Tetrahydrocannabinol

The most studied cannabinoid for its therapeutic effects for various ailments and/or symptoms.

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Tetrahydrocannabinol (THC)

Tetrahydrocannabinol or THC is the most abundant cannabinoid in most cannabis varieties and has the most potent psychoactive effect. It was Dr. Raphael Mechoulam who first discovered THC in 1964 and has since investigated its’ therapeutic potential. Currently, in international medical research portals, there are more than 8000 articles that analyze the use of tetrahydrocannabinol from a therapeutic approach.

THC is a partial agonist of the cannabinoid receptors CB1 and CB2 (it has a more potent effect on CB1) exerting analgesic, anti-inflammatory, antiemetic, orexigenic, anti-tumour, antiepileptic, anti-spastic and spasmolytic effects. Current studies have shown that in addition to its effect on CB1 and CB2 THC also acts on other receptors such as GPR55 or TRPV1-5, influencing this way on nociception, thermoregulation, salivary secretion, smooth muscle tone, heart rate and on the homeostasis of calcium and magnesium (Ligresti et al., 2016).[1]

The side effects of THC have been described as anxiety, psychoactive effects, depression, cholinergic deficit, loss of immediate memory, impairment of concentration capacity, an affectation of balance and coordination of movements, conjunctival hyperaemia (red eyes), mucosal dryness (dry mouth) and increased appetite and sleep.

Infographics on Tetrahydrocannabinol

Tetrahidrocannabinol | THC | Medical cannabis | Kalapa clinic

Therapeutic Effects of Tetrahydrocannabinol (THC)

THC or delta-9-tetrahydrocannabinol (Δ9-THC) has analgesic and anti-spasmodic effects and has the ability to relax all of the senses. It is also known to be an antagonist of several cannabinoids, such as CBD, which reduces the psychoactive effects of THC.

Como efectos secundarios del THC se han descrito ansiedad, efecto psicoactivo, depresión, déficit colinérgico, pérdida de la memoria inmediata, afectación de la capacidad de concentración, afectación del equilibrio y coordinación de movimentos, hiperemia conjuntival (ojos rojos), sequedad de mucosas y el aumento del apetito y del sueño.

Studied therapeutic effects

  • Analgesic
  • Antiemetic
  • Neuroprotector
  • Anti-inflammatory
  • Antispasmodic
  • Antispastic

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Clinical research on THC

There are currently numerous studies focused on the treatment of cancer using THC (and other cannabinoids), which have demonstrated anti-tumour effects in animal testing. Human trials are currently being conducted at universities in Israel and the United Kingdom. 

Until there are more references of trials where it is analyzed in humans, oncologic patients can use cannabinoid treatment as an adjuvant to the usual treatments, THC is able to palliate the typical adverse side effects of chemotherapy, such as nausea, vomiting, sleep deficit or lack of appetite.

There have also been several studies on the therapeutic potential of THC in Alzheimer, which investigate the potential neuroprotective effects for this type of pathology. They have also looked at its potential in states of dementia and as a treatment for periods of agitation and aggression.[2]

Among the most widely known therapeutic applications for THC is the treatment of multiple sclerosis and severe spasticity. It is normally administered via a mouth spray made of a THC | CBD ratio of 1:1, it is predominantly for patients who have not seen results with other types of anti-spastic treatments.

Use of synthetic THC drug to treat nausea and vomiting | Kalapa Clinic
Dronabidol (Marinol) is a synthetic THC drug to treat nausea and vomiting caused by chemotherapy, appetite loss and low weight in people with HIV

The entourage effect and Tetrahydrocannabinol

Most scientific studies on medicinal cannabis focus on the effects of different types of cannabinoids, especially THC and CBD. However, the cannabis plant has many more components than cannabinoids and other factors such as terpenes, which also produce their own effects, or the entourage effect, must be taken into account.

The entourage effect is the interaction between phytocannabinoids such as THC and the other elements present in the plant. In the case of Cannabis Sativa L, interactions between terpenes, flavonoids and at the time of ingestion, with endocannabinoids such as anandamide, are being studied.

It was the lack of information on the entourage effect that led Dr Ethan Russo of the University of Massachusetts to publish an essay on the synergy of phytocannabinoids and terpenes in 2011.

Sometimes, there are pathologies that cannot be treated with a cannabinoid alone. The synergy between different cannabinoids also produces the entourage effect, very useful for treating diseases where a single component is not enough. In this respect, several publications argue that THC explains the main medicinal benefits of cannabis, such as the analgesic effect.

However, there are other studies that support that CBD and other components of cannabis achieve synergy with THC, enhancing its benefits, antagonizing adverse effects, and producing less toxicity than with THC alone.

The range of effects of phytocannabinoids is very wide and that is why their applicability in future therapeutic applications needs to be further investigated. [4]

Similarly, these two terpenes and pinene may help to increase the effect of THC on dementia in Alzheimer’s patients. Linalool, together with caryophyllene and myrcene, can increase the effects of several cannabinoids on sleep problems. Finally, caryophyllene, myrcene and pinene may be useful in providing adjuvant support in treating addictions

Four basic mechanisms of synergy have recently been proposed (Wagner and Ulrich-Merzenich, 2009):1) multi-target effects; 2) pharmacokinetic effects such as improved solubility or bioavailability; 3) interactions of agents affecting bacterial resistance; and 4) modulation of adverse effects that can be achieved by the entourage effect.

Entourage effect of THC | Kalapa Clinic

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Use of THC in therapeutic treatments

THC is approved by the FDA to treat nausea and vomiting caused by chemotherapy in people who do not respond to other treatments. It is also used to stimulate appetite in HIV-positive people

Dronabinol (Marinol) is the synthetic form of THC that is found as capsules, oral solution or inhaled.

On the other hand, in Spain there is only one precedent for a medicine composed of Tetrahydrocannabinol called Sativex. This is a pharmacological solution developed by GW Pharma, composed of CBD and THC (1:1 ratio), indicated for the treatment of pain and spasticity in people with multiple sclerosis. [3]

Nabilone (Cesament) is another of the approved synthetic THC drugs used to palliate vomiting caused by chemotherapy

Tetrahydrocannabinol is one of the main molecules that generate the psychotropic effect of Cannabis

Molecular Structure of Tetrahydrocannabinol and Tetrahydrocannabinolic Acid | Kalapa Clinic
Molecular Structure of Tetrahydrocannabinol and Tetrahydrocannabinolic Acid

Tetrahydrocannabinol from a chemical perspective

THC, also known as delta-9-tetrahydrocannabinol (Δ9-THC) is the main generator of the psychotropic effect of cannabis.

As a secondary active metabolite of the plant, THC is believed to be present as a self-defence mechanism of the plant against herbivores.

Its molecular form is C21H30O2 and its molecular weight is 314.4636. Its melting point is 66ºC and its boiling point is 157ºC. At room temperature it forms a reddish crystallization .

It is a molecule insoluble in water, but soluble in organic solvents and fats.

THC is an INSOLUBLE molecule in water, but soluble in organic solvents and fats

Bibliography on Tetrahydrocannabinol and its therapeutic use

[1] Ligresti A, De Petrocellis L, Di Marzo V. From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Phar- macologyPhysiol Rev. 2016;96(4):1593-659

[2] Liu CS, Chau SA, Ruthirakuhan M, Lanctôt KL, Herrmann N. Cannabinoids for the Treatment of Agitation and Aggression in Alzheimer’s Disease. CNS Drugs. 2015 Aug;29(8):615-23. doi: 10.1007/s40263-015-0270-y

[3] Russo, E. B. (2011). Taming THC: potential cannabis synergy and phytocannabinoid‐terpenoid entourage effectsBritish journal of pharmacology, 163(7), 1344-1364.

[4] Russo, E., & Guy, G. W. (2006). A tale of two cannabinoids: the therapeutic rationale for combining tetrahydrocannabinol and cannabidiolMedical hypotheses, 66(2), 234-246.

[5] SEIC. Guía Básica sobre los cannabinoides. 2002.

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