THC - Tetrahydrocannabinol

General

THC is the abbreviation for tetrahydrocannabinol, the most famous cannabinoid among the phytocannabinoids. It is a colourless oil from the antiemetic substance class. Due to its psychoactive effect, THC is subject to the Narcotics Act in many countries, which makes possession and acquisition illegal in Germany.

Among the herbal cannabinoids, THC is still the strongest active ingredient in the cannabis plant and is best known for its intoxicating effect when consumed.

If you ask people what comes to mind when thinking of cannabinoids, the vast majority would immediately mention THC. THC is short for Delta-9-tetrahydrocannabinol. This is the substance that creates the 'high' often sought by cannabis users.

THC is probably to blame for the widespread and often one-sided reputation of cannabis. The origins of classing cannabis as a pure "drug plant" definitely lie in THC. But the psychoactive herbal cannabinoid can of course do more than trigger a hallucinogenic effect in the central nervous system.^[1]

Occurrence and emergence

Delta-9-tetrahydrocannabinol first emerges as an acid in the female cannabis plant. Cannabigerolic acid (CBGA for short) is formed when two molecules are condensed, geranyl pyrophosphate and olivetolic acid. This can then change into THC acid. Drying and heat split the molecules and THC (among others) is produced as a resinous-oily extract. Therefore, THC and CBG virtually share the same predecessor, even though their methods of action differ significantly.

Cultivated cannabis plants have a steadily increasing THC content. This is not least because regular cannabis consumption leads to a natural resistance to the effects of THC. Through the targeted cultivation of the female hemp plant, attempts are constantly being made to further raise the THC content. People think that the THC content of European cannabis plants has doubled in just a decade to meet the increased perception of resistance among consumers. In 2015, the THC content of plants sold in Europe averaged 10-20%.

THC demonstrably emerged as a drug in ancient Egypt.^[2]Cannabis pollen was found on mummies there and Seschat, the scribe and arithmetic master, is even considered a deity of hemp.

Even if American chemist Roger Adams laid the foundations with his work on the initial isolation and then identification of the cannabinoid, it was Israeli scientists from the Weizmann Institute of Science in Rechovot who were able to isolate THC in its pure form for the first time in 1964.

From the phytocannabinoid to the ECS

Plant cannabinoids are what we refer to in technical terms as phytocannabinoids. One of the best known is THC, i.e. tetrahydrocannabinol.

Delta-9-tetrahydrocannabinol is primarily found in the plant as an acid and it only changes to THC in warm temperatures and under UV light. Since fertilised and male hemp plants have less or hardly any THC, the production of cannabinoids usually takes place through separate sex plants.

Even though the mode of action of THC is still not fully understood, it is already known that the cannabinoid binds to two cell receptors in the central (CB1) and peripheral (CB2) nervous system. Together, they form part of the endocannabinoid system. This is a term for the body's own messenger substances, which have a similar effect to the consumption of THC. It regulates a variety of important functions in the human body. The individual receptors are distributed in our organs, throughout our organism and in our brain, for example, to ensure a properly-functioning metabolism.

Once THC has bound to CB1 receptors, signal transmissions in the central nervous system are influenced at synapses. Therefore, the balance of neurotransmitters is disturbed. This results in muscle relaxation, euphoria and a reduced pain sensation. This also applies to pain caused by chronic illnesses. Cognitive, psychomotor and limbic impairments can be experienced but are temporary. This happens because the receptors responsible are located in the "basal nuclei", the core areas of the cerebrum below the human cerebral cortex (cortex cerebri). The nerve cells there form the basis of our consciousness and all cognitive and motor processes.

CB2 receptors are primarily found in our immune system. This means they are critical for dealing with neuronal diseases with symptoms of inflammation or neuropathic pain. More information on that later.

Other type 2 receptors are found in the digestive tract, as well as in the immune system, the bones, the lungs and even within our largest organ: the skin.

The new discovery has been made by an international team of researchers who were able to decode the molecular structure of CB2 receptors. So, today we know that CB1 and CB2 receptors work closely together. If one cannabinoid receptor is stimulated by certain active ingredients, the other is weakened, sometimes even completely blocked. This finding is a big breakthrough, especially for medicine and the development of new, more effective medications.

THC and its effects

THC stimulates and activates the CB1 receptors. In healthy people with an intact nervous system, this change leads to a "chaotic" exchange of information. Physiological processes and normal bodily functions are turned on their head. This change in consciousness of our perception triggers the "high feeling". Other side effects of cannabis use include fatigue and lethargy. Since our endocannabinoid receptors are on our salivary glands, saliva production is also disrupted. This explains why cannabis users can often have a dry mouth after smoking cannabis. Red eyes are another side effect and are caused by different factors in combination. THC can cause blood pressure to drop and blood vessels to open. Our eyes produce less tears, which upsets the natural balance of our tear film. The result is reddish eyes.

During the ‘high’ that users experience, which lasts a few hours, THC levels start to break down. The phytocannabinoid is broken down in the lungs and the liver until completely excreted in stools and urine.

Since the human body breaks down cannabinoids rather slowly, regular cannabis use can still be detected in the urine four weeks later. This is because THC accumulates in fatty tissue and is only gradually released into the bloodstream. An Australian research team has also found that the concentration of THC in the blood does not always drop to a residual level below 3 nanograms/ml. During the study, some subjects showed a higher level one week after consumption. Study participants who were regular cannabis users also showed irregular increases and decreases in blood concentrations. This means that negative results can appear in a blood test one day then be positive just a few days later if the THC content suddenly increases without new consumption.

Sports activities and diet also have an influence on the THC content in the blood. If the metabolism is stimulated, THC can be released faster from the fatty tissue and get into the bloodstream faster.

THC and CBD

So far, scientists have assumed that THC is the only cannabinoid from the cannabis plant to have a psychoactive effect and cannabidiol, or CBD for short, can reduce this effect. This why growers have been careful to use female hemp plants. In recent years, they have been harvesting a decreasing proportion of CBD to guarantee the psychoactive effect, i.e. the classic drug intoxication of cannabis. This is despite a possibly increased THC tolerance limit.

However, new studies show a different picture of CBD. Participants in the study were divided into four different groups and consumed either THC only, CBD only or a THC-CBD mixture³.The last group inhaled a mock substance (placebo). All cannabinoids were inhaled through a vaporiser, i.e. not burned but only vaporised.

This showed that even pure CBD has a certain, albeit low, psychoactive effect on those who consume it.

Even the effect of CBD on THC has to be reconsidered. Participants from the group using a THC-CBD mixture showed a higher level of intoxication than consumers of pure THC.

One reason for this could be the two-phase effect of CBD. Since CBD can only weakly bind to receptors in the endocannabinoid system, the phytocannabinoid uses a different trick. It appears to be able to change and balance the properties of the ECS receptors, so that THC can better stimulate the CB1 and CB2 receptors when consumed at the same time. Above all, this interaction shows that research on cannabinoids and their effects is more complex than previously thought. We are still unable to grasp the full range of effects on the human body.

Artificial THC

Attempts have been made time and time again to manufacture THC as a synthetic drug. The main focus is on enabling consumers to “legally” acquire and consume synthetic cannabinoids with a comparable 'high' effect to THC.

Consumers report similar effects to those of cannabis. Potentially, these can be far stronger than the plant high.

This is partly due to uncontrolled production and unclear doses. Due to the wide variation in potency and structure of the various synthetic cannabinoids, it is easy to accidentally overdose.

The consequence is an incalculable and potentially life-threatening effect on consumers.

Consumption

Since the possession of THC is by and large illegal in Germany and many other parts of the world, studies cannot record the undisclosed number of consumers. According to a UN report, around 192 million people worldwide use cannabis. This makes the THC-rich plant the most frequently consumed drug on earth.

The most widespread method of consuming cannabis with THC is by smoking joints. Consumers either fill these with tobacco or consume the "grass" as a pure substance. Bongs, vaporisers, pipes and similar mediums are also used to consume THC. When THC is burned by the consumer, the cannabinoid creates the typical cannabis intoxication effect with a "high feeling".

Since THC can cause a drop in blood pressure, blood vessels open up. Mixed with a reduced production of tear fluid, which upsets the natural balance of human tear film, typically, many people who smoke cannabis get red eyes.

Since THC is very fat and oil-soluble, it can be included in high-fat dishes such as milky drinks and baked foods. This leads to popular methods of consumption such as what we call “hash brownies”.

Cannabis medications containing THC are also taken orally by patients. Intravenous administration is not an option.

Methods of action

Although research cannot clarify THC’s exact mechanism of action as yet (which is the case for most cannabinoids), we already know that THC controls the CB1 and CB2 receptors in the human endocannabinoid system. These receptors are mainly found in the central and peripheral nervous system.

THC travels through the lungs into the bloodstream. Once in the body, it mainly controls CB1 receptors but also CB2 receptors by binding in the brain. Using these binding sites as a point of departure, the cannabinoid takes effect on the nerve cells. It changes the release of neurotransmitters. Messenger substances in the nerve cells are modified and the psychoactive effect begins.

However, in general, we cannot say what effect it has on the human body. The cannabis 'high' depends not only on the original cannabis plant, but also on the individual consumer.

Therefore, we know, for example, that plants with a high CBD content can strengthen the ‘high’ produced by THC, while CBD has an opposite effect. Phytocannabinoids mutually influence and regulate each other.

THC can also bind to CB1 receptors in immune cells, gastrointestinal tissue, heart, lungs and other organs. The immune cells have CB2 receptors too and these can support cell growth.

Medical uses

Due to the many phytocannabinoids in the cannabis plant, which have a multitude of effects in the human body thanks to the endocannabinoid system, cannabis is still too commonly misunderstood as a universal miracle cure. Unfortunately, it is not possible to improve or even cure all diseases with medicines containing cannabis. However, if THC consumption is specific, it can have amazing effects.

In addition to problems with the memory, dementia also has numerous additional symptoms. Many patients complain about a change in the sense of taste, leading to a decrease in appetite. There is a risk of under-nourishment and malnutrition.

An accidental discovery in the late nineties revealed that THC can increase the appetite in Alzheimer's patients and help to reduce the risk of possible nutritional damage.

In August 2006, scientists from the Scripps Research Institute found that THC is able to fight a harmful Alzheimer's protein. It can inhibit the formation of amyloid plaques, the main marker of Alzheimer's disease. Then, the flow of information in the brain is influenced through receptors that bind, leading to a rearrangement of cellular communication. This can reduce confused behaviour.

Cancer patients not only struggle with the malignant disease itself during chemotherapy, but also with symptoms such as general pain, nausea, vomiting or loss of appetite.

THC itself is not a pain-blocking drug as indicated by the distribution of receptors in the brain, i.e. in the endocannabinoid system. Receptors considered as the binding point for THC are mainly in the frontal brain and limbic system. This is where emotions are processed and the sensation of pain is assessed, among others. Scientific tests have shown that although THC has no analgesic effect, it can help some patients to be less burdened by pain.

The amygdala is also located in the limbic system. It affects memories and has control over negative feelings such as fear and anger. Studies have found that tetrahydrocannabinol can inhibit activities in the amygdala’s anxiety centre and disrupt the transmission of information. However, this was not experienced by all participants when cannabinoid was administered. It is not clear why some people feel stronger effects from THC than others.

Peripheral, neuropathic pain affects the brain and spinal cord and the resulting pain symptoms are caused by damaged or diseased nerve structures. Since we already know that THC acts on the receptors in the brain, using the cannabinoid in medical cases for relevant patients makes quite a lot of sense. This is most noteworthy when those concerned do not want the common side effects of conventional medication.

In placebo tests, THC was administered to some of the participants as a 2.7mg THC spray. It is important to mention that CBD was also added to the spray. The spray dose was increased during the study and adjusted according to the reduction in pain desired by participants.

The success of THC compared to the effects of the placebo group was clearly visible in this study.^[4]

The tolerance and effect of the phytocannabinoid was shown in test subjects through improved sleep quality and generally improved well-being.

These findings make THC an effective medicine for patients suffering peripheral neuropathic pain if their symptoms have been resistant to procedures with other drugs.

Cannabinoid hyperemesis syndrome

Cannabis hyperemesis syndrome, or CHS for short, is a disease linked to the direct consumption of THC in cannabis.

The cluster of symptoms manifests as a cycle of general malaise, nausea, vomiting and abdominal pain.

However, due to the low number of cases, there is still no concrete evidence that this illness is actually directly related to excessive long-term cannabis use. As THC is an illegal drug and popular in many countries, some doctors are speculating as to a high number of unreported cases.

The relatively new disease was first described by four Australian scientists in 2004.^[5] Since conventional antiemetics and analgesics do not seem to have any effect, infusions are a recommended method for cannabis hyperemesis syndrome when someone is not taking in enough fluids in other ways. In the event that daily and excessive cannabis use is causing CHS symptoms, avoiding cannabis altogether in the future would be the best advice.

Other findings report that taking hot baths can also help to alleviate symptoms, but this has not been demonstrated through new studies.

^[1] https://de.wikipedia.org/wiki/Rechtslage_von_Cannabis

^[2] http://www.druglibrary.org/schaffer/hemp/history/first12000/1.htm

^[3] https://link.springer.com/article/10.1007%2Fs00406-019-00978-2

^[4] https://www.ncbi.nlm.nih.gov/pubmed/24420962

^[5] https://gut.bmj.com/content/53/11/1566