Cannabis: A Prehistoric Remedy for the Deficits of Existing and Emerging Anticancer Therapies

“Cannabis has been used medicinally for centuries and numerous species of this genus are undoubtedly amongst the primeval plant remedies known to humans.

Cannabis sativa in particular is the most reported species, due to its substantial therapeutic implications that are owed to the presence of chemically and pharmacologically diverse cannabinoids.

These compounds have long been used for the palliative treatment of cancer.

Recent advancements in receptor pharmacology research have led to the identification of cannabinoids as effective antitumor agents.

This property is accredited for their ability to induce apoptosis, suppress proliferative cell signalling pathways and promote cell growth inhibition.

Evolving lines of evidence suggest that cannabinoid analogues, as well as their receptor agonists, may offer a novel strategy to treat various forms of cancer.

This review summarizes the historical perspective of C. sativa, its potential mechanism of action, and pharmacokinetic and pharmacodynamic aspects of cannabinoids, with special emphasis on their anticancer potentials.”

http://www.xiahepublishing.com/ArticleFullText.aspx?sid=2&jid=3&id=10.14218%2FJERP.2017.00012

Cannabis products.

“Cannabis products. First row, left to right: Indian, Lebanese, Turkish and Pakistani hashish. Second row, left to right: Swiss hashish, Zairean marijuana, Swiss marijuana, Moroccan hash oil.”

The potential protective effects of cannabinoid receptor agonist WIN55,212-2 on cognitive dysfunction is associated with the suppression of autophagy and inflammation in an experimental model of vascular dementia.

Psychiatry Research Home

“Vascular dementia (VaD) is characteristic of chronic brain ischemia and progressive memory decline, which has a high incidence in the elderly. However, there are no effective treatments for VaD, and the underlying mechanism of its pathogenesis remains unclear.

This study investigated the effects of a synthetic cannabinoid receptor agonist WIN55,212-2 (WIN) on VaD, and molecular mechanisms of the effects.

These data indicate that WIN exerts a neuroprotective effect on the cognitive deficits of VaD rats, which may be associated with the suppression of excessive autophagy and inflammation.”

https://www.ncbi.nlm.nih.gov/pubmed/29945070

https://www.psy-journal.com/article/S0165-1781(17)31479-8/fulltext

Structure-Activity Relationship of Cannabis Derived Compounds for the Treatment of Neuronal Activity-Related Diseases.

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“Cannabis sativa active compounds are extensively studied for their therapeutic effects, beyond the well-known psychotropic activity. C. Sativa is used to treat different medical indications, such as multiple sclerosis, spasticity, epilepsy, ulcerative colitis and pain. Simultaneously, basic research is discovering new constituents of cannabis-derived compounds and their receptors capable of neuroprotection and neuronal activity modulation. The function of the various phytochemicals in different therapeutic processes is not fully understood, but their significant role is starting to emerge and be appreciated. In this review, we will consider the structure-activity relationship (SAR) of cannabinoid compounds able to bind to cannabinoid receptors and act as therapeutic agents in neuronal diseases, e.g., Parkinson’s disease.”

https://www.ncbi.nlm.nih.gov/pubmed/29941830

http://www.mdpi.com/1420-3049/23/7/1526

Pain Modulation after Oromucosal Cannabinoid Spray (SATIVEX®) in Patients with Multiple Sclerosis: A Study with Quantitative Sensory Testing and Laser-Evoked Potentials.

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“Delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) (nabiximols or Sativex®) is an oromucosal spray formulation containing THC and CBD at an approximately 1:1 fixed ratio. Its administration for the treatment of pain in patients with multiple sclerosis (MS) has been established.

MS patients generally complain of different kinds of pain, including spasticity-related and neuropathic pain. In this study, we compared and evaluated pain modulation and thermal/pain threshold of MS patients before and after THC/CBD administration.

Patients reported a significant reduction in pain.

Our results indicate that Sativex® therapy provides pain relief in MS patients and suggest that it might modulate peripheral cold-sensitive TRP channels.”

https://www.ncbi.nlm.nih.gov/pubmed/29933552

http://www.mdpi.com/2305-6320/5/3/59

Medical Cannabis in Patients with Chronic Pain: Effect on Pain Relief, Pain Disability, and Psychological aspects. A Prospective Non randomized Single Arm Clinical Trial.

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“There is an increasing interest in the medical use of cannabis, particularly in the treatment of chronic pain.

OBJECTIVES:

The aim is to evaluate the effects of cannabis use and the associated benefits reported by patients with various chronic pain diagnoses.

RESULTS:

Pain intensity records a statistically significant reduction from Baseline to 12 months follow up (X² 61.375; P<0,001); the im- provements from Baseline to 12 months follow up are also recorded in pain disability (X² 39.423; P<0,001) and in anxiety and depression symptoms (X²30.362; P<0,001; X²27.786; P<0,001).

CONCLUSIONS:

Our study suggest that Cannabis therapy, as an adjun- ct a traditional analgesic therapy, can be an efficacious tool to make more effective the management of chronic pain and its consequences on functional and psychological dimension. Further randomized, controlled trials are needed to confirm our conclusions.”

https://www.ncbi.nlm.nih.gov/pubmed/29938740

The adult motor phenotype of Dravet syndrome is associated with mutation of the STXBP1 gene and responds well to cannabidiol treatment.

Seizure - European Journal of Epilepsy Home

“Dravet syndrome is a terrible disease generally caused by mutations of the SCN1A gene. Recently others genes such as STXBP1 have been involved in the pathogenesis of the disease. The STXBP1 mutation in patients with Dravet Syndrome may additionally causes several parkinsonian features usually attributed to carriers of the SCN1A mutation. Management continues to be difficult that is why Cannabidiol emerged as valid option for treatment of this condition.”

https://www.ncbi.nlm.nih.gov/pubmed/29929108

https://www.seizure-journal.com/article/S1059-1311(17)30500-9/fulltext

Cannabinoids for Treatment of MS Symptoms: State of the Evidence.

Current Neurology and Neuroscience Reports

“Cannabis and cannabinoids have been used medically and recreationally for thousands of years and recently there has been a growing body of research in this area. With increased access now that medical marijuana is available in many jurisdictions, patients and providers want to know more about the evidence for benefits and risks of cannabinoid use.

This paper provides an overview of the available cannabinoid-based formulations, a summary of the highest quality evidence for the use of cannabinoids for treating spasticity and pain associated with multiple sclerosis (MS), and a discussion of possible dosing regimens based on information from these studies.

Two recent high-quality systematic reviews concluded that the only strong evidence for medical marijuana in neurological disorders was for reducing the symptoms of patient-reported spasticity and central pain in MS and that the only complementary and alternative medicine (CAM) intervention in MS with strong supportive evidence was cannabinoids.

Based on this review, they concluded that nabiximols (Sativex oral spray), oral cannabis extract (OCE), and synthetic tetrahydrocannabinol (THC) are probably effective at reducing patient-reported symptoms of spasticity in people with MS, but OCE and synthetic THC were not found to be effective for reducing physician-administered measures of spasticity.

In addition, nabiximols, OCE, and synthetic THC are probably effective at reducing MS-related pain. Cannabinoids were generally well-tolerated.

While cannabinoids have been studied for a variety of neurologic disorders, there is strongest evidence to indicate benefits in treatment of spasticity and neuropathic pain in multiple sclerosis. Although the best dose for an individual remains uncertain, most participants in the studies discussed in this paper used between 20 and 40 mg of THC a day in divided doses.”

https://www.ncbi.nlm.nih.gov/pubmed/29923025

https://link.springer.com/article/10.1007%2Fs11910-018-0859-x

Medicinal Cannabinoids in Palliative Care.

 British Journal of Clinical Pharmacology banner

“The treatment of symptoms in people with palliative diagnoses begins with meticulous clinical assessment with treatment choice (s) selected based on an understanding of the symptom aetiology and the evidence which underpins its treatment.

Increasingly the merits of palliative care have been established earlier in the disease trajectory where treatment outcomes may include increased survival and maintenance of function.

There is strong public support for the availability of medicinal cannabis, particularly for people with palliative diagnoses.

There are several areas where there is potential for symptom benefits through modulation of the endocannabinoid system, though clinical data to date has been inconclusive in key symptoms such as pain and nausea, and data from other settings such as chemotherapy-induced nausea and vomiting not readily extrapolated.

Ideally exploration of medicinal cannabinoids should occur within a clinical trial to accelerate the evidence base to inform practice. In people with refractory symptoms the consideration of unregistered products or off label prescribing should be guided by the potential influences of pharmacokinetic, pharmacodynamic and drug-drug interactions, supported by an informed discussion with the patient, and regular review of net clinical benefit.”

https://www.ncbi.nlm.nih.gov/pubmed/29923616

https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bcp.13671

Cannabidiol did not induce teratogenicity or neurotoxicity in exposed zebrafish embryos.

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“Cannabidiol (CBD) is a non-psychotomimetic compound of the Cannabis sativa that has been used for the treatment of severe epilepsy as well as other diseases of nervous system. However, toxicity studies of CBD have great relevance to guarantee the patients safety.

In this context, morphological analyses of zebrafish can contribute to evaluate the teratogenic potential, as well as evaluation of acetylcholinesterase activity and motor activity of zebrafish are valuable tools to verify the neurotoxicity potential. In the present work, we use this methodology to test the toxicity of CBD to zebrafish embryos.

No malformation was observed in morphological analysis of embryos exposed to all tested concentrations of CBD.

Embryos exposed to CBD did not show differences in acetylcholinesterase activity, but embryos exposed to CBD 20-300 μg/L were 1.4 up to 1.7-fold more active when compared to the control. Despite that, at 48 hpf, motor activity returned to control values.

Our results suggest that the effects observed after CBD exposure are intimately related to CB1 receptor that is present in zebrafish since early stages of development. The present work showed early light effects induced by CBD exposure in concentrations that did not alter biochemical activity.”

The impact of Cannabidiol treatment on regulatory T-17 Cells and neutrophil polarization in Acute Kidney Injury.

 American Journal of Physiology-Renal Physiology 0 0 cover image

“Hallmark features of acute kidney injury (AKI) include mobilization of immune and inflammatory mechanisms culminating in tissue injury. Emerging information indicates heterogeneity of neutrophils with pro- and anti-inflammatory functions (N1 and N2, respectively). Also, regulatory T-17 (Treg17) cells curtail Th-17-mediated pro-inflammatory responses. However, the status of Treg17 cells and neutrophil phenotypes in AKI are not established.

Further, cannabidiol exerts immunoregulatory effects but its impact on Treg17 cells and neutrophil subtypes is not established. Thus, we examined the status of Treg17 cells and neutrophil subtypes in AKI and determined whether cannabidiol favors regulatory neutrophils and T cells accompanied with renoprotection.

Importantly, cannabidiol treatment preserved ψm, reduced cell death and KIM-1 accompanied by restoration of N1 and N2 imbalance and preservation of Treg17 cells while decreasing Th-17 cells. The ability of cannabidiol to favor development of Treg17 cells was further established using functional mixed lymphocytic reaction. Subsequent studies showed higher renal blood flow and reduced serum creatinine in cannabidiol-treated IRI animals.

Collectively, our novel observations establish that renal IRI causes neutrophil polarization in favor of N1 and also reduces Treg17 cells in favor of Th-17, effects that are reversed by cannabidiol treatment accompanied with significant renoprotection.”

https://www.ncbi.nlm.nih.gov/pubmed/29897289