Analgesic Potential of Terpenes Derived fromCannabis sativa

Abstract

Pain prevalence among adults in the United States has increased 25% over the past two decades, resulting in high health-care costs and impacts to patient quality of life. In the last 30 years, our understanding of pain circuits and (intra)cellular mechanisms has grown exponentially, but this understanding has not yet resulted in improved therapies. Options for pain management are limited. Many analgesics have poor efficacy and are accompanied by severe side effects such as addiction, resulting in a devastating opioid abuse and overdose epidemic. These problems have encouraged scientists to identify novel molecular targets and develop alternative pain therapeutics. Increasing preclinical and clinical evidence suggests that cannabis has several beneficial pharmacological activities, including pain relief. Cannabis sativa contains more than 500 chemical compounds, with two principle phytocannabinoids, Δ 9 -tetrahydrocannabinol (Δ 9 -THC) and cannabidiol (CBD). Beyond phytocannabinoids, more than 150 terpenes have been identified in different cannabis chemovars. Although the predominant cannabinoids, Δ 9 -THC and CBD, are thought to be the primary medicinal compounds, terpenes including the monoterpenes β -myrcene, α -pinene, limonene, and linalool, as well as the sesquiterpenes β -caryophyllene and α -humulene may contribute to many pharmacological properties of cannabis, including anti-inflammatory and antinociceptive effects. The aim of this review is to summarize our current knowledge about terpene compounds in cannabis and to analyze the available scientific evidence for a role of cannabis-derived terpenes in modern pain management. Significance Statement Decades of research have improved our knowledge of cannabis polypharmacy and contributing phytochemicals, including terpenes. Reform of the legal status for cannabis possession and increased availability (medicinal and recreational) have resulted in cannabis use to combat the increasing prevalence of pain and may help to address the opioid crisis. Better understanding of the pharmacological effects of cannabis and its active components, including terpenes, may assist in identifying new therapeutic approaches and optimizing the use of cannabis and/or terpenes as analgesic agents.

Medical Cannabis: Toward a New Policy and Health Model for an Ancient Medicine

“…In addition to phytocannabinoids, the Cannabis genus also produces non-cannabinoid compounds, including terpenoids ( 12 ), which may also be medically useful ( 13 – 15 ). The pharmacological contributions of minor cannabinoids and non-cannabinoid compounds have been highlighted and popularized under the term “entourage effect” ( 16 , 17 ).…”

Hemp Seed Oil in Association with β-Caryophyllene, Myrcene and Ginger Extract as a Nutraceutical Integration in Knee Osteoarthritis: A Double-Blind Prospective Case-Control Study

“…Among the several components of Cannabis Sativa, as flavonoids, vitamins, fatty acids, sterols, lignanamides, spiroindans, and alkaloids that may have health benefits [ 21 ], terpenes represent a very attractive option for pain treatment [ 22 ]. In particular, β-caryophyllene (BCP), a bicyclic sesquiterpene very present in Cannabis Sativa, has been widely investigated and highly appreciated for its low toxicity and considerable safety profile [ 23 ].…”

Anti-Inflammatory and Analgesic Properties of the Cannabis Terpene Myrcene in Rat Adjuvant Monoarthritis

“…In addition to being found in hops, thyme, and bay leaves, myrcene is the most prevalent monoterpene in Cannabis . In preclinical studies, administration of essential oils rich in myrcene have been found to have analgesic and anti-inflammatory properties [ 2 , 3 ]. Eremanthus erythropappus (10% myrcene) and Bougainvillea glabra (4% myrcene) increased hindpaw withdrawal time in mice and rats in response to noxious heat while reducing paw licking in mice injected with formalin [ 4 , 5 ].…”

“…In joints, cannabinoid receptor activation locally can alter synovial blood flow, leukocyte trafficking, and joint oedema [ 17 , 18 , 19 , 20 ]. Since some terpenes can act directly on cannabinoid receptors and alter the pharmacokinetics of phytocannabinoids [ 3 , 21 ], the interaction between terpenes and the endocannabinoid system warrants further investigation.…”