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

β-caryophyllene is a FDA-approved food additive that can activate the endocannabinoid system. R

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

The endocannabinoid system consists of cannabinoid receptor type 1 (CB1) and CB2 receptors. R

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)

1. May Increase Longevity And Mitochondrial Function

BCP may increase longevity. R 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 atherosclerosis. R

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 Curcumin, EGCG or Baicalin. R

9. Lightens The Skin

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

10. May Improve Oral Hygiene

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

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 chemotherapy. R

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:

• General Liver Inflammation: R

• Liver Scarring due to alcohol R

• Non-Alcoholic Fatty Liver Disease (NALFD) R

• Reducing High Levels of Triglycerides (Hypertriglyceridemia) R R

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

Diet:

• Allspice R

• Anise Seeds R

• Arugula R

• Asparagus R

• Avocados R R

• Basil R

• Bay Leaf R R

• Bell Peppers R

• Black Cumin Seed R

• Black Pepper (BCP is what makes pepper spicy) R R

• Blood Oranges R

• Blueberries R

• Caraway R

• Cardamom R

• Carrots R

• Cayenne

• Cedar Bay Cherries R R

• Celery R

• Chamomile R

• Cinnamon R

• Cloves R R

• Corn R

• Coriander R

• Cow's Milk (if the cow eats a BCP rich diet) R

• Cubeb Pepper R

• Curry R R

• Dill R

• Elderberries R

• Fennel R

• Figs R

• Ginger R R R

• Grapefruit R

• Grapes R

• Guanabana R

• Guava R R

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

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

• 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