades into the chemistry and pharmacology of marijuana and its many compounds, including cannabidiol.

There are historical and recent scientific developments that support the use of cannabidiol in rare severe epilepsy syndromes.”

https://www.ncbi.nlm.nih.gov/pubmed/31385740

https://www.tandfonline.com/doi/abs/10.1080/15504263.2019.1645372?journalCode=wjdd20