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Increasing interest in phytotherapy has led to a focused exploration of plant-derived bioactive compounds, particularly terpenes, for their potential therapeutic properties. The analgesic effects of major terpenes have piqued the interest of the scientific and medical communities. There is an extensive amount of published research on terpenes that highlights the pharmacology, mechanistic pathways, and potential applications of these potent compounds.
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Terpenes are known for their wide-ranging biological activities. They offer promising avenues for pain management due to their analgesic properties. For this reason, we’ve narrowed down our focus to not only analgesic research, but also the major terpene classifications, and terpenes that have been studied the most.
You will find terpenes in all plants, but one plant in particular that has sparked a dramatic increase in terpene awareness and research is cannabis. The rise of legalization of cannabis in the United States and around the world has led to a boom in research over the past decade as more researchers have gained access to this once somewhat elusive research topic.
A scientific review of available published research regarding the analgesic potential of terpenes derived from cannabis was recently published in Pharmacological Reviews. After reviewing over 200 published studies there was enough evidence to conclude that, “Overall, cannabis terpenes have a high potential for pain management, alone or as adjunctive therapeutics, and are attractive compounds for the development of terpene-based analgesics given their generally-recognized-as-safe status with low side effect and toxicity profiles.”
The Classification of Terpenes
Terpenes are classified into subclasses according to their carbon unit count. The most common terpenes found in cannabis are monoterpenes and sesquiterpenes, composed of two and three isoprene units respectively.
Monoterpenes
Monoterpenes, with 10 carbon atoms (C10), are categorized into acyclic, monocyclic, and bicyclic types, often characterized by their strong aroma and presence in plant essential oils.
Limonene
Limonene, a cyclic monoterpene prevalent in Citrus species, exhibits significant anxiolytic and anti-inflammatory properties. Used as an analgesic against chemical irritant-induced pain, it effectively blocks pain behaviors at doses of 50 mg/kg or more. Although limonene doesn’t reduce thermal measures of pain effectively, it shows efficacy against inflammatory and neuropathic model-induced mechanical allodynia, suggesting potential therapeutic value in pain management.
Terpinene & Terpineol
Terpinene, found in Eucalyptus species and C. sativa, have anti-inflammatory effects. Essential oil from fingered citron, which contains γ-terpinene, may reduce inflammation. α-Terpineol, a constituent of tea tree oil, exhibits dose-dependent antinociception in certain pain models, and non-dose-dependent antinociception in others. It can reduce pain directly and indirectly by decreasing inflammation.
Pinenes
α-Pinene, a monoterpene present in many plants, hasn’t been widely studied for its analgesic properties. However, antinociceptive effects have been noted in essential oils containing this terpene. β-Pinene, on the other hand, has demonstrated analgesic and anti-inflammatory effects in various models, as have other β-pinene-containing oils.
Linalool
Linalool, a monoterpene found in essential oils of various aromatic plants, exhibits significant antinociceptive properties. It is used in traditional medicine as an analgesic and anti-inflammatory remedy. Studies have observed its effectiveness in different pain models, including capsaicin-induced pain and acetic acid-induced writhing response. Its anti-inflammatory, anticoagulant, anticonvulsant, and antioxidant properties have also been recognized. Overall, linalool is a potent bioactive agent with potential therapeutic benefits in managing pain and inflammation.
Myrcene
β-Myrcene, a monoterpene found in cannabis, hops, and other plants, has been studied since the 1990s for its potential pain-relieving properties. Initial research showed that β-myrcene could produce antinociception in certain pain tests when administered intraperitoneally or orally. Despite these findings, the exact mechanisms through which β-myrcene works remain largely unknown due to limited published research.
Geraniol
Geraniol, a sweet-smelling monoterpenoid found in cannabis and other aromatic plants, is known for its analgesic, anti-inflammatory, and anticancer properties. Recent studies have shown it to be a potent anti-inflammatory agent that operates by blocking the MAPK/NF-κB signaling pathways, as evidenced in experiments with human mast cell line 1 and allergic rhinitis mice models.
Sesquiterpenes
Sesquiterpenes, with 15 carbon atoms (C15), are secondary metabolites found in cannabis in various forms – linear, mono-, bi-, and tricyclic.
Caryophyllene
β-caryophyllene (BCP), a bicyclic sesquiterpene alkene, is one of the most abundant terpenes in C. sativa extract. It’s highly regarded for its low toxicity and safety. It’s believed to act as a full agonist for the CB2 receptor. A study demonstrated its effectiveness in altering antinociceptive thresholds to thermal stimuli in naïve animals after oral administration at doses ranging from 1 to 10 mg/kg.
Bisabolol
Bisabolol, or levomenol, is a minor terpene in cannabis and a major component in chamomile. Widely used in cosmetics, it has shown significant antinociceptive properties in animal pain and inflammation models. It notably reduced orofacial nociceptive behavior in mice and displayed anti-inflammatory effects, suggesting potential therapeutic use.
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Humulene
Humulene, also known as α-humulene or α-caryophyllene, is a common terpene in Cannabis species and hops. Despite being a major component, few studies have explored its analgesic and anti-inflammatory properties. Given its potent antinociceptive and anti-inflammatory effects, humulene warrants further in-depth research to fully understand its potential benefits.
Nerolidol
Nerolidol, also known as peruviol or penetrol, is a sesquiterpene alcohol found in C. sativa and other aromatic plants. It has demonstrated antinociceptive and anti-inflammatory properties in animal models, significantly reducing paw edema, acetic acid-induced abdominal contraction, and licking in the formalin test. These benefits were achieved without impairing motor function, suggesting nerolidol could be used for its analgesic effects.
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As you can see, there is compelling evidence of the analgesic effects of many major terpenes found in cannabis and other plants. Highlighting their significant antinociceptive and anti-inflammatory properties, the research available underscores the need for further exploration. The findings suggest that these terpenes could potentially contribute to breakthroughs in pain management, opening up new avenues for natural, therapeutic interventions.
References:
- Busa, E. Et al. Analgesic Potential of Terpenes Derived from Cannabis sativa. Pharmacological Reviews. 2021, 73 (4) 1269-1297; DOI:https://doi.org/10.1124/pharmrev.120.000046 Journal Impact Factor: 20.479 Times Cited: 21
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