Accurate Education – Marijuana (Cannabis): Terpenes and Pain

Terpenes and Pain

It is likely that the constituent in marijuana most responsible for pain benefits is THC. In fact, patients using marijuana for pain relief most commonly report that the most effective strains often have an equal balance of THC and CBD.  However, these two cannabinoids are not the whole story for cannabis and pain. The wide range of analgesic benefits derived from different marijuana strains cannot be explained by THC and CBD alone, other constituents also play a significant role, especially the terpenes.

Terpenes have a great deal of popular support for their pain benefits although most of this support appears to be anecdotal, meaning based on word of mouth opinions rather than actual meaningful research studies.  What research is available is largely limited to pre-clinical (animal or lab-based) studies. The following terpenes are most commonly referenced for their benefits for pain although β-Caryophyllen has by far the strongest evidence while the others have very weak evidence, mostly for neuropathic pain.

• β-Caryophyllene
• Myrcene
• Humulene
• Linalool
• Pinene
• Limonene

β-Caryophyllene (BCP) and Pain

Pre-clinical research indicates that β-Caryophyllene (VP: 266•F; 130°C)) has anti-inflammatory and analgesic properties and also facilitates wound healing. Unfortunately, clinical research with humans is still very limited.

The anti-inflammatory properties of BCP have been extensively shown in different mouse models of disease. A recent study shows that BCP synergizes with curcumin in exerting anti-inflammatory activity in an experimental in vitro model of osteoarthritis, strongly suggesting the potential benefit of a dual combination of these two compounds for the management of osteoarthritis. This curcumin synergy has also been found with the catechins found in green tea. Similar to curcumin, β-Caryophyllene suppresses inflammation by reducing levels of IL-1β, IL-6, through activity at  prostaglandin PGE-1 and at the NLRP3 inflammasome

Neuroinflammation and Pain Sensitization

Development of neuropathic pain is accompanied by the activation and proliferation of glia cells, immune cells in the spinal cord responsible for the development of neuroinflammation which leads to pain sensitization. β-Caryophyllene is thought to be effective against neuroinflammation by reducing activity of glial cells. Pain sensitization in the peripheral and central nervous system plays a pivotal role in the transition from acute to chronic pain. Hallmarks of pain sensitization include the manifestation of altered pain responses, such as painful hypersensitivity (mechanical allodynia and hyperalgesia). Neuroinflammation involving spinal neuronal facilitation and the activation of spinal microglia and astrocytes plays a fundamental roles in these processes.

Pre-clinical evidence shows that activation of CB2 receptors inhibits central sensitization and its contribution to the manifestation of chronic arthritis pain. These findings suggest that targeting CB2 receptors may have therapeutic potential for treating arthritis pain.   Early animal research in rats/mice have identified β-caryophyllene (BCP) as a selective full agonist and potent stimulator of the CB2 receptors.. In inflammatory hyperalgesia, indirect pain inhibition through CB2 receptors on mast and immune cells is possibly achieved by the reduction of prostanoids or cytokines release, which are responsible for peripheral nociceptor sensitization. Additionally, BCP activation of CB2 receptors on keratinocytes (superficial skin cells) stimulates the release of endogenous opioids, the β-endorphins. When combined with morphine, this provides an increased synergistic analgesic benefit.

CB2 is critically involved in the modulation of inflammatory and neuropathic pain. Based on animal studies, orally administered BCP reduces inflammatory pain and neuropathic pain. It has been shown to exhibit analgesic effects in neuropathic pain associated with chemotherapy, diabetes, and chronic nerve damage.  Chronic oral administration of BCP may reduce thermal hyperalgesia, mechanical allodynia and spinal neuroinflammation. No signs of tolerance to these effects after prolonged treatment have been identified.  This suggests BCP may be highly effective in the treatment of long lasting, debilitating pain states although additional studies are needed in humans.

Myrcene and Pain

Myrcene (VP: 334°F; 167°C) is sedating , aids insomnia and reduces anxiety but it has only very weak pre-clinical animal studies that suggest it may be helpful in the treatment of neuropathic pain. No human studies appear to be available to support targeting this terpene for use for pain other than topical use The research supporting myrcene for pain is mostly limited to animal and lab studies that do not include inhalation of myrcene and should not be extrapolated to smoking or vaping myrcene. Topical myrcene is purported to reduce pain produced by noxious thermal and mechanical stimuli as well as reducing acute inflammation. Rat studies have been performed with oral dosing of myrcene that support pain benefits crudely measured by  hot plate and acid-exposure testing.

Headache

In a 2018 study, “Patterns of medicinal cannabis use, strain analysis, and substitution effect among patients with migraine, headache, arthritis, and chronic pain in a medicinal cannabis cohort,” all subgroups of chronic pain patients, especially primary headache patients, responded best for pain with hybrid strains, particularly those with terpene profiles with dominant myrcene and Β-caryophyllene. In this study of the top 15 strains effective for migraine headaches all except two had myrcene contents ranging from 0.1% – 0.29%, with two outliers: 0.033% and  0.61%.

It is suggested that cannabis strains with myrcene in combination with THC, CBD and Β-caryophyllene may offer the best alternative combination for treating pain and headaches such as OG Shark.

Arthritis

It has been reported that arthritis patients prefer cannabis strains rich in myrcene to help manage their pain and inflammation. Myrcene has been evaluated for it benefit for arthritis in a 2022 animal study (rats) using an artificially induced model of arthritis. The data suggested that topical myrcene has the potential to reduce chronic arthritis pain and inflammation although repeated myrcene treatment had no effect on joint damage or production of inflammatory cytokines and therefor would not be expected to slow the progression of arthritis.