Br J Clin Pharmacol. Feb;75(2) doi: /j x. Cannabidiol as potential anticancer drug. Massi P(1), Solinas M, Cinquina. Over the past years, several lines of evidence support an antitumourigenic effect of cannabinoids including Δ9-tetrahydrocannabinol (Δ9-THC). Request PDF on ResearchGate | Cannabidiol as potential anticancer drug | Over the past years, several lines of evidence support an.
drug Cannabidiol anticancer as potential
Since the late s, a large body of evidence has accumulated demonstrating that various cannabinoids exert antitumour effects in a wide variety of experimental models of cancer, ranging from cancer cell lines in culture to genetically-engineered mice reviewed by Velasco et al. Multiple cannabinoids have shown this activity, including thc ; the endocannabinoids 2-arachidonoylglycerol and anandamide; and various synthetic cannabinoid receptor agonists that have either comparable affinity for the cb 1 and cb 2 receptors for example, WIN 55, or HU , a higher affinity for cb 1 for example, methanandamide , or a higher affinity for cb 2 for example, JWH Those findings strongly support that, aside from the role played by the endogenous cannabinoid system in cancer, pharmacologic stimulation of cb receptors is, in most cases, antitumourigenic.
Nonetheless, a few reports have proposed a tumour-promoting effect of cannabinoids 18 — Those apparently conflicting observations are discussed in the next subsection. Cannabinoids impair tumour progression at various levels. Their most prevalent effect is the induction of cancer cell death by apoptosis and the inhibition of cancer cell proliferation.
At least one of those actions has been demonstrated in almost all cancer cell types tested In addition, in vivo experiments have shown that cannabinoids impair tumour angiogenesis and block invasion and metastasis.
A significant amount of the research conducted so far on the mechanism of cannabinoid antitumour activity has focussed on glioma cells. Initial studies showed that thc and other cannabinoids induce the apoptotic death of glioma cells by cb 1- and cb 2-dependent stimulation of the de novo synthesis of the pro-apoptotic sphingolipid ceramide 23 , 32 — Further studies based on the analysis of the gene expression profile of thc -sensitive and -resistant glioma cells yielded further insight into the specific signalling events downstream of ceramide that are activated in cancer cells by cannabinoids Thus, it was found that treatment with thc results in enhanced expression of the stress-regulated protein p8 nupr 1 , a transcriptional regulator that has been implicated in the control of tumourigenesis and tumour progression 36 , together with several of its downstream targets, such as the endoplasmic reticulum er stress—related transcription factors atf 4 and chop , and the pseudokinase tribbles homologue 3 trib 3 This thc -triggered stimulation of the p8-regulated pathway Figure 1 enhances the inhibitory interaction of trib 3 with a pro-survival kinase, akt 37 , 38 , which leads to inhibition of the mammalian target of rapamycin complex 1 m torc 1 and the subsequent stimulation of autophagy-mediated cell death Here, the mechanism of cannabinoid-induced apoptosis in glioma, pancreatic, and hepatocellular carcinoma cells is depicted.
This signalling route could constitute the main mechanism of cannabinoid-induced cell death, with some variations inherent to different types of cancer cells. Autophagy is an essential cellular process participating in a number of physiologic functions within the cell 39 , Autophagy is primarily a cytoprotective mechanism, although its activation can also lead to cell death 40 — Cannabinoids induce autophagy in various types of cancer cells in culture, and pharmacologic or genetic inhibition of autophagy prevents cannabinoid antitumour action in various animal models of cancer Figure 1 , thus demonstrating that autophagy is important for cannabinoid antineoplastic activity 37 , 43 , Moreover, autophagy blockade prevents cannabinoid-induced apoptosis and cell death, whereas apoptosis blockade prevents cannabinoid-induced cell death, but not autophagy 37 , 43 , Those observations indicate that autophagy is upstream of apoptosis in the mechanism of cannabinoid-induced cell death Figure 1.
The importance of this pathway is highlighted by the ability of various chemical and genetic manipulations to block cannabinoid-induced cell death. The cannabinoid-evoked inhibition of akt was able to promote cycle arrest in breast cancer and melanoma cells, as well as apoptosis through additional mechanisms, including decreased phosphorylation of the pro-apoptotic protein bcl 2-associated agonist of cell death 45 and activation of the cyclin-dependent kinase inhibitory proteins p21 and p27 24 , 46 , 47 , leading to the subsequent decreased phosphorylation of the retinoblastoma protein, which would thus arrest the cell cycle.
At least part of that signalling route has also been found to be upregulated with cannabinoid treatment in other types of cancer cells, an observation which suggests that—with some variations—this pathway could be a general mechanism by which activation of cb 1 and cb 2 receptors promotes cancer cell death.
For example, in hepatocellular carcinoma cells, thc and the cb 2 receptor agonist JWH can trigger an er stress—dependent activation of amp -activated protein kinase that cooperates with the trib 3-mediated inhibition of the akt —m torc 1 axis in the stimulation of autophagy-mediated cell death In melanoma 46 , breast carcinoma 24 , 50 , and prostate carcinoma 51 cells, cannabinoids can induce cell-cycle arrest in concert with apoptosis 24 , 46 , Notably, cannabinoid antiproliferative action—at least in melanoma 46 and breast cancer 24 cells—also relies on akt inhibition.
Likewise, the effect of cannabinoids in hormone- dependent tumours might rely, at least in part, on the ability to interfere with the activation of growth factor receptors 12 , Some of those and other mechanisms 52 might participate, together with the autophagy-mediated cell death pathway, in the cytotoxic action of cannabinoids in various types of cancer cells.
However, further investigation is required to clarify the issue. Research conducted during the last few years has shed light on the intracellular signalling mechanisms underlying cannabinoid anticancer action. However, a number of important observations—in particular, those related to the role played by cannabinoid receptors in the triggering of the signals—remain to be clarified. For example, in contrast to the death-promoting action of cannabinoids on cancer cells, the viability of normal non-transformed cells is unaffected or, under certain conditions, even enhanced by cannabinoid challenge 33 — 35 , 37 , For example, thc treatment of astrocytes a cell type that expresses functional cb 1 receptors does not trigger the activation of er stress, upregulation of the p8 pathway, inhibition of the akt —m torc 1 axis, or stimulation of autophagy and apoptosis, even when concentrations of thc higher than those that promote glioma cell death are used 35 , Similar results were obtained for primary embryonic fibroblasts 35 , 41 and other types of non-transformed cells expressing functional cannabinoid receptors in comparison with their transformed counterparts 24 , 46 , 54 , Thus, stimulation of cannabinoid receptors seems to be coupled with the activation of different signalling mechanisms in transformed and non-transformed cells.
The precise molecular reasons for this variation in behaviour remain as an important open question in the cannabinoid field. Another intriguing observation is that, in some types of cancer cells such as glioma cells , pharmacologic blockade of either cb 1 or cb 2 prevents cannabinoid-induced cell death with similar efficacy 33 , 56 , and yet in other types of cancer cells pancreatic 48 , breast 24 , or hepatic 43 carcinoma cells, for example , antagonists of cb 2 but not of cb 1 inhibit cannabinoid antitumour actions.
The reason that cannabinoids produce their antitumour actions through one or the other of these receptor types depending on the type of cancer cell has yet to be established. Some cannabinoid receptor agonists promote cancer cell death more efficiently than other agonists that exhibit similar or even higher affinity for the cb 1 or cb 2 receptors.
For example, thc promotes cancer cell death in a cb 1- or cb 2-dependent manner or both at lower concentrations than does the synthetic cannabinoid receptor agonist WIN 55,, although the latter agent shows significantly higher affinity for cb 1 and cb 2 in binding assays 6.
Further work aimed at investigating, for example, cb receptor homo- or hetero-oligomerization in response to various cannabinoid agonists, their associations with specific domains in the plasma membrane such as lipid rafts, changes in the subcellular location of cb receptors, and the selective coupling to various G proteins and other signalling proteins, will be essential to answer the foregoing questions and to precisely define the role played by each cannabinoid receptor type as an anticancer signalling platform.
Notably, cannabidiol cbd , a phytocannabinoid with a low affinity for cannabinoid receptors 15 , and other marijuana-derived cannabinoids 57 have also been proposed to promote the apoptotic death of cancer cells acting independently of the cb 1 and cb 2 receptors. The mechanism by which cbd produces this effect has not as yet been completely clarified, but it seems to rely—at least in part—on its ability to enhance the production of reactive oxygen species in cancer cells 58 , It has also been proposed that cbd might activate trpv 2 receptors to promote glioma cell death In cancer cells, cannabinoids block the activation of the vascular endothelial growth factor vegf pathway, an inducer of angiogenesis.
Specifically, various elements of the cascade, such as the main ligand vegf and the active forms of its main receptors vegfr 1 and vegfr 2 , are downregulated with cannabinoid treatment of skin carcinomas 54 , gliomas 32 , 61 , and thyroid carcinomas In vascular endothelial cells, cannabinoid receptor activation inhibits proliferation and migration, and induces apoptosis 61 , Those and perhaps other cannabinoid-evoked actions result in a normalized tumour vasculature—that is, smaller and fewer vessels that are more differentiated and less leaky.
Likewise, cb 1 or cb 2 receptor agonists or both reduce the formation of distant tumour masses in animal models of both induced and spontaneous metastasis, and inhibit adhesion, migration, and invasiveness of glioma 64 , breast 65 , 66 , lung 67 , 68 , and cervical 68 cancer cells in culture. Those effects depend, at least in part, on the modulation of extracellular proteases such as matrix metalloproteinase 2 64 and their inhibitors such as tissue inhibitor of matrix metalloproteinases 1 Notably, pharmacologic inhibition of ceramide biosynthesis abrogates the antitumour and antiangiogenic effect of cb 1 or cb 2 receptor agonists or both in glioma xenografts, and decreases vegf production by glioma cells in vitro and in vivo Likewise, inhibition of matrix metalloproteinase 2 expression and glioma cell invasion is prevented by blocking ceramide biosynthesis and by knocking down p8 expression It is worth noting that cbd , by acting independently of the cb 1 and cb 2 receptors, produces a remarkable anti-tumour effect—including reduction of invasiveness and metastasis—in various animal models of cancer.
This effect of cbd seems to rely, at least in part, on the downregulation of the helix-loop-helix transcription factor inhibitor of dna binding 1 69 , Notably, stimulation of cannabinoid receptors can lead to important changes in the processes that regulate anti-tumour immunity. Thus, for example, treatment of mice with thc triggers a shift from Th1 to Th2 of cytokine profile 20 , 71 — 73 and induces mobilization of myeloid-derived suppressor cells 74 , two events that play a critical role in the suppression of antitumour immunity.
In agreement with that notion, stimulation of cb 2 has been proposed in some reports to enhance tumourigenesis by interfering with tumour surveillance by the immune system 20 , By contrast, cannabinoids can also enhance immune system—mediated tumour surveillance in some contexts: Those observations might be related to the ability of thc to reduce inflammation 75 , 76 , an effect that might prevent certain types of cancer 76 , For cannabinoid use to be clinically successful, anti-tumour effects will have to overcome immunosuppressive potentially tumour-promoting effects.
Additional studies should clarify the issue. For example, it could be conceivable to study the effect of cannabinoid administration on the generation and progression of tumours with varying sensitivity to cannabinoids and generated in immunocompetent or immunodeficient mice in which the expression of cb 1 or cb 2 receptors or both in cells from the immune system has been genetically manipulated.
Numerous studies have contributed to an appreciation of the heterogeneity of cancer, whereby each subtype of cancer—and even each individual tumour—exhibits a series of molecular characteristics that determines its behaviour and, in particular, its responsiveness to various anticancer drugs. In agreement with that line of reasoning, a recent report investigated the molecular features associated with the resistance of a collection of human glioma cell lines and primary cultures to cannabinoid antitumour action The study showed that, although the apoptotic effect of thc on glioma cells relied on the stimulation of cannabinoid receptors and activation of the p8-mediated autophagy pathway, the differences in the sensitivity to thc -induced cell death correlated with enhanced expression of a particular set of genes in the thc -resistant glioma cells rather than with the presence of different expression levels of cb 1 or cb 2 receptors Interestingly, upregulation of one of those genes, midkine MDK , which encodes a growth factor that was previously associated with increased malignancy and resistance to anticancer therapies in several types of tumours 77 , 78 , correlates with lower overall survival in patients with glioblastoma Moreover, mdk plays a direct role in the resistance to thc action through stimulation of anaplastic lymphoma kinase alk Thus, the stimulation of alk by mdk inhibits the thc -evoked autophagy-mediated cell-death pathway.
Further research should clarify whether that mechanism could also be responsible for the resistance to other therapies of cancer cells expressing high levels of mdk. Interestingly, in vivo silencing of MDK or pharmacologic inhibition of alk in a mouse xenograft model abolishes the resistance to thc treatment of established tumours derived from cannabinoid-resistant glioma cells Taken together, the foregoing findings support the idea that stimulation of the mdk — alk axis promotes resistance to thc antitumour action in gliomas and could help to set a foundation for the potential clinical use of thc in combination with inhibitors of the mdk — alk axis Figure 2.
Glioblastoma is highly resistant to current anticancer therapies 80 — Specifically, resistance of glioma cells to cannabinoid-induced cell death relies, at least in part, on enhanced expression of mdk and the subsequent activation of alk Likewise, enhanced expression of the heparin-bound epidermal growth factor receptor egfr ligand amphiregulin can promote resistance to thc antitumour action by stimulation of extracellular signal-regulated kinase erk The combination of thc with pharmacologic inhibitors of alk or genetic inhibition of MDK enhances cannabinoid action in resistant tumours, which provides a rationale for the design of targeted therapies capable of increasing cannabinoid antineoplastic activity Combinations of cannabinoids with classical chemotherapeutic drugs such as the alkylating agent temozolomide the benchmark agent for the management of glioblastoma 80 , 84 have been shown to produce a strong anticancer action in animal models Combining cannabinoids and temozolomide is thus a very attractive possibility for clinical studies aimed at investigating cannabinoid antitumour effects in glioblastoma.
Other potentially interesting strategies to enhance cannabinoid anticancer action still requiring additional experimental support from data obtained using preclinical models could be to combine cannabinoids with er stress or autophagy inducers or both or with inhibitors of the m torc 1 axis.
In line with that idea, alk inhibitors have started to be used in clinical trials for the management of non-small-cell lung cancer and other types of tumours 86 , Future research should clarify whether this mechanism of resistance to cannabinoid action operates in other types of tumours. In agreement with that possibility, MDK silencing enhanced the sensitivity of cannabinoid-resistant pancreatic cancer cells to thc -induced cell death The release by cancer cells of other growth factors has also been implicated in the mechanism of resistance to cannabinoid antitumour action.
Thus, increased expression of amphiregulin is associated with enhanced resistance to thc antitumour action in glioma xenografts Notably illustrating how the dose of cannabinoids could be crucial for optimal therapeutic effect, low submicromolar concentrations of thc or other synthetic cannabinoid agonists enhance the proliferation of several cancer cell lines in vitro.
That effect relies on activation of the protease adam 17, the shedding of heparin-bound egfr ligands including amphiregulin and the subsequent stimulation of the erk and akt pathways In line with that idea, a recent report showed that treatment with the synthetic cannabinoid CP 55, increases the proliferation of murine glioma cells engineered to express cb 1 or cb 2 receptors only when those receptors are coupled to akt activation Although a pro-tumourigenic effect has not been observed for the growth of tumour xenografts generated with glioma cells and treated with low doses of thc 85 , increased expression of amphiregulin promotes resistance to thc antitumour action through a mechanism that involves the egfr -dependent stimulation of erk and the subsequent inhibition of p8 and trb 3 expression.
Likewise, pharmacologic inhibition of egfr , erk 83 , or akt enhances the cell-death-promoting action of thc in glioma cultures unpublished observations by the authors , which suggests that targeting egfr and the akt and erk pathways could enhance the antitumour effect of cannabinoids. The use of combinational anticancer therapies has a number of theoretical advantages over single-agent strategies, because they allow for the simultaneous targeting of tumour growth, progression, and spread at various levels.
In line with that idea, recent observations suggest that the combined administration of cannabinoids with other anticancer drugs acts synergistically to reduce tumour growth. For example, the administration of thc and temozolomide exerts strong antitumour action in glioma xenografts, an effect that is also evident in temozolomide-resistant tumours A similar effect was observed when thc and cbd were combined with radiotherapy in animal models of glioma.
Interestingly, no toxicity was observed in mice treated with combinations of thc and temozolomide Because most patients with glioblastoma undergo temozolomide treatment, the foregoing findings indicate that the combined administration of temozolomide and cannabinoids could be therapeutically exploited for the management of glioblastoma Figure 2 and perhaps other tumour types such as melanoma Likewise, another study recently showed that the combined administration of gemcitabine the benchmark agent for the treatment of pancreatic cancer and various cannabinoid agonists synergistically reduced the viability of pancreatic cancer cells Other reports indicated that anandamide and HU might also enhance the anticancer activity of paclitaxel 89 and 5-fluorouracil 90 respectively.
An additional approach has been to combine thc with cbd , a phytocannabinoid that reduces although to a lower extent than thc the growth of several types of tumour xenografts through a still poorly-defined mechanism 59 , 91 , Combined administration of thc and cbd enhances the anticancer activity of thc and reduces the dose of thc needed to induce its tumour growth-inhibiting activity 85 , Moreover, the combination of thc and cbd together with temozolomide produces a striking reduction in the growth of glioma xenografts even when low doses of thc are used Likewise, the combination of thc , cbd , and radiotherapy also produced clear anticancer activity in an orthotopic model of glioma Notably, cbd was also shown to alleviate some of the undesired effects of thc administration such as convulsions, discoordination, and psychotic events, thus improving the tolerability of cannabis-based medicines As mentioned earlier, C.
Thus, we think that clinical studies aimed at analyzing the efficacy of cannabinoids as antitumour agents should be based on the use both of pure substances, such as thc and cbd , and of cannabis extracts containing controlled amounts of thc , cbd , and other cannabinoids. The clinical approval of cannabinoids is largely restricted to palliative uses in various diseases, but since the emergence of promising preclinical data, the antitumour effects of cannabinoids are beginning to be clinically assessed.
In a pilot phase i clinical study, 9 patients with actively- growing recurrent glioblastoma for whom standard therapy had previously failed underwent intracranial thc administration Under those conditions, cannabinoid delivery was safe and could be achieved without significant unwanted effects.
In addition, although no statistically significant conclusions can be extracted from a cohort of 9 patients, the results obtained in the study suggest that some patients responded—at least partially—to thc treatment in terms of a decreased tumour growth rate as evaluated by magnetic resonance imaging Importantly, analyses of samples obtained from 2 study patients before and after thc administration indicated that the molecular mechanism of cannabinoid antitumour action—namely, p8 and trib 3 upregulation 35 , 37 , m torc 1 inhibition 37 , stimulation of autophagy and apoptosis 11 , 35 , 37 , inhibition of cell proliferation 11 , decreased vegf signalling 32 , and matrix metalloproteinase 2 downregulation 64 delineated here earlier —also operates in vivo.
Those findings were encouraging and reinforced interest in the potential use of cannabinoids in cancer therapies. However, they also highlighted the need for further research aimed at optimizing the use of cannabinoids in terms of patient selection, combination with other anti-cancer agents, and use of other routes of administration.
Administration of endocannabinoids or inhibitors of endocannabinoid-degrading enzymes has been shown to reduce the growth of various tumour xenograft types 95 , 96 and could therefore be a reasonable strategy for targeting cannabinoid receptors for anticancer purposes.
However, as discussed here earlier, the role of the endocannabinoid system, including the endocannabinoid-degrading enzymes, in the control of tumour generation and progression is not well understood. Because enhancing endocannabinoid tone only has mild antitumour effects in mice and because no inhibitor of endocannabinoid degradation has yet been approved for use in humans, clinical studies aimed at analyzing the efficacy of cannabinoids as antitumour agents should be based on the use of plant-derived or synthetic agonists of cannabinoid receptors rather than on endocannabinoids or inhibitors of endocannabinoid degradation.
The long-known therapeutic properties of C. As already mentioned, C. However, pure drugs are more prone to standardization than complex molecular cocktails.
Thus, it would be ideal for studies aiming to investigate the anticancer actions of cannabinoids in patients to be performed comparatively with both pure substances and cannabis extracts containing controlled amounts of thc , cbd , and other cannabinoids.
The most widely used route of administration for recreational and self-medicating marijuana is smoking. Although thc and other phytocannabinoids are rapidly absorbed by inhalation, smoking is an unattractive clinical option. Preclinical work in animal models has typically used peri-tumoural administration of cannabinoids.
Likewise, in the only clinical trial in which a cannabinoid was assayed as an antitumour agent, thc was administered locally intracranial delivery to patients with glioblastoma multiforme Nevertheless, this route of administration has many obvious limitations.
Currently available cannabis-based medicines are administered as capsules or using an oromucosal spray Preclinical animal models have yielded data indicating that systemic oral or intraperitoneal administration of cannabinoids effectively decreases tumour growth GV, CS, and MG. Unpublished observations , and so it seems reasonable that future clinical studies with the goal of determining the efficacy of cannabinoids as antitumour agents use oral or oromucosal routes of administration.
Two currently ongoing clinical trials could shed some light on these issues. The other is a phase ii trial aimed at evaluating the effect of cbd as single treatment in patients with solid tumours https: Hopefully, in the near future, new clinical trials will start, helping to determine whether cannabinoids can be used, for other than their palliative effects, in the treatment of cancer patients.
It is widely believed that strategies aimed at reducing mortality from cancer should consist of targeted therapies capable of providing the most efficacious and selective treatment for each individual tumour and patient. Thus, the major focus of anticancer drug development has progressively moved from nonspecific chemotherapies to molecularly-targeted inhibitors. However, despite the huge amount of preclinical literature on how these rationally designed compounds work, their use in clinical practice is still limited.
How do cannabinoid-based medicines fit into this ongoing scenario? Consider glioma, the type of cancer in which the most detailed cannabinoid research has been conducted to date. As discussed here, engagement of a molecular target the cb receptors by a family of selective drugs thc and other cannabinoid agonists inhibits tumour growth in animal models through a well-established mechanism of action that also seems to operate in human patients.
Moreover, cannabinoids potentiate the antitumour efficacy of temozolomide and alk inhibitors in mice harbouring gliomas. However, further research is required to define the precise molecular cross-talk between cannabinoids and chemotherapeutic drugs and to optimize the pharmacology of preclinical cannabinoid-based combination therapies.
With respect to patient stratification, the particular individuals that are potentially responsive to cannabinoid administration should be unequivocally determined. To that end, high-throughput approaches should be implemented to find cannabinoid therapy—associated biomarkers in tumour biopsies or, ideally, in easily acquired fluids containing circulating cancer cells or enhanced levels of resistance factors that might have been released by cancer cells.
Such biomarkers would conceivably relate to cannabinoid pharmacodynamics—namely, expression and activity of cannabinoid receptors and their downstream cell-death-inducing effectors. The approach would be analogous to the biochemical evaluation of estrogen and ErbB2 receptors, which respectively predict benefit from endocrine therapies and trastuzumab in breast cancer.
Predictive markers to define the sensitivity of a particular tumour to cannabinoid-based therapies could also include the status of growth factors, such as mdk in gliomas, and their receptors and signalling partners. To summarize, cannabinoids induce tumour cell death and inhibit tumour angiogenesis and invasion in animal models of cancer, and there are indications that they act similarly in patients with glioblastoma. Given that cannabinoids show an acceptable safety profile, clinical trials testing them as single drugs or, ideally, in combination therapies in glioblastoma and other types of cancer are both warranted and urgently needed.
GW Pharmaceuticals and Cellmid fund part of the research conducted by our laboratory. Likewise, a portion of the data obtained by the authors concerning the antitumoural action of cannabinoids is included in three patent applications presented by GW Pharmaceuticals.
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Collectively, the non-psychoactive plant-derived cannabinoid CBD exhibits pro-apoptotic and anti-proliferative actions in different types of tumours and may also exert anti-migratory, anti-invasive, anti-metastatic and perhaps anti-angiogenic properties. On the basis of these results, evidence is emerging to suggest that CBD is a potent inhibitor of both cancer growth and spread. Interestingly , the anticancer effect of this compound seems to be selective for cancer cells, at least in vitro , since it does not affect normal cell lines.
The efficacy of CBD is linked to its ability to target multiple cellular pathways that control tumourigenesis through the modulation of different intracellular signalling depending on the cancer type considered.
The most common effect of CBD is the increase in ROS production that seems to be determinant for triggering its beneficial action in all the considered cancer cell types. In some cases lung, leukaemia, colon a clear contribution of these receptors has been demonstrated through the use of specific antagonists, but in other cancer types glioma and breast their relevance appears only marginal or absent.
Besides the in vitro data, the efficacy of CBD in reducing tumour growth and, in some cases, metastasization was confirmed in experimental animal models. However, the potential clinical application of CBD for cancer therapy needs some consideration. Its low toxicity is certainly a good starting point. The route of administration appears more problematic since CBD oral absorption is slow and unpredictable. Interestingly, this range of concentration was demonstrated to be active in inhibiting lung cancer cell invasion [ 52 , 53 ], thus suggesting that in some cases the oral route could be the appropriate choice.
Moreover, oromucosal administration may represent a first choice in the presence of nausea and vomiting. In the light of its safety record and considering that CBD is already currently used in patients with multiple sclerosis, the findings here summarized suggest that CBD might be worthy of clinical consideration for cancer therapy.
National Center for Biotechnology Information , U. Br J Clin Pharmacol. Published online Apr Author information Article notes Copyright and License information Disclaimer. Received Jan 30; Accepted Apr This article has been cited by other articles in PMC. Open in a separate window. Cannabinoids in the treatment of cancer Cannabinoids are currently used in cancer patients to palliate wasting, emesis and pain that often accompany cancer.
Table 1 Effects of cannabidiol on different types of cancer. CBD and breast cancer In Ligresti et al. CBD and glioma CBD also possesses anti-tumoural properties in gliomas, tumours of glial origin characterized by a high morphological and genetic heterogeneity and considered one of the most devastating neoplasms, showing high proliferative rate, aggressive invasiveness and insensitivity to radio- and chemotherapy. CBD and lung cancer Given the poor response of lung cancer to available therapy and its aggressive biological nature, a series of targets and new therapeutic strategies for their treatment are currently being investigated [ 47 — 50 ].
CBD and endocrine tumours Thyroid cancer is the most common endocrine malignancy and Ligresti et al. CBD and colon cancer Colon cancer is a major cause of morbidity and mortality in Western countries. CBD and angiogenesis Angiogenesis consists of the formation of new blood vessels from pre-existing ones and represents another promising therapeutic target for cancer therapy. Conclusion and future directions Collectively, the non-psychoactive plant-derived cannabinoid CBD exhibits pro-apoptotic and anti-proliferative actions in different types of tumours and may also exert anti-migratory, anti-invasive, anti-metastatic and perhaps anti-angiogenic properties.
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Cannabidiol as potential anticancer drug. Article date: February By: Paola Massi, Marta Solinas, Valentina Cinquina, Daniela Parolaro, in Volume Over the past years, several lines of evidence support an antitumourigenic effect of cannabinoids including Δ9‐tetrahydrocannabinol (Δ9‐THC). Cannabidiol as potential anticancer drug. Subject: Cancer - PUBLISHED VIA British Journal of Clinical Pharmacology. Author(s): Massi P, Solinas M, Cinquina V.