“Cannabis sativa L. (cannabis) is an annual diecious member of the Cannabaceae family. Since ancient times cannabis has been used by humans for its fiber, seed, as well as its psychoactive and medicinal resin. Despite a long history of use, the legal status of cannabis in modern times often depends on its intended use. Cannabis grown for its fiber or seed, commonly known as hemp, is legally cultivated in many nations. Cannabis used for its psychoactive properties, in North American commonly known as “marijuana,” has been illegal in most nations worldwide since the 1961 United Nations Single Convention on Narcotic Drugs. Recently however, laws concerning the legal status of cannabis are changing around the world. In the United States of America, many states have legalized cannabis for medical use, whereas some have even legalized cannabis for adult consumption. Uruguay recently legalized cannabis and laws in various countries within the European Union (EU) are also changing regarding cannabis. Due to its many and controversial uses, the taxonomic classification of cannabis has been the subject of both legal and scientific debate.

From a morphological perspective, three main types of cannabis have been described sativa, indica, and ruderalis. Generally sativa plants are described as taller and loosely branched, whereas indica is typically shorter, more densely branched, and conical in shape. Ruderalis is described as short (≤2 feet) at maturity and sparsely if at all branched.⁷Whether the genus Cannabis is monotypic and composed of just a single species (C. sativa) or polytypic and composed of multiple species is an old taxonomic debate. A more recent taxonomic classification dividing cannabis into seven putative taxa based on morphological, geographical, and genetic traits has been proposed.

Cannabinoids are a group of terpenophenolic compounds found in cannabis. Today over 100 cannabinoids from cannabis have been characterized. (−)-Trans-Δ⁹-tetrahydrocannabinol (THC) is considered the primary active ingredient responsible for the intoxicating and medical effects attributed to cannabis. THC has antiemetic, neuroprotectant, and anti-inflammatory properties as well as the ability to reduce certain forms of neuropathic and chronic pain. Another important cannabinoid, cannabidiol (CBD), has neuroprotective, anti-inflammatory, antipsychotic, and antiseizure properties without the intoxicating effects of THC. Other minor cannabinoids, such as cannabigerol (CBG), cannabichromene (CBC), and tetrahydrocannabivarin (THCV), also exhibit interesting pharmacological properties.

Since cannabinoids are the major active ingredients found in cannabis, it makes sense to classify cannabis from a chemotaxonomic perspective according to cannabinoid levels for both medical and legal purposes. Early studies noted that cannabis used for fiber tended to have higher levels of CBD, whereas cannabis used for drug purposes had higher levels of THC

Terpenoids represent another interesting group of biologically active compounds found in cannabis. Due to their volatile nature, the mono- and sesquiterpenoids found in cannabis contribute to the plants’ aroma and flavor. About 100 terpenoids have been identified in cannabis, many of which are found in other plants. Both cannabinoids and terpenoids are produced in the trichomes of cannabis, which are found at highest density on female flower buds.Terpenoids are usually present in cannabis flower buds in the 0.5–3.5% range and are found at significant levels in cannabis smoke and vapor. As biologically active compounds, terpenoids may play a role in the overall effects of herbal cannabis.

The popularly understood distinctions between indica and sativa may have more to do with aroma and subjective effects than plant morphology. Recent studies have shown that terpenoids are useful in distinguishing cannabis cultivars that have similar cannabinoid content. A study of cannabinoid and terpenoid profiles among medical cannabis samples analyzed by a cannabis testing laboratory in California found a continuum of terpenoid profiles among the wide variety of sample names.Another study found that cannabis samples described as indica contained more myrcene and hydroxylated terpenoids, whereas those described as sativa tended to contain more terpinolene, 3-carene, and a few specified sesquiterpenes.” http://online.liebertpub.com/doi/full/10.1089/can.2016.0040

“Due to its astonishing efficacy, nowadays cannabis is prescribed by physicians for the treatment of neurological, psychiatric, immunological, cardiovascular, gastrointestinal, and oncological conditions. The active principles inside plants have been exploited by humans for centuries, with Cannabis sativa being one of the oldest ever used for medicinal purposes. Surprisingly, contrary to whole plant extracts, medicinal products containing exclusively THC have been found to lack efficacy and lead to unbearable side effects. These results arise from the fact that these products lack other important co-factors typically found in the Phyto-complex, such as terpenoids and other cannabinoids that contribute to the synergistic effects seen with whole plant extracts.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482328/

“In silico discovery of terpenoid metabolism in Cannabis sativa. Due to their efficacy, cannabis based therapies are currently being prescribed for the treatment of many different medical conditions. Interestingly, treatments based on the use of cannabis flowers or their derivatives have been shown to be very effective, while therapies based on drugs containing THC alone lack therapeutic value and lead to increased side effects, likely resulting from the absence of other pivotal entourage compounds found in the Phyto-complex. Among these compounds are terpenoids,” https://www.ncbi.nlm.nih.gov/pubmed/28690830

“Terpenoids: natural products for cancer therapy.”  https://www.ncbi.nlm.nih.gov/pubmed/23092199

“Inhibition of tumor progression by naturally occurring terpenoids.”  https://www.ncbi.nlm.nih.gov/pubmed/21936626

“Terpenoids as anti-colon cancer agents – A comprehensive review on its mechanistic perspectives.” https://www.ncbi.nlm.nih.gov/pubmed/27940056

“The endocannabinoid system encompassing cannabinoid receptors, endogenous receptor ligands (endocannabinoids), as well as enzymes conferring the synthesis and degradation of endocannabinoids has emerged as a considerable target for pharmacotherapeutical approaches of numerous diseases. Besides palliative effects of cannabinoids used in cancer treatment, phytocannabinoids, synthetic agonists, as well as substances that increase endogenous endocannabinoid levels have gained interest as potential agents for systemic cancer treatment. Accordingly, cannabinoid compounds have been reported to inhibit tumor growth and spreading in numerous rodent models. The underlying mechanisms include induction of apoptosis, autophagy, and cell cycle arrest in tumor cells as well as inhibition of tumor cell invasion and angiogenic features of endothelial cells. In addition, cannabinoids have been shown to suppress epithelial-to-mesenchymal transition, to enhance tumor immune surveillance, and to support chemotherapeutics’ effects on drug-resistant cancer cells. However, unwanted side effects include psychoactivity and possibly pathogenic effects on liver health. Other cannabinoids such as the nonpsychoactive cannabidiol exert a comparatively good safety profile while exhibiting considerable anticancer properties. So far experience with anticarcinogenic effects of cannabinoids is confined to in vitro studies and animal models. Although a bench-to-bedside conversion remains to be established, the current knowledge suggests cannabinoid compounds to serve as a group of drugs that may offer significant advantages for patients suffering from cancer diseases. The present review summarizes the role of the endocannabinoid system and cannabinoid compounds in tumor progression.”

https://www.ncbi.nlm.nih.gov/pubmed/28826542

http://www.sciencedirect.com/science/article/pii/S105435891730039X?via%3Dihub

“GPR12 is a constitutively active, G_s protein-coupled receptor that currently has no confirmed endogenous ligands. GPR12 may be involved in physiological processes such as maintenance of oocyte meiotic arrest and brain development, as well as pathological conditions such as metastatic cancer. In this study, the potential effects of various classes of cannabinoids on GPR12 were tested using a cAMP accumulation assay.

Our data demonstrate that cannabidiol (CBD), a major non-psychoactive phytocannabinoid, acted as an inverse agonist to inhibit cAMP accumulation stimulated by the constitutively active GPR12. Thus, GPR12 is a novel molecular target for CBD.

CBD is a promising novel therapeutic agent for cancer, and GPR12 has been shown to alter viscoelasticity of metastatic cancer cells.

Since we have demonstrated that CBD is an inverse agonist for GPR12, this provides novel mechanism of action for CBD, and an initial chemical scaffold upon which highly potent and efficacious agents acting on GPR12 may be developed with the ultimate goal of blocking cancer metastasis.”

https://www.ncbi.nlm.nih.gov/pubmed/28888984

http://www.sciencedirect.com/science/article/pii/S0006291X1731759X

“Let’s get medicinal, says Olivia Newton-John, who has spoken out about the use of medicinal cannabis on a recent visit to Australia. “I will do what I can to encourage it. It’s an important part of treatment and it should be available,” the singer, who announced a second battle with breast cancer in May, told News Corp Australia. The Australian entertainer said the drug – which is legal in her home state of California – had helped her during her second fight against cancer.” https://www.stuff.co.nz/entertainment/celebrities/96702731/olivia-newtonjohn-champions-the-use-of-magical-miracle-medicinal-cannabis

“Olivia Newton-John’s cancer battle is going well… Thanks to cannabis oil!” http://lifestyle.one/closer/celebrity/news/olivia-newton-john-daughter-chloe-lattanzi-cannabis-oil-cancer/

“Olivia Newton-John Is Using Cannabis Oil To Treat Her Cancer”  https://www.inverse.com/article/32780-cannabis-oil-cancer-treatment-cannabinoid-chemotherapy

“OLIVIA NEWTON-JOHN USES MEDICINAL CANNABIS IN CANCER FIGHT”  http://www.wsfm.com.au/entertainment/the-feed/olivia-newton-john-uses-medicinal-cannabis-in-cancer-fight

“Olivia Newton-John uses medical marijuana to treat cancer”  https://www.buzz.ie/celebs/olivia-newton-john-drinks-cannabis-extract-numb-pain-cancer-253796

“Olivia Newton-John Talks Using Medical Marijuana In Cancer Treatment. “I use medical cannabis, which is really important to pain and healing. It’s an important part of treatment, and it should be available.”” https://www.thefix.com/olivia-newton-john-talks-using-medical-marijuana-cancer-treatment

“Nanotechnology has opened up a new, previously unimaginable world in cancer diagnosis and therapy, leading to the emergence of cancer nanomedicine and nanoparticle-aided radiotherapy. These nanoparticle drones can be programmed to deliver therapeutic payloads to tumor sites to achieve optimal therapeutic efficacy.

In this article, we examine the state-of-the-art and potential of nanoparticle drones in targeting lung cancer. Inhalation (INH) (air) versus traditional intravenous (“sea”) routes of navigating physiological barriers using such drones is assessed. Results and analysis suggest that INH route may offer more promise for targeting tumor cells with radiosensitizers and cannabinoids from the perspective of maximizing damage to lung tumors cells while minimizing any collateral damage or side effects.

As discussed earlier, nanoparticle drones are particularly attractive because they can also be loaded with drugs payload like cannabinoids. Cannabinoids, which are the bioactive components of Cannabis sativa and their derivatives, may exert palliative effects in cancer patients by preventing nausea, vomiting, and pain and by stimulating appetite .

Furthermore, studies indicate that cannabinoids can inhibit cancer cell growth in in vitro and in vivo. A Nature Reviews Cancer article and other recently published work highlight the potential of cannabinoids for treating cancer, working in synergy with radiotherapy and serving as radiosensitzers to enhance damage to lung tumor cells in particular. Consistent with this, our own experiments have confirmed the potential of cannabinoids in treating lung cancer, with results confirming that cannabinoids can enhance damage to cancer cells.

Overall, the use of nanoparticle drones administered via INH to enhance NRT, as highlighted in this article, may provide a good strategy for maximizing therapeutic efficacy in external beam NRT for lung cancer. Also there is growing evidence that cannabinoids can serve as radiosensitizers, enhance damage to tumor cells, slow tumor growth, and work synergistically with radiotherapy in cancer treatment.”

http://journal.frontiersin.org/article/10.3389/fonc.2017.00208/full

“Cannabis Science Announces Publication of Initial Research Results Using Nanoparticle Drones to Target Lung Cancer With Radiosensitizers and Cannabinoids in the Renowned Journal Frontiers in Oncology” https://ca.finance.yahoo.com/news/cannabis-science-announces-publication-initial-120522920.html

“Cannabis Science “Nanoparticle Drones to Target Lung Cancer with Radiosensitizers and Cannabinoids” Full Publication Released Today In Frontiers In Oncology” http://www.marketwired.com/press-release/cannabis-science-nanoparticle-drones-target-lung-cancer-with-radiosensitizers-cannabinoids-2234167.htm

“Prior phase 2/3 studies found that cannabinoids might provide adjunctive analgesia in advanced cancer patients with uncontrolled pain.

To assess adjunctive nabiximols (Sativex^®), an extract of Cannabis sativa containing two potentially therapeutic cannabinoids (Δ9-tetrahydrocannabinol and cannabidiol, in advanced cancer patients with chronic pain unalleviated by optimized opioid therapy.

Nabiximols was statistically superior to placebo on two of three quality-of-life instruments at week 3 and on all three at week 5.

The safety profile of nabiximols was consistent with earlier studies.

Although not superior to placebo on the primary efficacy endpoint, nabiximols had benefits on multiple secondary endpoints, particularly in US patients.

Nabiximols might have utility in patients with advanced cancer who receive a lower opioid dose, such as individuals with early intolerance to opioid therapy.”

https://www.ncbi.nlm.nih.gov/pubmed/28923526

http://www.jpsmjournal.com/article/S0885-3924(17)30465-7/fulltext

“Medical marijuana (MM) has become increasingly legal at the state level and accessible to children with serious illness. Pediatric patients with cancer may be particularly receptive to MM, given purported benefits in managing cancer-related symptoms. In this review, we examine the evidence for MM as a supportive care agent in pediatric oncology. We describe the current legal status of MM, mechanism of action, common formulations, and potential benefits versus risks for pediatric oncology patients. We offer suggestions for how providers might approach MM requests. Throughout, we comment on avenues for future investigation on this growing trend in supportive care.”

https://www.ncbi.nlm.nih.gov/pubmed/28926679

http://onlinelibrary.wiley.com/doi/10.1002/pbc.26826/abstract

“Basal cell carcinoma (BCC) arises from loss-of-function mutations in tumor suppressor patched homologue 1, which normally inhibits smoothened homologue in the sonic hedgehog signaling pathway. Vismodegib, a smoothened homologue inhibitor, is US Food and Drug Administration (FDA) approved for metastatic or locally advanced BCC that has recurred after surgery or for patients who are not candidates for surgery and radiation. Common adverse effects of vismodegib are muscle spasms, alopecia, dysgeusia, nausea, and weight loss. Muscle spasms worsen with duration of drug administration and may lead to drug discontinuation.

We report a case of vismodegib-related muscle spasm that was successfully treated with medical marijuana (MM).

During the first week of vismodegib and radiation, the patient started MM, having heard of its indication in the treatment of muscle cramps. She smoked 3 to 4 joints daily of Trainwreck strain, containing 18.6% tetrahydrocannabinol (THC), 0.0% cannabidiol (CBD), and 0.0% cannabinol. Her muscle spasms resolved immediately. She continued MM for 3.5 weeks, until the cost of MM became prohibitive. She reported no adverse effects from MM. Complete resolution of muscle spasms was sustained through the remaining 3.5 weeks of vismodegib. Complete blood count, comprehensive metabolic panel, and lactate dehydrogenase level were monitored throughout the study with no significant changes. As of 18 months posttreatment, the patient had a complete clinical response of her BCC.

One marijuana joint contains, on average, 0.66 g of marijuana, although the definition of a joint is highly variable. With any MM formulation, patients should start at a low dose and gradually titrate to effect. Additional studies could confirm safety and efficacy and better specify the optimal cannabinoid subtypes, preparations, and dosages that may be most beneficial for vismodegib-induced muscle spasms.”

http://www.jaadcasereports.org/article/S2352-5126(17)30124-8/fulltext

“A hypothetical link between marijuana smoking and cancer has been established based on a number of misleading assumptions. However, recent studies tend to suggest, if anything, an inverse association between marijuana use and cancers.

To test the hypothesis that marijuana smoking significantly lowers the risk of developing cancer in humans, we analyzed published data from a prospective cohort study on cancer incidence among nonsmokers (NS), marijuana-only smokers (MS), tobacco-only smokers (TS), and marijuana and tobacco smokers (MTS).

Using the log linear model to calculate the probability of developing each cancer form as a function of the interaction between marijuana and tobacco smoking, as well as functions of marijuana and tobacco smoking main effects whereby chi square statistics were calculated for the interaction and main effect estimates, we found that in all cases tested there was a significantly lower risk for MS compared to TS. Male and female TS had a greater probability of developing lung cancer than did MS. Males and females TS had a greater probability of developing lung cancer compared with NS. Males and female MTS had a slightly higher probability of developing lung cancer than did MS.

This difference was statistically significant: chi2 = 30.51, p < .00001, with a correlation coefficient of -0.75, Z = -7.84, p < .05. Male and female MTS had a lower probability of developing lung cancer than did TS. This difference was statistically significant: chi2 = 71.61, p = .00003, with a correlation coefficient of 0.61, Z = 5.06, p < .05.”

https://www.ncbi.nlm.nih.gov/pubmed/19004418

http://www.tandfonline.com/doi/abs/10.1080/02791072.2008.10400641

“Cannabis is purported to alleviate symptoms related to cancer treatment, although the patterns of use among cancer patients are not well known. This study was designed to determine the prevalence and methods of use among cancer patients, the perceived benefits, and the sources of information in a state with legalized cannabis.

METHODS:

A cross-sectional, anonymous survey of adult cancer patients was performed at a National Cancer Institute-designated cancer center in Washington State. Random urine samples for tetrahydrocannabinol provided survey validation.

RESULTS:

Nine hundred twenty-six of 2737 eligible patients (34%) completed the survey, and the median age was 58 years (interquartile range [IQR], 46-66 years). Most had a strong interest in learning about cannabis during treatment (6 on a 1-10 scale; IQR, 3-10) and wanted information from cancer providers (677 of 911 [74%]). Previous use was common (607 of 926 [66%]); 24% (222 of 926) used cannabis in the last year, and 21% (192 of 926) used cannabis in the last month. Random urine samples found similar percentages of users who reported weekly use (27 of 193 [14%] vs 164 of 926 [18%]). Active users inhaled (153 of 220 [70%]) or consumed edibles (154 of 220 [70%]); 89 (40%) used both modalities. Cannabis was used primarily for physical (165 of 219 [75%]) and neuropsychiatric symptoms (139 of 219 [63%]). Legalization significantly increased the likelihood of use in more than half of the respondents.

CONCLUSIONS:

This study of cancer patients in a state with legalized cannabis found high rates of active use across broad subgroups, and legalization was reported to be important in patients’ decision to use. Cancer patients desire but are not receiving information about cannabis use during their treatment from oncology providers.”

https://www.ncbi.nlm.nih.gov/pubmed/28944449

http://onlinelibrary.wiley.com/doi/10.1002/cncr.30879/abstract;jsessionid=793E288AAC342234D14BA7C96AEEDB74.f02t04?systemMessage=Wiley+Online+Library+will+be+unavailable+on+Saturday+7th+Oct+from+03.00+EDT+%2F+08%3A00+BST+%2F+12%3A30+IST+%2F+15.00+SGT+to+08.00+EDT+%2F+13.00+BST+%2F+17%3A30+IST+%2F+20.00+SGT+and+Sunday+8th+Oct+from+03.00+EDT+%2F+08%3A00+BST+%2F+12%3A30+IST+%2F+15.00+SGT+to+06.00+EDT+%2F+11.00+BST+%2F+15%3A30+IST+%2F+18.00+SGT+for+essential+maintenance.+Apologies+for+the+inconvenience+caused+.

“Study finds up to one-quarter of cancer patients use marijuana”  https://medicalxpress.com/news/2017-09-one-quarter-cancer-patients-marijuana.html

“Up to one-quarter of cancer patients use marijuana”  https://www.sciencedaily.com/releases/2017/09/170925095431.htm

“Cancer Patients Want to Use Marijuana, and with Good Reason”  https://www.inverse.com/article/36751-cancer-patients-want-to-use-marijuana-study-fred-hutchinson-cancer-research-center

“The use of Cannabis for medicinal purposes dates back to ancient times. Cannabis has been shown to kill cancer cells in the laboratory.” http://www.cancer.gov/about-cancer/treatment/cam/patient/cannabis-pdq#section/all

“Marijuana has been used in herbal remedies for centuries. More recently, scientists reported that THC and other cannabinoids such as CBD slow growth and/or cause death in certain types of cancer cells.” http://www.cancer.org/treatment/treatmentsandsideeffects/physicalsideeffects/chemotherapyeffects/marijuana-and-cancer

http://www.thctotalhealthcare.com/category/cancer/

“Cannabinoid receptors have been shown to interact with other receptors, including Tumor Necrosis Factor Receptor Superfamily (TNFRS) members, to induce cancer cell death. When cannabinoids and death-inducing ligands (including TRAIL) are administered together, they have been shown to synergize and demonstrate enhanced antitumor activity in vitro. Certain cannabinoid ligands have been shown to sensitize cancer cells and synergistically interact with members of the TNFRS, thus suggesting that the combination of cannabinoids with death receptor (DR) ligands induces additive or synergistic tumor cell death. This review summarizes recent findings on the interaction of the cannabinoid and DR systems and suggests possible clinical co-application of cannabinoids and DR ligands in the treatment of various malignancies.”

https://www.ncbi.nlm.nih.gov/pubmed/28948607

http://onlinelibrary.wiley.com/doi/10.1002/1873-3468.12863/abstract?systemMessage=Wiley+Online+Library+will+be+unavailable+on+Saturday+7th+Oct+from+03.00+EDT+%2F+08%3A00+BST+%2F+12%3A30+IST+%2F+15.00+SGT+to+08.00+EDT+%2F+13.00+BST+%2F+17%3A30+IST+%2F+20.00+SGT+and+Sunday+8th+Oct+from+03.00+EDT+%2F+08%3A00+BST+%2F+12%3A30+IST+%2F+15.00+SGT+to+06.00+EDT+%2F+11.00+BST+%2F+15%3A30+IST+%2F+18.00+SGT+for+essential+maintenance.+Apologies+for+the+inconvenience+caused+.

“Studies have revealed that cancer might be treated with cannabinoids since they can influence cancer cell survival. These findings suggest an alternative treatment option to chemo- and radiotherapy, that are associated with numerous adverse side-effects for the patients.

MATERIALS AND METHODS:

Viability staining was conducted on lung cancer, testicular cancer and neuroblastoma cells treated with different concentrations of the synthetic cannabinoid WIN 55,212-2 and the percentage of dead cells was compared. Activity of apoptosis-related enzymes was investigated by the presence of DNA ladder in gel electrophoresis.

RESULTS:

Treatment with different WIN 55,212-2 concentrations led to a significant dose-dependent reduction of cell viability. A DNA ladder was observed after WIN 55,212-2 treatment of testicular cancer and lung cancer cells.

CONCLUSION:

The application of WIN 55,212-2 was found to trigger cell death in the investigated cell lines. The decline in lung cancer and testicular cancer cell viability seems to have been caused by apoptosis. These findings may contribute to development of alternative cancer therapy strategies.”

https://www.ncbi.nlm.nih.gov/pubmed/29061818

“Although medical marijuana (MM) may have utility in the supportive care of children with serious illness, it remains controversial.

We investigated interdisciplinary provider perspectives on legal MM use in children with cancer.

Most pediatric oncology providers are willing to consider MM use in children with cancer and receive frequent inquiries.” https://www.ncbi.nlm.nih.gov/pubmed/29233937

http://pediatrics.aappublications.org/content/early/2017/12/08/peds.2017-0559.long

“Medical Marijuana For Children With Cancer Broadly Supported By Doctors. An overwhelming majority of health care professionals who care for children with cancer would be willing to help those children get medical marijuana” https://www.forbes.com/sites/tarahaelle/2017/12/12/medical-marijuana-for-children-with-cancer-broadly-supported-by-doctors/#3d31cf08795d

“Most doctors would allow medical marijuana for children with cancer, study finds. A considerable majority of medical physicians would help children treat cancer with medical cannabis, a new study suggests.” http://blog.sfgate.com/smellthetruth/2017/12/12/most-doctors-would-allow-medical-marijuana-for-children-with-cancer-study-finds/