Long-term cannabidiol treatment in patients with Dravet syndrome: An open-label extension trial.

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“Add-on cannabidiol (CBD) significantly reduced seizures associated with Dravet syndrome (DS) in a randomized, double-blind, placebo-controlled trial: GWPCARE1 Part B (NCT02091375). Patients who completed GWPCARE1 Part A (NCT02091206) or Part B, or a second placebo-controlled trial, GWPCARE2 (NCT02224703), were invited to enroll in a long-term open-label extension trial, GWPCARE5 (NCT02224573). We present an interim analysis of the safety, efficacy, and patient-reported outcomes from GWPCARE5.

METHODS:

Patients received a pharmaceutical formulation of highly purified CBD in oral solution (100 mg/mL), titrated from 2.5 to 20 mg/kg/d over a 2-week period, with their existing medications. Based on response and tolerance, CBD could be reduced or increased up to 30 mg/kg/d.

RESULTS:

By November 2016, a total of 278 patients had completed the original randomized trials, and 264 (95%) enrolled in this open-label extension. Median treatment duration was 274 days (range 1-512) with a mean modal dose of 21 mg/kg/d, and patients received a median of 3 concomitant antiepileptic medications. Adverse events (AEs) occurred in 93.2% of patients and were mostly mild (36.7%) or moderate (39.0%). Commonly reported AEs were diarrhea (34.5%), pyrexia (27.3%), decreased appetite (25.4%), and somnolence (24.6%). Seventeen patients (6.4%) discontinued due to AEs. Twenty-two of the 128 patients from GWPCARE1 (17.2%), all taking valproic acid, had liver transaminase elevations ≥3 times the upper limit of normal. In patients from GWPCARE1 Part B, the median reduction from baseline in monthly seizure frequency assessed in 12-week periods up to week 48 ranged from 38% to 44% for convulsive seizures and 39% to 51% for total seizures. After 48 weeks of treatment, 85% of patients/caregivers reported improvement in the patient’s overall condition on the Subject/Caregiver Global Impression of Change scale.

SIGNIFICANCE:

This trial shows that long-term CBD treatment had an acceptable safety profile and led to sustained, clinically meaningful reductions in seizure frequency in patients with treatment-resistant DS.”

https://www.ncbi.nlm.nih.gov/pubmed/30582156

https://onlinelibrary.wiley.com/doi/full/10.1111/epi.14628

Medical Cannabis in the Skilled Nursing Facility: A Novel Approach to Improving Symptom Management and Quality of Life.

Journal of the American Medical Directors Association Home

“Throughout the millennia, the cannabis plant has been utilized as a recognized therapy for pain relief and symptom management.

Following the Prohibition-era stigmatization and criminalization of all forms of cannabis of the early 20th century, there has been a recent nationwide and worldwide resurgence in interest and use of the cannabinoid compounds extracted from the cannabis plant, that is, medical cannabis.

Although at the Federal level, cannabis remains a Schedule I substance, 31 states have already decriminalized possession and use of medical cannabis for specific diagnoses.

It is noteworthy that many of these indicated diagnoses are prevalent in the skilled nursing facility (SNF). This creates regulatory concerns as SNFs and other healthcare facilities must maintain compliance with Federal laws, while balancing the individual resident’s rights to utilize medical cannabis where indicated.

The authors developed an innovative program that affords their residents the ability to participate in a state-approved medical cannabis program while remaining compliant with Federal law. As medical cannabis use becomes more widespread and accepted, clinicians providing medical care in healthcare facilities will encounter residents who may benefit from and request this alternative therapy.

Studies examining older adults that are utilizing medical cannabis legally have demonstrated significant decreases in prescription medication use, most notably a reduction in opioid analgesic usage. As such, medical cannabis should be viewed as an additional option in the clinician’s toolbox of therapeutic interventions for symptom relief.”

https://www.ncbi.nlm.nih.gov/pubmed/30580820

https://www.jamda.com/article/S1525-8610(18)30662-5/fulltext

Attenuation Effect of Cannabinoid Type 1 Receptor Activation on Methamphetamine-Induced Neurodegeneration and Locomotion Impairments among Male Rats.

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“A number of neuroimaging studies on human addicts have revealed that abuse of Methamphetamine (METH) can induce neurodegenerative changes in various brain regions like the cerebral cortex and cerebellum. Although the underlying mechanisms of METH-induced neurotoxicity have been studied, the cellular and molecular mechanisms of METH-induced neurotoxicity remain to be clarified.

Previous studies implicated that cannabinoid type 1 receptors (CB1Rs) exert neuroprotective effects on several models of cerebral toxicity, but their role in METH-induced neurotoxicity has been rarely investigated. Moreover, the cerebellum was considered as a potential target to evaluate the effects of cannabinoids on locomotion activity as the CB1Rs are most widely distributed in the molecular layer of cerebellum. Therefore, the present study was carried out to evaluate whether neurodegeneration induced in the cerebellum tissue implicated in locomotion deficit induced by METH.

FINDINGS:

The results of the present study demonstrated that repeated exposure to METH increased cerebellar degeneration level as compared to the saline and dimethyl sulfoxide (DMSO) groups. In addition, METH-treated rats showed hyperactivity as compared to the saline and DMSO groups. Pretreatment with WIN significantly attenuated neurodegeneration and hyperactivity induced by METH.

CONCLUSION:

The findings of this study provided evidence that CB1Rs may serve as a therapeutic strategy for attenuation of METH-induced locomotor deficits.”

https://www.ncbi.nlm.nih.gov/pubmed/30574283

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6294485/

Cannabis for cancer – illusion or the tip of an iceberg: a review of the evidence for the use of Cannabis and synthetic cannabinoids in oncology.

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“A flowering plant of variegated ingredients and psychoactive qualities, Cannabis has long been used for medicinal and recreational purposes.

Regulatory approvals have been gained across a broad range of palliative and therapeutic indications, and in some cases, included in standard treatment guidelines.

Areas covered: The use of Cannabis and cannabinoid-based-medicines in oncology is summarized in this article. Cannabinoids were classified according to natural and synthetic subtypes and their mechanisms of action expounded. The variability of available products is discussed in the clinical context and data regarding chemotherapy-induced nausea and vomiting, cancer-related pain, anorexia, insomnia and anxiety are presented.

Moreover, immunological and antineoplastic effects in preclinical and clinical trials are addressed. Concepts such as synergism or opposition with conventional treatment modalities, sequence of administration and dosage, molecular cross-talk and malignancy-cannabinoid congruence, are explored. Finally, side-effects, limitations in trial design and legislation barriers are related.

Expert opinion: Sufficient evidence supports use of Cannabis for palliative indications in oncology, however, patients should be carefully selected, guided and followed. Promising research suggests potent antineoplastic activity, but more data must be accrued before conclusions can be drawn.”

https://www.ncbi.nlm.nih.gov/pubmed/30572744

https://www.tandfonline.com/doi/abs/10.1080/13543784.2019.1561859?journalCode=ieid20

Culture and cannabinoid receptor gene polymorphism interact to influence the perception of happiness.

 Image result for plos one“Previous studies have shown that a cytosine (C) to thymine (T) single nucleotide polymorphism (SNP) of the human cannabinoid receptor 1 (CNR1) gene is associated with positive emotional processing.

C allele carriers are more sensitive to positive emotional stimuli including happiness. The effects of several gene polymorphisms related to sensitivity to emotional stimuli, such as that in the serotonin transporter gene-linked polymorphic region (5HTTLPR), on emotional processing have been reported to differ among cultures-e.g., between those that are independent and interdependent. Thus, we postulated that the effects of the CNR1 genotype on happiness might differ among different cultures because the concept of happiness varies by culture.

We recruited healthy male and female young adults in Japan, where favorable external circumstances determine the concept of happiness, and Canada, where the concept of happiness centers on positive inner feelings, and compared the effects of the CNR1 genotype on both subjective happiness levels (self-evaluation as being a happy person) and situation-specific happiness (happy feelings accompanying various positive events) by using a questionnaire.

We found that the effect of CNR1 on subjective happiness was different between the Japanese and Canadian groups. The subjective happiness level was the highest in Japanese individuals with the CC genotype, whereas in Canadian participants, it was the highest in individuals with the TT genotype. Furthermore, the effects of CNR1 genotype on situation-specific happiness were also different between the groups. Happiness accompanied with being surrounded by happy people was the highest among Japanese individuals with the CC genotype, whereas among Canadian individuals, it was the highest in TT genotype carriers.

These findings suggest that culture and CNR1 polymorphism interact to influence the perception of happiness.”

https://www.ncbi.nlm.nih.gov/pubmed/30576341

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0209552

“Genetic Variations in the Human Cannabinoid Receptor Gene Are Associated with Happiness” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3972248/

Alcohol Use and Risk of Related Problems Among Cannabis Users Is Lower Among Those With Medical Cannabis Recommendations, Though Not Due To Health.

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“A small body of work has started developing cannabis use “typologies” for use in treatment and prevention.

Two potentially relevant dimensions for classifying cannabis use typologies are medical versus recreational cannabis use and the co-use of cannabis and alcohol.

Here we compare alcohol use and related problems between cannabis users with and without medical cannabis recommendations.

Cannabis users with medical cannabis recommendations drink less and have fewer alcohol-related problems than those without recommendations, even after adjusting for health status.”

https://www.ncbi.nlm.nih.gov/pubmed/30573025

Cannabinoid receptor expression in estrogen-dependent and estrogen-independent endometrial cancer.

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“The lack of good diagnostic/prognostic biomarkers and the often late presentation of endometrial cancer (EC) hinders the amelioration of the morbidity and mortality rates associated with this primarily estrogen-driven disease, a disease that is becoming more prevalent in the population.

Previous studies on the expression of the classical cannabinoid receptors, CB1 and CB2, suggest these could provide good diagnostic/prognostic biomarkers for EC but those observations have been contradictory. In this study, we sought to resolve the inconsistency of CB1 and CB2 expression levels in different EC studies.

To that end, we used qRT-PCR and immunohistochemistry (IHC) for CB1 and CB2 in endometrial biopsies from women with or without EC and found that transcript levels for both CB1 and CB2 were significantly decreased by 90 and 80%, respectively in EC. These observations were supported by histomorphometric studies where CB1 and CB2 staining intensity was decreased in all types of EC.

These data suggest that the loss of both types of CB receptors is potentially involved in the development of or progression of EC and that CB1 and CB2 receptor expression could serve as useful histological markers and therapeutic targets in the treatment of or prevention of EC.”

https://www.ncbi.nlm.nih.gov/pubmed/30569804

https://www.tandfonline.com/doi/abs/10.1080/10799893.2018.1531890?journalCode=irst20

Cannaboinoid Antiemetic Therapy.

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“There are currently three cannabinoids available on the pharmaceutical market.  Dronabinol and Nabilone are both synthetic tetrahydrocannabinol (THC) which the FDA has approved for treatment of chemotherapy-induced nausea and vomiting (CINV) after the failure of a trial of first-line anti-emetics.  Both are also FDA approved to treat anorexia associated with AIDS.  Recently, the FDA has also approved a cannabidiol (CBD) product to treat seizures associated with Lennox-Gastaut Syndrome and Dravel Syndrome in pediatric patients. However, there is no FDA approved indication for its use as an anti-emetic.  Independently produced cannabidiol extracts are being used increasingly in the general population for many non-FDA approved indications, frequently including nausea and emesis.  In states that have decriminalized marijuana, both in recreational and medicinal contexts, products with varying ratios of cannabidiol and THC are also used for their anti-emetic properties.”

https://www.ncbi.nlm.nih.gov/pubmed/30571051

https://www.ncbi.nlm.nih.gov/books/NBK535430/

Effects of cannabidiol in males and females in two different rat models of depression.

Physiology & Behavior

“The current study explores the therapeutic potential of Cannabidiol (CBD), a compound in the Cannabis plant, using both sexes of 2 “depressive-like” genetic models, Wistar Kyoto (WKY) and Flinders Sensitive Line (FSL) rats. Rats ingested CBD (30 mg/kg) orally. In the saccharin preference test, following a previous report of a pro-hedonic effect of CBD in male WKY, we now found similar results in female WKY. CBD also decreased immobility in the forced swim test in males (both strains) and in female WKY. These findings suggest a role for CBD in treating mental disorders with prominent symptoms of helplessness and anhedonia.”

https://www.ncbi.nlm.nih.gov/pubmed/30571957

https://www.sciencedirect.com/science/article/abs/pii/S0031938418307509?via%3Dihub

Reduced Risk of Alcohol-Induced Pancreatitis With Cannabis Use.

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“Pancreatitis is an increasingly common clinical condition that causes significant morbidity and mortality. Cannabis use causes conflicting effects on pancreatitis development.

We conducted a larger and more detailed assessment of the impact of cannabis use on pancreatitis.

Concomitant cannabis and abusive alcohol use were associated with reduced incidence of acute and chronic pancreatitis (AP and CP).

Our findings suggest a reduced incidence of only alcohol-associated pancreatitis with cannabis use.”

https://www.ncbi.nlm.nih.gov/pubmed/30570765

https://onlinelibrary.wiley.com/doi/abs/10.1111/acer.13929