Targeting the endocannabinoid system as a potential anticancer approach.

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“The endocannabinoid system is currently under intense investigation due to the therapeutic potential of cannabinoid-based drugs as treatment options for a broad variety of diseases including cancer.

Besides the canonical endocannabinoid system that includes the cannabinoid receptors CB1 and CB2 and the endocannabinoids N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol, recent investigations suggest that other fatty acid derivatives, receptors, enzymes, and lipid transporters likewise orchestrate this system as components of the endocannabinoid system when defined as an extended signaling network.

As such, fatty acids acting at cannabinoid receptors (e.g. 2-arachidonoyl glyceryl ether [noladin ether], N-arachidonoyldopamine) as well as endocannabinoid-like substances that do not elicit cannabinoid receptor activation (e.g. N-palmitoylethanolamine, N-oleoylethanolamine) have raised interest as anticancerogenic substances.

Furthermore, the endocannabinoid-degrading enzymes fatty acid amide hydrolase and monoacylglycerol lipase, lipid transport proteins of the fatty acid binding protein family, additional cannabinoid-activated G protein-coupled receptors, members of the transient receptor potential family as well as peroxisome proliferator-activated receptors have been considered as targets of antitumoral cannabinoid activity. Therefore, this review focused on the antitumorigenic effects induced upon modulation of this extended endocannabinoid network.” https://www.ncbi.nlm.nih.gov/pubmed/29390896  http://www.tandfonline.com/doi/abs/10.1080/03602532.2018.1428344?journalCode=idmr20

“Anticancer mechanisms of cannabinoids”   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791144/
“Cannabinoids as Anticancer Drugs.”

Analysis of cannabinoids in commercial hemp seed oil and decarboxylation kinetics studies of cannabidiolic acid (CBDA).

Journal of Pharmaceutical and Biomedical Analysis

“Hemp seed oil from Cannabis sativa L. is a very rich natural source of important nutrients, not only polyunsaturated fatty acids and proteins, but also terpenes and cannabinoids, which contribute to the overall beneficial effects of the oil.

Hence, it is important to have an analytical method for the determination of these components in commercial samples. At the same time, it is also important to assess the safety of the product in terms of amount of any psychoactive cannabinoid present therein.

This work presents the development and validation of a highly sensitive, selective and rapid HPLC-UV method for the qualitative and quantitative determination of the main cannabinoids, namely cannabidiolic acid (CBDA), tetrahydrocannabinolic acid (THCA), cannabidiol (CBD), tetrahydrocannabinol (THC), cannabinol (CBN), cannabigerol (CBG) and cannabidivarin (CBDV), present in 13 commercial hemp seed oils.”

https://www.ncbi.nlm.nih.gov/pubmed/29182999

https://www.sciencedirect.com/science/article/pii/S0731708517322367?via%3Dihub

The Grass Might Be Greener: Medical Marijuana Patients Exhibit Altered Brain Activity and Improved Executive Function after 3 Months of Treatment.

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“The vast majority of states have enacted full or partial medical marijuana (MMJ) programs, causing the number of patients seeking certification for MMJ use to increase dramatically in recent years.

In the present study, MMJ patients seeking treatment for a variety of documented medical conditions were assessed prior to initiating MMJ treatment and after 3 months of treatment as part of a larger longitudinal study.

Following 3 months of treatment, MMJ patients demonstrated improved task performance accompanied by changes in brain activation patterns within the cingulate cortex and frontal regions.

Interestingly, after MMJ treatment, brain activation patterns appeared more similar to those exhibited by healthy controls from previous studies than at pre-treatment, suggestive of a potential normalization of brain function relative to baseline.

Moreover, patients in the current study also reported improvements in clinical state and health-related measures as well as notable decreases in prescription medication use, particularly opioids and benzodiapezines after 3 months of treatment.

Further research is needed to clarify the specific neurobiologic impact, clinical efficacy, and unique effects of MMJ for a range of indications and how it compares to recreational MJ use.”

https://www.ncbi.nlm.nih.gov/pubmed/29387010

https://www.frontiersin.org/articles/10.3389/fphar.2017.00983/full

Adolescent cannabis use and brain systems supporting adult working memory encoding, maintenance, and retrieval

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“Given prior reports of adverse effects of cannabis use on working memory, an executive function with a protracted developmental course during adolescence, we examined associations between developmental patterns of cannabis use and adult working memory (WM) processes.

Within repeated cannabis users, greater levels of total cannabis use were associated with performance-related increases in dorsolateral prefrontal cortex (DLPFC) activation during maintenance.

Surprisingly, however, at the group level, cannabis users generally performed better than participants who reported never using cannabis (faster RT, higher accuracy).”

https://www.ncbi.nlm.nih.gov/pubmed/29253654

https://www.sciencedirect.com/science/article/pii/S1053811917310637

“Why Pot Smokers Scored Higher Than Nonsmokers on This Memory Test. Among a sample of 28-year-olds who took a working-memory test while undergoing an MRI brain scan, individuals who started smoking marijuana in adolescence performed just as well or even better than individuals who never smoked cannabis, the study found.” https://www.livescience.com/61574-adolescent-cannabis-use-memory-study.html

Detection and Quantification of Cannabinoids in Extracts of Cannabis sativa Roots Using LC-MS/MS.

 

“A liquid chromatography-tandem mass spectrometry single-laboratory validation was performed for the detection and quantification of the 10 major cannabinoids of cannabis, namely, (-)-trans9-tetrahydrocannabinol, cannabidiol, cannabigerol, cannabichromene, tetrahydrocannabivarian, cannabinol, (-)-trans8-tetrahydrocannabinol, cannabidiolic acid, cannabigerolic acid, and Δ9-tetrahydrocannabinolic acid-A, in the root extract of Cannabis sativa. Acetonitrile : methanol (80 : 20, v/v) was used for extraction; d3-cannabidiol and d3– tetrahydrocannabinol were used as the internal standards. All 10 cannabinoids showed a good regression relationship with r2 > 0.99. The validated method is simple, sensitive, and reproducible and is therefore suitable for the detection and quantification of these cannabinoids in extracts of cannabis roots. To our knowledge, this is the first report for the quantification of cannabinoids in cannabis roots.”

https://www.ncbi.nlm.nih.gov/pubmed/29359294

https://www.thieme-connect.de/DOI/DOI?10.1055/s-0044-100798

Medical Cannabis: The Oncology Nurse’s Role in Patient Education About the Effects of Marijuana on Cancer Palliation

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“Cannabis, also known as marijuana, is legal either medicinally or recreationally in 29 states and the District of Columbia, with a majority of the U.S. adult population now living in states where cannabis is legal for medicinal use. As an advocate for patient autonomy and informed choice, the oncology nurse has an ethical responsibility to educate patients about and support their use of cannabis for palliation.

OBJECTIVES:

This article aims to discuss the human endocannabinoid system as a basis for better understanding the palliative and curative nature of cannabis as a medicine, as well as review cannabis delivery methods and the emerging role of the oncology nurse in this realm.

FINDINGS:

The oncology nurse can play a pivotal role in supporting patients’ use of cannabis for palliation”

https://www.ncbi.nlm.nih.gov/pubmed/29350699

https://cjon.ons.org/cjon/22/1/medical-cannabis-oncology-nurse-s-role-patient-education-about-effects-marijuana-cancer

Analysis of endocannabinoid receptors and enzymes in the post-mortem motor cortex and spinal cord of amyotrophic lateral sclerosis patients.

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“We have investigated the endocannabinoid system in the motor cortex of motor neuron disease (MND) patients.

CONCLUSION:

We have confirmed that CB2 receptors are elevated in the motor cortex of MND patients associated with the reactive gliosis. This phenomenon is previous to neuronal losses. We also found CB2 receptors in cortical and spinal motor neurons.

These observations support that targeting this receptor may serve for developing neuroprotective therapies in MNDs.”

https://www.ncbi.nlm.nih.gov/pubmed/29334787

http://www.tandfonline.com/doi/abs/10.1080/21678421.2018.1425454?journalCode=iafd20

History of marijuana use does not affect outcomes on the liver transplant waitlist.

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“Data are limited on marijuana use and its impact on liver transplant (LT) waitlist outcomes.

We aimed to assess the risk of waitlist mortality/delisting and likelihood of LT among prior marijuana users, and to determine the prevalence and factors associated with marijuana use.

Unlike illicit drug use, marijuana use was not associated with worse outcomes on the LT waitlist.”

https://www.ncbi.nlm.nih.gov/pubmed/29319619

https://insights.ovid.com/crossref?an=00007890-900000000-96711

https://journals.lww.com/transplantjournal/Abstract/onlinefirst/History_of_marijuana_use_does_not_affect_outcomes.96711.aspx

“Do Cannabinoids have a therapeutic role in transplantation? Transplantation is one critical area of medicine that requires the use of immunosuppressants. Cannabinoids have emerged as powerful drug candidates for the treatment of inflammatory and autoimmune diseases due to their immunosuppressive properties.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2923447/
“The history of donor cannabis smoking does not appear to affect early and mid-term outcomes after lung transplantation (LTx) and potentially improve the donor pool. As it does not seem to negatively affect the outcomes after LTx, it should not be per se considered a contraindication for lung donation.” https://www.ncbi.nlm.nih.gov/pubmed/28077504
THC In Marijuana Delays Organ Transplant Rejection In Mice. A new study suggests the active ingredient in marijuana delays the rejection of incompatible organs in mice.” http://www.iflscience.com/health-and-medicine/thc-marijuana-may-delay-organ-transplant-rejection/
“Δ9-Tetrahydrocannabinol attenuates allogeneic host-versus-graft response and delays skin graft rejection through activation of cannabinoid receptor 1 and induction of myeloid-derived suppressor cells” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4541500/
Cannabidiol Limits T Cell-Mediated Chronic Autoimmune Myocarditis: Implications to Autoimmune Disorders and Organ Transplantation. CBD may represent a promising novel treatment for management of autoimmune myocarditis and possibly other autoimmune disorders, and organ transplantation.” http://pubmedcentralcanada.ca/pmcc/articles/PMC5004721/
“Could CANNABIS help transplant patients? Drug ‘delays rejection of organs by slowing the immune system’s attack'” http://www.dailymail.co.uk/health/article-3279752/Could-CANNABIS-help-transplant-patients-Drug-delays-rejection-organs-slowing-immune-s-attack.html

Cannabis, cannabinoids, and health.

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“Cannabis does have therapeutic properties for certain indications.”   https://www.ncbi.nlm.nih.gov/pubmed/29302228

“The legislative policies that have been established to reduce the risks in relation to cannabis have long represented an obstacle to research concerning medical cannabis use. Improved knowledge of the endocannabinoid system and of exocannabinoids has proven that cannabis may have significant therapeutic effects.”  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5741114/

Cannabidiol for drug-resistant seizures in the Dravet syndrome

Journal of Paediatrics and Child Health

“Dravet syndrome (severe myoclonic epilepsy of infancy) is characterised by difficult-to-control seizures. Media reports and small clinical trials suggest that cannabidiol, a non-toxic extract of cannabis, can reduce seizure frequency. A recent multicentre randomised controlled trial of 120 children aged 2–18 years with Dravet syndrome supports its efficacy.

Over a 14-week period, children taking 20 mg/kg/day of cannabidiol had a 22.8% reduction (95% confidence interval 5.4–41.1) in seizure frequency compared to a 4-week baseline period. Median convulsive frequency fell from 12.4 to 5.9 per month on cannabidiol, while the placebo group had no change from baseline. No attempt was made to measure non-convulsive seizures (e.g. absences). Subjects took a median of three other anti-convulsant drugs during the trial. Adverse effects were common with cannabidiol, particularly somnolence, fatigue, loss of appetite, vomiting and diarrhoea. Eight patients in the cannabidiol group withdrew compared to one in the placebo group.

Nevertheless, 62% of caregivers in the cannabidiol group felt the patient’s overall condition had improved, using a validated global score, compared to 34% in the placebo group (P = 0.02). Unfortunately, the high rate of adverse events may have led to widespread loss of caregiver blinding, and the study is relatively short term. Nevertheless, the reduction in seizures is clinically relevant, and further longer-term randomised controlled trials are clearly warranted. ” https://www.ncbi.nlm.nih.gov/pubmed/29314377  http://onlinelibrary.wiley.com/doi/10.1111/jpc.13803/full