Tetrahydrocannabinol or THC: the psychoactive component of cannabis

The cannabis plant is one of the first plants ever cultivated by humans. It is known to have been used as food, as medicine and in religious rituals for more than two millennia (1, 2). As we will see in this article, the compounds it produces, especially THC, have had a great deal to do with how the plant has been used.

THC: the psychoactive compound in cannabis

What is THC?

Tetrahydrocannabinol, better known as THC, is a type of cannabinoid and the main psychoactive component found in the cannabis plant. Its full name is delta-9-tetrahydrocannabinol, abbreviated to delta-9-THC, which is the best-known and most studied form of THC.

Differences between CBD and THC

When was THC discovered?

THC was isolated from the Cannabis plant in 1964 by the renowned researcher Raphael Mechoulam.

Where is THC found in the plant?

THC, like other cannabinoids and the terpenes in cannabis, is found in the glandular trichomes of the Cannabis flower. These trichomes are more abundant in plants with unfertilised female flowers (10). Through a complicated process that takes place in the trichomes (known as cannabinoid biosynthesis), terpenoids and phytocannabinoids are formed from a common precursor, geranyl pyrophosphate (11).

This process gives rise to cannabinoids in their acid form, indicated by an “A” at the end of the cannabinoid's name. Delta-9-tetrahydrocannabinolic acid (THCA) is therefore the compound found naturally in the plant. Although this molecule can trigger a response in the body on its own, exposure to heat causes decarboxylation, so that it loses its acidic property and becomes the potent, bioactive neutral molecule we know as THC.

How much THC does cannabis contain?

To date, more than 100 phytocannabinoids have been identified in the flowers of Cannabis, including delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG), cannabichromene (CBC), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabinodiol (CBND), cannabinidiol (CBDL), among others (4). Of these, THC is the one found in the highest proportion and the one to which the plant's psychoactive effect is attributed.

The concentration of tetrahydrocannabinol in cannabis plants can vary from one strain to another, but it generally stays above 18% THC for commercial purposes. This percentage is the result of years of plant breeding to produce THC-rich chemotypes or strains, and so enhance their effects on users (12).

THC saliva test: what to do if you test positive

Likewise, types of cannabis with a very low tetrahydrocannabinol content have now been developed. That is why you can buy CBD flower in many European countries, where it is advertised as “legal weed”, because it keeps THC levels below the legal limit (between 0.3 and 1%, depending on the country).

Phytocannabinoids such as THC are chemicals that are able to interact with the endocannabinoid system. They are not exclusive to cannabis: they can also be found in plants such as *Echinacea (E. purpurea, E. angustifolia and E. pallida)*, Sichuan buttons or electric daisy (Acmella oleracea), paper daisy *(Helichrysum umbraculigerum) *and the liverwort radula (Radula marginata; 3).

Effects of THC

How does THC work?

*Cannabis sativa *is a plant of varied hues that stands out from others for its aroma, a characteristic it owes to certain chemical substances present in its flower. These substances, called terpenes and terpenoids, together with phytocannabinoids, are the main components of the cannabis flower, and therapeutic and psychoactive effects are attributed to them.

Tetrahydrocannabinol is the phytocannabinoid responsible for the psychoactive effect of the Cannabis plant. This effect occurs because THC is a partial agonist of cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2).

By exhibiting this affinity, THC activates the endocannabinoid system and triggers mechanisms that produce neurobehavioural signs.

What does it mean to say that THC is psychoactive?

Any substance that produces an altered state of consciousness or affects mental activity is considered psychoactive. Tetrahydrocannabinol, for example, produces signs or symptoms including reduced mobility, hypothermia, analgesia and catalepsy, which together are known as the cannabinoid tetrad (6).

The entourage effect and THC

The effect of cannabis is not only due to THC binding to endocannabinoid receptors (CB1 and CB2). Its potency is said to be linked to the terpenes and terpenoids also found in the flower. The herbal synergy (7) resulting from the combination of all the components that make up the cannabis plant gives rise to the entourage effect.

The entourage effect refers to the potentiation or diminution of the effectiveness of cannabis when its various components act together.

For example, the effectiveness of cannabis oil in treating acne may not only be due to the presence of cannabinoids, but also to their synergy with limonene, a terpenoid present in cannabis flowers and known for its antibacterial action. Another example is that the presence of CBD, or cannabidiol, in the cannabis plant reduces the side effects that can arise when THC is administered on its own (8).

Does CBD reduce the effects of THC?

In the Cannabis plant, the entourage effect is due to the fact that it contains more than 500 terpenes, terpenoids and cannabinoids (9), which make possible a huge number of combinations capable of modulating the effect of THC. For this reason, it cannot feasibly be reproduced in the laboratory and, consequently, the entourage effect remains a hypothesis.

The fact that the entourage effect cannot be reproduced artificially is evidence that natural products can be powerful tools that science cannot accurately measure.

Uses of THC: the therapeutic potential of cannabis

In the past, even before THC was isolated, cannabis plants had more balanced concentrations of phytocannabinoids and, perhaps because of this, better therapeutic effects. Although, now that plants are so potent, cannabis has been scientifically linked to negative effects, all is not lost. Medical cannabis is still a valid concept, as some of its effects continue to benefit users.

In the brain, THC can act as an anti-inflammatory agent (13, 14), produce mild bronchodilator activity (15, 16) and be used as an analgesic (16, 17). However, its use should be subject to a strict risk–benefit assessment, ideally under the supervision of a healthcare professional.

Long-term regular use of high-THC cannabis can cause irreversible damage as a result of the effect of THC on the brain.

THC as a treatment

What diseases is cannabis used for?

Although THC poses a risk to neuronal function, its use is encouraged to relieve complex conditions for which no effective treatments exist.

Some of these conditions are multiple sclerosis, neuropathic pain and fibromyalgia. In addition, cannabis can be a palliative treatment to relieve the effects of chemotherapy in cancer patients (18).

For other diseases, or for recreational purposes, it is recommended that cannabis be used in the form of strains containing low concentrations of THC.

Cannabis plants that are predominantly rich in CBD, with very low levels of THC, such as hemp, avoid the unwanted psychoactive effects that THC-rich cannabis can produce.

Approved medical uses of THC

• Chronic pain (19, 20)
• Multiple sclerosis (21)
• Pain, nausea and vomiting caused by chemotherapy (22, 23)
• Fibromyalgia treatment (24)
• Rescue analgesia after surgery (25). Requires close monitoring by a healthcare professional.
• Improved appetite (26)

What are the long-term effects of THC?

What happens when you use cannabis regularly is not exactly what you would want for your brain. Although in the short term cannabis can bring pleasant, enjoyable sensations, there are also mental health risks linked to chronic THC use. Bear in mind that the beneficial and harmful effects of cannabis on the brain vary from person to person. It can certainly be a supportive tool for people with cancer, multiple sclerosis, fibromyalgia or chronic pain, but in the end it is up to the doctor to decide whether it can help with a particular disease.

Is cannabis bad for the brain?

Much remains to be discovered about THC and cannabis

The composition of cannabis flowers is complex and difficult to characterise fully. All cannabis plants, whether or not they are of the same strain or chemotype, will show some degree of variation between them, as the formation of terpenes, terpenoids and cannabinoids depends on soil quality, environmental growing conditions and the particular phenotype.

The cannabis plant began to be studied in greater detail after the isolation of THC, but its intricate composition offers a wide range of possibilities that continue to be the subject of research today.

* This post is dedicated to the memory of the father of cannabinoid science, Professor Raphael Mechoulam, who passed away on 9 March 2023.