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Unlocking the Secrets to Brain Health with Beta-caryophyllene

Why does brain health matter?

Your brain controls much of your daily functioning. A healthy brain provides many benefits: higher levels of creativity, improved problem-solving skills, ability to communicate, better memory, and clearer thinking. Human brains are highly complex organs that deserve good care to keep them working at their best. Unfortunately, there are a lot of conditions that can impact brain health. These conditions and disorders include:

  • Vascular diseases

  • Degenerative diseases

  • Brain tissue injuries

  • Inflammation

  • Malnutrition and vitamin deficiencies

  • Immune-mediated diseases

  • Behavioral health

  • Insomnia

  • Addiction

  • Excessive or lack of endocannabinoid system (ECS) health dysfunction

  • Isolation/hyperstimulation

Model of brain with neurodegenerative disorders

The Heavy Impact of Neurodegenerative Diseases

Neurodegenerative diseases range from epilepsy, Alzheimer’s disease and other dementias, strokes, migraine headaches, Parkinson’s disease, brain injuries, neuroinfections, multiple sclerosis (MS) and other related disorders. They all share a common underlying cause – the nervous system cells (neurons) in the brain and spinal cord deteriorate, lose function and eventually die. The number of Americans suffering from neurodegenerative diseases is staggering:

  • Alzheimer’s disease – 5 million

  • Parkinson’s – 1 million

  • Multiple sclerosis (MS) – 400,000

  • Amyotrophic lateral sclerosis (ALS) – 30,000

  • Huntingdon’s disease – 30,000

  • Chronic traumatic encephalitis (CTE) - it is estimated that between 1.6 and 3.8 million sports-related mTBIs occur annually, and sport-related head injuries make up 20% of TBI cases in the United States each year (Safinia C, Bershad EM, Clark HB, SantaCruz K, Alakbarova N, Suarez JI, Divani AA. Chronic Traumatic Encephalopathy in Athletes Involved with High-impact Sports. J Vasc Interv Neurol. 2016 Oct;9(2):34-48. PMID: 27829969; PMCID: PMC5094259.)

Because most of these diseases are diagnosed mid-to late-life, this number is expected to grow as the U.S. population ages. The care of individuals with these conditions can create serious economic burdens on their families. The U.S. Government estimates that annual cost to the U.S. from Alzheimer’s disease and related dementias, Parkinson’s disease, ALS and spinal muscular atrophy was over $655 billion dollars in 2020. This number includes direct medical and non-medical costs, as well as indirect costs from lost productivity and unpaid caregiving hours. The Alzheimer’s Association estimates that 15.3 billion hours of unpaid caregiving were provided by families, friends, and community members.


Model of brain with medical stethoscope

Keeping Your Brain Healthy

There are many ways to help your brain stay healthy and fit. Sleep, diet, exercise and staying socially connected are daily activities that have tremendous impact on our brain’s wellness levels. The Cleveland Clinic has a short assessment that helps you figure out where you can make the biggest difference to support your brain’s health. The assessment measures six different areas:

  1. Physical exercise

  2. Food and nutrition

  3. Medical health

  4. Sleep and relaxation

  5. Mental fitness

  6. Social interactions

Their goal is to get people taking positive steps towards improving brain health and lowering the risk of brain diseases. Take the Cleveland Clinic’s Brain Health Challenge https://healthybrains.org/pillars/

Diagram of human endocannabinoid system

The Endocannabinoid System and Our Nervous System

Researchers are exploring how our body’s endocannabinoid system (ECS) is linked to brain health. The endocannabinoid system is a network of cannabinoid receptors and ligands that connects to all of the body’s major organs and systems, including our central nervous, endocrine, and immune systems. It plays a critical role in our body’s ability to maintain homeostasis (balance), and acts as a “master regulator” for many important body functions. When these receptors are activated, they enable two-way communication between body systems; something previously thought to be impossible. When our endocannabinoid system is out of balance, we experience distress.


When it comes to interacting with our brain, the endocannabinoid system is widely expressed in the limbic system, prefrontal cortical areas, and brain structures regulating neuroendocrine stress responses, which explains the key role of this system in the control of emotions. The ECS maintains brain homeostasis throughout our life, from early development to death, affecting brain plasticity (the brain’s ability to change as a result of experience) and repair, learning, memory, and moods.


Plate of food for brain health

Taking Care of Your Endocannabinoid System

Practice of regular physical and/or mind-body mindfulness and meditative activities have been shown to modulate our body’s endocannabinoid levels. Research has proven that an enhanced ECS is involved in positively regulating pain, inflammation, metabolic and cardiovascular functions, as well as general immune responses (asthma, allergy, and arthritis) and even tumor expansion, including in the brain and/or in the rest of the body.


To build and maintain a healthy endocannabinoid system, healthcare professionals recommend an unprocessed, whole food-based diet that includes balanced omega-3 and -6 polyunsaturated fatty acids, 7-8 hours of sleep, regular physical exercise, mindfulness and meditation exercises, as well as positive social interaction and connections. All of these are important in maintaining healthy endocannabinoid levels. Cognitive challenges (puzzles, games, crossword or sudoku, learning languages, participating in hobbies, group sports, etc.) and positive emotional interactions might strengthen the ECS, which is built around a network of neuro-synapses that modify human behavior.


Deficiencies of the endocannabinoid system are associated with brain disorders and neurotransmitter deficiencies, such as the critical transmission of acetylcholine in Alzheimer’s disease, dopamine in parkinsonian syndromes, and serotonin and norepinephrine in depression.


Phytocannabinoids that have been well-studied include compounds derived from the cannabis plant: cannabidiol (CBD), cannabinol (CBN), tetrahydrocannabinol (THC), tetrahydrocannabivarin (THCV), cannabinol (CBN), cannabidiol (CBD), cannabidivarin (CBDV), cannabigerol (CBG), and cannabichromene (CBC). Other less well-known but effective phytocannabinoids include members of the terpene family, such as curcumin, limonene, pinene, and beta-caryophyllene (BCP).


Many of these chemical compounds have been proven to have many medicinal properties like anticancer, antimicrobial, antifungal, antiviral, antihyperglycemic, analgesic, anti-inflammatory, and antiparasitic (Franklin et al. 2001). Terpenes are also used to enhance skin penetration and prevent inflammatory diseases (Franklin et al. 2001).


In particular, BCP is an established phytocannabinoid plentifully found in many edible plant spices, such as black pepper, rosemary, and cinnamon. Food and Drug Administration (FDA) and European Food Safety Authority (EFSA) approved this safe, non-toxic natural compound as a flavor enhancer and in cosmetics. BCP has numerous pharmacological actions, including neuroprotective, antioxidant, anti-inflammatory, cholesterol-lowering effect, cytotoxic activity against various cancer cell lines, and antimicrobial activities. Furthermore, preclinical studies show that BCP attenuates cardiotoxicity, gouty arthritis and inflammation, Parkinson’s disease, kidney dysfunction, and cerebral ischemia/reperfusion injury. doi: 10.26355/eurrev_202211_30391 Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120914/


Protecting Brain Health with Beta-caryophyllene

Dementia & Alzheimer’s Disease

Despite extensive research on Alzheimer’s disease (AD), its diagnosis and treatment

remain challenging, and no effective therapies are currently available. Alzheimer’s is a neurodegenerative disease whose major risk factor is age (Nguyen and Endres, 2021). After decades of research, scientists have concluded that beta-amyloid plaques, which are abnormal levels of a naturally occurring protein that have clumped together, collect between neurons and disrupt cell function. In addition, tau proteins, responsible for neuron's internal support, disorganize themselves into intracellular neurofibrillary tangles. Thus, these plaques and tangles are associated with disrupting normal brain synapse function and causing neuron cell death.


Recent studies suggest that terpenes such as beta-caryophyllene (BCP) have anti-inflammatory and antioxidant effects that promote brain health and provide neuroprotection in different cognitive damage animal models. In addition, they found that BCP exerts a positive effect on reducing the beta-amyloid load, which is significant in the treatment of Alzheimer’s.

Source: Protective Effects of (E)-β-Caryophyllene (BCP) in Chronic Inflammation

Department of Life Sciences and Systems Biology, University of Turin, Italy

Published: 26 October 2020 https://pubmed.ncbi.nlm.nih.gov/33114564/


Neuro‐inflammation + Migraine

Neuroinflammation is a central feature of several degenerative diseases such as autoimmune disorders and multiple sclerosis. The endocannabinoid system seems to play an important role in regulating inflammation and the body’s pain response.


Chronic pain is a serious social burden. It has been estimated that around 10% of the population worldwide suffers from long-lasting pain, including migraines.

Source: Wong J.J., Côté P., Tricco A.C., Rosella L.C. Examining the effects of low back pain and mental health symptoms on healthcare utilisation and costs: A protocol for a population-based cohort study. BMJ Open. 2019;9:e031749. doi: 10.1136/bmjopen-2019-031749. - DOI - PMC - PubMed


The neuroprotective role of substances acting at cannabinoid receptors against pain and neurodegenerative diseases has been extensively demonstrated [165]. This evidence is important, as beta-caryophyllene activates CB2 receptors throughout the body and in the brain. Indeed, several studies demonstrated the efficacy of beta-caryophyllene to treat neuropathies and pain.

  • Due to its lipophilicity (ability of a chemical compound to dissolve in fats, oils, or lipids), BCP easily penetrates cell membranes and the blood-brain-barrier, while still presenting good oral bioavailability (Bioavailability refers to the extent a substance or drug becomes completely available to its intended biological destination(s))

  • Significant dose-dependent antinociceptive (inhibits or blocks the sensation of pain) responses were produced by BCP without the presence of gastric damage, unlike typical pain drugs.

Source: The Food Additive β-Caryophyllene Exerts Its Neuroprotective Effects Through the JAK2-STAT3-BACE1 Pathway Ocean University of China, China Feb. 2022 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8919047/


Epilepsy

Epilepsy is a neurological disease, and recurrent epileptic seizures and behavioral comorbidities such as depression, anxiety, psychosis, and cognitive deficits largely affect the quality of life of the patients with epilepsy and their families [177]. Beta-caryophyllene (BCP) has been found to be effective in reducing anticonvulsant activity against seizures induced by pentylenetetrazole in mice. Since no adverse effects were observed when BCP was administered at the concentration of 100 mg/kg b.w., and because of the lack of genotoxicity [178], this compound is considered a potential new anticonvulsant therapy [179]. Moreover, BCP is clinically useful as an adjunct treatment against seizure spread and status epilepticus as well as prevention of broader implications caused by oxidative stress, neurotoxicity and cognitive impairments [180].


Mental Health

The search for medicines to relieve pain and cure various neurological diseases is an ancient (up to 60,000 years ago) process and is still ongoing. Use of medicinal plants and/or plant‐derived natural products to alleviate behavioral concerns such as anxiety, depression and psychoses continues to gain interest from scientists owing to their safety profile, higher efficacy, and age‐old use in various traditional practices.


Chronic and uncontrolled stress are common causes of anxiety and depression, which alter the nervous, endocrine, and immune system, even causing neuroinflammation. These changes evoke the cognitive symptoms and physiologic changes of depression such as feeling melancholy, lack of motivation, and helplessness.


The endocannabinoid system controls cognitive and emotional responses related with stress through the interaction with its receptors. Beta-Caryophyllene (BCP) is a CB2-R activator that provides anti-inflammatory, anti-anxiety, antidepressant and anti-addiction effects with no psychotic effects, since there is no THC content, unlike cannabis-derived compounds like CBD [Oliveira, Asth]. Experimental results show that BCP reduces pro-inflammatory mediators thus preventing chronic pathologies characterized by inflammation and oxidative stress, in particular metabolic and neurological diseases [Scandiffio].


Conclusion

BCP offers a comprehensive approach To pain, epilepsy, migraine, neuroinflammation and degenerative diseases working through the body’s master regulatory endocannabinoid system. BCP is an FDA approved dietary supplement without toxicity or adverse effects. The science is well established in hundreds of pre-clinical studies that elaborate on the benefits and lack of side effects from this natural food derivative.


More resources from Blair Medical Group:

To learn more about the endocannabinoid system and beta-caryophyllene, visit our resource section. Read about how our endocannabinoid system works as a master regulator, and how it interacts with other systems. https://www.blairmedicalgroup.com/endocannabinoid-system


Neurodegenerative Diseases & Beta-Caryophyllene - 20+ page technical research summary
Neurodegenerative Diseases & Beta-Caryophyllene technical research summary

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Unlocking the power of beta-caryophyllene for brain health 4-page brochure


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Additional research resources:

  • A systematic review on the neuroprotective perspectives of beta‐caryophyllene Phytotherapy Research. 2018;1–13. https://pubmed.ncbi.nlm.nih.gov/30281175/

  • da Silva Oliveira GL, da Silva JCCL, Dos Santos C L da Silva AP, Feitosa CM, de Castro Almeida FR. Anticonvulsant, Anxiolytic and Antidepressant Properties of the β-caryophyllene in Swiss Mice: Involvement of Benzodiazepine-GABAAergic, Serotonergic and Nitrergic Systems. Curr Mol Pharmacol. 2021;14(1):36-51. doi: 10.2174/1874467213666200510004622. PMID: 32386503.

  • Asth L, Cruz LC, Soyombo N, Rigo P, Moreira FA. Effects of β-caryophyllene, A Dietary Cannabinoid, in Animal Models of Drug Addiction. Curr Neuropharmacol. 2022 Sep 27. doi: 10.2174/1570159X20666220927115811. Epub ahead of print. PMID: 36173065.

  • Scandiffio R, Geddo F, Cottone E, Querio G, Antoniotti S, Gallo MP, Maffei ME, Bovolin P. Protective Effects of (E)-β-Caryophyllene (BCP) in Chronic Inflammation. Nutrients. 2020 Oct 26;12(11):3273. doi: 10.3390/nu12113273. PMID: 33114564; PMCID: PMC7692661.

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