Caryophyllene (or β-Caryophyllene) is a common and often abundant terpene found in cannabis strains. Its distinctive flavor contributes to the spiciness of black pepper and can be found in high amounts in cloves, hops, and rosemary.

It has the distinction of being the first known “dietary cannabinoid” with GRAS (Generally Recognized as Safe) status and having approval by the FDA for food use.  

Caryophyllene-rich cannabis strains may have specific medicinal effects due to this terpene’s effect on our body’s endocannabinoid system (ECS).  The ECS helps the body regulate many functions, and contains receptors throughout the body to help it do this.  The two receptors we know about are CB1 which is in the central nervous system (brain and nerves of the spinal cord), and CB2 which is in the peripheral nervous system (nerves in your extremities), the digestive system, and specialized cells in the immune system.  Cannabinoids like CBD and THC found in cannabis plants are known to activate these cannabinoid receptors.  Over the last decade, caryophyllene has gained the attention of scientists when it was discovered to be one of the first non-cannabinoids to directly activate cannabinoid receptors. 

β-Caryophyllene was one of the first cannabis-derived compounds other than THC, CBD, and CBN shown to bind directly to endocannabinoid receptors. In fact, it was one of the first cannabis-derived compounds with a fundamentally different structure from the classical cannabinoids that interacts with the ECS. β-Caryophyllene is known to selectively bind to the ECS’s CB2 receptor; therefore, it is sometimes also classed as an atypical cannabinoid. The CB1 receptor is responsible for the psychoactive effects associated with certain cannabinoids such as THC. However, CB2, particularly in peripheral tissues in the body, is a therapeutic target for treatment of inflammation, pain, atherosclerosis, and osteoporosis

CB2 receptors are found in immune tissues throughout the body and are increased in the brain in disease or following injury. Their activation reduces inflammation, which lessens pain and reduces the damaging consequences that chronic inflammation has on brain function and risk for developing brain diseases.

The data suggest that, in many cases, caryophyllene can provide pain relief. In one study, scientists injected mice with caryophyllene and found that they experienced less pain than those treated with the control solution. Furthermore, caryophyllene enhanced the pain-reducing strength of low-dose morphine. This could be one reason why those using prescription opioids from pain are often able to decrease their dose of opioids when they begin using medical cannabis.

There are numerous inflammatory diseases that affect the digestive tract. Colitis is one such disease where inflammation of the intestines causes pain, diarrhea, abdominal cramping, and even increases risk for cancer. In mice that were experimentally given colitis, treatment with caryophyllene helped by decreasing inflammation in the colon.

The activation of CB2 receptors by caryophyllene certainly plays a role in its anti-pain effects, but it also contributes to its ability to protect the body and brain from disease. For instance, brain inflammation plays a substantial role in the onset and progression of Alzheimer’s disease. In a mouse model of Alzheimer’s disease, caryophyllene activated CB2 and PPAR-γ receptors and reduced hallmark features of Alzheimer’s such as the accumulation of brain plaques. These actions also protect against the cognitive decline that characterizes this model of disease.

Additionally, β-Caryophyllene has now been shown to be beneficial for osteoarthritis, diabetes, anxiety and depression, and liver fibrosis. In cancer studies, β-caryophyllene demonstrated synergy with the chemotherapy drug Paclitaxel on human tumor cell lines, and alone it stimulates apoptosis and suppresses tumor growth. In a Caenorhabditis elegans model, β-caryophyllene modulated stress-related genes and extended the lifespan of the organism. Importantly, it has been shown to be orally bioavailable; therefore, it would provide an important medicinal benefit to oral cannabis preparations.