By Jokūbas Žiburkus, PHD and Ahmad Abdulla

Why do some strains of cannabis contain the same amount of THC and CBD, but have different medicinal effects? In the last issue, we learned that molecular diversity of cannabis and its beneficial properties are well beyond just THC and CBD. To start with, in its natural raw form, cannabis contains the fullest spectrum of medicinal components, including non-psychoactive acidic cannabinoids, terpenes, flavonoids, and omega amino acids. Likewise, the raw juice of any plant contains the widest spectrum of therapeutic molecules preserved in their natural form. Cannabis juice or juice concentrates prepared at low temperatures and high pressures (such as supercritical CO2 extraction or cold alcohol and cold separation) will contain a broad spectrum of acidic cannabinoids, terpenes, chlorophyll and other components. Collectively, diversity of chemical compounds gives rise to the cannabis entourage effect – the sum total of synergistic medicinal and euphoric effects associated with distinct cannabis strains or cultivars.

“Cannabis entourage” is not a new concept. In fact, due to the continuous and widespread practice of holistic medicine, whole herb(s) preparations remain the preferred method for various healing practices. What is relatively new in our understanding of cannabis is that with the advent of modern chromatography (separation of mixtures) in the 1960’s, scientists have been able to isolate different molecules from cannabis. Chromatography together with mass spectroscopy (measures masses), allows for the careful dissection of hundreds of chemical constituents of the cannabis plant. The newer technique of high performance liquid chromatography (HPLC) can be performed at low temperatures. This is important when isolating compounds that have low boiling temperatures, like acidic cannabinoids and terpenes. The expanded knowledge of the most dominant components in the thousands of available cannabis strains will reveal how distinct cannabis entourage components ‘jive’ with the individual psyche and physiology.

Our daily entourage and its relationship with the cannabis entourage will likely become a significant premise in individualized cannabis medicines. We typically forget that we have our distinct terpene entourages, and are highly selective about the smells we prefer in our environments, on our hair, and our bodies. In fact, body odors and the accompanying smells are strong sexual attractants. Yes, some of us are ‘lavenders’, others are ‘pines’ or ‘citruses’, and some others are “hot and spicy.” These daily terpene entourage preferences could be linked to maintaining overall physical and emotional well-being; and should be considered when selecting cannabis flowers.

The co-evolution of plants, like cannabis, hops or lavender with the human body and mind, allow our brains to select pleasant, agreeable smells and to differentiate repulsive smells as potentially harmful to our bodies1,2. The human endocannabinoid system and the cannabis plants have undoubtedly co-evolved. As such, the endocannabinoid system is one of the major homeostatic and regulatory body systems, with many functions yet to be unveiled.

As discussed in the previous issue, science has accepted the fact that different essential oils and their aromas have therapeutic effects3. When you smell, your brain forms a precise neuronal activity map, which are cellular representations of thoughts, emotions and behavior. These olfactory perceptions and memories, in the case of cannabis are then associated with certain physiological and psychological effects. Although cannabis often enhances

desired effects, such as improved mood and sleep, or an increased appetite, it can also augment undesired, negative moods or anxiety. Cannabis users should document these experiences and use them as valuable indicators for selecting a specific cannabis strain/entourage. Applying critical thinking skills when selecting a specific cannabis flower, may very well promote one’s overall state of health and well-being.

The more knowledge a person has about their own daily entourage the better they can understand their cannabis needs and feel empowered to select a more agreeable cannabis entourage. So if your body and mind seek spicy or peppery flavors in cannabis and in your diet, then there is something in that nutritional and medicinal entourage that benefits your body and mind. It is important to keep in mind that the final cannabis entourage output will depend on the grow conditions, the soil, nutrients, harvest time, curing process, trimming, extraction, formulation, and many other variables. The final entourage depends on the grower and the process, as much as it does on the strain.


One of the dominant terpenes found in certain strains of cannabis is beta caryophyllene. We found that some terpene profiles posted by Analytical 360 laboratory for some strains exceeded 1% of caryophyllene. For example, HPLC analysis of ‘Candyland 1’ and ‘Industrial Plant CBD’ flower showed that they contain a whopping 1.6% of caryophyllene. Other recently tested strains with high caryophyllene content were: ‘Cookies’ (1.3%), ‘Medi Haze’ (1.1%), ‘Super Silver Haze’ (1.25% caryophyllene oxide), and ‘Cookies and Cream’ wax (1.7%). There are undoubtedly many more strains and cultivars where beta-caryophyllene is the main or one of the dominant terpenes. It is also not uncommon that waxes and concentrates prepared using cold temperatures, contain higher percentages of cannabinoids and terpenes. Beta caryophyllene is also found in several other plants, such as hops, cloves, and peppers (discussed in a recent article by Dr. Russo4). Hops and cannabis are the closest relatives, both members of the canabaceae family and the higher Rose order. Peppers, on the other hand, are not closely related to the canabaceae family. They are members of the Piperales order and the piperaceae family. Like cannabis, peppers are also flowering plants (angiosperms), but the main similarity between these two different plants lies in the expression of our featured sesquiterpene beta caryophyllene (BCP). BCP is arguably the most abundant, best studied terpene, with potentially the highest therapeutic potential.

Peppers, compared to cannabis, can contain much higher amounts of beta caryophyllene. While the common pepper (piper nigrum) contains a modest 7% BCP, the West African Ashanti pepper pod contains up to 60% of BCP5. BCP gives peppers the spicy and bitter taste. Some, raw hemp or high THC cannabis extracts that contain high levels of BCP will have a bitter and spicy taste and smell. Beta caryophyllene is the FDA approved food additive, also regarded as GRAS (generally regarded as safe). That means that BCP can be added to any food or beverage. Because BCP has many reported medicinal properties, one should take a note of BCP in their diets or in their cannabis products.


It turns out that beta caryophyllene is not only found in cannabis and peppers, but that it actually interacts with our body’s endogenous cannabinoid system. The ECS in our bodies consists of endogenously synthesized endocannabinoid molecules (anandamide and 2-AG), their synthesizing and degrading enzymes, and cannabinoid receptors 1 and 2 (CB1 and CB2). CB1 receptors found in high densities in the brain are intoxicating and promote hunger. CB2 receptors have lower expression levels in the brain than CB1. CB2 receptors instead are found in the peripheral body organs, like the spleen, pancreas, and the immune system cells. BCP is one of the most selective natural agents of the CB2 receptors6.

BCP is a cannabimimetic compound. It activates CB2 receptors and is involved in the regulation of the inflammatory processes and the immune system function. BCP has been shown to have analgesic and anti-inflammatory properties in mouse models of pain. CB2 activation by BCP, exerts anti-anxiety properties, and appears to have protective effects in the digestive system as well. A recent review in Cancer Medicine, highlights BCP’s anti-cancer properties and the ability to enhance some chemotherapy treatments7. Several authors suggest that because multiple activities of BCP are analgesic and anti- inflammatory, and contain anti-cancerous properties, this molecule may become ‘particularly valuable in oncology’.

Another important chemical in pepper that most of us are familiar with is capsaicin. Interestingly, capsaicin also has analgesic properties, because it alleviates pain by binding to another protein receptor called TRPV (transient receptor potential vanilloid) receptors8. Thus, peppers have BCP and capsaicin, packing a spicy, hot, anti-inflammatory punch. The same goes for cannabis, whereby major cannabinoids like THC and CBD target TRPV channels as well and contain anti-inflammatory properties (in part mediated by BCP). In sum, the flowering cousins like peppers and cannabis seem to share some of the same biological targets and may exert synergies with other components of the cannabis plant.

The cannabis and healthcare communities’ knowledge regarding terpenes and the entourage effect are increasingly gaining traction and influencing scientific and clinical applications. In order to collectively advance the safe and effective use of cannabis, much more cross-talk is needed between the growers, product developers, dispensary owners, consumers, and healthcare professionals. Indeed, healthcare professionals recommending medical cannabis must be aware that THC and CBD are not the only important components of the cannabis plant. Thus, understanding the distinct components of cannabis and its beneficial synergies and/ or potential harm, is the key to unlocking the most effective individualized cannabis therapies.

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