Minor Cannabinoids: Biosynthesis, Molecular Pharmacology and Potential Therapeutic Uses

Summary & key facts

This paper reviews what scientists know about the smaller, less-studied chemicals in the cannabis plant, called minor cannabinoids. It explains how these compounds come from a common parent molecule and how they can act on many parts of cells, including the brain’s cannabinoid receptors. The authors say early clinical reports hint these minor cannabinoids might help with things like nerve pain, some brain diseases, epilepsy and skin problems, but the evidence is still limited and more research is needed. The review also notes that progress was slowed for decades because of strict legal rules around cannabis.

Key facts:

• Besides the well-known THC and CBD, the cannabis plant makes more than 120 other cannabinoids that appear in smaller amounts.
• These minor cannabinoids come from a shared parent molecule called cannabigerolic acid, which the plant converts into many different compounds.
• Laboratory studies show minor cannabinoids can act on many targets in the body. These include the brain’s cannabinoid receptors (called CB1 and CB2), certain ion channels, and serotonin-related receptors.
• Because they affect multiple cell signals and might work together, minor cannabinoids have a plausible biological reason to have medical effects.
• Early clinical reports suggest minor cannabinoids may have potential benefits for neuropathic (nerve) pain, some neurodegenerative diseases, epilepsy, cancer-related issues, and skin disorders, but this evidence is still preliminary.
• Research into cannabis chemistry and pharmacology was limited for many years because laws classified cannabis as a high-restriction drug, which slowed scientific progress.
• The discovery and study of THC and CBD led to finding the body’s endocannabinoid system and the cloning of CB1 and CB2 receptors in the 1990s, which opened the door to studying other cannabinoids.

Abstract

The medicinal use of Cannabis sativa L. can be traced back thousands of years to ancient China and Egypt. While marijuana has recently shown promise in managing chronic pain and nausea, scientific investigation of cannabis has been restricted due its classification as a schedule 1 controlled substance. A major breakthrough in understanding the pharmacology of cannabis came with the isolation and characterization of the phytocannabinoids trans-Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). This was followed by the cloning of the cannabinoid CB1 and CB2 receptors in the 1990s and the subsequent discovery of the endocannabinoid system. In addition to the major phytocannabinoids, Δ9-THC and CBD, cannabis produces over 120 other cannabinoids that are referred to as minor and/or rare cannabinoids. These cannabinoids are produced in smaller amounts in the plant and are derived along with Δ9-THC and CBD from the parent cannabinoid cannabigerolic acid (CBGA). While our current knowledge of minor cannabinoid pharmacology is incomplete, studies demonstrate that they act as agonists and antagonists at multiple targets including CB1 and CB2 receptors, transient receptor potential (TRP) channels, peroxisome proliferator-activated receptors (PPARs), serotonin 5-HT1a receptors and others. The resulting activation of multiple cell signaling pathways, combined with their putative synergistic activity, provides a mechanistic basis for their therapeutic actions. Initial clinical reports suggest that these cannabinoids may have potential benefits in the treatment of neuropathic pain, neurodegenerative diseases, epilepsy, cancer and skin disorders. This review focuses on the molecular pharmacology of the minor cannabinoids and highlights some important therapeutic uses of the compounds.

Topics

Cannabis and Cannabinoid Research Forensic Toxicology and Drug Analysis GABA and Rice Research

Categories

Health Sciences Medicine Pharmacology

Tags

Biology Cannabinoid Chemistry Computational biology Internal medicine Medicine Molecular Pharmacology Pharmacology Receptor Synthetic cannabinoids

Substances

Cannabis

Conditions & symptoms

Chronic Pain Chronic pain