Monthly Archives: May 2019

Using Cannabis to Treat Cancer-Related Pain.

Posted on by
Reply

Seminars in Oncology Nursing

“OBJECTIVE: To describe which cannabinoids and terpenes are effective for treating pain.

CONCLUSION: Cannabis and cannabinoid medicines, as modulators of the endocannabinoid system, offer novel therapeutic options for the treatment of cancer-related pain, not only for patients who do not respond to conventional therapies, but also for patients who prefer to try cannabis as a first treatment option.

IMPLICATIONS FOR NURSING PRACTICE: Understanding the endocannabinoid system, cannabinoids, terpenes, routes of administration, potential drug interactions, clinical implications, and potential side effects ensures nurses can better assist patients who use cannabis for the treatment of cancer pain.”

https://www.ncbi.nlm.nih.gov/pubmed/31053395

https://www.sciencedirect.com/science/article/pii/S0749208119300609?via%3Dihub

Cannabidiol attenuates aggressive behavior induced by social isolation in mice: Involvement of 5-HT1A and CB1 receptors.

Posted on by
Reply

Progress in Neuro-Psychopharmacology and Biological Psychiatry

“Long-term single housing increases aggressive behavior in mice, a condition named isolation-induced aggression or territorial aggression, which can be attenuated by anxiolytic, antidepressant, and antipsychotic drugs.

Preclinical and clinical findings indicate that cannabidiol (CBD), a non-psychotomimetic compound from Cannabis sativa, has anxiolytic, antidepressant, and antipsychotic properties. Few studies, however, have investigated the effects of CBD on aggressive behaviors.

Here, we investigated whether CBD (5, 15, 30, and 60 mg/kg; i.p.) could attenuate social isolation-induced aggressive behavior in the resident-intruder test.

Taken together, our findings suggest that CBD may be therapeutically useful to treat aggressive behaviors that are usually associated with psychiatric disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/31054943

https://www.sciencedirect.com/science/article/pii/S0278584618308340?via%3Dihub

“cannabidiol reduces aggressiveness, study concludes”  https://globalhealthnewswire.com/2019/07/31/cannabidiol-reduces-aggressiveness-study-concludes/

Palmitoylethanolamide and Cannabidiol Prevent Inflammation-induced Hyperpermeability of the Human Gut In Vitro and In Vivo-A Randomized, Placebo-controlled, Double-blind Controlled Trial.

Posted on by
Reply

Issue Cover

“We aimed to examine, for the first time, the effect of cannabidiol (CBD) and palmitoylethanolamide (PEA) on the permeability of the human gastrointestinal tract in vitro, ex vivo, and in vivo.

RESULTS:

In vitro, PEA, and CBD decreased the inflammation-induced flux of dextrans (P < 0.0001), sensitive to PPARα and CB1 antagonism, respectively. Both PEA and CBD were prevented by PKA, MEK/ERK, and adenylyl cyclase inhibition (P < 0.001). In human mucosa, inflammation decreased claudin-5 mRNA, which was prevented by CBD (P < 0.05). Palmitoylethanolamide and cannabidiol prevented an inflammation-induced fall in TRPV1 and increase in PPARα transcription (P < 0.0001). In vivo, aspirin caused an increase in the absorption of lactulose and mannitol, which were reduced by PEA or CBD (P < 0.001).

CONCLUSION:

Cannabidiol and palmitoylethanolamide reduce permeability in the human colon. These findings have implications in disorders associated with increased gut permeability, such as inflammatory bowel disease.”

https://www.ncbi.nlm.nih.gov/pubmed/31054246

https://academic.oup.com/ibdjournal/article-abstract/25/6/1006/5341970?redirectedFrom=fulltext

Cannabidiol: A Review of Clinical Efficacy and Safety in Epilepsy.

Posted on by
Reply

Pediatric Neurology

“Several new antiepileptic medicines became available for clinical use in the last two decades. However, the prognosis of epilepsy remains unchanged, with approximately one-third of patients continuing to have drug-resistant seizures. Because many of these patients are not candidates for curative epilepsy surgery, there is a need for new seizure medicines with better efficacy and safety profile.

Recently, social media and public pressure sparked a renewed interest in cannabinoids, which had been used for epilepsy since ancient times. However, physicians have significant difficulty prescribing cannabinoids freely because of the paucity of sound scientific studies.

Among the two most common cannabinoids, cannabidiol has better antiepileptic potential than tetrahydrocannabinol. The exact antiepileptic mechanism of cannabidiol is currently not known, but it modulates a number of endogenous systems and may have a novel anticonvulsant effect. However, it has broad drug-drug interactions with several agents, including inducer and inhibitor of CYP3A4 or CYP2C19. Cannabidiol can cause liver enzyme elevation, especially when co-administered with valproate.

The US Food and Drug Administration (FDA) has approved pharmaceutical-grade cannabidiol oil for two childhood-onset catastrophic epilepsies: Dravet syndrome and Lennox-Gastaut syndrome.

The Drug Enforcement Agency also reclassified this product as a schedule V agent. However, other cannabidiol products remain as a schedule I substance and are primarily used without regulation. Additionally, the FDA-approved pharmaceutical-grade cannabidiol oil is expensive, and insurance companies might approve this only for the designated indications.

In despair, many individuals may resort to unregulated medical cannabis products in an attempt to control seizures. Rather than spontaneous treatment without medical supervision, adequate medical oversight is indicated to monitor and manage the proper dose, side effects, validity of the product, and drug-drug interactions.”

https://www.ncbi.nlm.nih.gov/pubmed/31053391

https://www.pedneur.com/article/S0887-8994(18)31168-8/fulltext

Pharmacokinetics and Tolerability of Multiple Doses of Pharmaceutical-Grade Synthetic Cannabidiol in Pediatric Patients with Treatment-Resistant Epilepsy.

Posted on by
Reply

“Prior studies have evaluated the use of various constituents of cannabis for their anti-seizure effects. Specifically, cannabidiol, a non-psychoactive component of cannabis, has been investigated for treatment-resistant epilepsy, but more information is needed particularly on its use in a pediatric population.

OBJECTIVE:

The objective of this study was to evaluate the pharmacokinetics and safety of a synthetic pharmaceutical-grade cannabidiol oral solution in pediatric patients with treatment-resistant epilepsy.

RESULTS:

Overall, 61 patients across three cohorts received one of three doses of cannabidiol oral solution (mean age, 7.6 years). The age composition was similar in the three cohorts. There was a trend for increased cannabidiol exposure with increased cannabidiol oral solution dosing, but overall exposure varied. Approximately 2-6 days of twice-daily dosing provided steady-state concentrations of cannabidiol. A bi-directional drug interaction occurred with cannabidiol and clobazam. Concomitant administration of clobazam with 40 mg/kg/day of cannabidiol oral solution resulted in a 2.5-fold increase in mean cannabidiol exposure. Mean plasma clobazam concentrations were 1.7- and 2.2-fold greater in patients receiving clobazam concomitantly with 40 mg/kg/day of cannabidiol oral solution compared with 10 mg/kg/day and 20 mg/kg/day. Mean plasma norclobazam values were 1.3- and 1.9-fold higher for patients taking clobazam plus 40 mg/kg/day of cannabidiol oral solution compared with the 10-mg/kg/day and 20-mg/kg/day groups. All doses were generally well tolerated, and common adverse events that occurred at > 10% were somnolence (21.3%), anemia (18.0%), and diarrhea (16.4%).

CONCLUSIONS:

Inter-individual variability in systemic cannabidiol exposure after pediatric patient treatment with cannabidiol oral solution was observed but decreased with multiple doses. Short-term administration was generally safe and well tolerated.”

https://www.ncbi.nlm.nih.gov/pubmed/31049885

https://link.springer.com/article/10.1007%2Fs40263-019-00624-4

Higher cannabidiol plasma levels are associated with better seizure response following treatment with a pharmaceutical grade cannabidiol.

Posted on by
Reply

“The objective of this study was to determine the relationship between cannabidiol (CBD) dose, CBD plasma level, and seizure control in a large open-label single-center study.

METHODS:

All participants with treatment-refractory epilepsy participating in our expanded access program (EAP) were approached for participation. Highly purified grade CBD (Epidiolex®) dosing was weight-based and could be increased every 2 weeks by 5 mg/kg/day up to a maximum dosage of 50 mg/kg/day depending on tolerance and seizure control. Seizure counts were obtained at each visit with frequency calculated per 2-week periods. Cross-sectional plasma peak levels of CBD were obtained ~4 h after dosing in consecutively presenting patients.

RESULTS:

We evaluated 56 adults and 44 children (100 total; 54 female) at two time points – one before initiating CBD and one at the time of CBD plasma level testing. There was a positive linear correlation between CBD dosage (range from 5 to 50 mg/kg/day) and level (range from 7.1-1200 ng/mL) in all participants (r = 0.640; p < 0.001). The quantile regression model supported the notion of increased CBD levels being associated with improvement in seizure frequency after adjusting for age – specifically, a 100 ng/mL increase in CBD level was associated with approximately two counts reduction in seizure frequency per time period (1.87 96% confidence interval [CI] 0.34-3.39; p = 0.018). In participants with the same CBD level, differences in seizure improvement did not depend on age (p = 0.318).

CONCLUSIONS:

In this open-label study, we found evidence of a linear correlation between CBD dosage and plasma levels, and that higher dose/levels are associated with a higher response rate for seizure improvement. Children and adults responded to CBD similarly. However, seizure control response rates suggest children may respond to lower dosages/plasma levels than adults. Findings reported in this study are specific to Epidiolex® and should not be extrapolated to other CBD products.”

https://www.ncbi.nlm.nih.gov/pubmed/31048098

https://www.epilepsybehavior.com/article/S1525-5050(19)30051-4/fulltext

Oral Cannabidiol Prevents Allodynia and Neurological Dysfunctions in a Mouse Model of Mild Traumatic Brain Injury.

Posted on by
Reply

 Image result for frontiers in pharmacology“Neurological dysfunctions are the most impactful and persistent consequences of traumatic brain injury (TBI). Indeed, previous reports suggest that an association between TBI and chronic pain syndromes, as well anxio-depressive behaviors, tends to be more common in patients with mild forms of TBI. At present, no effective treatment options are available for these symptoms.

In the present study, we used a weight drop mild TBI mouse model to investigate the effect of a commercially available 10% Cannabidiol (CBD) oil on both the sensorial and neuropsychiatric dysfunctions associated with mild TBI through behavioral and biomolecular approaches.

TBI mice developed chronic pain associated with anxious and aggressive behavior, followed by a late depressive-like behavior and impaired social interaction. Such behaviors were related with specific changes in neurotransmitters release at cortical levels.

CBD oral treatment restored the behavioral alterations and partially normalized the cortical biochemical changes.

In conclusion, our data show some of the brain modifications probably responsible for the behavioral phenotype associated with TBI and suggest the CBD as a pharmacological tool to improve neurological dysfunctions caused by the trauma.”

https://www.ncbi.nlm.nih.gov/pubmed/31040777

https://www.frontiersin.org/articles/10.3389/fphar.2019.00352/full

Marijuana for Parkinson’s Disease?

Posted on by
Reply

 Image result for innov clin neurosci

“Marijuana is popular in the United States and is being widely legalized for recreational and medicinal purposes. It remains a Schedule 1 substance without fully proven risks and benefits; yet, it is increasingly available in many US states and territories.

Cannabis might have medicinal efficacy in Parkinson’s disease as a form of medical marijuana. Endocannabinoid receptors exist throughout the nervous system and are documented to influence receptors affecting a wide variety of areas. Neuroprotective aspects might be induced by cannabis exposure that might yield benefit against the nigrostriatal degeneration of patients with Parkinson’s disease.

Animal investigations support suggestions of improvement in bradykinesia and/or tremors, but this is unsubstantiated in human studies. However, some patient surveys and anecdotal or case reports indicate that marijuana attenuates some motor manifestations of parkinsonism and also of non-motor, mood and/or cognitive symptoms. Medical marijuana might benefit motor and nonmotor aspects of Parkinson’s disease patients. Currently, these assertions are not substantiated in human investigations and cannabis can also induce side effects. Until studies clarify the safety and efficacy of pharmacotherapy with cannabis products, medical marijuana remains largely without scientific endorsement. Research has yet to document the full benefits, risks, and clinical applications of marijuana as a treatment for patients with Parkinson’s disease.”

https://www.ncbi.nlm.nih.gov/pubmed/31037227

Emerging evidence for the antidepressant effect of cannabidiol and the underlying molecular mechanisms.

Posted on by
Reply

Journal of Chemical Neuroanatomy

“Significant limitations with the currently available antidepressant treatment strategies have inspired research on finding new and more efficient drugs to treat depression. Cannabidiol (CBD) is a non-psychotomimetic component of Cannabis sativa, and emerges in this regard as a promising compound. In 2010, we were the first laboratory to demonstrate that CBD is effective in animal models of predictive of antidepressant effect, a finding now confirmed by several other groups. Recent evidence suggests that CBD promotes both a rapid and a sustained antidepressant effect in animal models. CBD has a complex pharmacology, with the ability to interact with multiple neurotransmitter systems involved in depression, including the serotonergic, glutamatergic, and endocannabinoid systems. Moreover, CBD induces cellular and molecular changes in brain regions related to depression neurobiology, such as increased Brain Derived Neurotrophic Factor (BDNF) levels and synaptogenesis in the medial prefrontal cortex, as well as it increases neurogenesis in the hippocampus. This review presents a comprehensive critical overview of the current literature related to the antidepressant effects of CBD, with focus at the possible mechanisms. Finally, challenges and perspectives for future research are discussed.”

https://www.ncbi.nlm.nih.gov/pubmed/31039391

https://www.sciencedirect.com/science/article/pii/S0891061818302114?via%3Dihub

Comparison of different methods for the extraction of cannabinoids from cannabis.

Posted on by
Reply

 Publication Cover

“Cannabis oils, namely concentrated cannabis extracts, are getting plenty of attention because of their therapeutic potential for treatment of patients with cancer, HIV, multiple sclerosis and several other pathologies. Here we propose the use of ultrasound-assisted extraction (UAE) and microwave-assisted extraction (MAE) as alternative methods to the current protocols followed by pharmacists, the only authorized to manipulate standardized Cannabis. A third method, consisting of the use of Tween 20 as surfactant, was considered. Our best extraction methodology for commercial hemp extraction was applied to medicinal cannabis. Here we report the results obtained for ‘Eletta campana’, ‘Carmagnola selezionata’, Bediol®, FM2® and Bedrocan®.”

https://www.ncbi.nlm.nih.gov/pubmed/31035854

https://www.tandfonline.com/doi/abs/10.1080/14786419.2019.1601194?journalCode=gnpl20