“Cardiovascular disease (CVD) is a global epidemic representing the leading cause of death in some Western countries. Endocannabinoids and cannabinoid‐related compounds may be a promising approach as therapeutic agents for cardiovascular diseases. This review highlights the potential of cannabinoids and their receptors as targets for intervention. In summary, the endocannabinoid system is highly active in cardiovascular disease states. Modulation of the ECS, CB1, and TRPV1 antagonism, as well as CB2 agonism, have proven to modulate disease state and severity in CVD. Studies are underway to develop drugs to change the course of cardiovascular diseases. If therapeutic potential resides in a single molecule component or a derivative, then production and regulation of the therapy are straightforward. If the efficacious agent is a complex mixture that reflects some or all of the secondary metabolome complexity of Cannabis sativa, then safe and consistent production become challenging.” http://jaha.ahajournals.org/content/7/14/e009099https://www.ncbi.nlm.nih.gov/pubmed/30006489]]>
Author Archives: David Worrell
Novel mechanism of cannabidiol-induced apoptosis in breast cancer cell lines.
“Studies have emphasized an antineoplastic effect of the non-psychoactive, phyto-cannabinoid, Cannabidiol (CBD). However, the molecular mechanism underlying its antitumor activity is not fully elucidated.
Herein, we have examined the effect of CBD on two different human breast cancer cell lines: the ER-positive, well differentiated, T-47D and the triple negative, poor differentiated, MDA-MB-231 cells.
In both cell lines, CBD inhibited cell survival and induced apoptosis in a dose dependent manner as observed by MTT assay, morphological changes, DNA fragmentation and ELISA apoptosis assay. CBD-induced apoptosis was accompanied by down-regulation of mTOR, cyclin D1 and up-regulation and localization of PPARγ protein expression in the nuclei and cytoplasmic of the tested cells.
The results suggest that CBD treatment induces an interplay among PPARγ, mTOR and cyclin D1 in favor of apoptosis induction in both ER-positive and triple negative breast cancer cells, proposing CBD as a useful treatment for different breast cancer subtypes.”
“Programmed Cell Death (Apoptosis)” http://www.ncbi.nlm.nih.gov/books/NBK26873/
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Open-label use of Highly* purified CBD (Epidiolex®) in patients with CDKL5 deficiency disorder and Aicardi, Dup15q, and Doose syndromes.
“We studied our collective open-label, compassionate use experience in using cannabidiol (CBD) to treat epilepsy in patients with CDKL5 deficiency disorder and Aicardi, Doose, and Dup15q syndromes. This open-label drug trial provides class III evidence for the long-term safety and efficacy of cannabidiol (CBD) administration in patients with treatment-resistant epilepsy (TRE) associated with CDKL5 deficiency disorder and Aicardi, Dup15q, and Doose syndromes. Adjuvant therapy with CBD showed similar safety and efficacy for these four syndromes as reported in a diverse population of TRE etiologies.” https://www.ncbi.nlm.nih.gov/pubmed/30006259 https://www.epilepsybehavior.com/article/S1525-5050(18)30191-4/fulltext
“Medical cannabis for epilepsy approved in FDA first” https://www.medicalnewstoday.com/articles/322283.php
]]>Integrating endocannabinoid signaling in the regulation of anxiety and depression
“Brain endogenous cannabinoid (eCB) signaling seems to harmonize appropriate behavioral responses, which are essential for the organism’s long-term viability and homeostasis. Dysregulation of eCB signaling contributes to negative emotional states and increased stress responses. An understanding of the underlying neural cell populations and neural circuit regulation will enable the development of therapeutic strategies to mitigate behavioral maladaptation and provide insight into the influence of eCB on the neural circuits involved in anxiety and depression. This review focuses on recent evidence that has added a new layer of complexity to the idea of targeting the eCB system for therapeutic benefits in neuropsychiatric disease and on the future research direction of neural circuit modulation.” https://www.nature.com/articles/s41401-018-0051-5]]>
Effectiveness of Raw, Natural Medical Cannabis Flower for Treating Insomnia under Naturalistic Conditions.
“Background: We use a mobile software application (app) to measure for the first time, which fundamental characteristics of raw, natural medical Cannabis flower are associated with changes in perceived insomnia under naturalistic conditions.
Methods: Four hundred and nine people with a specified condition of insomnia completed 1056 medical cannabis administration sessions using the Releaf AppTM educational software during which they recorded real-time ratings of self-perceived insomnia severity levels prior to and following consumption, experienced side effects, and product characteristics, including combustion method, cannabis subtypes, and/or major cannabinoid contents of cannabis consumed. Within-user effects of different flower characteristics were modeled using a fixed effects panel regression approach with standard errors clustered at the user level.
Results: Releaf AppTM users showed an average symptom severity reduction of -4.5 points on a 0⁻10 point visual analogue scale (SD = 2.7, d = 2.10, p < 0.001). Use of pipes and vaporizers was associated with greater symptom relief and more positive and context-specific side effects as compared to the use of joints, while vaporization was also associated with lower negative effects. Cannabidiol (CBD) was associated with greater statistically significant symptom relief than tetrahydrocannabinol (THC), but the cannabinoid levels generally were not associated with differential side effects. Flower from C. sativa plants was associated with more negative side effects than flower from C. indica or hybrid plant subtypes.
Conclusions: Consumption of medical Cannabis flower is associated with significant improvements in perceived insomnia with differential effectiveness and side effect profiles, depending on the product characteristics.”
https://www.ncbi.nlm.nih.gov/pubmed/29997343
http://www.mdpi.com/2305-6320/5/3/75
“Marijuana use is increasing worldwide, and it is ever more likely that patients presenting with acute myocardial infarctions (AMI) will be marijuana users. However, little is known about the impact of marijuana use on short-term outcomes following AMI.
Accordingly, we compared in-hospital outcomes of AMI patients with reported marijuana use to those with no reported marijuana use. We hypothesized that marijuana use would be associated with increased risk of adverse outcomes in AMI patients.
Interestingly, marijuana-using patients were significantly less likely to die, experience shock, or require an IABP post AMI than patients with no reported marijuana use.
These results suggest that, contrary to our hypothesis, marijuana use was not associated with increased risk of adverse short-term outcomes following AMI.
Furthermore, marijuana use was associated with decreased in-hospital mortality post-AMI.”
“Δ9-Tetrahydrocannabinol (THC), the principle psychoactive ingredient in Cannabis, is widely used for its therapeutic effects in a large variety of diseases, but it also has numerous neurological side effects. The 
“Recent surveys suggest that many parents are using illicit cannabis extracts in the hope of managing seizures in their children with epilepsy. In the current Australian study we conducted semi-structured interviews with families of children with diverse forms of epilepsy to explore their attitudes towards and experiences with using cannabis extracts.
Contrary to family’s expectations, most samples contained low concentrations of cannabidiol, while Δ9-tetrahydrocannabinol was present in nearly every sample. These findings highlight profound variation in the illicit cannabis extracts being currently used in Australia and warrant further investigations into the therapeutic value of cannabinoids in epilepsy.
The phenomenon is not without supporting scientific evidence. Many preclinical studies have identified potent anticonvulsant effects of various cannabinoids in animal models of epilepsy, and a mechanistic understanding of such effects is emerging.
A considerable proportion of families reported cannabis extracts being “effective” in reducing their child’s seizure burden and improving their overall condition, with one family reporting seizure-freedom in their child for at least 12 months. Over half of the cannabis extracts were associated with families reducing or ceasing their use of the child’s conventional antiepileptic drugs.”