Antinociceptive effects of minor cannabinoids, terpenes and flavonoids in Cannabis

Abstract

Cannabis has been used for centuries for its medicinal properties. Given the dangerous and unpleasant side effects of existing analgesics, the chemical constituents of Cannabis have garnered significant interest for their antinociceptive, anti-inflammatory and neuroprotective effects. To date, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) remain the two most widely studied constituents of Cannabis in animals. These studies have led to formulations of THC and CBD for human use; however, chronic pain patients also use different strains of Cannabis (sativa, indica and ruderalis) to alleviate their pain. These strains contain major cannabinoids, such as THC and CBD, but they also contain a wide variety of cannabinoid and noncannabinoid constituents. Although the analgesic effects of Cannabis are attributed to major cannabinoids, evidence indicates other constituents such as minor cannabinoids, terpenes and flavonoids also produce antinociception against animal models of acute, inflammatory, neuropathic, muscle and orofacial pain. In some cases, these constituents produce antinociception that is equivalent or greater compared to that produced by traditional analgesics. Thus, a better understanding of the extent to which these constituents produce antinociception alone in animals is necessary. The purposes of this review are to (1) introduce the different minor cannabinoids, terpenes, and flavonoids found in Cannabis and (2) discuss evidence of their antinociceptive properties in animals.

Intervertebral disc degeneration and how it leads to low back pain

“…Activation of CB2R suppresses MMP‐9, 13, induces type II collagen and SOX‐9 (SRY‐box transcription factor‐9) expression restoring ECM integrity through the AMPK/GSK3β pathway. 147 , 148 , 149 , 150 , 151 , 152 , 153 , 154 , 155 , 156 …”

“…Signaling through CB2R prevents anti‐oxidative stress, inducing protective anti‐inflammatory and anti‐senescent effects on NP cells, inhibits IVDD in‐vitro and in‐vivo in a rat acupuncture model and human IVD. Activation of CB2R suppresses MMP‐9, 13, induces type II collagen and SOX‐9 (SRY‐box transcription factor‐9) expression restoring ECM integrity through the AMPK/GSK3β pathway 147–156 …”

An update on animal models of intervertebral disc degeneration and low back pain: Exploring the potential of artificial intelligence to improve research analysis and development of prospective therapeutics

“…CBD acts through the cannabinoid CB1 and CB‐2 receptors, three G protein coupled‐receptors (adenosine receptor subtype 2A, serotonin receptor subtype 1A and G protein‐coupled receptor 55), one ligand‐gated ion channel (transient receptor potential vanilloid channel‐1, TRPV‐1) and one nuclear factor (peroxisome proliferator‐activated receptor γ, PPAR). CBD has been used in the management of epilepsy, 353 , 354 Alzheimer's disease, 355 pain alleviation in MS, 307 neurological responses in Parkinson's disease, 308 , 313 chronic pain 305 , 306 , 309 , 312 including LBP. 311 CBD has been evaluated in a double blind randomized clinical trial for the relief of central neuropathic pain in MS. 307 …”

“…This proposal warrants further investigation. CBD has been used in the management of epilepsy, 353,354 Alzheimer's disease, 355 pain alleviation in MS, 307 neurological responses in Parkinson's disease, 308,313 chronic pain 305,306,309,312 including LBP. 311 CBD has been evaluated in a double blind randomized clinical trial for the relief of central neuropathic pain in MS. 307…”

Immune Responses Are Differentially Regulated by Root, Stem, Leaf, and Flower Extracts of Female and Male CBD Hemp (Cannabis sativa L.) Plants

“…Approximately 100 bioactive compounds are found in hemp tissues, among which cannabidiol (CBD) and tetrahydrocannabinol (THC) are the two most produced molecules [4]. A complete understanding of changes in the hemp phytochemical profile, in the context of the synthesis routes, physiological dynamics and bioactivity is critically lacking, especially when focusing on the secondary metabolites with bioactive potential for human health such as cannabinoids, terpenes and phenolics [1,10]. Among the reported therapeutic uses of hemp, such as for the treatment of refractory epilepsies, infections, tumors, nausea, pain and inflammation, the latter stands out for its historical ethnobotanical support and needs further proof of clinical efficiency [2,11].…”