The use of cannabis in supportive care and treatment of brain tumor

Issue Cover

“Anticancer Effects of Cannabinoids may be able to Prolong Life.

Cannabinoids are multitarget substances. Currently available are dronabinol (synthetic delta-9-tetrahydrocannabinol, THC), synthetic cannabidiol (CBD) the respective substances isolated and purified from cannabis, a refined extract, nabiximols (THC:CBD = 1.08:1.00); and nabilone, which is also synthetic and has properties that are very similar to those of THC.

Cannabinoids have a role in the treatment of cancer as palliative interventions against nausea, vomiting, pain, anxiety, and sleep disturbances. THC and nabilone are also used for anorexia and weight loss, whereas CBD has no orexigenic effect. The psychotropic effects of THC and nabilone, although often undesirable, can improve mood when administered in low doses. CBD has no psychotropic effects; it is anxiolytic and antidepressive.

Of particular interest are glioma studies in animals where relatively high doses of CBD and THC demonstrated significant regression of tumor volumes (approximately 50% to 95% and even complete eradication in rare cases). Concomitant treatment with X-rays or temozolomide enhanced activity further. Similarly, a combination of THC with CBD showed synergistic effects. Although many questions, such as on optimized treatment schedules, are still unresolved, today’s scientific results suggest that cannabinoids could play an important role in palliative care of brain tumor patients.

THC, a partial CB1, CB2 agonist, has the stigma of psychotropic effects that are mediated by CB1 stimulation. However, CB1 stimulation is necessary for improving mood and appetite and many other effects. At present, it is hard to imagine a better approach than adjusting THC doses individually to balance wanted versus unwanted effects. Generally, higher doses are needed to achieve analgesic and antiemetic effects. Even much higher, supraphysiologic oral doses would be needed to combat tumors.

Combinations were synergistic under many circumstances such as in pain and antitumor studies. Cannabinoids differ in their antitumor activities and probably in their mechanisms and targets, which is a rationale for combinations. However, for many pharmacological effects (except against tumors) roughly 10-times higher daily doses are needed for CBD compared to THC.

In summary, the endocannabinoid system is likely playing a crucial role in palliative care. The future will show whether an optimized treatment strategy with cannabinoids can also prolong life of brain tumor patients by their virtue to combat cancer cells.”

https://academic.oup.com/nop/article/4/3/151/2918616

“Cannabinoid Drug Prolongs the Life of Brain Tumor Patients in Phase II Trials”  https://labiotech.eu/gw-pharmaceuticals-brain-tumor/

Reefer to the Rescue: The Dope on Cannabidiol as a Multi-Symptom Panacea for Dravet Syndrome

American Epilepsy Society

“Dravet syndrome (DS) is a debilitating developmental disorder typified by severe seizures and delayed onset of psychomotor deficits.

In addition to increasing the risk for sudden unexpected death in epilepsy (SUDEP), the medically refractory status epilepticus in DS can be life-threatening, which makes it crucial to identify drugs to reduce seizures.

The quest for a viable drug to limit seizures in DS has intersected with the recent excitement over the potential use of cannabinoids as antiepileptic agents, leading to extensive anecdotal reports of the potential for cannabinoids to limit seizures in DS

Cannabinoids are active derivatives of the marijuana plant, Cannabis sativa.

The study reveals a strong preclinical basis for the use of CBD in DS. They find that CBD pre-treatment reduces both duration and severity of thermally-induced behavioral seizures.

In conclusion, Kaplan and colleagues provide the first preclinical demonstration that CBD may help alleviate seizures in a mouse model of DS validating the translational potential of CBD in patients with DS.

The demonstration that CBD improves deficits in social interactions in DS launches an exciting therapeutic possibility of alleviating behavioral impairments that persist beyond the seizures and pave the way for mechanistic studies that could positively impact treatment of autism spectrum disorders.”

http://epilepsycurrents.org/doi/10.5698/1535-7597.18.2.118?code=amep-site

Cannabis for Chronic Pain: Challenges and Considerations.

Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy banner

“The National Academies of Sciences, Engineering, and Medicine has found substantial evidence that cannabis (plant) is effective for the treatment of chronic pain in adults, and moderate evidence that oromucosal cannabinoids (extracts, especially nabiximols) improve short-term sleep disturbances in chronic pain. ”

https://www.ncbi.nlm.nih.gov/pubmed/29637590

https://onlinelibrary.wiley.com/doi/abs/10.1002/phar.2115

Therapeutic cannabinoids in multiple sclerosis: immunomodulation revisited.

Publication cover image

Cannabinoids are compounds with pleiotropic properties that act on the cannabinoid receptors, CB1 and CB2, and are divided into endocannabinoids, the endogenous ligands of these receptors, synthetic cannabinoids and phytocannabinoids.

The latter are derived from the plant Cannabis sativa. The therapeutic and psychoactive properties of this plant have been observed and used for centuries.

Of the over 60 compounds that are unique to Cannabis sativa, the substances that have been attributed the greatest therapeutic potential are Δ9 – tetrahydrocannabinol (THC) and cannabidiol (CBD), both of which, used alone or combined with each other, have become approved drugs.”

https://www.ncbi.nlm.nih.gov/pubmed/29633480

https://onlinelibrary.wiley.com/doi/abs/10.1111/ene.13658

Anti-inflammatory properties of cannabidiol, a non-psychotropic cannabinoid, in experimental allergic contact dermatitis.

Journal of Pharmacology and Experimental Therapeutics

“Phytocannabinoids modulate inflammatory responses by regulating the production of cytokines in several experimental models of inflammation.

Cannabinoid type-2 (CB2) receptor activation was shown to reduce the production of the monocyte chemotactic protein-2 (MCP-2) chemokine in polyinosinic-polycytidylic acid [poly-(I:C)]-stimulated human keratinocyte (HaCaT) cells, an in vitro model of allergic contact dermatitis (ACD).

We investigated if non-psychotropic cannabinoids like cannabidiol (CBD) produced similar effects in this experimental model of ACD.

This is the first demonstration of the anti-inflammatory properties of CBD in an experimental model of ACD.”

No Acute Effects of Cannabidiol on the Sleep-Wake Cycle of Healthy Subjects: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study

Image result for frontiers in pharmacology

“Cannabidiol (CBD) is a component of Cannabis sativa that has a broad spectrum of potential therapeutic effects in neuropsychiatric and other disorders. However, few studies have investigated the possible interference of CBD on the sleep-wake cycle.

The aim of the present study was to evaluate the effect of a clinically anxiolytic dose of CBD on the sleep-wake cycle of healthy subjects in a crossover, double-blind design.

The drug did not induce any significant effect.

Different from anxiolytic and antidepressant drugs such as benzodiazepines and selective serotonin reuptake inhibitors, acute administration of an anxiolytic dose of CBD does not seem to interfere with the sleep cycle of healthy volunteers. The present findings support the proposal that CBD do not alter normal sleep architecture.

Cannabidiol may play a therapeutic role in sleep regulation.

We found no differences between CBD and placebo in respect to polysomnographic findings or cognitive and subjective measures in a sample of healthy subjects. Unlike widely used anxiolytic and antidepressant drugs such as benzodiazepines and SSRIs, the acute administration of an anxiolytic dose of CBD does not appear to interfere with the sleep cycle of healthy volunteers. Future studies should address the effects of CBD on the sleep-wake cycle of patient populations as well as evaluate the chronic effects of CBD in larger samples of patients with sleep and neuropsychiatric disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/29674967

https://www.frontiersin.org/articles/10.3389/fphar.2018.00315/full

Cannabidiol to Improve Mobility in People with Multiple Sclerosis

Image result for frontiers in neurology

“Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) that affects an estimated 2.3 million people worldwide. The symptoms of MS are highly varied but frequently include pain, muscle spasticity, fatigue, inflammation, and depression. These symptoms often lead to reduced physical activity, negatively impact functional mobility, and have a detrimental impact on patients’ quality of life.

Although recent years have seen significant advances in disease modifying therapy, none of the current treatments halts or cures MS related symptoms. As a consequence, many people with MS (PwMS) look for alternative and complementary therapies such as cannabis.

The cannabis plant contains many biologically active chemicals, including ~60 cannabinoids. Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) are typically the most concentrated chemical components of cannabis and believed to primarily drive therapeutic benefit.

There is evidence that CBD has a number of beneficial pharmacological effects. It is anti-inflammatory, antioxidative, antiemetic, antipsychotic, and neuroprotective. The review of 132 original studies by Bergamaschi et al. describes the safety profile of CBD by highlighting that catalepsy is not induced and physiological parameters (heart rate, blood pressure, and body temperature) are not altered. Moreover, psychomotor and psychological functions are not negatively affected. High doses of up to 1,500 mg per day and chronic use have been repeatedly shown to be well tolerated by humans.

Additionally, there is also evidence that CBD may reduce the negative psychotropic effects, memory impairment, and appetite stimulation, anxiety and psychotic-like states of THC while enhancing its positive therapeutic actions.

 Anecdotal reports indicate that an increasing number of PwMS use cannabis (medical marijuana) as a supplement to improve their mobility.

Based on the following considerations, it is our opinion that CBD supplementation maybe advisable for PwMS to reduce fatigue, pain, spasticity, and ultimately improve mobility. “

https://www.frontiersin.org/articles/10.3389/fneur.2018.00183/full

Cannabidiol regulates behavioural alterations and gene expression changes induced by spontaneous cannabinoid withdrawal.

British Journal of Pharmacology banner

“Cannabidiol (CBD) represents a promising therapeutic tool for treating cannabis use disorder (CUD).

This study aimed to evaluate the effects of CBD on the behavioural and gene expression alterations induced by spontaneous cannabinoid withdrawal.

CONCLUSION AND IMPLICATIONS:

The results suggest that CBD alleviates spontaneous cannabinoid withdrawal and normalises associated gene expression changes. Future studies are needed to determine the relevance of CBD as a potential therapeutic tool for treating CUD.”

https://www.ncbi.nlm.nih.gov/pubmed/29624642

https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bph.14226

Therapeutic Effects of Prolonged Cannabidiol Treatment on Psychological Symptoms and Cognitive Function in Regular Cannabis Users: A Pragmatic Open-Label Clinical Trial.

Cannabis and Cannabinoid Research cover image

“Chronic cannabis use has been associated with impaired cognition and elevated psychological symptoms, particularly psychotic-like experiences. While Δ9-tetrahydrocannabinol (THC) is thought to be primarily responsible for these deleterious effects, cannabidiol (CBD) is purported to have antipsychotic properties and to ameliorate cognitive, symptomatic, and brain harms in cannabis users. However, this has never been tested in a prolonged administration trial in otherwise healthy cannabis users. Here, we report the first study of prolonged CBD administration to a community sample of regular cannabis users in a pragmatic trial investigating potential restorative effects of CBD on psychological symptoms and cognition.

Results: CBD was well tolerated with no reported side effects; however, participants retrospectively reported reduced euphoria when smoking cannabis. No impairments to cognition were found, nor were there deleterious effects on psychological function. Importantly, participants reported significantly fewer depressive and psychotic-like symptoms at PT relative to BL, and exhibited improvements in attentional switching, verbal learning, and memory. Increased plasma CBD concentrations were associated with improvements in attentional control and beneficial changes in psychological symptoms. Greater benefits were observed in dependent than in nondependent cannabis users.

Conclusions:Prolonged CBD treatment appears to have promising therapeutic effects for improving psychological symptoms and cognition in regular cannabis users. Our findings require replication given the lack of a placebo control in this pragmatic trial, but suggest that CBD may be a useful adjunct treatment for cannabis dependence.”

Cannabis in epilepsy: From clinical practice to basic research focusing on the possible role of cannabidivarin.

 Epilepsia Open banner

“Cannabidivarin (CBDV) and cannabidiol (CBD) have recently emerged among cannabinoids for their potential antiepileptic properties, as shown in several animal models.

We report the case of a patient affected by symptomatic partial epilepsy who used cannabis as self-medication after the failure of countless pharmacological/surgical treatments.

After cannabis administration, a dramatic clinical improvement, in terms of both decrease in seizure frequency and recovery of cognitive functions, was observed, which might parallel high CBDV plasma concentrations.

Our patient’s electroclinical improvement supports the hypothesis that cannabis could actually represent an effective, well-tolerated antiepileptic drug.

Moreover, the experimental data suggest that CBDV may greatly contribute to cannabis anticonvulsant effect through its possible GABAergic action.”

https://www.ncbi.nlm.nih.gov/pubmed/29588939

https://onlinelibrary.wiley.com/doi/abs/10.1002/epi4.12015