Hexacannabitriol: The anti-cancer cannabinoid?

Scientists have recently discovered four new natural cannabinoids, one of which is believed to have excellent chemopreventive and anticancer properties—at least in the laboratory. Although these cannabinoids are derivatives or analogs of CBD, research shows that they may surpass the CBD as an Antioxidant. These new cannabinoids, particularly hexacannabitriol, possess a functional group called 2-hydroxy-delta-1,7-hexomethylene, which facilitates their interaction with oxidative stress regulators.

Plant-derived cannabinoids, the phytocannabinoids, exhibit a wide variety of structures. This diversity manifests itself in the form of functional groups such as carboxyl groups (COOH), hydroxyl groups (OH), oxygen, carbon, and hydrogen. The functional group attached to a cannabinoid plays a key role in determining which receptor the cannabinoid can affect. This is why cannabinoids produce different effects.

Since CBD was first officially isolated in the 1940s, scientists have worked tirelessly to study cannabis-derived compounds and how they might benefit humans. These tireless efforts have led to the discovery of cannabinoid acids, analogs of the major cannabinoids with shortened or lengthened carbon chains, and some with oxidatively modified structures. Approximately 150 cannabinoids have been reported, most of which possess unique therapeutic or other potential.

A recent article published in the Journal of National Products reported the existence of four new cannabinoids, namely

• Anhydrocannabimovene
• 1,2-dihydroxycannabidiol
• 3,4-dehydro-1,2-dihydroxycannabidiol
• Hexacannabitriol

There’s no need to get worked up about the names; these are simply CBD compounds with an extra hydrogen atom in their structure. They form after prolonged exposure of CBD hemp to air or through the enzymatic conversion of CBD. However, research has yet to determine how long CBD-rich hemp must be exposed to air to produce these cannabinoids.

Although the four new cannabinoids share certain similarities with CBD, hexacannabitriol (HCBT) is believed to have greater chemopreventive and anticancer properties than the others.

What do we know about hexocannabitriol?

How is it formed?

Hexacannabitriol (HCBT) is a hydroxylated derivative of CBD. It shares certain structural similarities with CBD and cannabitriol (CBT). While cannabitriol is formed when THC-containing hemp is exposed to air for a long period of time, hexacannabitriol is formed through the enzymatic conversion of CBD via hydrogenation or oxidation. The enzymes involved in this conversion have not yet been identified.

How does it interact with receptors?

Hexacannabitriol (HCBT) is a non-intoxicating cannabinoid that shows promise in cancer treatment. Although it was first reported in 2022, researchers believe it may have better chemopreventive and anticancer properties than CBD, its parent compound. HCBT does not interact with CB receptors, but it has been observed to play a key role as an antioxidant.

The structural difference between CBD and HCBT plays a key role in how CBD can interact with CB receptors, whereas HCBT cannot. The receptors contain binding pockets that interact specifically with particular molecules or structures within a cannabinoid compound. The nature of the binding pocket and the molecules present in cannabinoids determine their ability to bind.

For example, research shows that a minimum of 3 carbon atoms is required to initiate an interaction with the CB1 receptors, and that this activity increases with the number of carbon atoms. This is why most long-chain cannabinoids interact more potently with receptors.

HCBT has strong antioxidant properties due to the hydrogenated portion of its compound. Research shows that the higher the number of OH and COOH groups in a cannabinoid, the greater its antioxidant activity is likely to be. This is why acidic cannabinoids have more potent antioxidant properties than their neutral forms.

It should be noted that free radicals play a key role in the development of cancer. They disrupt the body’s internal balance and create an environment conducive to the growth of cancer cells. The continuous accumulation of free radicals can lead to oxidative stress, which damages cells. However, this activity is controlled by two main regulators known as Nrf2 (nuclear erythroid 2-related factor) and BACH1 (BTB domain and CNC homolog 1).

Nrf2 is a major regulator of the’homeostasis (internal balance) of cells. It is activated in response to oxidative stress and inflammation and plays a key role in how we respond to various forms of stress. Under normal conditions, the degradation of the Nrf2 protein is low. When cells are exposed to oxidative stress, they inhibit the degradation of Nrf2, causing it to become stabilized. Increasing Nrf2 levels using chemopreventive agents helps protect cells against oxidative stress and damage. This is important for triggering cytoprotection (cell protection) against several chronic diseases linked to inflammation and pro-oxidant compounds.

Current research has revealed the potential role of hexacannabitriol in the activation of Nrf2 components. Nrf2 components are activated by the 2-hydroxy-delta1,7-hexomethylene present in hexacannabitriol.

Chemopreventive agents can enhance the expression of Nrf2 target genes and induce cytoprotective enzymes. This may play an important role in reducing environmental stressors that contribute to the burden of inflammation, cancer, and other degenerative diseases.

Is hexacannabitriol safe?

Hexacannabitriol was extracted from hemp and produced through the oxidation of CBD in air. As a hemp-derived cannabinoid that shares certain similarities with CBD, it is non-intoxicating and is present only in trace amounts in the plant. At this time, there are no products containing HCBT. Most of the information regarding its anticancer and chemopreventive effects comes solely from a laboratory report.

Since it is present in trace amounts in hemp, people who want to try HCBT will have to settle for a synthetic compound. This solution is risky, however, because some synthetic cannabinoids may not be safe for humans.