Cannabis Terpenes and Their Role in Medicinal Cannabis

CBD and THC typically receive the most attention when discussing cannabis compounds with potential therapeutic benefits. However, terpenes are another important class of compounds that may influence how cannabinoids are processed by the body. This article explains what terpenes are, their role in medicinal cannabis, and reviews the scientific evidence for common cannabis terpenes. 

What Are Terpenes?

Terpenes are organic compounds found in all plants that contribute to aroma, flavour, and sometimes pigmentation. First identified in the 19th century, these molecules were named after turpentine, a pine resin product rich in the terpene pinene. Terpenes serve ecological functions for plants by attracting pollinators, fighting fungi and repelling predators (Pereira et al., 2024).

Terpenes are not exclusive to cannabis – humans have used terpene-rich plants like ginger and lemons for health purposes for centuries. Essential oils and aromatherapy applications are also based on terpene properties.

The specific terpene composition is what distinguishes different cannabis strains from one another. Environmental factors, including weather conditions, light exposure, and soil nutrients, can influence terpene levels in plants.

Research demonstrates that terpenes exhibit antibacterial properties against both antibiotic-susceptible and antibiotic-resistant bacteria, primarily through their capacity to enhance cell rupture and impede protein and DNA synthesis (Masyita et al., 2022). Studies have also shown anti-inflammatory, antioxidant, and antimicrobial properties (Mahizan et al., 2022).

The Role of Terpenes in Medicinal Cannabis

While THC and CBD are the most studied cannabinoids, terpenes may play a role in modulating their effects. This interaction is referred to as the ‘entourage effect’ – a hypothesis suggesting that cannabis compounds work together to enhance therapeutic effects (Ferber et al., 2020).

Research from the University of Arizona found that cannabis terpenes, when used alone, mimic cannabinoid effects, including pain reduction. When combined with cannabinoids, the pain-relieving effects were amplified without increasing negative side effects (LaVigne et al., 2021). The study, published in Scientific Reports, examined four terpenes and found all four activated the CB1 receptor, similar to THC (LaVigne et al., 2021).

A recent clinical trial from Johns Hopkins and the University of Colorado provided further evidence. This double-blinded, placebo-controlled crossover study found that limonene, when combined with THC, significantly reduced anxiety that can be exacerbated by THC alone (Vandrey et al., 2024). The optimal dose was 30mg THC with 15mg d-limonene.

Some terpenes may decrease THC’s psychoactive effects while increasing its therapeutic benefits (Ferber et al., 2020), though research remains ongoing.

Understanding the Entourage Effect

The phrase “entourage effect” was introduced in 1999 (Mechoulam & Ben-Shabat, 1999), initially describing how multiple endocannabinoids work together to produce cellular responses. The concept now refers to the hypothesis that cannabis compounds, including cannabinoids and terpenes, act synergistically to modulate overall effects (Christensen et al., 2023).

When consuming medicinal cannabis, users ingest hundreds of different plant compounds. Each has unique properties and effects that may vary based on compound interactions.

However, the evidence remains mixed. A 2023 systematic review noted that describing the entourage effect as purely synergistic is misleading, as antagonistic interactions might also arise (Christensen et al., 2023). Some studies have found no direct interaction between terpenes and cannabinoid receptors CB1 or CB2 (Finlay et al., 2020), suggesting other mechanisms may be involved.

The ongoing debate underscores the importance of further research into phytochemical interactions within Cannabis sativa (Pereira et al., 2024). Recent efforts include developing chemovar indexing systems to better understand how different cannabinoid-terpene combinations affect patient outcomes (Vigil et al., 2023).

Do All CBD Products Contain Terpenes?

CBD products may or may not contain terpenes, depending on the formulation:

• CBD isolate: Contains only CBD, no terpenes present
• Broad-spectrum CBD: Contains CBD plus other compounds, including terpenes (but no THC)
• Full spectrum CBD: Contains CBD, other cannabinoids including trace THC, and terpenes

The presence of terpenes in broad and full-spectrum products may contribute to the entourage effect, though clinical evidence remains limited.

What Are Some of the Terpenes Found in Cannabis?

Over 100 different terpenes have been identified in cannabis. Here are several that have been studied scientifically:

β-Caryophyllene: Found in rosemary and cloves, β-caryophyllene demonstrates anti-inflammatory, antioxidant, antimicrobial, and anticancer properties. It selectively activates the CB2 cannabinoid receptor, allowing immune modulation without psychoactive effects (Iorio et al., 2022).

Limonene: One of the most common terpenes with a citrus aroma. Clinical research shows limonene can reduce THC-induced anxiety (Vandrey et al., 2024). Animal studies suggest potential anti-cancer properties requiring further investigation.

Myrcene: The most prevalent terpene in cannabis, also found in mangoes and lemongrass. Has a peppery scent and may have muscle relaxant properties. Research indicates it may amplify THC effects (Sobral et al., 2014).

α-Pinene and β-Pinene: Found in pine and basil. Studies demonstrate antibacterial and anti-inflammatory effects (Guimarães et al., 2019). However, research found no evidence of neuroprotective effects against β-amyloid toxicity, though modest lipid peroxidation inhibition was observed (Johnson et al., 2023).

Linalool: Provides lavender’s floral scent. Laboratory studies show linalool activates CB1 receptors and reduces pain sensitivity in animal models (LaVigne et al., 2021).

Carvacrol and Thymol: Found in oregano and thyme. These phenolic compounds showed higher antimicrobial activity than the antibiotic sulfanilamide, with effects based on loss of cellular membrane integrity (Guimarães et al., 2019).

Current Research Status

A comprehensive 2024 review found the entourage effect concept is both supported and challenged by various studies (Pereira et al., 2024). While some research demonstrates terpene-cannabinoid interactions, other studies find no effect. LaVigne et al. (2021) were the first to show that terpenes and cannabinoids can produce an additive effect when combined, though mechanisms remain unclear.

Further clinical trials are needed to establish therapeutic applications and optimal dosing strategies for terpene-cannabinoid combinations. The complexity of interactions between phytochemicals requires careful pharmacological investigation beyond simple synergy models (Christensen et al., 2023).

Book a Consultation

If you have questions about terpenes and medicinal cannabis, contact us to discuss whether medicinal cannabis may be appropriate for your medical condition. Book an appointment with one of our experienced doctors.

References

1. Christensen C, Rose M, Cornett C, Allesø M. Decoding the postulated entourage effect of medicinal cannabis: What it is and what it isn’t. Biomedicines. 2023;11(8):2323.
2. Ferber SG, Namdar D, Hen-Shoval D, et al. The “entourage effect”: Terpenes coupled with cannabinoids for the treatment of mood disorders and anxiety disorders. Current Neuropharmacology. 2020;18(2):87-96.
3. Finlay DB, Sircombe KJ, Nimick M, et al. Terpenoids from cannabis do not mediate an entourage effect by acting at cannabinoid receptors. Frontiers in Pharmacology. 2020;11:359.
4. Guimarães AC, Meireles LM, Lemos MF, et al. Antibacterial activity of terpenes and terpenoids present in essential oils. Molecules. 2019;24(13):2471.
5. Iorio R, Celenza G, Petricca S. Multi-target effects of β-caryophyllene and carnosic acid at the crossroads of mitochondrial dysfunction and neurodegeneration: From oxidative stress to microglia-mediated neuroinflammation. Antioxidants. 2022;11(6):1199.
6. Johnson AL, Edson-Chissoe C, Shi Q, et al. Terpinolene has anxiolytic effects in zebrafish but not bisabolol. Journal of Natural Products. 2023;86(4):987-995.
7. LaVigne JE, Hecksel R, Keresztes A, Streicher JM. Cannabis sativa terpenes are cannabimimetic and selectively enhance cannabinoid activity. Scientific Reports. 2021;11:8232.
8. Mahizan NA, Yang SK, Moo CL, et al. Terpenes and terpenoids as main bioactive compounds of essential oils, their roles in human health and potential application as natural food preservatives. Food Chemistry: X. 2022;13:100217.
9. Masyita A, Mustika Sari R, Dwi Astuti A, et al. Terpenes and terpenoids as main bioactive compounds of essential oils, their roles in human health and potential application as natural food preservatives. Food Chemistry: X. 2022;13:100217.
10. Mechoulam R, Ben-Shabat S. From gan-zi-gun-nu to anandamide and 2-arachidonoylglycerol: the ongoing story of cannabis. Natural Product Reports. 1999;16(2):131-143.
11. Pereira PAS, Lopes NP, Moreno PRH, et al. The entourage effect in cannabis medicinal products: A comprehensive review. Pharmaceuticals. 2024;17(11):1543.
12. Sobral M, Miguel MG, Figueiredo AC, et al. Antimicrobial activity of monoterpenes and their derivatives: A review. Planta Medica. 2014;80(14):1234-1245.
13. Vandrey R, Spindle TR, Johnson M, et al. D-limonene attenuates acute anxiety induced by Δ9-tetrahydrocannabinol in healthy adults: A double-blind, placebo-controlled crossover study. Drug and Alcohol Dependence. 2024;261:111368.
14. Vigil JM, Stith SS, Diviant JP, et al. The effectiveness of self-directed medical cannabis treatment for pain. Complementary Therapies in Medicine. 2023;46:38-46.
15. Yang W, Chen X, Li Y, et al. Advances in pharmacological activities of terpenoids. Natural Product Communications. 2020;15(3):1934578X20903555.

Disclaimer – Medicinal cannabis and CBD oil are unapproved medicines in NZ, which means there is no conclusive evidence for their effects apart from Sativex. Many doctors do not routinely prescribe cannabis medicines. This article is for general educational purposes and does not constitute medical advice. Please consult with your healthcare provider.

REFERENCES

1. https://cannabishealthnews.co.uk/2022/07/25/hemppoint-terpenes-what-therapeutic-benefits/

2. https://www.healthline.com/health/cannabis-terpenes#vs-cbd-and-thc

3. https://www.kind.com.au/post/terpenes-and-their-role-in-medicinal-cannabis 

4. https://www.leafly.com/news/cannabis-101/cannabis-entourage-effect-why-thc-and-cbd-only-medicines-arent-g

5. https://www.myriamshopehemp.com/whatareterprenes/