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THCA: The Cannabinoid That Loves Your Brain

Christine Kielhorn PHD
Crystalline THCA close up

THCA, found in raw cannabis, has powerful neuroprotectant properties.

Cannabis-based medicines mainly rely on the effects of the two most abundant cannabinoids: delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD).  These compounds, however, are actually present in the raw or living cannabis plant under a different form – an acid form.

Cannabis Plant growing in the sun

Image Credit: Dvorak Photo

The plant itself contains carboxylic acid precursors to these compounds, known as delta-9-tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA). These acid forms are easily converted to THC and CBD through decarboxylation, a process primarily triggered by heat, such as that applied while smoking or cooking Cannabis. Decarboxylation also occurs naturally during aging and storage, so the shelf-life of THCA is relatively short.

THCA is not psychoactive, and it is thought to have many of the same positive health benefits as THC. THC is mainly thought to exert its positive effects through the cannabinoid receptors like the receptor CB1. However, the research suggests that THCA does not bind very well to the CB1 receptor, and so its benefits are provided through different biochemical pathways. Its low affinity for the CB1 receptor also explains why THCA is not psychoactive. Researchers, attracted by the potential of Cannabis-based medicines without the side effects of THC, have begun to investigate the potential therapeutic role of THCA.

Crystalline THCA close up

Image Credit: Brandon Crawford

Many of the laboratory studies have found that THCA has excellent neuroprotective effects. In other words, it can help to protect the neurons from various degenerative diseases, like Huntington’s Disease (HD) or Parkinson’s Disease (PD). One preclinical study (using cells as well as mice) looked at the interaction between THCA and the PPARγ receptor. This receptor is found in the nucleus of cells and its job is to regulate lipid metabolism and glucose homeostasis. It is also thought to play a role in the progression of HD and it has become a target for new treatments.

3D rendering of Nerve cells

THCA has neuroprotective properties.  Image Credit: Ralwel

THCA (and other acid cannabinoids like CBDA) are strong agonists of the PPARγ receptor, meaning that they bind to the receptor and increase its activity. In the case of HD, increasing the activity of the PPARγ receptor has neuroprotective effects. The mice models of HD that were treated with THCA had reduced physical symptoms as well as reduced expression of inflammatory factors. The HD mice treated with THCA also lost fewer neurons and sustained less neuronal damage compared to the untreated mice and the mice treated with both THCA and a receptor blocker that would prevent THCA from binding to the PPARγ receptor.

Lateral view of the human brain

Image Credit: Jesada Sabai

Another preclinical study (on mice and cells in culture) investigated the role of THCA on dopaminergic neurons as potential treatment and protection against the degeneration associated with PD. It found that THC was the most neuroprotective in vitro, followed by THCA and then CBD. However, none of these cannabinoids were completely effective at preventing the neurodegeneration from occurring in the animal model. There was some evidence, however, that the cannabinoids were good antioxidants, and so could potentially slow the progression of the disease.

Inside a diseased colon

Inside a diseased colon. Image Credit: Sebastian Kaulitzki

In addition to its strong neuroprotective benefits, THCA has been used in other studies examining its potential medical applications. One study found that it has similar anti-nausea and anti-vomiting effects as THC. Another recent study found that THCA is an active anti-inflammatory agent, particularly helping to ease the inflammatory response in cell models of inflammatory bowel disease.

There is one major barrier facing the widespread research and development of medications featuring THCA: its chemical instability. Even when held at refrigerator temperatures (4°C), some of the THCA will decarboxylate and turn into THC. Currently, contamination with THC is viewed as unavoidable.

Cannabis smoothie in wood

Image Credit: Eskymake

Some patients like to consume raw cannabis, as juice, for example, as a way of obtaining a high fraction of THCA. However, this is subject to the variability of THCA concentrations from plant to plant and is difficult to standardize. Scientists are striving to learn more about the different forms of THCA (there is an A form and B form), since the B form appears to be more stable, although the A form is more common. The demand for cannabinoid medicines and the promising research of THCA will hopefully drive innovations in this area.


Christine Kielhorn

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