CB2 / CNR2 Cancer Research Results

CB2 / CNR2, Cannabinoid receptor type 2: Click to Expand ⟱
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Type:

CB2 / CNR2 : Druggable immune-enriched cannabinoid receptor involved in microglia, inflammation, immune-cell signaling, pain, neuroprotection, and tumor-immune regulation.

-when a product binds selectively to the CB2 receptors(modulates up) and not the CB1 receptor, it non-psychoactive and therapeutically appealing.
-activation of the CB2 receptor can suppress pro-inflammatory cytokines production, helping to create an anti-tumor immune environment

Field Suggested Entry
Target CB2 / CNR2
Full Name Cannabinoid receptor type 2
Target Class G-protein-coupled receptor; Gi/o-coupled cannabinoid receptor
Primary Biology Immune modulation, microglial activation, inflammatory signaling, cytokine regulation, leukocyte behavior, pain/inflammation signaling
Cancer Relevance Medium and context-dependent: may suppress inflammation or tumorigenesis in some settings, but may also support immune suppression or tumor progression depending on tumor type and immune context
AD Relevance Medium-high: microglial CB2 activation is a promising neuroinflammation strategy, with encouraging preclinical evidence in AD models but limited clinical validation
Therapeutic Direction Usually selective CB2 agonism/modulation for neuroinflammation and inflammatory disease; cancer direction is tumor-context-dependent
Key Product Links β-caryophyllene, PEA, CBD/cannabinoid-system modulators, endocannabinoids, omega-3-derived lipid mediators


Scientific Papers found: Click to Expand⟱
6511- BCP,    Improvement of Oxidative Stress and Mitochondrial Dysfunction by β-Caryophyllene: A Focus on the Nervous System
- Review, AD, NA
*CB2 / CNR2↑, selective cannabinoid receptor 2 (CB2) agonist
*Bacteria↓, numerous pharmacological activities such as antibacterial (e.g., Helicobacter pylori), antioxidant, anti-inflammatory, analgesic (e.g., neuropathic pain), anti-neurodegenerative and anticancer properties.
*antiOx↑,
*Inflam↓,
*NP/CIPN↓,
*neuroP↑,
AntiCan↑,
*ROS↓, β-caryophyllene in reducing oxidative stress and mitochondrial dysfunction, and its possible links with neuroprotection.
*mtDam↓,
*GSH↑, β-caryophyllene (50 mg/kg/day, i.p. for 4 weeks) ↑ GSH, SOD and CAT. Inhibit lipid peroxidation. ↓ IL-1β, IL-6, and TNF-α levels. ↓ COX-2 and iNOS expression.
*SOD↑,
*Catalase↑,
*lipid-P↓,
*IL1β↓,
*IL6↓,
*TNF-α↓,
*COX2↓,
*iNOS↓,
*NRF2↑, β-caryophyllene (34, 102 and 306 mg/kg/day, p.o.). ↑ Nrf2 and HO-1 expression. Restored SOD and CAT activity and expression.
*HO-1↑,
*AChE↓, Syzygium aromaticum (L.) Merr. and L.M. Perry (0.05 mL/kg and 0.1 mL/kg) ↓ AChE activity, lipid peroxidation levels

6519- BCP,    beta-Caryophyllene: A Sesquiterpene with Countless Biological Properties
- Review, Nor, NA
*CB2 / CNR2↑, is a selective phytocannabinoid agonist of type 2 receptors (CB2-R)
*Inflam↓, via inhibiting the main inflammatory mediators, such as inducible nitric oxide synthase (iNOS), Interleukin 1 beta (IL-1 beta), Interleukin-6 (IL-6), tumor necrosis factor-alfa (TNF-alpha)
*iNOS↓,
*IL1β↓,
*IL6↓,
*TNF-α↓,
*NF-kB↓, NF-kappa B), cyclooxygenase 1 (COX-1), cyclooxygenase 2 (COX-2). P
*COX1↓,
*COX2↓,
*PPARα↑, activation of PPAR-alpha and PPAR-gamma receptors.
*PPARγ↑,
*BioEnh↑, Nevertheless, it inhibits various cytochrome P450 isoforms (above all, CYP3A4), which metabolise xenobiotics, leading to adverse effects, due to drug levels over therapeutic window.

6516- BCP,    β-Caryophyllene, a CB2-Receptor-Selective Phytocannabinoid, Suppresses Mechanical Allodynia in a Mouse Model of Antiretroviral-Induced Neuropathic Pain
- in-vivo, Nor, NA
*NP/CIPN↓, BCP could be useful for prevention and treatment of antiretroviral-induced neuropathic pain
*Inflam↓, via reducing the inflammatory response, and attenuates mechanical allodynia through CB2 receptor activation.
*CB2 / CNR2↑,

6515- BCP,  Xan,    Advancing Brain Health Naturally: β-Caryophyllene and Xanthohumol as Neuroprotective Agents
- Review, AD, NA
*neuroP↑, β-caryophyllene and xanthohumol have demonstrated significant neuroprotective potential in preclinical models.
*BioAv↝, advanced drug-delivery systems, including polymer- and lipid-based nano- and microscale carriers. Such advancements not only enhance the bioavailability and therapeutic potential of these phytochemicals
*CB2 / CNR2↑, selective agonist of cannabinoid type 2 receptors (CB2-R)
*Inflam↓, BCP demonstrates anti-inflammatory properties by suppressing key inflammatory mediators, including inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), nuclear factor kappa B (NF-κB),
*iNOS↓,
*IL1β↓,
*IL6↓,
*TNF-α↓,
*NF-kB↓,
*COX1↓, and cyclooxygenases COX-1 and COX-2.
*COX2↓,
*PPARα↑, actions are partly mediated through activation of peroxisome proliferator-activated receptors, particularly PPAR-α and PPAR-γ.
*PPARγ↑,
*ROS↓, decreased the generation of reactive oxygen species (ROS)
*tau↓, XAN has been shown to directly inhibit the fibrillization tau protein and disaggregate existing fibrils, effectively reducing tau-induced apoptosis in cellular models of AD
*NRF2↑, XAN has been consistently shown to activate the Nrf2/HO-1 pathway, enhancing antioxidant defenses and reducing reactive oxygen species (ROS) levels
*HO-1↑,
*AChE↓, XAN: its ability to inhibit cholinesterases (AChE and BChE) supports its potential for symptomatic treatment of AD,
*BChE↓,
*BioAv↓, XAN’s clinical translation is hindered by poor oral bioavailability and limited BBB penetration.

6512- BCP,    Beta-Caryophyllene Exhibits Anti-Proliferative Effects through Apoptosis Induction and Cell Cycle Modulation in Multiple Myeloma Cells
- in-vitro, MM, NA
CB2 / CNR2↑, BCP treatment reduced cell proliferation through CB2R stimulation;
BAX↑, BCP considerably increased the pro-apoptotic protein Bax and decreased the anti-apoptotic molecule Bcl-2.
Bcl-2↓,
Casp3↑, increase in caspase 3 protein levels was detected following BCP incubation, thus demonstrating its anti-proliferative effect through apoptosis activation.
TumCP↓,
Apoptosis↑,
Akt↓, BCP regulated AKT, Wnt1, and beta-catenin expression,
Wnt↓, 100 μM showed a significant decrease in p-Akt and β-catenin protein
β-catenin/ZEB1↓,
TumCCA↑, downregulating the cell cycle
Inflam↓, with significant antioxidant, anti-inflammatory, chemo-preventive, neuroprotective, and anti-proliferative effects
chemoPv↑,
neuroP↑,
*BioAv↝, However, BCP is poorly aqueous-soluble and is sensitive to light, oxygen, humidity, and high temperatures; for this reason, its bioavailability may be affected,
CB2 / CNR2↑, BCP selectively binds CB2R [24,25], and as a result, it does not induce any psychoactive effects related to CB1 receptor binding.
tumCV↓, BCP Reduces Cancer Cells Viability

6495- BCP,    Beta-caryophyllene is a dietary cannabinoid
*CB2 / CNR2↑, we report that the widespread plant volatile (E)-β-caryophyllene [(E)-BCP] selectively binds to the CB2 receptor (Ki = 155 ± 4 nM) and that it is a functional CB2 agonist.
*other↝, Intriguingly, (E)-BCP is a common constituent of the essential oils of numerous spice and food plants and a major component in Cannabis.
*Inflam↓, and as a macrocyclic antiinflammatory cannabinoid in Cannabis
*TNF-α↓, (E)-BCP Inhibits Lipopolysaccharide (LPS)-Stimulated TNF-α and IL-1β Expression in Peripheral Blood.
*IL1β↓,
*ERK↓, (E)-BCP Inhibits Lipopolysaccharide-Stimulated Erk1/2 and JNK1/2 Activation in Primary Monocytes.
*JNK↓,

6503- BCP,    The Potential Therapeutic Role of Beta-Caryophyllene as a Chemosensitizer and an Inhibitor of Angiogenesis in Cancer
- Review, Var, NA
ChemoSen↑, Beta-Caryophyllene (BCP), was highlighted in several recent preclinical studies to enhance chemo-sensitization in chemo-resistant tumors and to efficiently inhibit angiogenesis and cancer cells’ ability to invade and metastasize.
angioG↓,
TumCI↓,
TumMeta↓,
ROS↑, BCP seems to work as a dual modulator of oxidative stress, increasing reactive oxygen species (ROS) in cancer cells, and thus enhancing apoptosis, but reducing ROS in normal cells to protect them from damage
*ROS↓,
chemoP↑,
CB2 / CNR2↑, important issue in BCP is its ability to bind to the body’s cannabinoid receptor 2 (CB2), where it binds selectively to the CB2 receptors and not the CB1 receptor, which makes it non-psychoactive and therapeutically appealing.
Inflam↓, activation of the CB2 receptor by BCP can suppress pro-inflammatory cytokines production, helping to create an anti-tumor immune environment
AntiTum↑,
*BioAv↑, Beta-Caryophyllene, a food additive approved by the Food and Drug Administration, is efficiently absorbed in the gastro-intestinal tract and can penetrate the blood–brain barrier and has a well-established safety profile, making it an attractive biom
*BBB↑,
Apoptosis↑, Induces apoptosis and suppresses proliferative activity of lung cancer cells
TumCP↑,
TumCCA↑, Induces G1 cell cycle arrest by dysregulating cyclins and other molecules
RadioS↑, GBM: Works as a potential radiosensitizer for improving RT outcomes by inhibiting DNA repair, inducing apoptosis, and suppressing anti-apoptotic and survival pathways
DNArepair↓,
ROS↑, BC: Enhances sensitization and promotes the cigarette smoke condensate (CSC)-induced apoptosis in MDA-MB-468 cells, mainly by triggering oxidative stress and inhibition of STAT3
STAT3↓,
*BioEnh↑, BCP is considered a key component in black pepper’s ability to enhance nutrient absorption, including compounds like curcumin.
Pain↓, BCP in cloves further supports their role in pain management and infection prevention.
AntiBio↓,
ROS↑, selectively induce apoptosis and oxidative stress in cancer cells while sparing normal cells at lower concentrations.
Dose↝, I50, for many cancer cell lines typically ranges from 19 to 64 μM
NF-kB↓, Beta-Caryophyllene was reported to inhibit the central to the regulators of inflammation, NF-κB and MAPK pathways, leading to a decrease in pro-inflammatory cytokine (TNF-α, IL-1β, and IL-6) production
MAPK↓,
TNF-α↓,
IL1β↓,
IL6↓,
cl‑PARP↑, through increasing the levels of cleaved PARP, caspases and Bax, and the downregulation of Bcl-2, directly by interaction with CB2.
Casp↑,
BAX↑,
Bcl-2↓,
VEGF↓, BCP blocks migration of endothelial cells by inhibiting the secretion of VEGF, and thus blocking the activity of the tyrosine kinase VEGFR2
VEGFR2↓,
MMP2↓, BCP can also prohibit the secretion of MMP-2, p-p38 and p-ERK
p‑p38↓,
p‑ERK↓,
EPR↑, BCP was suggested to accumulate in the cancer cell membrane, altering the cells’ permeability, leading to the accumulation of anticancer drugs, and consequently strengthening the drugs’ activity.
P-gp↓, direct inhibition of P-glycoprotein (P-gp/ABCB1) and multidrug resistance-associated protein 1 (MRP1/ABCC1), which are overexpressed in resistant tumors
MRP1/ABCC1↓,
*NRF2↑, Importantly, BCP’s selective antioxidant activity—activating Nrf2 in normal cells while increasing ROS in cancer cells—minimizes off-target toxicity,
*antiOx↑,


Showing Research Papers: 1 to 7 of 7

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 7

Pathway results for Effect on Cancer / Diseased Cells:


NA, unassigned(tgid=0) ⓘ

AntiBio↓, 1,  

Redox & Oxidative Stress(tgid=1) ⓘ

ROS↑, 3,  

Cell Death(tgid=5) ⓘ

Akt↓, 1,   Apoptosis↑, 2,   BAX↑, 2,   Bcl-2↓, 2,   Casp↑, 1,   Casp3↑, 1,   MAPK↓, 1,   p‑p38↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

tumCV↓, 1,  

DNA Damage & Repair(tgid=10) ⓘ

DNArepair↓, 1,   cl‑PARP↑, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

TumCCA↑, 2,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

p‑ERK↓, 1,   STAT3↓, 1,   Wnt↓, 1,  

Migration(tgid=13) ⓘ

MMP2↓, 1,   TumCI↓, 1,   TumCP↓, 1,   TumCP↑, 1,   TumMeta↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 1,   EPR↑, 1,   VEGF↓, 1,   VEGFR2↓, 1,  

Barriers & Transport(tgid=15) ⓘ

P-gp↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

CB2 / CNR2↑, 3,   IL1β↓, 1,   IL6↓, 1,   Inflam↓, 2,   NF-kB↓, 1,   TNF-α↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

ChemoSen↑, 1,   Dose↝, 1,   MRP1/ABCC1↓, 1,   RadioS↑, 1,  

Clinical Biomarkers(tgid=22) ⓘ

IL6↓, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 1,   AntiTum↑, 1,   chemoP↑, 1,   chemoPv↑, 1,   neuroP↑, 1,   Pain↓, 1,  
Total Targets: 45

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 2,   Catalase↑, 1,   GSH↑, 1,   HO-1↑, 2,   lipid-P↓, 1,   NRF2↑, 3,   ROS↓, 3,   SOD↑, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

mtDam↓, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

PPARα↑, 2,   PPARγ↑, 2,  

Cell Death(tgid=5) ⓘ

iNOS↓, 3,   JNK↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

other↝, 1,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

ERK↓, 1,  

Barriers & Transport(tgid=15) ⓘ

BBB↑, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

CB2 / CNR2↑, 5,   COX1↓, 2,   COX2↓, 3,   IL1β↓, 4,   IL6↓, 3,   Inflam↓, 5,   NF-kB↓, 2,   TNF-α↓, 4,  

Synaptic & Neurotransmission(tgid=18) ⓘ

AChE↓, 2,   BChE↓, 1,   tau↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 1,   BioAv↑, 1,   BioAv↝, 2,   BioEnh↑, 2,  

Clinical Biomarkers(tgid=22) ⓘ

IL6↓, 3,  

Functional Outcomes(tgid=23) ⓘ

neuroP↑, 2,   NP/CIPN↓, 2,  

Infection & Microbiome(tgid=24) ⓘ

Bacteria↓, 1,  
Total Targets: 35

Scientific Paper Hit Count for: CB2 / CNR2, Cannabinoid receptor type 2
7 Beta-Caryophyllene
1 xanthohumol
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

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