Phytochemical Aspects and Therapeutic Perspective of Cannabinoids in Cancer Treatment

Cannabis sativa L. – dried pistillate inflorescences and trichomes on their surface. (a) dried pistillate inflorescences (50% of the size); (b) non‐cystolithic trichome; (c) cystolithic trichome; (d) capitate‐sessile trichome; (e) simple bulbous trichome; (f) capitate‐stalked trichome (400×).

“Cannabis sativa L. (Cannabaceae) is one of the first plants cultivated by man and one of the oldest plant sources of fibre, food and remedies.

Cannabinoids comprise the plant‐derived compounds and their synthetic derivatives as well as endogenously produced lipophilic mediators. Phytocannabinoids are terpenophenolic secondary metabolites predominantly produced in CannabissativaL.

The principal active constituent is delta‐9‐tetrahydrocannabinol (THC), which binds to endocannabinoid receptors to exert its pharmacological activity, including psychoactive effect. The other important molecule of current interest is non‐psychotropic cannabidiol (CBD).

Since 1970s, phytocannabinoids have been known for their palliative effects on some cancer‐associated symptoms such as nausea and vomiting reduction, appetite stimulation and pain relief. More recently, these molecules have gained special attention for their role in cancer cell proliferation and death.

A large body of evidence suggests that cannabinoids affect multiple signalling pathways involved in the development of cancer, displaying an anti‐proliferative, proapoptotic, anti‐angiogenic and anti‐metastatic activity on a wide range of cell lines and animal models of cancer.”

https://www.intechopen.com/books/natural-products-and-cancer-drug-discovery/phytochemical-aspects-and-therapeutic-perspective-of-cannabinoids-in-cancer-treatment

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

Medical Cannabis for Neuropathic Pain.

Current Pain and Headache Reports

“Many cultures throughout history have used cannabis to treat a variety of painful ailments. Neuropathic pain is a complicated condition that is challenging to treat with our current medications.

Recent scientific discovery has elucidated the intricate role of the endocannabinoid system in the pathophysiology of neuropathic pain. As societal perceptions change, and legislation on medical cannabis relaxes, there is growing interest in the use of medical cannabis for neuropathic pain.

We examined current basic scientific research and data from recent randomized controlled trials (RCTs) evaluating medical cannabis for the treatment of neuropathic pain.

These studies involved patients with diverse etiologies of neuropathic pain and included medical cannabis with different THC concentrations and routes of administration. Multiple RCTs demonstrated efficacy of medical cannabis for treating neuropathic pain, with number needed to treat (NNT) values similar to current pharmacotherapies.

Although limited by small sample sizes and short duration of study, the evidence appears to support the safety and efficacy of short-term, low-dose cannabis vaporization and oral mucosal delivery for the treatment of neuropathic pain.

The results suggest medical cannabis may be as tolerable and effective as current neuropathic agents; however, more studies are needed to determine the long-term effects of medical cannabis use. Furthermore, continued research to optimize dosing, cannabinoidratios, and alternate routes of administration may help to refine the therapeutic role of medical cannabis for neuropathic pain.”

https://www.ncbi.nlm.nih.gov/pubmed/29388063

https://link.springer.com/article/10.1007%2Fs11916-018-0658-8

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

NeuroImage

“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

Cannabis Use, Lung Cancer, and Related Issues.

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“The cannabis plant and its derivatives have been exploited for centuries for recreational and medicinal purposes with millions of regular users around the world.

The recreational use of cannabis is reflective of its neuropsychiatric effects such as anxiolysis and euphoria. However, cannabis appears to have an emerging therapeutic role, especially in chronic disease and as an adjunct to cancer treatment.

Increasing evidence supports cannabis in the management of chemotherapy induced nausea and vomiting and for pain management, but studies are limited particularly by difficulties associated with standardized dosing estimates and inability to accurately assess biologic activities of compounds in cannabis and derivative products.

Smoking cannabis has not been proven to be a risk factor in the development of lung cancer but the data are limited by small studies, misclassification due to self-reporting of usage, small numbers of heavy cannabis smoking and confounding of risk associated with known causative agents for lung cancer such as parallel chronic tobacco use.

Cannabis and its biologically effective derivatives warrant additional research, ideally controlled trials where the CBD and the THC strength and usage are controlled and documented.”

https://www.ncbi.nlm.nih.gov/pubmed/29374567

“Good News: There’s No Definitive Link Between Marijuana Use and Lung Cancer” http://www.esquire.com/lifestyle/health/news/a52634/marijuana-lung-cancer/ 

“Study Shows No Proven Link Between Weed-Smoking and Lung Cancer”  http://www.complex.com/life/2017/01/weed-study-lung-cancer

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

Cannabinoid CB1 and CB2 Receptors, and Monoacylglycerol Lipase Gene Expression Alterations in the Basal Ganglia of Patients with Parkinson’s Disease.

Neurotherapeutics

“Previous studies suggest that the endocannabinoid system plays an important role in the neuropathological basis of Parkinson’s disease (PD).

This study was designed to detect potential alterations in the cannabinoid receptors CB1 (CB1r) and CB2 (A isoform, CB2Ar), and in monoacylglycerol lipase (MAGL) gene expression in the substantia nigra (SN) and putamen (PUT) of patients with PD.

The results of the present study suggest that CB1r, CB2r, and MAGL are closely related to the neuropathological processes of PD.

Therefore, the pharmacological modulation of these targets could represent a new potential therapeutic tool for the management of PD.”

https://www.ncbi.nlm.nih.gov/pubmed/29352424

https://link.springer.com/article/10.1007%2Fs13311-018-0603-x

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/