The 21+ Benefits Of Beta-Caryophyllene (The Common Cannabinoid)

Beta-Caryophyllene Is A Very Common Cannabinoid

β-caryophyllene is a FDA-approved food additive that can activate the endocannabinoid systemR

It is found in many plants, fragrances, preservatives, additives, and flavoring agents. R R

 
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Basics

The endocannabinoid system consists of cannabinoid receptor type 1 (CB1) and CB2 receptorsR

Cannabis (THC and CBD) as well arachidonic acid are common endocannabinoids that bind nonselectively to both CB1 and CB2 receptors. R

CB1 receptors are primarily responsible for the psychomodulatory effects of cannabis (marijuana), whereas CB2 receptors are powerful at treating inflammation, pain, atherosclerosis, and osteoporosis. R

Beta-Caryophyllene (BCP) can bind to CB2 receptors (strong) and activate many of benefits of the endocannabinoid system. R

Some Of The Key Takeaways About BCP:

  • It improves metabolism (by increasing mitochondrial function)
  • It protects against neurodegeneration (by reducing a leaky blood-brain barrier and inflammation)
  • It reduces pain (by upregulating natural endorphins)

Benefits Of Beta-Caryophyllene

1. May Increase Longevity And Mitochondrial Function

BCP may increase longevityR R

For example, in worms, BCP can modulate stress and prolong lifespan (by 11-22%). R

BCP can also increase SIRT1, CREB, PGC-1α, and PPAR-gamma, 4 genes that improve mitochondrial function. R R

2. Protects The Brain

BCP can reduce neuroinflammation (inflammation in the brain) and increase antioxidant levels in the brain. R R

For example, BCP can activate the pathway Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) to increase glutathione levels which can protect against glutamate-induced oxidative stress. R

By regulating glutamate and CB2 activation, BCP can protect against N-Methyl-D-Aspartate (NMDA)-induced excitotoxicicity. R

For example, BCP can reduce seizures in animal models of epilepsy. R

3. May Improve Stroke Outcome

BCP can decrease brain damage after stroke. R

During stroke, BCP can reduce swelling, neuronal damage and mitochondrial dysfunction in the brain. R R

It can also help a leaky blood-brain barrier after stroke. R

BCP can also help with hypoxia-induced neuroinflammation by upregulating NRF2 and Heme Oxygenase-1 (HO-1). R R

4. Protects The Vascular System

 
 

By improving blood flow to the brain, BCP can help with Vascular Dementia (VD). R

BCP can also reduce high levels of cholesterol (hypercholesterolemia). R R

It can also reduce stress to the heart. R

It may also suppress the development of atherosclerosisR

5. May Prevent Alzheimer's Disease

BCP may help prevent Alzheimer's Disease (AD). R

By activating CB2 receptors and upregulating PPAR-gamma, BCP can reduce amyloid beta-plaques and immune-induced inflammation in the brain, thus mitigating cognitive dysfunction. R R

It can pass the blood-brain barrier and induce neurogenesis by increasing Brain-Derived Neurotrophic Factor (BDNF) levels. R 

BCP also has other ways increasing neurogenesis independently of BDNF (and NGF). R

6. May Help With Parkinson's Disease

In Parkinson's Disease (PD), loss of dopamine and oxidative stress are hallmarks of the disease. R

By activating CB2 receptors, BCP can inhibit dopamine loss and oxidative stress in the brain. R

For example, BCP can protect against MPTP (a toxin used to destroy dopamine neurons in animal studies)-induced damage to the substantia nigra (the part of the brain most sensitive to dopamine loss in PD). R

7. May Help Multiple Sclerosis

BCP may also help with Multiple Sclerosis (MS) by reducing TH1 and TH17 pro-inflammatory cytokines. R R R

By increasing Treg anti-inflammatory cytokines (such as IL-10), BCP may help reduce the progression and symptoms of MS, such as neuropathy and pain. R

8. Protects The Gut

BCP may help with Inflammatory Bowel Diseases (IBD). R R

For example, BCP can reduce inflammation in the colon by activating CB2 and PPAR-gamma receptors. R R

These anti-inflammatory effects can be enhanced when combined with CurcuminEGCG or Baicalin. R

9. Lightens The Skin

BCP can reduce melanin synthesis and may help with skin-whitening. R

10. May Improve Oral Hygiene

 
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BCP may inhibit dental plaque buildup. R

It may also prevent gingivitis. R

11. Is An Anti-Microbial

BCP has anti-bacterial activity against:

  • Aerococcus viridans R
  • Bacillus cereus R R 
  • Enterococcus faecalis R
  • Escherichia coli R R
  • Fusobacterium nucleatum R
  • Haemophilus haemoglobinophilus R
  • Lactobacillus casei R
  • Lactococcus lactis R
  • Mycobacterium bovis R
  • Porphyromonas gingivalis R
  • Proteus vulgaris R
  • Pseudomonas aeruginosa R R
  • Salmonella typhimurium R
  • Staphylococcus aureus R R
  • Streptococcus mitis R
  • Streptococcus mutans R
  • Streptococcus sobrinus R
  • Streptococcus sanguinis R
  • Yersinia enterocolitica R
  • Vibrio parahaemolyticus R

BCP has anti-fungal activity against:

  • Acrophialophora fusispora R
  • Aspergillus flavus R
  • Aspergillus fumigates R
  • Aspergillus niger R
  • Aspergillus parasiticum R
  • Aspergillus tubingensis R
  • Candida parapsilosis R
  • Fusarium solani R
  • Penicillium madriti R
  • Penicillium purpurogenum R
  • Penicillium viridicatum R

BCP has anti-parasitic activity against:

  • Leishmania amazonensis R
  • Termites R

BCP may also help prevent tick bites (from malaria) and mosquito bites (from the virus Aedes aegypti), reducing the chances of developing Yellow Fever, Dengue Fever and Chikungunya. R R

12. May Reduce Depression And Anxiety

BCP may reduce depressive and obsessive-compulsive symptoms. R

It may also reduce anxiety (without affecting motor coordination) and may help with General Anxiety Disorder (GAD). R

13. Helps With Sleep

BCP can decrease the time it takes to get to sleep and increase sleep time. R

14. Relieves Pain

 
 

BCP may help relieve chronic pain and neuropathy. R 

By working on the opioid system and endocannabinoid system, BCP can increase natural endorphins and reduce inflammation. R R R

It may also be applied topically and locally to areas of pain. R

BCP can help reduce muscle spasms and muscle pain. R R R

It may have synergistic effects with DHA against pain. R

It may also potentiate the analgesic action of morphine. R

Also, BCP may increase testosterone and estrogen levels in those with chronic pain. R

15. May Prevent Cancer

BCP may help prevent cancer. R R

For example, in an animal study where mice were fed a high fat diet, BCP could inhibit tumor growth. R

Its anti-cancer effects may be stronger if BCP is oxidized. R R

Oxidized BCP (CPO) can inhibit the growth of cancer cells and induces apoptosis (self destruction) by suppressing PI3K, AKT, mTOR, and S6K1 and increasing MAPK. R

CPO/BCP have beneficial effects against:

  • Brain Cancer (BCP and CPO) R
  • Breast Cancer (BCP and CPO) R R
  • Cervical Cancer (CPO) R
  • Colon Cancer (BCP) R
  • Gastric/Stomach Cancer (CPO) R
  • Lymphatic Cancer (BCP) R R
  • Multiple Myeloma (CPO) R
  • Ovarian Cancer (CPO) R
  • Pancreatic Cancer (BCP) R
  • Prostate Cancer (CPO) R
  • Skin Cancer/Melanoma (BCP) R

BCP and CPO can enhance the effects of some anti-cancer drugs, such as paclitaxel and doxorubicin. R R R R

BCP can also help with pain and neuropathy from chemotherapyR

16. Helps With Alcohol Addiction

BCP may help with alcohol addiction. R

For example, in a study where mice were addicted to alcohol, BCP administration could reduce the mice's dependence to alcohol. R

17. May Improve Bone Density And Improve Weight Loss

 
 

BCP may help with weight loss by activation of PPAR-gamma. R

It may do this by increasing bone mineralization (beneficial for osteoporosis) and reducing adipogenesis (beneficial against obesity). R R

18. Protects The Kidneys

By activation of CB2 receptors, BCP may protect the kidneys from inflammation and oxidative stress. R

19. Protects Against Diabetes

High doses of BCP (orally) may have beneficial effects on glucose levels. R

For example, BCP has been found to balance glucose levels in diabetic rats, similar to glibenclamide, a standard anti-diabetic drug. R

BCP may stop the development of insulin resistance by protection of pancreatic beta-cells from hyperglycemia and by enhancement of insulin/glucose signaling. R R R

20. Improves Liver Function

By activation of ACC1, AMPK, CB2 and PPAR-gamma, BCP may help with:

BCP combines well with Milk Thistle to improve liver function. R

21. May Affect Sex Organs

Endometriosis is when tissue abnormally grows outside lining of the uterus. R 

In animal studies, BCP has shown to improve symptoms of endometriosis without affecting fertility. R

Although, in studies with male mice, BCP may act as a male contraceptive by decreasing sperm viability and sperm count (but not decreasing overall sperm production). R

Natural Sources Of Beta-Caryophyllene

 
 

Diet:

Herbs, Supplements, And Oils:

Drugs:

Other:

  • Arabidopsis thaliana R
  • Boenninghausenia albiflora R
  • Cajeput oil (from fish) R
  • Golden Trumpet R
  • Hansfordia sinuosae (Sponge-Associated fungus) R
  • Inula cappa R
  • Leucas aspera R R
  • Lion's Heart R
  • Marsypianthes chamaedrys R
  • Mikania micrantha R
  • Moluccella spinosa R
  • Peperomia serpens R
  • Perovskia abrotanoides R
  • Pestalotiopsis (from endophytic fungus) R
  • Phoebe lanceolata R
  • Pokeweed (toxic to humans) R
  • Polyalthia cerasoides R
  • Pterodon emarginatus R
  • Pulicaria sicula R
  • Pycnocycla caespitosa R
  • Rumphella antipathies (Formosan Gorgonian Coral has Rumphellols A and B) R
  • Spiranthera odoratissima R

Caveats

BCP is "generally regarded as safe" by the FDA and is safe even in high doses. R R R R

BCP combined with DIM works well to shift the CB1/CB2 activation ratio away from CB1 receptor activation. R

Paradoxically, CB2 activation may make eczema worse (in mice). R

This may be because if BCP becomes oxidized into BCP oxide, it may cause moderate allergies and oxidative stress (so that may be good against cancer). R R

Make sure to limit BCP's exposure to open air, as it may autoxidize when exposed to air (supplements may have a better ability to reduce oxygenation vs oils/fruits). R

Like all CB2 agonists, BCP may cause TH2 polarization (which may be good depending on your immune system). R

BCP may accumulate in fat tissue, which may be partly the reason why why some people feel better after burning off fat. R

Mechanism Of Action

 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5288380/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5288380/

 

Simple: 

  • Increases ACC1 R
  • Increases AMPK R
  • Increases Arf6 R
  • Increases Bcl-2 R R
  • Increases BDNF R
  • Increases Caspase-3 (inhibits it in the colon) R R
  • Increases CAT R
  • Increases CB2 R R
  • Increases Cdc42 R
  • Increases Claudin-5 R
  • Increases Endorphins R
  • Increases Estrogen R
  • Increases FOXO3 R
  • Increases GAP43 R R
  • Increases GPx R
  • Increases GSH R
  • Increases GST R
  • Increases HO-1 R
  • Increases IL-4 R
  • Increases IL-10 R R
  • Increases NRF2 R R
  • Increases Occludin R
  • Increases PGC-1alpha R
  • Increases PPAR-alpha R
  • Increases PPAR-gamma R
  • Increases Rac1 R
  • Increases SIRT1 R
  • Increases SOD R R
  • Increases Synapsin R
  • Increases Synaptophysin R
  • Increases Testosterone R
  • Increases ZO-1 R
  • Reduces α7-nAChRs R
  • Reduces Bax R
  • Reduces BACE1 R
  • Reduces cAMP R
  • Reduces CD14 R
  • Reduces Col1a1 R
  • Reduces COX-2 R
  • Reduces CREB (increases in stroke) R R
  • Reduces E-Selectin R
  • Reduces Erk1/2 R
  • Reduces FAAH R
  • Reduces FOXO1 R
  • Reduced GFAP R
  • Reduces HMG-CoA reductase R
  • Reduced Iba-1 R
  • Reduces ICAM-1 R
  • Reduces IFN-gamma R
  • Reduces IKKα/β R
  • Reduces IL-1beta R
  • Reduces IL-6 R
  • Reduces IL-8 R
  • Reduces IL-12 R R
  • Reduces IL-17 R
  • Reduces JNK1/2 R
  • Reduces KC R
  • Reduces Ki-67 R
  • Reduces LDL R
  • Reduces LTB4 R
  • Reduces MAPK R
  • Reduces MCP-1 R
  • Reduces MD2 R
  • Reduces MDA R
  • Reduces Melanin R
  • Reduces MIP2 R
  • Reduces MMP9 R
  • Reduces MPO R
  • Reduces MITF R
  • Reduces NAG R
  • Reduces NF-kB R
  • Reduces NO R R
  • Reduces NOX-2 R
  • Reduces NOX-4 R
  • Reduces P-Selectin R
  • Reduces PGE2 R
  • Reduces P53 R
  • Reduces SREBP-1c R
  • Reduces TGF-b1 R
  • Reduces Timp1 R
  • Reduces TLR4 R R
  • Reduces TNF-alpha R
  • Reduces TRP-1 R
  • Reduces TRP-2 R
  • Reduces Tyrosinase R
  • Reduces T-bet R
  • Reduces VCAM-1 R
  • Reduces 3-NT R
  • Reduces 4-HNE R

Advanced:

  • β-caryophyllene (BCP) selectively binds to and (fully) agonizes the CB2 receptor. R
  • It selectively binds to the CP55,940 binding site (i.e., THC binding site) in the CB2 receptor, leading to cellular activation and anti-inflammatory effects. R
  • Upon binding to the CB2 receptor, BCP inhibits adenylate cylcase, leads to intracellular calcium transients and weakly activates the mitogen-activated kinases Erk1/2 and p38 in primary human monocytes. R
  • BCP inhibits lipopolysaccharide (LPS)-induced proinflammatory cytokine expression in peripheral blood and attenuates LPS-stimulated Erk1/2 and JNK1/2 phosphorylation in monocytes. R
  • BCP is a potent antagonist of homomeric nicotinic acetylcholine receptors (α7-nAChRs) and devoid of effects mediated by serotonergic and GABAergic receptors. R
  • BCP may prevent cleavage of amyloid-beta plaque by inhibiting beta-secretase (BACE1). R
  • In the colon, BCP can reduce keratinocyte-derived chemokine (KC)/CXCL1, macrophage-inflammatory protein-2 (MIP2) N-acetyl-glucosamine (NAG), caspace-3, and Ki-67 via induction of CB2 and Peroxisome Proliferator-Activated Receptor-Gamma (PPARγ) and possibly by an increase in CD4+ FoxP3+ regulatory T cells (T-regs), but no effect on IL-10 or TGF-b1. R
  • In kupffer cells, BCP inhibits activation of toll-like receptor 4 (TLR4) and receptor for advanced-glycation end products (RAGE). R
  • In stroke, BCP suppresses apoptosis via PI3K/AKt signaling pathway activation. R
  • BCP pre-treatment before stroke decreases BBB permeability and neuronal apoptosis, mitigates oxidative stress damage and the release of inflammatory cytokines, down-regulates Bax expression, metalloproteinase-9 activity (MMP-9) and expression, and up-regulates claudin-5, occludin, ZO-1, growth-associated protein-43 and Bcl-2 expression. R
  • In animal models of AD, BCP reduces neuroinflammation in the cerebral cortex, but not the hippocampus. R
  • In models of stroke, BCP can increase AMPK and CREB, thus increasing BDNF. R
  • In models of MS, BCP selectively increases the infiltration/differentiation of Treg and inhibits Th1 myelin-specific cells in the CNS through activation of the CB2 cannabinoid receptor and reduce CD4+ and CD8+ T cells. R
  • In models of melanoma, BCP reduces melanin production by decreasing MITF, TRP-1, TRP-2 and tyrosinase expression. R
  • In the liver, β-caryophyllene prevents the translocation of sterol regulatory element-binding protein-1c (SREBP-1c) into the nucleus and forkhead box protein O1 (FoxO1) into the cytoplasm through AMPK signaling, and consequently, induces a significant downregulation of fatty acid synthase (FAS) and upregulation of adipose triglyceride lipase. R
  • It also was able to significantly improve liver structure, and reduced fibrosis and the expression of Col1a1, Tgfb1 and Timp1 genes. R
  • In worms, BCP was able to mimic caloric restriction (via insulin regulation), reduce ROS and lipofuscin in cells (regulating cellular stress), and increasing SOD-3, SKN-1 and GST-4 by binding to SIR-2.1, SKN-1 392 and DAF-16, and modulating eat-2. R
  • In worms BCP upregulated mRNA of daf-16,, sod-2, sod-3, hsp-70, sir-2.1, skn-1, gst-4, and gst-7. R
  • Oxidized BCP (CPO) down-regulates the expression of various downstream gene products that mediate cell proliferation (cyclin D1), survival (bcl-2, bcl-xL, survivin, IAP-1, and IAP-2), metastasis (COX-2 and c-Myc), angiogenesis (VEGF), invasion (MMP 9 and ICAM-1) and STAT3, but increases the expression of p53, p21, and tyrosine phosphatase SHP-1. R R
  • CPO can also reduce T-cell differentiation, IFN-γ production, and Th1-assocaited genes (T-bet, and IL-12Rβ2). R R

More Research

  • BCP in cigarette butts may prevent some of the genotoxic effects of cigarettes. R
  • E. Coli can be genetically engineered to produce BCP from vinegar. R
  • In plants, BCP can reduce photosynthesis. R