Many scientific studies report cannabinoids exert a wide range of
growth-inhibiting effects on cancer cells,
- Stopping cells from dividing.
- Triggering cell
death, through a mechanism called
- Preventing new blood vessels from growing into tumors
a process termed angiogenesis.
- Reducing metastasization by
stopping cells from moving or invading neighboring tissue.
- Speeds up
internal 'waste disposal machine' autophagy which can lead to cell
Conclusion: In 1975, Munson discovered that
cannabinoids suppress Lewis lung carcinoma cell growth. The mechanism of this
action was shown to be inhibition of DNA synthesis. Antiproliferative action on
some other cancer cells was also found.
Conclusion: This review will summarize the
anti-cancer properties of the cannabinoids.
Results emerging from preclinical studies
suggest cannabinoids elicit effects at different levels of cancer progression,
including inhibition of proliferation, neovascularization, invasion and
chemoresistance, induction of apoptosis and autophagy as well as enhancement of
tumour immune surveillance.
Cannabinoid compounds have been reported to
inhibit tumor growth and spreading in numerous rodent models. The underlying
mechanisms include induction of apoptosis, autophagy, and cell cycle arrest in tumor
cells as well as inhibition of tumor cell invasion and angiogenic features of
endothelial cells. In addition, cannabinoids have been shown to suppress
Conclusion: The results of the newest study
focused on the association between cannabinoids use and cancer risk showed no
significant association between increased cancer incidence and cannabinoids use
and it does not depend on the amount of used cannabis.
Conclusion: Control of the cellular
proliferation has become a
focus of major attention as opening new therapeutic possibilities for the
use of cannabinoids as potential antitumor agents. The capacity of endogenous
and synthetic cannabinoids to induce apoptosis of
different tumoral cells in culture and in vivo, the mechanism underlying
and the potential therapeutic applications are discussed in this review.
Conclusion: The development of
CB2-selective anticancer agents could be advantageous in light of
the unwanted central effects exerted by CB1 receptor ligands.
Conclusion: Cannabinoids are potential
Conclusion: The cannabinoid quinone HU-331 is
a highly specific inhibitor of topoisomerase II, compared with most known
anticancer quinones. It might represent a new potent anticancer drug.
Conclusion: These data
lead us to consider
cannabidiol hydroxyquinone (HU-331) to have high potential as a new
antiangiogenic and anticancer drug.
Conclusion: These findings provide a novel
mechanism underlying the anti-invasive action of cannabidiol and imply its use
as a therapeutic option for the treatment of highly invasive cancers.
Conclusion: Phytocannabinoids and cannabis
extracts exert some of their pharmacological actions also by interacting with
TRPA1 and TRPM8 channels, with potential implications for the treatment of pain
Conclusion: These findings support a role for
p38 MAPK in CB2 receptor-induced apoptosis of human leukaemia
Conclusion: CB2 receptor activation
signals apoptosis via a ceramide-dependent
stimulation of the mitochondrial intrinsic pathway.
Conclusion: These findings constitute the
first evidence for an "astroprotective" role of cannabinoids: (i) cannabinoids
rescue primary astrocytes from C(2)-ceramide-induced apoptosis in a dose- and
time-dependent manner; (ii) triggering of this anti-apoptotic signal depends on
the phosphatidylinositol 3-kinase/protein kinase B pathway; (iii) ERK and its
downstream target p90 ribosomal S6 kinase might be also involved in the
protective effect of cannabinoids; and (iv) cannabinoids protect astrocytes
from the cytotoxic effects of focal C(2)-ceramide administration in
Conclusion: Apart from their proapoptotic and
antiproliferative action, recent research has shown that cannabinoids may
likewise affect tumor cell angiogenesis, migration, invasion, adhesion, and
Conclusion: The potential use of cannabinoids
to retard tumor growth and spreading is even more appealing considering that
they show a good safety profile, regarding toxicity, and are already used in
cancer patients as palliatives to stimulate appetite and to prevent devastating
effects such as nausea, vomiting and pain.
Conclusion: The abundant expression and
distribution of CB2 receptors in glioblastoma and particularly
endothelial cells of glioblastoma indicate that impaired tumor growth in
presence of CB may be associated with CB2 activation. Selective
CB2 agonists might become important targets attenuating vascular
endothelial growth factor (VEGF) signalling and thereby diminishing
neoangiogenesis and glioblastoma growth.
Conclusion: Here, we describe the signaling
pathway that mediates cannabinoid-induced apoptosis of tumor cells.
Conclusion: Cannabinoid-treated tumors showed
an increased number of apoptotic cells. This was accompanied by impairment of
tumor vascularization, as determined by altered blood vessel
morphology and decreased
expression of proangiogenic factors
Conclusion: Data confirm the ability of
cannabinoids to induce cell death in different tumor models.
These data suggest that anandamide blocks
human breast cancer cell
proliferation through CB1-like receptor-mediated inhibition of
endogenous prolactin action at the level of prolactin
Anandamide is synthesized via phospholipase D-mediated
hydrolysis of N-arachidonoyl-phosphatidylethanolamine, and degraded by the
fatty acid amide hydrolase (FAAH) into arachidonic acid and ethanolamine.
2-AG is synthesized via diacylglycerol (DAG) lipase (DAGL) a-mediated
hydrolysis of DAG, and degraded by FAAH into arachidonic acid and glycerol, or
by monoacylglycerol lipase.
Conclusion: CBD represents the first nontoxic
exogenous agent that can significantly decrease Id-1 expression in
metastatic breast cancer cells leading to
the down-regulation of tumor aggressiveness.
Cannabinoid receptor agonists are capable of
reducing proliferation and inducing apoptosis in diverse cancer cells such as
cancer, and melanoma, we evaluated whether CB1 is a potential
drug target in rhabdomyosarcoma. Conclusion:
These results support the notion that cannabinoid receptor agonists could
represent a novel targeted approach for treatment of translocation-positive
Conclusion: Anandamide was the first brain
metabolite shown to act as a ligand of "central" CB1 cannabinoid
receptors. Anandamide blocks
breast cancer cell proliferation through CB1-like
receptor-mediated inhibition of endogenous prolactin action at the level of
Conclusion: Results obtained in a panel of
tumor cell lines clearly indicate that, of the five natural compounds tested,
cannabidiol is the most potent inhibitor of cancer cell growth (IC(50) between
6.0 and 10.6 microM), with significantly lower potency in noncancer cells.
Conclusion: The first report showing not only
that cannabinoids regulate JunD but, more generally, that JunD activation
reduces the proliferation of cancer cells, which points to a new target to
inhibit breast cancer
Conclusion: We found a correlation between
CB(2) expression and histologic grade of the tumors. There was also an
association between CB(2) expression and other markers of prognostic and
predictive value, such as estrogen receptor, progesterone receptor, and
ERBB2/HER-2 oncogene. Importantly, no significant CB(2) expression was detected
in nontumor breast tissue. Taken together, these data might set the bases for a
cannabinoid therapy for the management of breast
The anticancer effects of the omega-3 long
chain polyunsaturated fatty acids
(LCPUFA), EPA and DHA may be due, at least in part, to conversion to their
respective endocannabinoid derivatives, eicosapentaenoyl-ethanolamine (EPEA)
and docosahexaenoyl-ethanolamine (DHEA). Attenuation of cell viability,
migration and invasion of
malignant cells indicates a potential adjunct nutritional therapeutic use
of these LCPUFAs and/or their endocannabinoids in treatment of
Our results show that both
?9-tetrahydrocannabinol, the most abundant and potent cannabinoid in marijuana,
and JWH-133, a non-psychotropic CB2 receptor-selective agonist,
reduce tumor growth, tumor number, and the amount/severity of lung
Treatment with CBD significantly reduces
primary tumor mass as well as the size and number of lung metastatic foci in
two models of metastasis.
CBDA does not require CBs to exert its
anti-migration activity in MDA-MB-231 cells.
Conclusion: WIN-55,212-2 or other
non-habit-forming cannabinoid receptor agonists could be developed as novel
therapeutic agents for the treatment of prostate cancer.
Conclusion: This study defines the involvement
of CB(2)-mediated signalling in the in vivo and in vitro growth inhibition of
prostate cancer cells and suggests that CB(2) agonists have potential
therapeutic interest and deserve to be explored in the management of prostate
Conclusion: THC caused apoptosis in a
dose-dependent manner. Morphological and biochemical changes induced by THC in
prostate PC-3 cells shared the characteristics of an apoptotic phenomenon.
We conclude that endocannabinoids are capable
of halting the growth of prostate cancer cells through activation of apoptotic
The direct effects of phosphatase induction on
reduced phosphokinase protein expression was confounded by a parallel decrease
in most (total) kinase proteins.
Conclusion: Cannabinoids have shown antitumor
effects in many types of cancer models, CB2 may be a viable
therapeutic target for the treatment of anaplastic thyroid carcinoma.
Conclusion: New insights into the mechanism of
Met-F-AEA action, and could have significance in providing a basis for the
management of thyroid carcinoma.
Pancreatic ductal adenocarcinoma is an
antagonistic internecine ailment of the exocrine pancreas with < 8% of
patients surviving within a 5-year period. One of the significant barriers to
effective treatment is the immunosuppressive pancreatic tumor microenvironment
and development of resistance to treatment.
In this study, we
investigate a new non-cannabinoid, non-psychoactive derivative of cannabis,
called FBL-03G, to assess its potential for the treatment of pancreatic cancer.
We hypothesize that the use of FBL-03G will have therapeutic potential and can
enhance radiotherapy during the treatment of pancreatic cancer. To investigate
this hypothesis, in vitro studies were first carried out with and without
radiotherapy (RT). In vitro studies, in vivo studies were also conducted in
small animals employing FBL-03G sustainably delivered from smart radiotherapy
biomaterials, allowing continual exposure of the tumor to the cannabis
derivative payloads over time.
FBL-03G, a flavonoid derived from
Cannabis sativa L., is the unnatural isomer of Cannflavin B, a metabolite of
Cannabis. Through a bioactivity guided isolation approach, 11 flavonoids were
isolated using flash chromatography and characterized by nuclear magnetic
resonance (NMR) and mass spectrometry (MS) methods. Generated spectroscopic
data for FBL-03G were similar to those of the following 11 previously isolated
and characterized compounds of the Cannabis plant; apigenin, Chrysoeriol,
kaempferol, luteolin, quercetin, vitexin, isovitexin, orientin and prenylated
flavonoids including Cannflavin A, Cannflavin B and Cannflavin C. The molecules
were further screened for kinase inhibition, and chrysoeriol (Cresorol)
demonstrated significant activity against FLT3, FLT3-ITD, and FLT3-D835Y and
moderate activity against CSF1R. FBL-03G demonstrated significant activity
against CSF1R kinase and moderate activity against FLT3, FLT3-ITD, FLT3-D835Y,
CK2a, CK2a2, Aurora A, Aurora B, Aurora C, and Pim2.
From the results of
this study, the key findings include, observation that a non-cannabinoid
derivative of cannabis can enhance radiotherapy treatment outcomes in-vitro and
in-vivo. Secondly, the sustained delivery of the cannabis derivative FBL-03G
from smart radiotherapy biomaterials (SRBs) results in tumor growth inhibition
of both locally treated and distant untreated tumors, with and without radiotherapy.
The use of smart
radiotherapy biomaterials (SRBs) was recently proposed as a novel approach to
deliver cannabinoids, allowing for prolonged exposure of tumor cells to these
cannabis derivatives, which is expected to be more effective.
Conclusion: Our results demonstrate that
Cannabinoids produce a
significant cytotoxic effect via a receptor-independent mechanism.
Conclusion: Results presented here show that
cannabinoids lead to apoptosis
of pancreatic tumor cells via a CB(2) receptor and de novo synthesized
ceramide-dependent up-regulation of p8 and the endoplasmic reticulum
stress-related genes ATF-4 and TRB3.
Cannabinoids inhibit the glycolytic pathway:
To assess whether a restriction of the
energetic metabolism by cannabinoids could be responsible for the
enhancement of the cellular AMP level, we performed a targeted metabolomic
Cannabinoids inhibit the Krebs cycle: To further examine the
involvement of the energetic metabolism in the induction of AMPK-mediated
autophagy by cannabinoids, we analysed the critical metabolites of the Krebs
Lymphomas may be broadly divided into
non-Hodgkin (90%) and Hodgkin (10%) types. Most lymphomas (90%) are of
βlymphocyte origin but can
also be T lymphocyte or natural killer cell.
The malignant lymphomas, including both
Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL), represent a diverse group
of diseases that arise from a clonal
proliferation of lymphocytes. Each of the more than 30 unique types of
lymphoma is a disease with a distinct natural history. This biologic
heterogeneity gives rise to marked differences among the lymphomas with respect
to epidemiology, pathologic characteristics, clinical presentation, and optimal
Clonal expansion of the germinal center B
cells of human reactive lymph nodes was analyzed. By micromanipulation, 28
germinal centers were microdissected from three nonneoplastic lymph nodes that
had been fixed with formalin. Immunoglobulin heavy chain variable (V) region
gene rearrangement was examined by seminested polymerase chain reaction (PCR)
using two sets of primers (FR2-J and FR3A-J). An oligoclonal development (one
to five clones) was found in each germinal center. Depending on the primer
used, four or five (16%) of the germinal centers showed a single rearrangement
band. The average number of βlymphocyte clones in each germinal center was
approximately 2.5. Next, the authors analyzed 50 endoscopic biopsy specimens
from 6 patients with non-mucosa-associated lymphoid tissue (MALT) type gastric
lymphoma, 25 patients with chronic gastritis, and 19 patients with nonspecific
colitis. In addition to the samples from the 6 patients with malignant
lymphoma, 8 of 44 biopsy samples (18.2%) from patients diagnosed as having
chronic gastritis or nonspecific colitis showed one or two amplified bands.
These results indicate that PCR analysis of immunoglobulin heavy chain V region
gene rearrangement in small biopsy specimens could be misleading, causing
overdiagnosis of reactive
lymphoid tissue as βlymphocyte clonal proliferation.
Lymphomas are classified based on the normal
counterpart, or cell of origin, from which they arise. Because
lymphocytes have physiologic immune
functions that vary both by lineage and by stage of differentiation, the
classification of lymphomas arising from these normal lymphoid populations is
complex. Recent genomic data have contributed additional depth to this
Expert commentary: Lymphoma classification is a continually
evolving field that needs to be responsive to new clinical, pathological, and
molecular understanding of lymphoid neoplasia.
Conclusion: The cytotoxic effect of a
cannabinoid is enhanced by modulation of ceramide metabolism.
Conclusion: Induction of apoptosis in
mantle cell lymphoma.
Conclusion: Cannabinoids induce growth
inhibition and apoptosis in mantle cell lymphoma.
Conclusion: Cannabinoid receptor ligands will
have efficiency in reducing tumor burden in malignant lymphoma overexpressing
CB1 and CB2.
Conclusion: Culture of primary acute
cells with THC in vitro reduced cell viability and induced
Recent advances in the molecular understanding
of gliomas suggest some potential reasons for the failure of more targeted
therapies in gliomas. Specifically, the histologic-based glioma classification
is composed of multiple different molecular subtypes with distinct biology,
natural history, and prognosis. First, the field is faced with the difficulty
of reinterpreting the results of prior studies and retrospective data using the
new classifications to clarify prognostic assessments and treatment
recommendations for patients. Second, the new classifications and insights
require rethinking the design and stratification of future clinical trials.
Last, these observations provide the essential framework for the development
and testing of new specific targeted therapies for particular glioma
Gliomas are the most common primary
intracranial tumor, representing 81% of
tumors. Although relatively rare, they cause significant mortality and
morbidity. A small portion of these tumors are caused by Mendelian disorders,
including neurofibromatosis, tuberous sclerosis, and Li-Fraumeni syndrome.
Conclusion: Cannabinoids seem to be selective
antitumoral compounds, as they kill glioma cells, but not their non-transformed
anti-proliferative, anti-invasive, anti-metastatic and pro-apoptotic effects in
different cancer types, both in vitro and in vivo in animal models, after local
or systemic administration.
Conclusion: A pilot clinical trial on patients
with glioblastoma multiforme demonstrated their good safety profile together
and remarkable antitumor effects.
Conclusion: In contrast with their role in
THC-mediated death, both CB1 and CB2 partially protected
glioma against Arachidonylethanolamide-induced apoptosis.
Conclusion: This study defines
COX-2 as a hitherto unknown
target by which a cannabinoid induces apoptotic death of glioma cells.
Conclusion: The nonpsychoactive CBD was able
to produce a significant antitumor activity both in vitro and in vivo, thus
suggesting a possible
application of CBD as an antineoplastic agent.
Conclusion: TIMP-1 down-regulation may be a
hallmark of cannabinoid-induced inhibition of glioma progression.
Conclusion: Results demonstrate that
cannabinoids target glioma stem-like cells,
differentiation, and inhibit gliomagenesis, thus giving further support to
their potential use in the management of malignant gliomas.
THC can promote the autophagic
death of human cancer
cells and provide
evidence that cannabinoid administration may be an effective therapeutic
strategy for targeting human cancers.
Conclusion: Cannabinoid-induced inhibition of
MMP-2 expression and cell invasion was prevented by blocking ceramide
biosynthesis and by knocking-down
the expression of the stress
Conclusion: THC-induced apoptosis in glioma
C6.9 cells relys on a CBI receptor-independent
sphingomyelin (sphingophospholipids) breakdown.
Conclusion: Cannabinoids were shown to induce
apoptosis of glioma cells in vitro and tumor regression in vivo.
Conclusion: Δ9-THC is shown to
significantly affect viability of GBM cells via a mechanism that appears to
elicit G(1) arrest due to downregulation of E2F1 and Cyclin A.
Conclusion: Tumors growing in the brains of
mice were drastically slowed down when THC/CBD was used with irradiation.
The present investigation confirms the
antiproliferative and antiinvasive effects of CBD in U87-MG cells.
Estrogenic induction of cannabinoid
CB1 receptor in human colon cancer cell lines.
Conclusion: The CB1 receptor can be
considered an estrogen-responsive gene.
Cannabinoid receptor activation induces
apoptosis through tumor necrosis factor alpha-mediated ceramide de novo
synthesis in colon cancer cells.
Conclusion: The present study shows that
either CB1 or CB2 receptor activation induces apoptosis
through ceramide de novo synthesis in colon cancer cells.
Δ9-tetrahydrocannabinol inhibits RAS-MAPK and PI3K-AKT survival
signalling and induces BAD-mediated apoptosis in colorectal cancer cells.
Conclusion: These data suggest an important
role for CB1 receptors and BAD in the regulation of apoptosis in
colorectal cancer cells. The use of THC, or selective targeting of the
CB1 receptor, may represent a novel strategy for colorectal cancer
Conclusions: The present study shows that
either CB1 or CB2 receptor activation induces apoptosis
through ceramide de novo synthesis in colon cancer cells. Our data unveiled,
for the first time, that TNF-α acts as a link between cannabinoid receptor
activation and ceramide production.
Results: CBD BDS and CBD reduced cell
proliferation in tumoral, but not in healthy, cells.
apoptosis in Jurkat leukaemia
lymphocytes is regulated by translocation of Bad to mitochondria.
Conclusion: Raf-1/MEK/ERK/RSK-mediated Bad
translocation played a critical role in THC-induced apoptosis in Jurkat
Conclusion: The results from this study reveal
that cannabidiol, acting through CB2 and regulation of Nox4 and
p22(phox) expression, may be a novel and highly selective treatment for
Conclusion: These data suggest that the
intrinsic pathway plays a more critical role in THC-induced apoptosis while the
extrinsic pathway may facilitate apoptosis via cross-talk with the intrinsic
Conclusion: One of the
most intriguing findings was that THC-induced cell death was preceded by
significant changes in the expression of genes involved in the
mitogen-activated protein kinase (MAPK) signal transduction pathways.
Conclusion: A role of COX-2 and PPARgamma in
MA-induced apoptosis was confirmed in another human cervical cancer cell line
(C33A) and in human lung
carcinoma cells (A549).
Conclusion: Using Matrigel invasion assays we
found a cannabidiol-driven impaired invasion of human cervical cancer (HeLa,
C33A) and human lung
cancer cells (A549) that was reversed by antagonists to both CB(1) and
CB(2) receptors as well as to transient receptor potential vanilloid 1 (TRPV1).
These findings provide a novel mechanism underlying the anti-invasive action of
cannabidiol and imply its use as a therapeutic option for the treatment of
highly invasive cancers.
Women with gynecologic cancer report a strong
interest in the use of non-prescription cannabis products for management of
cancer-related symptoms. Practitioners in the field of gynecologic oncology
should be aware of the frequency of use of non-prescription cannabis amongst
their patients as well as the growing desire for guidance about the use of
cannabis derivatives. A substantial number of patients report decreased
reliance on opioids when using cannabis derivatives for pain control.
Conclusion: Both thymocytes and EL-4 thymoma
cells are susceptible to CBD-induced apoptosis.
Conclusion: Thymocytes and splenocytes exposed
to THC in vivo exhibited apoptosis upon in vitro culture. Together, these
results suggest that in vivo exposure to THC can lead to significant
suppression of the immune
response by induction of apoptosis.
Conclusion: THC retards
cholangiocarcinoma cell growth
Conclusion: Cannabinoid antiproliferative
action on melanoma cells was due, at least in part, to cell cycle arrest at the
G1-S transition via inhibition of the prosurvival protein Akt and
hypophosphorylation of the pRb retinoblastoma protein tumor suppressor.
Conclusion: Previous studies have indicated
the antitumoral effect of human melanocytes, human melanoma cell lines
expressing CB1 receptor (CB1), and of the peritumoral
administration of endocannabinoids. Our studies revealed that systemic
administration of a stable CB1 agonist, ACEA, into SCID mice
specifically inhibited liver colonization of human melanoma cells.
Conclusion: Although the global incidence of
cutaneous melanoma is increasing, survival rates for patients with metastatic
disease remain <10%. our findings suggest that THC activates noncanonical
autophagy-mediated apoptosis of melanoma cells, suggesting that cytotoxic
autophagy induction with Sativex warrants clinical evaluation for metastatic
Our findings suggest that phytocannabinoids
and cannabis extracts exert some of their pharmacological actions also by
interacting with TRPA1 and TRPM8 channels, with potential implications for the
treatment of pain and cancer.
Conclusion: The high expression level of CB(1)
and CB(2) receptors commonly found in malignant astrocytomas precludes the use
of cannabinoids as therapeutics, unless AKT is concomitantly inhibited, or
cannabinoids are applied at concentrations that bypass CB(1) and CB(2)
receptors, yet still activate ERK1/2.
Conclusion:Our pooled results showed no
significant association between the intensity, duration, or cumulative
consumption of cannabis smoke and the risk of
lung cancer overall or in never
Conclusion: There was significant inhibition
of the subcutaneous tumor growth and lung metastasis of A549 cells in
THC-treated animals as compared to vehicle-treated controls. Tumor samples from
THC-treated animals revealed antiproliferative and antiangiogenic effects of
Conclusion: Our data indicate that
cannabinoids induce ICAM-1, thereby conferring TIMP-1 induction and subsequent
decreased cancer cell invasiveness