Understanding Caryophyllene: The Crossover Terpene

Cannabis dried flower and medical marijuana pills with green leaves over wood background
Caryophyllene is one of the most abundant terpenes in medical marijuana. It has a unique ability to bind directly with the body's natural endocannabinoid system to enhance immunity functions and reduce cellular damage caused by inflammation and oxidative stress. It is found in both sativa and indica cultivars and has pain-relieving, relaxing, and anti-anxiety effects.
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Caryophyllene-rich cannabis strains are known for warm, woody, and spicy scent profiles and their ability to promote relaxed but non-sedating clarity. But there is a lot more to the “pepper terpene.” Of the more than 150 known terpenes found in marijuana, caryophyllene stands alone for its unique ability to directly influence the human body’s immune and nervous systems.

What Is Caryophyllene And How Is It Different?

Caryophyllene is a dietary terpene that is abundant in pepper, certain citrus fruits, and spices such as cloves, cinnamon, thyme, and oregano. It is safe for human consumption, with no known undesirable side effects. Caryophyllene is also one of the most common terpenes found in marijuana, second only to myrcene in abundance. It takes several forms in cannabis: alpha-caryophyllene, beta-caryophyllene and caryophyllene-oxide.

In recent years, alpha-caryophyllene is more often referred to as humulene. It’s found in hops, sage, and ginseng and has a scent profile that trends toward musty and earthy. The second form, caryophyllene-oxide, is common in citrus fruits and has a scent profile described as fresh and woody.

Both compounds are known to provide a range of therapeutic benefits similar to other terpenes found in medical marijuana. Think of them as supporting characters to the star of the show, which is beta-caryophyllene (also written as β-caryophyllene or BCP), a terpene that is abundant in black pepper, cloves, basil, oregano, rosemary, and marijuana.

Caryophyllene is unique among the known terpenes in the cannabis plant. Unlike other cannabis terpene regulars such as myrcene, pinene, limonene, and linalool, which are classified as monoterpenes, caryophyllene is a sesquiterpene with a significantly more complex and larger molecular profile. Its profile also includes a cyclobutane ring, which is a rare molecular element not found in any other known cannabis terpene.

Beyond these chemical distinctions, the science gets complex and ultimately isn’t important at the consumer level. The takeaway for medical marijuana patients is that caryophyllene is different and that this difference gives caryophyllene transformer-like superpowers to provide healing effects usually reserved for cannabinoids.

Understanding The Human Endocannabinoid System

The widespread cultural adoption of marijuana that began in the 1960s triggered a subsequent wave of cannabis research. A majority of those first-generation studies focused on the effects of two major cannabinoids: THC (which possesses psychoactive properties) and, to a lesser extent, non-psychoactive CBD.

This early research led to the discovery of the human endocannabinoid system), which is spread throughout the body. This discovery was followed several years later by the revelation that natural compounds found in cannabis could connect with the ECS system. Noted cannabis researcher Peter Grinspoonexplains:

To stimulate these receptors, our bodies produce molecules called endocannabinoids, which have a structural similarity to molecules in the cannabis plant. The cannabis plant essentially works its effect by hijacking this ancient cellular machinery.

The cannabinoids found in marijuana connect with two distinct types of cannabinoid receptorsin the human body:

  • CB1 receptors are concentrated in the brain and central nervous system, regulating appetite, sleep, pain, cognitive function, metabolism, stress, and immune function.
  • CB2 receptors are found throughout the body’s immune system, are abundant in white blood cells, and concentrate in lymphoid organs such as the spleen (which provides important immunity protection).

 

THC and minor cannabinoids such as THCV and CBN bind with CB1 receptors, and are responsible for marijuana’s well-known psychoactive effects. By contrast, non-psychoactive cannabinoids such as CBD, CBG and CRC bind primarily to CB2 receptors to influence and activate immune functions.

The Entourage Effect

As the study of medical marijuana progressed, more attention focused on the expanded role terpenes might play in therapeutic effects. Known as the entourage effect, this concept is based on indications that the hundreds of terpenes, minor cannabinoids, and flavonoids contained in cannabis work together to enhance medical marijuana’s therapeutic benefits. While still a theory, ongoing researchfrom Israel provides new insights into these potentially synergistic effects.

As one of the most common and highly bioactive terpenes in cannabis, caryophyllene, may play a major role in the cannabis entourage effect. But there’s another reason why it is now the most studied of all cannabis terpenes.

What Are The Benefits Of Caryophyllene?

Caryophyllene’s Immune-Boosting Cb2 Connection

In 2008, a European research group confirmed that beta-caryophyllene could connect directly to CB2 receptors (leading to suggestions that it should be reclassified as an “atypical cannabinoid”). This bonding capability creates unique health-promoting and immunity-boosting activity and triggers many of the same beneficial effects attributed to cannabinoids like CBD and CBG. One of the most important of these is the ability to act as an anti-inflammatory agent.

Provides Natural Relief From Chronic Inflammation, Pain And Oxidative Stress

Inflammation is the body’s natural response to injury or infection. Injured tissues swell as they are filled with an influx of white blood cells and lipid molecules that promote healing and fight infection. Injury also activates pain receptors that remind the body to take it easy and pay special attention to the injured area

But when this healing activity becomes overstimulated or prolonged by unresolved conditions, the result is persistent pain and chronic inflammation. If left untreated, chronic inflammation causes tissue damage and cell death, damages DNA and raises the risk of heart disease, cancer, Type-2 diabetes, and other debilitating conditions.

Pharmacy shelves are filled with a wide assortment of anti-inflammatory drugs including over-the-counter products such as aspirin, ibuprofen, and naproxen, plus a wide range of prescription-controlled nonsteroidal anti-inflammatory drugs (NSAID). While beneficial for short-term pain and inflammation relief, the long-term use of these drugs may cause stomach problems, elevate blood pressure, and create other health risks.

Endocannabinoids and caryophyllene may offer a natural alternative to NSAID drugs for managing long-term pain and chronic inflammation. Laboratory research shows that while beta-caryophyllene may not provide immediate pain relief, it is quite effective for controlling chronic inflammation and addressing long-lasting, debilitating pain. In addition, it appears to be safe for long-term consumption, and the body does not build up tolerance against its pain-relieving and anti-inflammatory effects.

Chronic inflammation can trigger the cellular overproduction of free radicals, resulting in oxidative stress. If left unchecked, this process can lead to DNA damage and increase the risk of a laundry list of diseases that includes diabetes, cancer, atherosclerosis, hypertension, Alzheimer’s disease, and more. Research published in the journal Cell Biochemistry shows that caryophyllene provides protection from oxidative stress and can help control the over-production of free radicals. Caryophyllene also shows promise in protecting against oxidative stress associated with diabetes.

May Have Life-Extending Potential

There is evidence that beta-caryophyllene’s ability to reduce and manage oxidative stress may have life-prolong effects by controlling reactive oxygen species (ROS). These cell-signaling molecules are part of the body’s normal biologic processes. But when the body is under stress from injury, infection or toxic substances, ROS levels spike and begin to cause cellular damage.

A research group in India studied roundworms that mirror many human biological functions. When worms suffering from oxidative stress were given beta-caryophyllene essential oil their ROS levels decreased significantly and were then maintained at healthy levels. As a result of this treatment, the worm’s lifespans were increased by 22 percent. Similar results were reported by China’s Huainan University, where worms treated with a clove essential oil showed significantly increased lifespans.

Caryophyllene Reduces Alcohol And Tobacco Cravings

The relationship between cannabis use and alcohol consumption is nuanced and mixed. A study published in Psychology of Addictive Behaviours reports that college students who use marijuana drink less alcohol. A Colorado study found that heavy drinkers use marijuana as a substitute to cut down on their alcohol consumption and are less susceptible to bouts of binge drinking when using marijuana.

When the question is posed only to medical marijuana patients, the answer appears to be less about dual substance abuse. A 2020 Canadian survey found that the legalization of medical cannabis resulted in a decrease in alcohol consumption, with 44% of respondents reporting that they drank less each month.

The link between responsible cannabis use and reduced alcohol consumption has a biological component, and caryophyllene is involved in this phenomenon. Lab-based studies show that activating CB2 endocannabinoid receptors reduces the urge to drink alcohol.  A study conducted by the United Arab Emirates University confirms that the consumption of beta-caryophyllene can reduce alcohol cravings and intake. Not surprisingly, there are suggestions that caryophyllene-based medications could help treat alcohol addiction.

There’s also good news for cannabis users who still enjoy a few drinks. A study published in the British Journal of Pharmacology found that beta-caryophyllene protects against alcohol-related liver damage and alcoholic steatohepatitis (i.e., alcoholic fatty liver disease).

Giving up cigarettes is not easy, but a dose of caryophyllene might help. In a study sponsored by the National Institute on Drug Abuse, a drop of black pepper essential oil reduced the intensity of nicotine cravings in laboratory animal subjects, while also delaying their next impulse to seek out tobacco.

Additional Therapeutic Benefits Of Caryophyllene

Because beta-caryophyllene connects to CB2 cannabinoid receptors in the same way as cannabinoids, it delivers many of the same protective and healing effects. A brief summary of known benefits include:

  • Non-Sedating Relaxation: Caryophyllene doesn’t have sedating effects (except in very high doses) and, instead, creates a state of relaxation by reducing stress, anxiety, and pain.
  • Wound Healing: Damaged skin enjoys faster cellular repair when treated with a topical beta-caryophyllene formula.
  • Improved Memory: Beta-caryophyllene can reverse age-related memory impairment by reducing the damaging effects of neuroinflammation.
  • Cardiovascular Protection: Caryophyllene shows promise for combating atherosclerosis, promoting heart health, and protecting against diabetes-related heart disease. It may also reduce the risk of heart attacks.

Is Caryophyllene Found In Sativa Or Indica Strains?

As one of the most prevalent terpenes in cannabis, caryophyllene is found in the majority of sativa and indica strains, as well as in the many hybrid cultivars now on the market. It is rarely the dominant terpene, but can have a significant influence on the user experience based on its combination of calming, anxiety-reducing, and mental-clarifying effects.

How To Vape Caryophyllene

Because it is a sesquiterpene, beta-caryophyllene is less volatile than monoterpenes such as myrcene, pinene, and limonene, and it is less susceptible to loss when vaporized. Beta-caryophyllene has a boiling point in the 480°F / 250°C range but suggested vaping temperatures for optimum delivery of benefits are significantly lower in the range of 320°F / 165°C. Higher temperatures in the  495°F / 257°C range are recommended to access the anti-inflammatory and antioxidant benefits of caryophyllene-oxide.

Which Marijuana Strains Have More Caryophyllene?

Because caryophyllene is present in a wide range of cannabis strains, it can influence the overall effects of sativa-dominant, indica-dominant, and hybrid strains alike. This versatility allows medical marijuana patients to reap similar therapeutic benefits from caryophyllene-rich marijuana whether they select a strain for sedative relaxation or energizing mental clarity. A sampling of popular options includes:

  • Chemdawg: Balanced sativa and indica heritage strain with elevated THC content. Known for its cerebral but relaxing effects. Recommended for pain and anxiety relief.
  • Gelato: Caryophyllene-dominant sativa/indica hybrid with elevated THC levels. Relaxing while promoting creativity, focus and euphoric effects.
  • Skywalker OG: Indica-leaning hybrid with pronounced pain-relieving effects. Known for creating mellow yet euphoric effects, heightened awareness and enhanced creativity.
  • Bubba Kush: An extremely popular indica-dominant strain with balanced THC/CBD content. Physically sedative, mentally calming and sleep-promoting effects. Also used to manage chronic pain.
  • Candyland: Sativa dominant strain used to control pain and relieve muscle tension. Provides mood-enhancing experiences.
  • Gorilla Glue/ GG4: Sativa dominant hybrid strain with a high THC content. Provides stress and anxiety relief but may produce “couch lock” levels of sedation.

 

Do You Have Questions About Medical Marijuana?

If you are looking for information on cannabis therapies, CannaMD’s state-certified network of medical marijuana doctors is here to answer questions and provide advice. Contact the CannaMD team at (855) 420-9170 today. Ready to get your card and purchase legal cannabis products? You can find out if you qualify for medical marijuana treatment with our quick online application!

Updated: November 21, 2024

Article Written By:

Pierce Hoover

Pierce Hoover is a career journalist with more than three decades of experience in print, broadcast and online writing, editing and reporting, with more than 5,000 articles published in national and international print media and online. His focus on medical marijuana therapies mirrors his broader interest in science-based alternative medical practices.

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