Tag Archives: treatment

Role of the endocannabinoid system in the formation and development of depression.

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“Two types of cannabinoid (CB) receptors have been described in the human body: CB1 and CB2 receptors. CB1 receptor distribution may be related to the cannabinoid functions of memory and cognition regulation as well as motor control.

In addition, the endocannabinoid system (ECS) related to CB1 receptors may be involved in human emotion regulation, especially depression occurrence. Indeed, CB1 receptors are all distributed in depression associated neuroanatomical structures and neural circuits.

Both animal experiments and clinical studies have demonstrated that impairment of the ECS pathway is present in depression models and patients, and application of both CB1 receptor agonists and anandamide (cannabinoid-like substance) degradation inhibitors produce similar biochemical and behavioral effects as antidepressants.

These findings provide a solid basis for understanding the ECS role in the formation and development of depression. Therefore, it can be inferred that the ECS may have an important function in both depression treatment and the effects of antidepressants.”

https://www.ncbi.nlm.nih.gov/pubmed/29441900

Cannabinoid-induced cell death in endometrial cancer cells: involvement of TRPV1 receptors in apoptosis.

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Journal of Physiology and Biochemistry

“Among a variety of phytocannabinoids, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most promising therapeutic compounds. Besides the well-known palliative effects in cancer patients, cannabinoids have been shown to inhibit in vitro growth of tumor cells.

Likewise, the major endocannabinoids (eCBs), anandamide (AEA) and 2-arachidonoylglycerol (2-AG), induce tumor cell death.

The purpose of the present study was to characterize cannabinoid elements and evaluate the effect of cannabinoids in endometrial cancer cell viability.

These data indicate that cannabinoids modulate endometrial cancer cell death.

Selective targeting of TPRV1 by AEA, CBD, or other stable analogues may be an attractive research area for the treatment of estrogen-dependent endometrial carcinoma.

Our data further support the evaluation of CBD and CBD-rich extracts for the potential treatment of endometrial cancer, particularly, that has become non-responsive to common therapies.”

https://www.ncbi.nlm.nih.gov/pubmed/29441458

https://link.springer.com/article/10.1007%2Fs13105-018-0611-7

Efficacy of artisanal preparations of cannabidiol for the treatment of epilepsy: Practical experiences in a tertiary medical center.

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“Medically refractory epilepsy continues to be a challenge worldwide, and despite an increasing number of medical therapies, approximately 1 in 3 patients continues to have seizures.

Cannabidiol (CBD), one of many constituents of the Cannabis sativa or marijuana plant, has received renewed interest in the treatment of epilepsy. While highly purified CBD awaits Food and Drug Administration (FDA) approval, artisanal formulations of CBD are readily available and are seeing increased use in our patient population.

Although randomized controlled trials of CBD are ongoing and promising, data regarding artisanal formulations of CBD are minimal and largely anecdotal. Here, we report a retrospective study to define the efficacy of artisanal CBD preparations in children with epilepsy.

Given the known interaction between CBD and clobazam, we also conducted a subgroup comparison to determine if clobazam use was related to any beneficial effects of CBD. Additionally, we compared response rates with CBD and with clobazam alone within an overlapping patient cohort. A pediatric cohort with epilepsy of 108 patients was identified through a medical record search for patients using CBD oil.

The addition of CBD resulted in 39% of patients having a >50% reduction in seizures, with 10% becoming seizure-free. The responder rate for clobazam was similar. No patients achieved CBD monotherapy, although the weaning of other antiepileptic drugs (AEDs) became possible in 22% of patients. A comparable proportion had AED additions during CBD therapy. With concomitant use of clobazam, 44% of patients had a 50% reduction in seizures upon addition of CBD compared with 33% in the population not taking clobazam; this difference was not statistically significant. The most common reported side effect of CBD was sedation in less than 4% of patients, all of whom were also taking clobazam.

Increased alertness and improved verbal interactions were reported in 14% of patients in the CBD group and 8% of patients in the CBD and clobazam group. Benefits were more marked in the CBD alone group, in contrast to the CBD and clobazam group, but this difference was not statistically significant.

In summary, these findings support efficacy of artisanal CBD preparations in seizure reduction with few significant side effects. The response to CBD was independent of concurrent clobazam use, although clobazam may contribute to the sedation seen with concurrent CBD use.”

 https://www.ncbi.nlm.nih.gov/pubmed/29429908
“In this retrospective study, we report that artisanal CBD is helpful in the treatment of medically refractory seizures.”
http://www.epilepsybehavior.com/article/S1525-5050(18)30009-X/fulltext

Acute ethanol inhibition of adult hippocampal neurogenesis involves CB1 cannabinoid receptor signaling.

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Alcoholism: Clinical and Experimental Research

“Chronic ethanol exposure has been found to inhibit adult hippocampal neurogenesis in multiple models of alcohol addiction. Together, these findings suggest that acute CB1R cannabinoid receptor activation and binge ethanol treatment reduce neurogenesis through mechanisms involving CB1R. ”   https://www.ncbi.nlm.nih.gov/pubmed/29417597  http://onlinelibrary.wiley.com/doi/10.1111/acer.13608/abstract

“Alcohol-induced neurodegeneration” http://www.diva-portal.org/smash/record.jsf?pid=diva2%3A666727&dswid=174

“Defective Adult Neurogenesis in CB1 Cannabinoid Receptor Knockout Mice.  Pharmacological studies suggest a role for CB1 cannabinoid receptors (CB1R) in regulating neurogenesis in the adult brain.”  http://molpharm.aspetjournals.org/content/66/2/204.full

“Activation of Type 1 Cannabinoid Receptor (CB1R) Promotes Neurogenesis in Murine Subventricular Zone Cell Cultures”   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3660454/

“Several studies and patents suggest that the endocannabinoid system has neuro-protective properties and might be a target in neurodegenerative diseases”  https://www.ncbi.nlm.nih.gov/pubmed/27364363

“The endocannabinoid system and neurogenesis in health and disease.”   https://www.ncbi.nlm.nih.gov/pubmed/17404371

“The role of cannabinoids in adult neurogenesis. Pharmacological targeting of the cannabinoid system as a regulator of neurogenesis may prove a fruitful strategy in the prevention or treatment of mood or memory disorders.”  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4543605/

“Regulation of Adult Neurogenesis by Cannabinoids”  https://www.researchgate.net/publication/264424221_Regulation_of_Adult_Neurogenesis_by_Cannabinoids

“Delta-9-Tetrahydrocannabinol (∆9-THC) Induce Neurogenesis and Improve Cognitive Performances of Male Sprague Dawley Rats. Administration of ∆9-THC was observed to enhance the neurogenesis in the brain, especially in hippocampus thus improved the cognitive function of rats.”  https://www.ncbi.nlm.nih.gov/pubmed/28933048

“Cannabidiol Reduces Aβ-Induced Neuroinflammation and Promotes Hippocampal Neurogenesis through PPARγ Involvement. CBD was observed to stimulate hippocampal neurogenesis.”  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3230631/

“Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects. Chronic administration of the major drugs of abuse including opiates, alcohol, nicotine, and cocaine has been reported to suppress hippocampal neurogenesis in adult rats. Plant-derived, or synthetic cannabinoids may promote hippocampal neurogenesis. Cannabinoids appear to be the only illicit drug whose capacity to produce increased hippocampal newborn neurons is positively correlated with its anxiolytic- and antidepressant-like effects. In summary, since adult hippocampal neurogenesis is suppressed following chronic administration of opiates, alcohol, nicotine, and cocaine, the present study suggests that cannabinoids are the only illicit drug that can promote adult hippocampal neurogenesis following chronic administration.”  https://www.jci.org/articles/view/25509

 

The endocannabinoid system in canine Steroid-Responsive Meningitis-Arteritis and Intraspinal Spirocercosis.

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“Endocannabinoids (ECs) are involved in immunomodulation, neuroprotection and control of inflammation in the central nervous system (CNS).

Activation of cannabinoid type 2 receptors (CB2) is known to diminish the release of pro-inflammatory factors and enhance the secretion of anti-inflammatory cytokines.

Furthermore, the endocannabinoid 2-arachidonoyl glycerol (2-AG) has been proved to induce the migration of eosinophils in a CB2 receptor-dependent manner in peripheral blood and activate neutrophils independent of CB activation in humans.

The present study revealed an upregulated endocannabinoid system in dogs with inflammatory CNS diseases, highlighting the endocannabinoid system as a potential target for treatment of inflammatory CNS diseases.”

https://www.ncbi.nlm.nih.gov/pubmed/29408878

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0187197

Cannabinoid Receptors in Diabetic Kidney Disease.

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 Current Diabetes Reports

“The purpose of this review is to examine and summarize studies assessing the relevance of the endocannabinoid system (ECS) in diabetic kidney disease (DKD).

Endocannabinoids and endocannabinoid receptors of type 1 (CB1R) and of type 2 (CB2R) are present in the normal kidney. Expression of CB1R and CB2R is altered in experimental DKD.

Studies in experimental animals and cultured kidney cells show a beneficial effect of peripheral CB1R blockade and CB2R activation in DKD and an even greater efficacy of a combined treatment.

Preclinical studies confirm that both CB1R and CB2R are implicated in the pathogenesis of DKD and may represent novel targets for treatment.”

https://www.ncbi.nlm.nih.gov/pubmed/29399721

https://link.springer.com/article/10.1007%2Fs11892-018-0975-7 

Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial.

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“Patients with Lennox-Gastaut syndrome, a rare, severe form of epileptic encephalopathy, are frequently treatment resistant to available medications.

No controlled studies have investigated the use of cannabidiol for patients with seizures associated with Lennox-Gastaut syndrome.

We therefore assessed the efficacy and safety of cannabidiol as an add-on anticonvulsant therapy in this population of patients.

Add-on cannabidiol is efficacious for the treatment of patients with drop seizures associated with Lennox-Gastaut syndrome and is generally well tolerated.“

https://www.ncbi.nlm.nih.gov/pubmed/29395273

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)30136-3/fulltext

“This study is registered with ClinicalTrials.gov, number NCT02224690.”

“Cannabidiol for drop seizures in Lennox-Gastaut syndrome”  http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)30135-1/fulltext

“Cannabidiol Reduces Drop Seizures in Lennox-Gastaut Syndrome”  https://www.neurologyadvisor.com/epilepsy/cannabidiol-reduces-drop-seizures-in-lennox-gastaut-syndrome/article/739544/

“Cannabidiol helps reduce drop attacks in people with Lennox-Gastaut syndrome, study shows” https://www.epilepsy.org.uk/news/news/cannabidiol-helps-reduce-drop-attacks-people-lennox-gastaut-syndrome-study-shows-68090

“‘Pharma Grade’ CBD Effective in Lennox-Gastaut”  https://www.medscape.com/viewarticle/891810

“Cannabidiol Efficacious for Lennox-Gastaut Drop Seizures”  https://www.doctorslounge.com/index.php/news/pb/78004

Epidemiological characteristics, safety and efficacy of medical cannabis in the elderly.

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“There is a substantial growth in the use of medical cannabis in recent years and with the aging of the population, medical cannabis is increasingly used by the elderly.

We aimed to assess the characteristics of elderly people using medical cannabis and to evaluate the safety and efficacy of the treatment.

Our study finds that the therapeutic use of cannabis is safe and efficacious in the elderly population. Cannabis use may decrease the use of other prescription medicines, including opioids.”

https://www.ncbi.nlm.nih.gov/pubmed/29398248

“Medical cannabis significantly safer for elderly with chronic pain than opioids: study” https://medicalxpress.com/news/2018-02-medical-cannabis-significantly-safer-elderly.html
“Medical cannabis significantly safer for elderly with chronic pain than opioids” https://www.eurekalert.org/pub_releases/2018-02/aabu-mcs021318.php

CBD Enhances the Anticancer Effects of THC

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“Δ9-Tetrahydrocannabinol (Δ9-THC) and other cannabinoids can act as direct anticancer agents in multiple types of cancer in culture and in vivo.
Cannabidiol Enhances the Inhibitory Effects of  Δ9-Tetrahydrocannabinol on Human GlioblastomaCell Proliferation and Survival.
Δ9-THC and Cannabidiol Inhibit the Growth of Multiple Glioblastoma Cell Lines.
Cannabidiol Enhances the Inhibitory Effects of Δ9-THC on Glioblastoma Cell Growth.
Combination treatments with cannabinoids may improve overall efficacy”
https://www.scribd.com/document/50154001/CBD-Enhances-the-Anticancer-Effects-of-THC-Journal-MCT-Marcu

“Cannabidiol Enhances the Inhibitory Effects of Δ9-Tetrahydrocannabinol on Human Glioblastoma Cell Proliferation and Survival”   http://mct.aacrjournals.org/content/9/1/180.full

Direct modulation of the outer mitochondrial membrane channel, voltage-dependent anion channel 1 (VDAC1) by cannabidiol: a novel mechanism for cannabinoid-induced cell death.

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“Cannabidiol (CBD) is a non-psychoactive plant cannabinoid that inhibits cell proliferation and induces cell death of cancer cells and activated immune cells.

Here, we studied the effects of CBD on various mitochondrial functions in BV-2 microglial cells.

Our findings indicate that CBD treatment leads to a biphasic increase in intracellular calcium levels and to changes in mitochondrial function and morphology leading to cell death.

Single-channel recordings of the outer-mitochondrial membrane protein, the voltage-dependent anion channel 1 (VDAC1) functioning in cell energy, metabolic homeostasis and apoptosis revealed that CBD markedly decreases channel conductance.

Finally, using microscale thermophoresis, we showed a direct interaction between purified fluorescently labeled VDAC1 and CBD.

Thus, VDAC1 seems to serve as a novel mitochondrial target for CBD.

The inhibition of VDAC1 by CBD may be responsible for the immunosuppressive and anticancer effects of CBD.”

https://www.ncbi.nlm.nih.gov/pubmed/24309936

“The non-psychoactive plant cannabinoid, cannabidiol (CBD), alone has strong anti-inflammatory and immunosuppressive effects in diverse animal models of disease such as diabetes, cancer, rheumatoid arthritis and multiple sclerosis. In addition, CBD has been reported to have anxiolytic, antiemetic and antipsychotic effects. Moreover, CBD has been shown to possess antitumor activity in human breast carcinoma and to effectively reduce primary tumor mass, as well as size and number of lung metastasis in preclinical animal models of breast cancer.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3877544/

“In summary, in this study we have identified VDAC1 as a new molecular target for CBD. Our study suggests that CBD-induced cell death may occur through the inhibition of VDAC1 conductance and that this interaction may be responsible for the anticancer and immunosuppressive properties of CBD.”

https://www.nature.com/articles/cddis2013471

“Voltage-Dependent Anion Channel 1 As an Emerging Drug Target for Novel Anti-CancerTherapeutics.” https://www.ncbi.nlm.nih.gov/pubmed/28824871

“Finally, small molecules targeting VDAC1 can induce apoptosis. VDAC1 can thus be considered as standing at the crossroads between mitochondrial metabolite transport and apoptosis and hence represents an emerging cancer drug target.”  https://www.ncbi.nlm.nih.gov/pubmed/25448878