Breast Cancer And CBD Oil

CBDISTILLERY

Buy CBD Oil Online

Cannabinoids and Hormone Receptor-Positive Breast Cancer Treatment Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Medical Cannabis Cannabis refers to a family of plants from which marijuana and hemp are produced. These plants are grown around the world and have been used in herbal remedies for centuries.

Cannabinoids and Hormone Receptor-Positive Breast Cancer Treatment

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

Abstract

Breast cancer (BC) is the most common cancer in women worldwide. Approximately 70–80% of BCs express estrogen receptors (ER), which predict the response to endocrine therapy (ET), and are therefore hormone receptor-positive (HR+). Endogenous cannabinoids together with cannabinoid receptor 1 and 2 (CB1, CB2) constitute the basis of the endocannabinoid system. Interactions of cannabinoids with hypothalamic–pituitary–gonadal axis hormones are well documented, and two studies found a positive correlation between peak plasma endogenous cannabinoid anandamide with peak plasma 17β-estradiol, luteinizing hormone and follicle-stimulating hormone levels at ovulation in healthy premenopausal women. Do cannabinoids have an effect on HR+ BC? In this paper we review known and possible interactions between cannabinoids and specific HR+ BC treatments. In preclinical studies, CB1 and CB2 agonists (i.e., anandamide, THC) have been shown to inhibit the proliferation of ER positive BC cell lines. There is less evidence for antitumor cannabinoid action in HR+ BC in animal models and there are no clinical trials exploring the effects of cannabinoids on HR+ BC treatment outcomes. Two studies have shown that tamoxifen and several other selective estrogen receptor modulators (SERM) can act as inverse agonists on CB1 and CB2, an interaction with possible clinical consequences. In addition, cannabinoid action could interact with other commonly used endocrine and targeted therapies used in the treatment of HR+ BC.

Keywords: hormone receptor, breast cancer, cannabinoids, treatment, CBD, THC, estrogen, cannabinoid receptor

1. Hormone-Receptor Positive Breast Cancer

Breast cancer (BC) is the most common cancer in women worldwide [1]. Approximately 70% to 80% BCs express estrogen receptors (ER) and are therefore hormone receptor-positive (HR+). Furthermore, 65% of these cancers are also progesterone receptor (PR)-positive and PR expression is used as a biomarker of ER signaling [2,3]. Expression of ERs predicts the efficacy of endocrine therapy (ET), which is the cornerstone of the management of HR+ BCs [4,5,6]. One third of tumors that express ERs have primary resistance to treatment with ET, and in the long term, most of the patients develop secondary resistance [7]. ERs are steroid receptors that bind various endogenous (17β-estradiol, estrone, estriol, estetrol) and exogenous estrogens or mimetics. Two types of ERs have been identified; ERα and ERβ. BC oncogenesis is mediated primarily by ERα [8]. ERs act as a transcription factor that translocates into the nucleus and binds with estrogen-response elements (ERE). ERα-regulated gene expression promotes cancer cell proliferation and cell viability [9]. The activation of ERβ has antiproliferative effects in hormone receptor-positive MCF-7 and T-47D BC cell lines. ERβ overexpression downregulates cell cycle-related genes and DNA replication. ERβ inhibits cell proliferation by c-myc, cyclin D1, and cyclin A gene transcription repression and causing an increase in expression of p21 and p27, inducing G2 cell cycle arrest [10].

2. Cannabinoids and the Endocannabinoid System

Cannabinoid receptors (CBRs) are membrane G-protein coupled receptors (GPCR). Cannabinoid receptor 1 (CB1) was discovered in 1988, which was followed by the discovery of cannabinoid receptor 2 (CB2) in 1993. Recent studies have shown that cannabinoids can activate other receptors, i.e., GPR18, GPR119, TRPV1, and GPR55 which is considered by some as a CB3 receptor [11,12,13]. CBRs can be activated by endogenous or exogenous cannabinoids, which can be of natural or synthetic origin. Endogenous cannabinoids are substances produced by the human body. The most studied are N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol (2-AG). Together with CBRs, the endogenous cannabinoids constitute the basis of the endocannabinoid system [14]. Delta-9-tetrahydrocannabinol (THC) is the main psychoactive component of Cannabis sativa and is therefore an exogenous phytocannabinoid and a non-selective agonist of CB1 and CB2 [15]. Cannabidiol (CBD) is another phytocannabinoid abundant in Cannabis sativa and is emerging as potential therapeutic agent [16]. In comparison with THC, it displays lower CB1 and CB2 affinity and acts as an inverse agonist at the CB2 [17]. Synthetic cannabinoids are a heterogeneous group of substances and can be selective agonists of CB1 or CB2 [18,19]. Synthetic THC analogue dronabinol is used in palliative treatment (alongside the standard therapy) for hard to manage symptoms of anorexia, weight loss, and sleep disorders [20,21].

3. Cannabinoid Receptor 1

CB1 is a GPCR associated receptor [22]. The receptor is encoded by the gene CNR1, which is referred to as a canonical sequence, due to the identification of two other CB1 splice variants [22,23,24]. Canonical CB1 expression and function is best described in the central and peripheral nervous system. CB1 expression is not limited to the nervous system, as expression is present in other peripheral tissues, i.e., cardiovascular, gastrointestinal, immune system, skeletal muscle, pancreatic, fat tissue, etc. The function of CB1 in the majority of the tissues is still under investigation [22]. Apart from widespread localization across the body, the CB1 is shown to have different localization sites on the cellular level. CB1 is dominantly localized on the plasma membrane, but further research has shown that internalized (endosome) and intracellularly (mitochondria, lysosome) located receptors are also present. These subpopulations are shown to have diverse functions from membrane bound CB1. CB1 is a Gi/o type of GPCR ( Figure 1 ), which means that once activated, it inhibits adenylyl cyclase (AC) activity and blocks the accompanying pathway of cyclic adenosine monophosphate (cAMP) formation and protein kinase A (PKA) activation ( Figure 1 ). Another inhibitory function of CB1 is the ability to suppress an influx of Ca2+ ions by closing voltage-gated calcium channels. CB1 mechanism is not limited to inhibiting signal pathways: the receptor is shown to activate several proteins from the mitogen-activated protein kinases (MAPK) family and phosphoinositide-3-kinase/protein kinase B (PI3K/AKT) pathway. CB1 regulates physiological processes such as appetite, learning, memory, pain regulation, energy metabolism, reproductive and cardiovascular system functions. In addition, CB1 is expressed in different tissues under pathological conditions, including cancer. [24]. There is evidence of increased CB1 expression in prostate cancer, pancreatic cancer, colon cancer, hepatocellular carcinoma, non-Hodgkin lymphoma, and astrocytoma [25].

Cannabinoid receptor 1 (CB1) crystal structure and mode of action.

4. Cannabinoid Receptor 2

CB2 is a GPCR-associated receptor with two known isoforms and is encoded by the gene CNR2. In comparison to CNR1, the CNR2 is shorter and possesses only 44% sequence homology [24]. Isoform CB2A is found in the testis and lower brain regions, while CB2B is more present in tissues of the immune system [26]. Due to its abundance in the immune system, CB2 was discovered in macrophage cells isolated from the spleen [24]. Human leukocytes, such as B- and T-cells, basophiles, eosinophils, mast cells, macrophages, natural killer (NK) cells, and neutrophils have all been shown to express CB2 [24]. Apart from being widely present in the immune system, CB2 can be found in other tissues, i.e., the gastrointestinal tract, cardiovascular and reproductive system, adipose tissue, and in the liver with moderate expression [24]. It was initially believed that CB2 expression is limited to the extracranial tissues, but new research has proven otherwise, as CB2 presence has been found in the brain, although with lower expression intensity. The main function of CB2 is to trigger pro-inflammatory or anti-inflammatory effects in immune cells, depending on the binding ligand, while neural CB2 expression is connected to nociception and neuroinflammation. Even though both CBRs are GPCR ( Figure 2 ), the CB1’s signal pathway is significantly more clarified in comparison to CB2 [23,26]. CB2 was also shown to be a Gi/o type of GPCR, which means that it inhibits AC activity and lowers cAMP levels; however, it is unable to block voltage-gated ion channels ( Figure 2 ). CB2 (just as CB1) is able to activate proteins of the MAPK and PI3K family, and their respective pathways. The receptor is shown to be involved in calcium metabolism by activating the phospholipase C (PLC)/inositol 1,4,5-triphosphate (IP3) pathway, which consequently increases intracellular and mitochondrial Ca2+ levels ( Figure 2 ) [27]. CB2 expression is increased in breast cancer, hepatocellular carcinoma, glioma, and astrocytoma [25].

Cannabinoid receptor 2 (CB2) crystal structure and mode of action.

5. Cannabinoids in Connection with the Hypothalamic-Pituitary-Gonadal Axis

Interactions of cannabinoids with hypothalamic-pituitary-gonadal axis hormones are well documented in animal models. There is evidence that the acute administration of THC lowers serum luteinizing hormone (LH) and gonadotropin-releasing hormone (GnRH) secretion in ovariectomized female and intact male rats [28,29,30]. Lower concentrations of GnRH result in lower circulating estrogen levels. Anandamide produces similar results in both female and male rats [31]. Cannabinoids could modulate the release of GnRH through their effect on hypothalamic GnRH-releasing neurons that have a high density of CB1 and low density of CB2 [32]. Fatty acid amide hydrolase (FAAH) is responsible for anandamide degradation [33] and estrogens decrease FAAH activity in the mouse uterus [34]. Two studies found a positive correlation between peak plasma anandamide with peak plasma 17β-estradiol, LH, and follicle-stimulating hormone (FSH) levels at ovulation in healthy premenopausal women [35,36]. A possible mechanism responsible for this phenomenon is that increased levels of estrogens at ovulation inhibit FAAH activity and consequently increase endocannabinoid plasma levels [37].

6. Cannabinoids and Hormone Receptor-Positive Breast Cancer (Preclinical Evidence)

There is evidence that molecular pathways between CBRs and estrogens overlap, and this could impact pathogenesis of common diseases, including HR+ BC [38]. Most of the preclinical studies have explored the effects of cannabinoids on BC cell lines. De Petrocellis et al. showed that anandamide can inhibit the proliferation of ER positive MCF-7 and T-47D BC cell lines. The anti-proliferative effect of anandamide was due to the inhibition of DNA synthesis and not toxic effects or apoptosis. There was a reduction of cells in the S phase of the cell cycle. Anandamide suppressed prolactin (PRL) receptor synthesis and the prolactin-induced response. The authors concluded that anandamide blocks human BC cell proliferation through the CB1-like receptor-mediated inhibition of prolactin action at the level of PRL [39]. In contrast to these findings, Hanlon et al. found that JWH-015 (CB2 selective agonist) reduced the viability of MCF-7 cells by inducing apoptosis using a calcium-dependent, cell cycle-independent mechanism. In addition, JWH-015 inhibited the MAPK/ERK intracellular pathway [40]. Meck et al. showed that anandamide inhibits AC and activates MAPK in MCF-7 cells, resulting in inhibitory effects on cell proliferation, PRL receptor expression, and tropomyosin receptor kinase (Trk) levels [41]. There is evidence that anandamide and 2-AG inhibit the proliferation of PRL-responsive human BC cells through the downregulation of the PRL receptor [42]. Another study showed that THC fails to activate ERs and reduces 17β-estradiol induced proliferation of the MCF-7 cell line by a probable ER-independent mechanism [43]. THC and CBD are unable to stimulate the EREtkCAT reporter gene transiently transfected into MCF-7 cells and therefore fail to act as agonists at ER [44]. Furthermore, THC inhibits 17β-estradiol/ERα signaling by up-regulating ERβ, and antiproliferative effects on BC may be modulated by expression levels of ERα in the presence of 17β-estradiol. It was suggested that THC could be categorized as a selective ER modulator (SERM) because of its potential to modulate ER interactions [45]. Takeda showed that growth stimulatory effects of THC are mediated by the products of cyclooxygenase 2 (COX-2) and that THC action is modulated by 17β-estradiol. COX-2 and aromatase individually participate in the proliferation of BC cells induced by THC [46]. In most of the studies, non-selective CB1 and CB2 agonists (anandamide, THC) were used and their action resulted in the decreased proliferation of cancer cells. However, Sarnataro et al. showed that rimonabant (a synthetic selective CB1 antagonist) inhibits the proliferation of ER positive BC cells through a lipid raft-mediated mechanism. The growth of the highly invasive metastatic ER negative MDA-MB-231 cell line was more inhibited in comparison to ER positive T47D and MCF-7. The anti-proliferative effect was completely lacking in the absence of the CB1, suggesting that the antiproliferative effect of rimonabant was CB1-dependent [47]. Blasco-Benito et al. evaluated the antitumor efficacy of pure THC with that of a botanical drug preparation made from fresh cannabis flowers. The botanical drug preparation was more potent than pure THC in producing antitumor responses in cell culture and animal models of different BC subtypes, including the HR+ subtype [48].

7. Cannabinoids and Hormone Receptor-Positive Breast Cancer (Clinical Evidence)

Perez-Gomez et al. analyzed a large series of human BC tissue sections. CB2 was expressed by 75.6% of human breast adenocarcinomas, regardless of the subtype. CB2 expression was highly associated to human epidermal growth factor 2 (HER2) positive tumors, while no association between CB2 expression and HR+ or triple-negative BC (TNBC) was detected. Interestingly, nontumor breast tissue did not express CB2. In addition, there was an association between the higher expression of CB2 in HER2 positive disease and the decreased overall survival, higher probability of local recurrence and developing distant metastases. This association was not observed in HR+ patients [49]. Andradas et al. found an association between GPR55 expression and basal/TNBC subtype. They analyzed the publicly available The Cancer Genome Atlas (TCGA) microarray data sets and found that women with basal/TNBC and high tumor GPR55 mRNA expression had reduced overall survival and reduced metastasis-free survival in comparisson to those with low GPR55 mRNA levels [50]. There is no clinical evidence evaluating the effect of exogenous or endogenous cananbinoids on treatment outcomes and/or disease prognosis of any BC subtype.

See also  CBD Oil Under The Tongue

8. Cannabinoids and Specific Hormone Receptor-Positive Breast Cancer Treatments

The standard ET of HR+ BC consists of ovarian suppression with GnRH agonists, SERM tamoxifen, selective ER degrader (SERD) fulvestrant, and aromatase inhibitors (AIs). Mammalian target of rapamycin (mTOR) inhibitor everolimus, cyclin-dependent kinase inhibitors (CDKi) and PI3K inhibitor alpelisib are approved in combination with ET.

8.1. Selective Estrogen Receptor Modulators

SERMs are synthetic nonsteroidal exogenous compounds that bind to ER with high affinity and block estrogen binding, consequently inhibiting ER-mediated gene expression. Treatment with SERMs, tamoxifen in particular, has decreased mortality due to BC by 25%–30% [51]. Tamoxifen acts as an antagonist at ERα and ERβ [52,53]. Other tamoxifen actions include an increase in cellular oxidative status, inhibition of protein kinase C (PKC), elevation of cytosolic and mitochondrial calcium levels, modulation of mitogen-activated protein kinase 8 (MAPK 8) activity, and induction of transforming growth factor beta (TGF-ß) production and secretion [52]. Many mechanisms associated with resistance to tamoxifen have been identified; they include mutations in genes encoding ERs and changes in signaling pathways that lead to ER independent signaling [54]. Two recent studies have shown that tamoxifen and several other SERMs can act as CB1 and CB2 modulators ( Figure 3 ). Tamoxifen and its metabolite 4-hydroxy-Tam (4-OH-Tam) bind to CB1 and CB2 with a moderately high affinity, reducing AC inhibition produced by constitutively active CBs [55,56]. Raloxifene, which is a SERM used in the prevention of BC, also acts as a CB2 inverse agonist [57].

In addition to its action on estrogen receptors (ER), tamoxifen (TAM) acts as an inverse agonist at cannabinoid receptors 1 and 2 (CB1 and CB2). The clinical significance of inverse agonist action on cannabinoid receptors is unknown.

Blasco-Benito et al. applied a combination of THC or cannabis drug preparation with tamoxifen to ER positiveT47D cell cultures. Submaximal concentrations of tamoxifen in combination with pure THC and cannabis drug preparation decreased the viability in an additive manner. The additive effects observed between tamoxifen and cannabinoids in cell cultures was not evident in vivo [48]. There are no clinical studies evaluating the effect of cannabinoids on treatment with tamoxifen.

8.2. Gonadotropin-Releasing Hormone Agonists

GnRH agonists are used for ovarian suppression in premenopausal women with BC. They are used in combination with tamoxifen or an AI. GnRH agonist work by decreasing the release of gonadotropins from hypophysis and in consequence inhibiting production of estrogens by the gonads. Acute administration of THC decreases serum LH and GnRH secretion in ovariectomized female and intact male rats [29,30]. Anandamide and 2-AG produces similar results in both female and male rats [31]. After their release, anandamide and 2-AG are transported into GnRH neurons that express CB1 and CB2 and are coupled to Gi/Go proteins. The activation of CBRs in GnRH neurons leads to the inhibition of GnRH secretion. CBR agonist WIN 55,212-2 can block the pulsatile release of GnRH from the immortalized GnRH neurons. When a CB agonist CP 55,940 is delivered into the third ventricle of adult female mice, estrous cycles are prolonged by at least 2 days [32].

8.3. Aromatase Inhibitors

AIs lower plasma estrogen concentration through the inhibition of the aromatase, which is an enzyme that converts androgens to estrogens in the peripheral tissues. As estrogens are predominantly produced in peripheral tissues of the body in postmenopausal women, AIs are the standard option in the treatment of postmenopausal women with HR+ BC in all settings [58,59]. Takeda et al. reported the modulation of THC-induced BC cell growth by cyclooxygenase and aromatase in the ER positive MCF-7 BC cell line. 17β-Estradiol produced by aromatase interferes with THC-induced cell growth, which is more prominent in low 17β-estradiol environments. THC-mediated BC cell growth is stimulated by co-treatment with AIs. It has therefore been suggested that THC could act as an exacerbating agent when co-treated with estrogen-lowering drugs [46]. There are no clinical studies evaluating the effect of cannabinoids on treatment with AI.

8.4. Selective Estrogen Receptor Degraders

Fulvestrant binds to ERα, blocking its dimerization, DNA binding, and nuclear uptake. In addition, it increases ERα degradation with protein degradation processes [60,61]. Fulvestrant is used in the treatment of metastatic HR+ BC in postmenopausal women [62]. Fulvestrant increases ERβ expression in MCF-7 cell lines and animal models [63]. Takeda et al. demonstrated a concentration-dependent up-regulation of ERβ mRNA and protein in MCF-7 cells exposed to THC ( Figure 4 ). Overexpression of ERβ reduced the reporter gene activity of ERα, and its activity was additionally downregulated by THC. The study concluded that THC disrupts estrogen-signaling through the up-regulation of ERβ [45]. There are no clinical studies evaluating the effect of cannabinoids on treatment with fulvestrant.

Fulvestrant (FUL) and tetrahydrocannabinol (THC) both up-regulate estrogen receptor beta (ERβ). FUL increases degradation of estrogen receptor alpha (ERα).

8.5. Inhibitors of Cyclin Dependent Kinases

CDKi are small chemical compounds that inhibit the function of CDKs. CDKs are protein kinases involved in regulating the cell cycle. CDK 4/6 binds with cyclin D to phosphorylate Rb protein. The phosphorylation of Rb protein releases E2F which causes the gene transcription needed for a G1/S transition. Three CDK 4/6 inhibitors (palbociclib, ribociclib, and abemaciclib) are used in the treatment of metastatic HR+, HER2 negative BC. CDK 4/6 inhibitors are indicated only in combination with endocrine therapy (AI or fulvestrant) [64,65,66,67]. Laezza et al. showed that anandamide analogue (Met-F-AEA) induces S-phase cell cycle arrest and decreases the percentage of cells in G2/M phase in the MDA-MB-231 line. This was correlated with checkpoint kinase 1 (CHK1) activation, Cdc25A degradation, and suppression of cyclin-dependent kinase 2 (CDK2) activity [68]. Caffarel et al. showed that THC arrests BC cell lines in G2/M through the downregulation of cyclin-depended kinase 1 (CDK1). In addition, CDK1-overexpressing cells are less sensitive to THC. THC increased the number of cells in the G0-G1 compartment and decreased the number of cells in S phase. Interestingly, the proliferation of normal human mammary epithelial cells was less affected by THC in comparison to BC cell lines [69]. There are no clinical studies evaluating the effect of cannabinoids on treatment with CDK 4/6 inhibitors.

8.6. mTOR and PI3K Inhibitors

PI3K/AKT/ mTOR pathway is the most frequently altered pathway in cancer [70]. Everolimus is an oral protein kinase inhibitor of the mTOR serine/threonine kinase signal transduction pathway and is used in combination with exemestane, a steroidal aromatase inhibitor, for the treatment of HR+, HER2 negative metastatic BC in postmenopausal women [71]. Alpelisib is a selective oral inhibitor of the PI3K catalytic subunit p110α that has shown synergistic antitumor activity with ET against HR+/PIK3CA mutated BC [70] and is used in clinical practice in combination with fulvestrant [72]. Shrivastava et al. found that CBD inhibits AKT and mTOR signaling in TNBC MDA-MB-231 BC cell lines. CBD decreases levels of phosphorylated mTOR, 4EBP1, and cyclin D1 [73]. There is evidence that CBD can suppress the activation of the epidermal growth factor receptor (EGF/EGFR) signaling pathway and its downstream target AKT in TNBC cell lines and animal models [74] and that THC and JWH-133 (selective CB2 agonist) reduce ErbB2-driven BC progression in MMTV-neu mice through AKT pathway inhibition [75]. There are no clinical studies evaluating the effect of cannabinoids on treatment with everolimus or alpelisib.

9. Conclusions

Interactions of cannabinoids with hypothalamic-pituitary-gonadal axis hormones are well-documented and two studies found a positive correlation between peak plasma anandamide with peak plasma 17β-estradiol, LH, and FSH levels at ovulation in healthy premenopausal women. There is also increasing evidence that cannabinoids can affect HR+ BC and that ET affects the endocannabinoid system. In most of the preclinical studies, non-selective CB1 and CB2 agonists (i.e., anandamide, THC) were used, which have inhibited proliferation of ER positive BC cell lines. Evidence for antitumor cannabinoid action in HR+ BC in animal models is less clear. Studies have shown that tamoxifen and several other SERMs can act as inverse agonists on CB1 and CB2, an interaction that has possible clinical consequences. There is some clinical evidence indicating CB2 expression in patients with HER2 positive tumors is linked to decreased overall survival, higher probability of local recurrence, and development of distant metastases. Similarly, GPR55 expression in basal/TNBC was linked to reduced overall and metastasis-free survival. Such association was not observed in HR+ BC, however this does not mean that cannabinoids and/or CBRs are not important in HR+ BC setting. Indeed, there are many possible interactions between HR+ BC and exogenous and endogenous cannabinoids. To our knowledge there are no clinical trials evaluating the effect of cannabinoids on BC treatment outcomes and/or prognosis. The interactions between HR+ BC and cannabinoids are complex and the clinical significance of such interactions is currently impossible to predict. Use of cannabinoids in palliative medicine is well established [76], however clinical trials are needed to determine safety of cannabinoid treatment in other BC settings. Until further evidence is available, caution should be exercised by physicians and patients when using cannabinoid preparations in a HR+ (as well as in any other) BC setting.

Acknowledgments

The text was edited by Kristina Alice Waller.

Author Contributions

L.D. conceived and wrote the article. F.K. contributed with review on CBRs and draw the Figure 1 and Figure 2 . S.B. and N.D. reviewed and edited the article. All authors have read and agreed to the published version of the manuscript.

Funding

This study was founded by the Slovenian Research Agency (ARRS) research programs P1-0390 and P3-0321.

Conflicts of Interest

The authors declare no conflict of interest.

References

1. Ghoncheh M., Pournamdar Z., Salehiniya H. Incidence and Mortality and Epidemiology of Breast Cancer in the World. Asian Pac. J. Cancer Prev. 2016; 17 :43–46. doi: 10.7314/APJCP.2016.17.S3.43. [PubMed] [CrossRef] [Google Scholar]

2. Rozeboom B., Dey N., De P. ER+ metastatic breast cancer: Past, present, and a prescription for an apoptosis-targeted future. Am. J. Cancer Res. 2019; 9 :2821–2831. [PMC free article] [PubMed] [Google Scholar]

3. Waks A.G., Winer E.P. Breast Cancer Treatment: A Review. JAMA. 2019; 321 :288–300. doi: 10.1001/jama.2018.19323. [PubMed] [CrossRef] [Google Scholar]

4. Mosly D., Turnbull A., Sims A. Predictive markers of endocrine response in breast cancer. World J. Exp. Med. 2018; 8 :1–7. doi: 10.5493/wjem.v8.i1.1. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

5. Krop I., Ismaila N., Andre F. Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women with Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline Focused Update. J. Clin. Oncol. 2017; 35 :2838–2847. doi: 10.1200/JCO.2017.74.0472. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

6. Burstein H.J., Curigliano G., Loibl S. Estimating the benefits of therapy for early-stage breast cancer: The St. Gallen International Consensus Guidelines for the primary therapy of early breast cancer 2019. Ann. Oncol. 2019; 30 :1541–1557. doi: 10.1093/annonc/mdz235. [PubMed] [CrossRef] [Google Scholar]

7. Szostakowska M., Trębińska-Stryjewska A., Grzybowska E.A. Resistance to endocrine therapy in breast cancer: Molecular mechanisms and future goals. Breast Cancer Res. Treat. 2019; 173 :489–497. doi: 10.1007/s10549-018-5023-4. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

8. Balfe P.J., McCann A.H., Welch H.M. Estrogen receptor beta and breast cancer. Eur. J. Surg. Oncol. 2004; 30 :1043–1050. doi: 10.1016/j.ejso.2004.06.019. [PubMed] [CrossRef] [Google Scholar]

9. Lumachi F., Brunello A., Maruzzo M. Treatment of estrogen receptor-positive breast cancer. Curr. Med. Chem. 2013; 20 :596–604. doi: 10.2174/092986713804999303. [PubMed] [CrossRef] [Google Scholar]

10. Yoko O., Hirotaka I. Clinical significance of estrogen receptor β in breast and prostate cancer from biological aspects. Cancer Sci. 2015; 106 :337–343. [PMC free article] [PubMed] [Google Scholar]

11. Ryberg E., Larsson N., Sjögren S. The orphan receptor GPR55 is a novel cannabinoid receptor. Br. J. Pharmacol. 2007; 152 :1092–1101. doi: 10.1038/sj.bjp.0707460. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

12. McHugh D., Hu S.S., Rimmerman N. N-arachidonoyl glycine, an abundant endogenous lipid, potently drives directed cellular migration through GPR18, the putative abnormal cannabidiol receptor. BMC Neurosci. 2010; 11 :44. doi: 10.1186/1471-2202-11-44. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

13. Brown A.J. Novel cannabinoid receptors. Br. J. Pharmacol. 2007; 152 :567–575. doi: 10.1038/sj.bjp.0707481. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

14. Di Marzo V., Piscitelli F. The Endocannabinoid System and its Modulation by Phytocannabinoids. Neurotherapeutics. 2015; 12 :692–698. doi: 10.1007/s13311-015-0374-6. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

15. Console-Bram L., Marcu J., Abood M.E. Cannabinoid receptors: Nomenclature and pharmacological principles. Prog. Neuropsychopharmacol. Biol. Psychiatry. 2012; 38 :4–15. doi: 10.1016/j.pnpbp.2012.02.009. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

16. Pisanti S., Malfitano A.M., Ciaglia E. Cannabidiol: State of the art and new challenges for therapeutic applications. Pharmacol. Ther. 2017; 175 :133–150. doi: 10.1016/j.pharmthera.2017.02.041. [PubMed] [CrossRef] [Google Scholar]

17. Thomas A., Baillie G.L., Phillips A.M. Cannabidiol displays unexpectedly high potency as an antagonist of CB1 and CB2 receptor agonists in vitro. Br. J. Pharmacol. 2007; 150 :613–623. doi: 10.1038/sj.bjp.0707133. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

18. Mills B., Yepes A., Nugent K. Synthetic Cannabinoids. Am. J. Med. Sci. 2015; 350 :59–62. doi: 10.1097/MAJ.0000000000000466. [PubMed] [CrossRef] [Google Scholar]

19. Castaneto M.S., Gorelick D.A., Desrosiers N.A. Synthetic cannabinoids: Epidemiology, pharmacodynamics, and clinical implications. Drug Alcohol Depend. 2014; 144 :12–41. doi: 10.1016/j.drugalcdep.2014.08.005. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

20. Badowski M.E., Yanful P.K. Dronabinol oral solution in the management of anorexia and weight loss in AIDS and cancer. Ther. Clin. Risk Manag. 2018; 14 :643–651. doi: 10.2147/TCRM.S126849. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

21. Walsh D., Nelson K.A., Mahmoud F.A. Established and potential therapeutic applications of cannabinoids in oncology. Support Care Cancer. 2003; 11 :137–143. doi: 10.1007/s00520-002-0387-7. [PubMed] [CrossRef] [Google Scholar]

22. Arnau B.G., Edgar S.-G., Luigi B. Version 1. F1000Res. F1000 Faculty Rev-990. [(accessed on 22 February 2020)]; Available online: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879932/

23. Ryberg E., Vu H.K., Larsson N. Identification and characterisation of a novel splice variant of the human CB1 receptor. FEBS Lett. 2005; 579 :259–264. doi: 10.1016/j.febslet.2004.11.085. [PubMed] [CrossRef] [Google Scholar]

See also  Pros And Cons Of CBD Oil For Dogs

24. Zou S., Kumar U. Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System. Int. J. Mol. Sci. 2018; 19 :833. [PMC free article] [PubMed] [Google Scholar]

25. Pisanti S., Picardi P., D’Alessandro A. The endocannabinoid signaling system in cancer. Trends Pharmacol. Sci. 2013; 34 :273–282. doi: 10.1016/j.tips.2013.03.003. [PubMed] [CrossRef] [Google Scholar]

26. Liu Q.-R. Species differences in cannabinoid receptor 2 (CNR2 gene): Identification of novel human and rodent CB2 isoforms, differential tissue expression, and regulation by cannabinoid receptor ligands. Genes Brain Behav. 2009; 8 :519–530. doi: 10.1111/j.1601-183X.2009.00498.x. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

27. Turcotte C., Blanchet M.R., Laviolette M. The CB2 receptor and its role as a regulator of inflammation. Cell Mol. Life Sci. 2016; 73 :4449–4470. doi: 10.1007/s00018-016-2300-4. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

28. Tyrey L. Delta-9-Tetrahydrocannabinol suppression of episodic luteinizing hormone secretion in the ovariectomized rat. Endocrinology. 1978; 102 :1808–1814. doi: 10.1210/endo-102-6-1808. [PubMed] [CrossRef] [Google Scholar]

29. Tyrey L. Delta 9-Tetrahydrocannabinol. A potent inhibitor of episodic luteinizing hormone secretion. J. Pharmacol. Exp. Ther. 1980; 213 :306–308. [PubMed] [Google Scholar]

30. Kumar M.S., Chen C.L. Effect of an acute dose of delta 9-THC on hypothalamic luteinizing hormone releasing hormone and met-enkephalin content and serum levels of testosterone and corticosterone in rats. Subst Alcohol Actions Misuse. 1983; 4 :37–43. [PubMed] [Google Scholar]

31. Scorticati C., Fernández-Solari J., De Laurentiis A. The inhibitory effect of anandamide on luteinizing hormone-releasing hormone secretion is reversed by estrogen. Proc. Natl. Acad. Sci. USA. 2004; 101 :11891–11896. doi: 10.1073/pnas.0404366101. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

32. Gammon C.M., Freeman G.M.J., Xie W. Regulation of gonadotropin-releasing hormone secretion by cannabinoids. Endocrinology. 2005; 146 :4491–4499. doi: 10.1210/en.2004-1672. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

33. Cravatt B.F., Giang D.K., Mayfield S.P. Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides. Nature. 1996; 384 :83–87. doi: 10.1038/384083a0. [PubMed] [CrossRef] [Google Scholar]

34. MacCarrone M., De Felici M., Bari M. Downregulation of anandamide hydrolase in mouse uterus by sex hormones. Eur. J. Biochem. 2000; 267 :2991–2997. doi: 10.1046/j.1432-1033.2000.01316.x. [PubMed] [CrossRef] [Google Scholar]

35. El-Talatini M.R., Taylor A.H., Konje J.C. The relationship between plasma levels of the endocannabinoid, anandamide, sex steroids, and gonadotropins during the menstrual cycle. Fertil Steril. 2010; 93 :1989–1996. doi: 10.1016/j.fertnstert.2008.12.033. [PubMed] [CrossRef] [Google Scholar]

36. Cui N., Wang L., Wang W. The correlation of anandamide with gonadotrophin and sex steroid hormones during the menstrual cycle. Iran. J. Basic Med. Sci. 2017; 20 :1268–1274. [PMC free article] [PubMed] [Google Scholar]

37. Gorzalka B.B., Dang S.S. Minireview: Endocannabinoids and gonadal hormones: Bidirectional interactions in physiology and behavior. Endocrinology. 2012; 153 :1016–1024. doi: 10.1210/en.2011-1643. [PubMed] [CrossRef] [Google Scholar]

38. Dobovišek L., Hojnik M., Ferk P. Overlapping molecular pathways between cannabinoid receptors type 1 and 2 and estrogens/androgens on the periphery and their involvement in the pathogenesis of common diseases (Review) Int. J. Mol. Med. 2016; 38 :1642–1651. doi: 10.3892/ijmm.2016.2779. [PubMed] [CrossRef] [Google Scholar]

39. De Petrocellis L., Melck D., Palmisano A. The endogenous cannabinoid anandamide inhibits human breast cancer cell proliferation. Proc. Natl. Acad. Sci. USA. 1998; 95 :8375–8380. doi: 10.1073/pnas.95.14.8375. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

40. Hanlon K.E., Lozano-Ondoua A.N., Umaretiya P.J. Modulation of breast cancer cell viability by a cannabinoid receptor 2 agonist, JWH-015, is calcium dependent. Breast Cancer. 2016; 8 :59–71. [PMC free article] [PubMed] [Google Scholar]

41. Melck D., Rueda D., Galve-Roperh I. Involvement of the cAMP/protein kinase A pathway and of mitogen-activated protein kinase in the anti-proliferative effects of anandamide in human breast cancer cells. FEBS Lett. 1999; 463 :235–240. doi: 10.1016/S0014-5793(99)01639-7. [PubMed] [CrossRef] [Google Scholar]

42. Melck D., De Petrocellis L., Orlando P. Suppression of nerve growth factor Trk receptors and prolactin receptors by endocannabinoids leads to inhibition of human breast and prostate cancer cell proliferation. Endocrinology. 2000; 141 :118–126. doi: 10.1210/endo.141.1.7239. [PubMed] [CrossRef] [Google Scholar]

43. von Bueren A.O., Schlumpf M., Lichtensteiger W. Delta(9)-tetrahydrocannabinol inhibits 17beta-estradiol-induced proliferation and fails to activate androgen and estrogen receptors in MCF7 human breast cancer cells. Anticancer Res. 2008; 28 :85–89. [PubMed] [Google Scholar]

44. Ruh M.F., Taylor J.A., Howlett A.C. Failure of cannabinoid compounds to stimulate estrogen receptors. Biochem. Pharmacol. 1997; 53 :35–41. doi: 10.1016/S0006-2952(96)00659-4. [PubMed] [CrossRef] [Google Scholar]

45. Takeda S., Yoshida K., Nishimura H. Δ(9)-Tetrahydrocannabinol disrupts estrogen-signaling through up-regulation of estrogen receptor β (ERβ) Chem. Res. Toxicol. 2013; 26 :1073–1079. doi: 10.1021/tx4000446. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

46. Takeda S., Yamamoto I., Watanabe K. Modulation of Delta9-tetrahydrocannabinol-induced MCF-7 breast cancer cell growth by cyclooxygenase and aromatase. Toxicology. 2009; 259 :25–32. doi: 10.1016/j.tox.2009.01.024. [PubMed] [CrossRef] [Google Scholar]

47. Sarnataro D., Pisanti S., Santoro A., Gazzerro P. The cannabinoid CB1 receptor antagonist rimonabant (SR141716) inhibits human breast cancer cell proliferation through a lipid raft-mediated mechanism. Mol. Pharmacol. 2006; 70 :1298–1306. doi: 10.1124/mol.106.025601. [PubMed] [CrossRef] [Google Scholar]

48. Blasco-Benito S., Seijo-Vila M., Caro-Villalobos M. Appraising the “entourage effect”: Antitumor action of a pure cannabinoid versus a botanical drug preparation in preclinical models of breast cancer. Biochem. Pharmacol. 2018; 157 :285–293. doi: 10.1016/j.bcp.2018.06.025. [PubMed] [CrossRef] [Google Scholar]

49. Pérez-Gómez E., Andradas C., Blasco-Benito S. Role of cannabinoid receptor CB2 in HER2 pro-oncogenic signaling in breast cancer. J. Natl. Cancer Inst. 2015; 107 :77. doi: 10.1093/jnci/djv077. [PubMed] [CrossRef] [Google Scholar]

50. Andradas C., Blasco-Benito S., Castillo-Lluva S. Activation of the orphan receptor GPR55 by lysophosphatidylinositol promotes metastasis in triple-negative breast cancer. Oncotarget. 2016; 7 :47565–47575. doi: 10.18632/oncotarget.10206. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

51. International Breast Cancer Study Group. Colleoni M., Gelber S. Tamoxifen after adjuvant chemotherapy for premenopausal women with lymph node-positive breast cancer: International Breast Cancer Study Group Trial 13–93. J. Clin. Oncol. 2006; 24 :1332–1341. [PubMed] [Google Scholar]

52. Radin D.P., Patel P. Delineating the molecular mechanisms of tamoxifen’s oncolytic actions in estrogen receptor-negative cancers. Eur. J. Pharmacol. 2016; 781 :173–180. doi: 10.1016/j.ejphar.2016.04.017. [PubMed] [CrossRef] [Google Scholar]

53. Barkhem T., Carlsson B., Nilsson Y. Differential response of estrogen receptor alpha and estrogen receptor beta to partial estrogen agonists/antagonists. Mol. Pharmacol. 1998; 54 :105–112. doi: 10.1124/mol.54.1.105. [PubMed] [CrossRef] [Google Scholar]

54. Viedma-Rodríguez R., Baiza-Gutman L., Salamanca-Gómez F. Mechanisms associated with resistance to tamoxifen in estrogen receptor-positive breast cancer (review) Oncol. Rep. 2014; 32 :3–15. doi: 10.3892/or.2014.3190. [PubMed] [CrossRef] [Google Scholar]

55. Prather P.L., FrancisDevaraj F., Dates C.R. CB1 and CB2 receptors are novel molecular targets for Tamoxifen and 4OH-Tamoxifen. Biochem. Biophys. Res. Commun. 2013; 441 :339–343. doi: 10.1016/j.bbrc.2013.10.057. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

56. Franks L.N., Ford B.M., Prather P.L. Selective Estrogen Receptor Modulators: Cannabinoid Receptor Inverse Agonists with Differential CB1 and CB2 Selectivity. Front Pharmacol. 2016; 7 :503. doi: 10.3389/fphar.2016.00503. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

57. Nelson H.D., Smith M.E., Griffin J.C., Fu R. Use of medications to reduce risk for primary breast cancer: A systematic review for the U.S. Preventive Services Task Force. Ann. Intern. Med. 2013; 158 :604. doi: 10.7326/0003-4819-158-8-201304160-00005. [PubMed] [CrossRef] [Google Scholar]

58. Mauri D., Pavlidis N., Polyzos N.P., Ioannidis J.P. Survival with aromatase inhibitors and inactivators versus standard hormonal therapy in advanced breast cancer: Meta-analysis. J. Natl. Cancer Inst. 2006; 98 :1285. doi: 10.1093/jnci/djj357. [PubMed] [CrossRef] [Google Scholar]

59. Campos S.M., Guastalla J.P., Subar M. A comparative study of exemestane versus anastrozole in patients with postmenopausal breast cancer with visceral metastases. Clin. Breast Cancer. 2009; 9 :39. doi: 10.3816/CBC.2009.n.007. [PubMed] [CrossRef] [Google Scholar]

60. Lee C.I., Goodwin A., Wilcken N. Fulvestrant for hormone-sensitive metastatic breast cancer. Cochrane Database Syst. Rev. 2017; 1 :CD011093. doi: 10.1002/14651858.CD011093.pub2. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

61. DeFriend D.J., Howell A., Nicholson R.I. Investigation of a new pure antiestrogen (ICI 182780) in women with primary breast cancer. Cancer Res. 1994; 54 :408. [PubMed] [Google Scholar]

62. Howell A., Robertson J.F., Abram P. Comparison of fulvestrant versus tamoxifen for the treatment of advanced breast cancer in postmenopausal women previously untreated with endocrine therapy: A multinational, double-blind, randomized trial. J. Clin. Oncol. 2004; 22 :1605. doi: 10.1200/JCO.2004.02.112. [PubMed] [CrossRef] [Google Scholar]

63. Mishra A.K., Abrahamsson A., Dabrosin C. Fulvestrant inhibits growth of triple negative breast cancer and synergizes with tamoxifen in ERα positive breast cancer by up-regulation of ERβ Oncotarget. 2016; 7 :56876–56888. doi: 10.18632/oncotarget.10871. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

64. Finn R.S. The Cyclin-Dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): A randomised phase 2 study. Lancet Oncol. 2015; 16 :25–35. doi: 10.1016/S1470-2045(14)71159-3. [PubMed] [CrossRef] [Google Scholar]

65. Tripathy D. Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): A randomised phase 3 trial. Lancet Oncol. 2018; 18 :904–915. doi: 10.1016/S1470-2045(18)30292-4. [PubMed] [CrossRef] [Google Scholar]

66. Johnston S. MONARCH 3 final PFS: A randomized study of abemaciclib as initial therapy for advanced breast cancer. NPJ Breast Cancer. 2019; 17 :5. doi: 10.1038/s41523-018-0097-z. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

67. Matutino A., Joy A.A., Brezden-Masley C. Hormone receptor–positive, HER2-negative metastatic breast cancer: Redrawing the lines. Curr. Oncol. 2018; 25 :S131–S141. doi: 10.3747/co.25.4000. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

68. Laezza C., Pisanti S., Crescenzi E. Anandamide inhibits Cdk2 and activates Chk1 leading to cell cycle arrest in human breast cancer cells. FEBS Lett. 2006; 580 :6076–6082. doi: 10.1016/j.febslet.2006.09.074. [PubMed] [CrossRef] [Google Scholar]

69. Caffarel M.M., Sarrió D., Palacios J. Delta9-tetrahydrocannabinol inhibits cell cycle progression in human breast cancer cells through Cdc2 regulation. Cancer Res. 2006; 66 :6615–6621. doi: 10.1158/0008-5472.CAN-05-4566. [PubMed] [CrossRef] [Google Scholar]

70. Mayer I.A., Abramson V.G., Formisano L. A Phase Ib Study of Alpelisib (BYL719), a PI3Kα-Specific Inhibitor, with Letrozole in ER+/HER2-Metastatic Breast Cancer. Clin. Cancer Res. 2017; 23 :26–34. doi: 10.1158/1078-0432.CCR-16-0134. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

72. André F., Ciruelos E., Rubovszky G. Alpelisib for PIK3CA-Mutated, Hormone Receptor–Positive Advanced Breast Cancer. N. Engl. J. Med. 2019; 380 :1929–1940. doi: 10.1056/NEJMoa1813904. [PubMed] [CrossRef] [Google Scholar]

73. Shrivastava A., Kuzontkoski P.M., Groopman J.E. Cannabidiol induces programmed cell death in breast cancer cells by coordinating the cross-talk between apoptosis and autophagy. Mol. Cancer Ther. 2011; 10 :1161–1172. doi: 10.1158/1535-7163.MCT-10-1100. [PubMed] [CrossRef] [Google Scholar]

74. Elbaz M., Nasser M.W., Ravi J. Modulation of the tumor microenvironment and inhibition of EGF/EGFR pathway: Novel anti-tumor mechanisms of Cannabidiol in breast cancer. Mol. Oncol. 2015; 9 :906–919. doi: 10.1016/j.molonc.2014.12.010. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

75. Caffarel M.M., Andradas C., Mira E. Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibition. Mol. Cancer. 2010; 9 :196. doi: 10.1186/1476-4598-9-196. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

76. Kisková T., Mungenast F., Suváková M. Future Aspects for Cannabinoids in Breast Cancer Therapy. Int. J. Mol. Sci. 2019; 20 :1673. doi: 10.3390/ijms20071673. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Articles from Cancers are provided here courtesy of Multidisciplinary Digital Publishing Institute (MDPI)

Medical Cannabis

Cannabis refers to a family of plants from which marijuana and hemp are produced. These plants are grown around the world and have been used in herbal remedies for centuries.

Cannabis refers to a family of plants from which marijuana and hemp are produced. These plants are grown around the world and have been used in herbal remedies for centuries.

In modern times, marijuana has generally been viewed as a recreational drug. But there is growing interest in its medical uses. The terms “medical marijuana,” “medical cannabis,” “medical hemp,” or “medical CBD” refer to the use of products made from the cannabis plant to treat certain health conditions.

Many people diagnosed with cancer report that cannabis products are effective for managing their symptoms and treatment side effects. There is some research supporting the use of medical cannabis for managing certain conditions, but federal laws in the United States make it difficult to study medical cannabis.

It’s important to know that cannabis is not a cure or treatment for cancer itself, even though there are many such claims online. You should not use medical cannabis instead of proven cancer treatments.

What are cannabinoids?

Cannabis plants contain many chemicals known as cannabinoids. Cannabinoids cause certain effects when you consume them. They do this by interacting with your body’s endocannabinoid system, which actually produces its own cannabinoids called “endocannabinoids.” Scientists are still working to understand how the endocannabinoid system works, but it seems to play a role in many processes in your body.

The research done on cannabis so far suggests that most of its medical benefits are related to the effects of two main cannabinoids:

THC (delta-9-tetrahydrocannabinol), which causes the high associated with marijuana

CBD (cannabidiol), which does not cause a high

THC and CBD seem to offer different medical benefits. A good example of these differences can be seen when comparing the only cannabinoid medicines approved by the U.S. Food and Drug Administration (FDA): Marinol (chemical name: dronabinol) and other synthetic THC medicines are approved to treat nausea caused by chemotherapy. The CBD medicine Epidiolex is approved to treat seizure disorders in children.

Different forms of cannabis contain different amounts or combinations of cannabinoids. Marijuana contains enough THC to cause a high (more than 0.3%) and varying amounts of CBD. Hemp contains mostly CBD and only trace amounts of THC, which does not cause a high.

Cannabis products made from extracted oils can contain all or mostly THC or CBD, or different combinations. “Whole plant” marijuana products are often grouped by “strains” to describe their balance of THC and CBD. Whole plant or “full spectrum” products often contain other cannabinoids that can cause other effects.

The effects of cannabinoids also vary depending on how they are consumed. The most common ways to consume medical cannabis are:

See also  Trunature CBD Oil

eating “edibles” or taking capsules, oils, or tinctures by mouth, which can take one to a few hours to take effect and can last for up to 6 hours

inhaling cannabis smoke or vapor, which takes effect within minutes and fades over a few hours

What conditions is medical cannabis used for?

It’s extremely important to know that cannabis is not a cure or treatment for breast cancer, despite many claims. It’s dangerous to use cannabis instead of proven cancer therapies. It’s also important to talk to your doctor before using cannabis products to make sure it won’t interact or interfere with any of your medicines or treatments.

People use cannabis products to manage cancer symptoms, treatment side effects, and other challenges along the cancer journey. The most common reasons people with breast cancer use cannabis are to manage:

pain (including joint and muscle aches, discomfort, and stiffness)

anxiety and stress

nausea, vomiting, and loss of appetite caused by chemotherapy

Some studies support the use of cannabis for these conditions. Still, because marijuana is federally illegal in the United States, research on medical cannabis to manage cancer symptoms and treatment side effects is limited.

Patient surveys have provided important insights about how people use medical cannabis. About 42% of people diagnosed with breast cancer who completed our survey said they used medical cannabis products to manage breast cancer symptoms or treatment side effects. The people who used medical cannabis ranged in age, cancer stage, and treatment phase, and most (75%) found it to be “very” or “extremely” helpful.

But again, it’s important to talk to your doctor about using cannabis products, especially during cancer treatment, to make sure it’s a safe option for you. If you find that your doctor is not knowledgeable or experienced with cannabis, you may want to seek advice from an oncologist who participates in your state or country’s medical cannabis program.

“It’s important for people to know that anything they ingest that produces a change in their bodies is acting like a drug, and it has the potential for side effects, interactions with other drugs, as well as benefits,” said Virginia F. Borges, M.D., MMSc., professor of medicine and director of the Breast Cancer Research Program at the University of Colorado Cancer Center. “People have to be as diligent about researching medical marijuana as they would be with any other supplement or drug they were taking.”

Because marijuana has been legal for both medical and recreational use in Colorado for many years, Dr. Borges has cared for a number of breast cancer patients who use or have used medical cannabis to ease treatment side effects.

“I’ve mainly seen it used in conjunction with prescription drugs to control pain and other side effects in patients living with metastatic disease,” she said. “It’s rare that a person living with metastatic breast cancer would have only one side effect to manage. So, by adding in medical marijuana, it often allows me to cut back on the number of drugs I prescribe. With a high-quality source for medical marijuana and knowing how it affects an individual, using medical marijuana can put more control back in the hands of my patient.”

Is medical cannabis legal?

The legal status of cannabis for either recreational or medical use varies across the world and continues to change. It’s important to understand the laws in your state or country before you purchase or use cannabis.

Marijuana (the form of cannabis that contains more than 0.3% THC — enough to cause a high) is illegal nationwide under federal law in the United States. At the same time, most U.S. states have passed their own laws either legalizing the use of marijuana entirely or to treat certain medical conditions. But even in states where marijuana is legal, U.S. federal government employees and people who work for companies that receive federal grant funding cannot legally use marijuana under the Drug-Free Workplace Act.

Many other countries also allow the use of medical marijuana, including Australia, Canada, the United Kingdom, and many others in Europe and South America.

Marijuana laws vary from state to state in the U.S. Some states allow people with certain health conditions to get a medical marijuana card through their doctor, which allows them to buy cannabis products at an approved dispensary. Other states only allow the medical use of CBD to treat certain serious conditions. In states where marijuana is legal for recreational use, anyone of legal age can buy cannabis products from a dispensary, but some of these shops carry medical products that are only available to people with certain health conditions.

If marijuana is legal where you live, it’s important to know that quality control of these products can be uncertain. Most cannabis products, even those sold at medical dispensaries, are not regulated like other medicines. They may contain contaminants such as mold, heavy metals, and pesticides, and the labels may include incorrect information about types, doses, and ingredients. You can ask the dispensary for a “certificate of analysis” for the products you might buy, which tells you about ingredients, dose, and contaminants.

Medical cannabis is not approved by the FDA for use in people with cancer. But three synthetic THC medicines have been approved to treat nausea and vomiting caused by chemotherapy:

Cesamet (chemical name: nabilone)

Marinol (chemical name: dronabinol)

Syndros (chemical name: dronabinol in liquid form)

In Canada and some European countries, Sativex (chemical name: nabiximols), an oral spray containing equal amounts of THC and CBD, is approved for the treatment of certain types of pain related to cancer.

Epidiolex, a medicine with CBD extracted from marijuana, is FDA-approved for use in children with severe seizure disorders. It is not approved for people with cancer, but studies are ongoing.

CBD products can be made from marijuana or hemp (the form of cannabis that contains only trace amounts of THC and does not cause a high). In the U.S., CBD products have typically only been available at medical marijuana dispensaries.

However, the U.S. Congress passed a federal law called the 2018 Farm Bill. This law made it legal for companies to produce and sell CBD products made from hemp. Now, many more companies are selling CBD products. You’ve probably seen them everywhere from grocery stores and pharmacies to gas stations and online ads.

But just because CBD products made from hemp are sold everywhere, in all kinds of products, and their legal restrictions have been loosened, you shouldn’t assume they are safe, effective, or even legal where you live (some state laws still consider hemp CBD illegal).

Like all cannabis products, hemp CBD products are not regulated the same way medicines are. So it’s hard to know if they are made safely, contain contaminants, or are labeled accurately. It’s also illegal for companies to market any cannabis product as a cure, treatment, or dietary supplement. The FDA has warned many companies that have marketed CBD products in this way.

Medical grade CBD products from a medical marijuana dispensary or an independent pharmacy are likely a safer and more effective option, because you can ask for a certificate of analysis that tells you about the ingredients, dose, and if there are contaminants such as mold, heavy metals, or pesticides.

What to expect when using medical cannabis

The ways cannabis can affect you depends on many factors and can be hard to predict. The effects of cannabis can vary from person to person.

Also, cannabis comes in a variety of strains, each with different potency and amounts or combinations of cannabinoids. Of note, products that contain THC may cause a high, while products with CBD only or trace amounts of THC will not.

The way you consume cannabis can also influence the effects. Cannabis products come in many different forms, including:

edibles, such as cookies, candy, mints, or brownies

gelcaps or pills

dried leaves or buds for smoking, vaporizing, or making tea

tinctures or sprays that are used under the tongue or along the gum line

oils for inhaling with a vape pen or vaporizer

oils for mixing into tea, honey, or food

creams and other products that are applied to the skin

Eating edibles or taking oils by mouth can take one to a few hours to take effect and can last up to about 6 hours. It can be difficult to know the dose in some edibles and how long the effects will last. Oils, sprays, and tinctures may give you more control over the dose you take.

Inhaling cannabis smoke or vapor takes effect within minutes and fades more rapidly. Inhaling can give you more control over the dose you take, when the effects will start, and how long they will last. But many oncologists prefer that their patients not smoke or vaporize cannabis products, especially during active cancer treatment that can affect the lungs or immune system. That’s one reason why it’s important to talk to your doctor before you start using cannabis.

Every person’s situation is unique. The best forms and doses of medical cannabis and the reasons for using it will vary from person to person.

Side effects and safety of medical cannabis

Information on cannabis side effects is limited because research on medical cannabis in people with cancer is limited. Side effects are also likely to vary depending on the dose you take and the amounts and combinations of THC and CBD in each product.

Reported side effects of marijuana, which has THC, include:

increased heart rate

low blood pressure

dizziness and falling

tiredness, fatigue, sleepiness

CBD is usually well-tolerated, but reported side effects include:

drowsiness and fatigue

It’s not well understood how cannabis products may interact with other medicines, including cancer therapies. That’s why it’s important to talk to your doctor about using medical cannabis both before and during treatment. Working together, you can come up with the best way to relieve your symptoms.

“The medicines and therapies you use can interact with each other. They may meet up and cause no effect, a beneficial effect, or a harmful effect,” said Marisa Weiss, M.D., founder and chief medical officer of Breastcancer.org and director of breast radiation oncology at Lankenau Medical Center. “For example, a helpful effect is when cannabis reduces nausea from chemotherapy. But a harmful effect can happen if cannabis interferes with the benefit of chemotherapy or increases the risk of lung damage during radiation and chemotherapy if cannabis is smoked or vaped.”

Important things to consider before using medical cannabis

If you decide that you’re interested in trying medical cannabis to treat your breast cancer symptoms or treatment side effects, here are some things to consider before you do:

Talk to your doctor: As with all vitamins, supplements, herbs, and over-the counter medicines, always tell your doctor if you are using any type of cannabis product to make sure it won’t interact or interfere with your cancer treatments.

Find a doctor in a medical marijuana program: If you live in a place where medical marijuana is legal, make an appointment with a doctor who participates in your state or country’s medical marijuana program. These are doctors who are trained and certified to qualify patients for medical cannabis and oversee their care. Some states also certify trained nurses, physician’s assistants, and pharmacists to qualify patients for medical cannabis.

Find a medical cannabis dispensary you are comfortable with: Most oncologists prefer that their patients get their medical cannabis products from a medical cannabis dispensary if they are available where you live. Medical dispensaries focus on medical patients rather than just recreational users. They should have knowledgeable staff members or a pharmacist who can answer your questions about their products. It can be helpful to call the dispensary ahead of time to explain the issues you’re having and ask if you can schedule an appointment with a knowledgeable staff member. Ask if there is a pharmacist or doctor available at the dispensary. You should share a complete list of medications and supplements you’re taking to avoid any unsafe interaction between products. You also should let the dispensary know if you have any allergies. For example, if you’re allergic to coconut, then you should avoid the commonly used coconut oil-based products.

Learn about different medical cannabis products: Every medical cannabis dispensary has its own menu of products. Depending on where you live, medical cannabis dispensaries may have pharmacists on staff who can review your unique situation and make tailored recommendations. When choosing products, it’s important to understand the different effects of THC and CBD. THC and CBD each offer different medical benefits. For example, CBD may be better at easing anxiety, while THC may be better at controlling nausea caused by chemotherapy. THC and CBD are present in different levels in different strains of marijuana. Most medical cannabis products are made by extracting these cannabinoids from the cannabis plant and putting different amounts of them into the products. The label on the product usually shows the ratio of THC to CBD. Hemp products mostly contain CBD, but can have trace levels of THC and other cannabinoids which are unlikely to be listed on the label. It’s also important to ask questions about the safety and quality of the products you are buying. Some doctors who certify people for medical marijuana suggest asking the dispensary staff member some general questions before you start talking about your symptoms and side effects, such as:

How useful was this post?

Click on a star to rate it!

Average rating 3 / 5. Vote count: 1

No votes so far! Be the first to rate this post.