Tag Archives: cannabinoid

Successful use of pure cannabidiol for the treatment of super-refractory status epilepticus.

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Epilepsy & Behavior Case Reports

“We present the case of a child with long-standing, super-refractory status epilepticus (SRSE) who manifested prompt and complete resolution of SRSE upon exposure to pure cannabidiol. SRSE emerged in the context of remote suspected encephalitis with previously well-controlled epilepsy. We discuss the extent to which response may be specifically attributed to cannabidiol, with consideration and discussion of multiple potential drug-drug interactions. Based on this case, we propose that adjunctive cannabidiol be considered in the treatment of SRSE.”

https://www.ncbi.nlm.nih.gov/pubmed/30596011

“Adjunctive cannabidiol may be effective in the treatment of super refractory status epilepticus. Given the paucity of evidence-based therapies for SRSE as well as the prompt and enduring response that accompanied the adjunctive administration of CBD in this patient, CBD should be a consideration in the treatment of SRSE.”

https://www.sciencedirect.com/science/article/pii/S2213323218300513?via%3Dihub

Theoretical Explanation for Reduced Body Mass Index and Obesity Rates in Cannabis Users

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“Obesity is treatment-resistant, and is linked with a number of serious, chronic diseases. Adult obesity rates in the United States have tripled since the early 1960s.

Recent reviews show that an increased ratio of omega-6 to omega-3 fatty acids contributes to obesity rates by increasing levels of the endocannabinoid signals AEA and 2-AG, overstimulating CB1R and leading to increased caloric intake, reduced metabolic rates, and weight gain.

Cannabis, or THC, also stimulates CB1R and increases caloric intake during acute exposures.

The present meta-analysis reveals significantly reduced body mass index and rates of obesity in Cannabis users, in conjunction with increased caloric intake.

We provide for the first time a causative explanation for this paradox, in which rapid and long-lasting downregulation of CB1R following acute Cannabis consumption reduces energy storage and increases metabolic rates, thus reversing the impact on body mass index of elevated dietary omega-6/omega-3 ratios.

Evidence suggests that, in the United States, many people may actually achieve net health benefits from moderate Cannabis use, due to reduced risk of obesity and associated diseases.”

https://www.liebertpub.com/doi/10.1089/can.2018.0045?_ga=2.221453528.1791159238.1546024140-1083808004.1546024140

“Reduced Body Mass Index and Obesity Rates in Cannabis Users”  https://www.genengnews.com/insights/reduced-body-mass-index-and-obesity-rates-in-cannabis-users/?fbclid=IwAR3a0wbfGoPwAR-pYQGCeLz-KYUFdiLJoj6Ja7rTTNGBYwkjIGw1fUjf5LI

 

n-3 polyunsaturated N-acylethanolamines are CB2 cannabinoid receptor-preferring endocannabinoids

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 Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids“Anandamide, the first identified endogenous cannabinoid and TRPV1 agonist, is one of a series of endogenous N-acylethanolamines, NAEs. We have generated novel assays to quantify the levels of multiple NAEs in biological tissues and their rates of hydrolysis through fatty acid amide hydrolase. This range of NAEs was also tested in rapid response assays of CB1, CB2 cannabinoid and TRPV1 receptors. The data indicate that PEA, SEA and OEA are not endocannabinoids or endovanilloids, and that the higher endogenous levels of these metabolites compared to polyunsaturated analogues are a correlate of their slow rates of hydrolysis. The n-6 NAEs (AEA, docosatetraenoyl and docosapentaenoyl derivatives) activated both CB1 and CB2 receptors, as well as TRPV1 channels, suggesting them to be ‘genuine’ endocannabinoids and ‘endovanilloids’. The n-3 NAEs (eicosapentaenoyl, docosapentaenoyl and docosahexaenoyl derivatives) activated CB2 receptors and some n-3 NAEs (docosapentaenoyl and docosahexaenoyl derivatives) also activated TRPV1 channels, but failed to activate the CB1 receptor. We hypothesise that the preferential activation of CB2 receptors by n-3 PUFA NAEs contributes, at least in some part, to their broad anti-inflammatory profile.”

https://www.ncbi.nlm.nih.gov/pubmed/30591150

https://www.sciencedirect.com/science/article/pii/S1388198118302026?via%3Dihub

Cannabidiol reduces seizures and associated behavioral comorbidities in a range of animal seizure and epilepsy models.

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“Epilepsy is a progressive neurological disease characterized by recurrent seizures and behavioral comorbidities. We investigated the antiseizure effect of cannabidiol (CBD) in a battery of acute seizure models. Additionally, we defined the disease-modifying potential of chronic oral administration of CBD on associated comorbidities in the reduced intensity status epilepticus-spontaneous recurrent seizures (RISE-SRS) model of temporal lobe epilepsy (TLE).

RESULTS:

CBD was effective in a battery of acute seizure models in both mice and rats following intraperitoneal administration. In the pilocarpine-induced status epilepticus rat model, CBD attenuated maximum seizure severity following intravenous administration, further demonstrating CBD’s acute antiseizure efficacy in this rat model. We established that oral CBD attenuated the time-dependent increase in seizure burden and improved TLE-associated motor comorbidities of epileptic rats in the RISE-SRS model without affecting gait. Chronic administration of CBD after the onset of SRS ameliorated reference memory and working memory errors of epileptic animals in a spatial learning and memory task.

SIGNIFICANCE:

The present study illustrates that CBD is a well-tolerated and effective antiseizure agent and illustrates a potential disease-modifying effect of CBD on reducing both seizure burden and associated comorbidities well after the onset of symptomatic seizures in a model of TLE.”

https://www.ncbi.nlm.nih.gov/pubmed/30588604

https://onlinelibrary.wiley.com/doi/full/10.1111/epi.14629

Knowledge, Attitudes, and Perceptions of Cannabinoids in the Dermatology Community

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“Recent research has identified potential uses of cannabinoids in dermatology, including psoriasis, atopic dermatitis, and wound healing.

This study examined dermatology providers’ knowledge, attitudes, and perceptions on therapeutic cannabinoids using a 20-question online survey.

The response rate was 21% (n=531). Most responders thought cannabinoids should be legal for medical treatment (86%). Nearly all (94%) believed it is worthwhile to research dermatologic uses of cannabinoids. 55% reported at least one patient-initiated discussion about cannabinoids in the last year. Yet, 48% were concerned about a negative stigma when proposing cannabinoid therapies to patients. While most responders (86%) were willing to prescribe an FDA-approved cannabinoid as a topical treatment, fewer (71%) were willing to prescribe an oral form. 64% of respondents did not know that cannabidiol is not psychoactive and 29% did not know that tetrahydrocannabinol is psychoactive.

 

CONCLUSIONS:

Dermatology providers are interested in prescribing cannabinoids and patients are speaking about cannabinoids with their dermatologists. However, providers’ fund of knowledge on this subject is lacking. These results highlight the need for further education and research to detangle the dermatologic benefits and risks of cannabinoids.”

https://www.ncbi.nlm.nih.gov/pubmed/30586258

“Cannabinoid system in the skin – a possible target for future therapies in dermatology.” https://www.ncbi.nlm.nih.gov/pubmed/19664006

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.

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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