Tetrahydrocannabinol

Tetrahydrocannabinol, is a colorless oil with the molecular formula: C21H30O2. Tetrahydrocannabinol is apsychoactive substance, belongs to the cannabinoids, is practically insoluble in water, but highly solublein diethyl ether. Tetrahydrocannabinol is found in plants of the hemp genus(cannabis). The substance is a potent agonist of the cannabinoid receptor1(CB1), which mediates the psychotropic effects and activation of the reward pathway (Rong C et al. 2017).

THC is highly lipophilic. It can be isolated by extraction from THC-containing plant material using non-polar and weakly polar solvents such as n-alkanes, acetone, isopropyl alcohol or ethanol. After evaporation of the solvent, a resinous, oil-like extract remains. The composition of the extract depends on the choice of solvent. Under suitable conditions, very high THC concentrations of up to 90 % can be achieved. This extract is also known as hash oil.

THC is mainly extracted from the hemp plant (Cannabis indica). The unfertilized female flowers are particularly rich in THC (about 2-30%); the THC content of the other parts of the plant is much lower (just under 1%).

There is no THC in the seeds of the plant. The leaves near the flower contain about 5 to 6% THC. Male plants contain very little THC, unlike female plants.

Cannabidiol can be extracted from the terpene limonene or by other methods from low-THC commercial hemp and then converted to THC. This process is expensive.

In the cannabis plant, tetrahydrocannabinol is predominantly present as THC acid. Cannabigerolic acid is formed by enzymatic condensation from the two precursors geranyl pyrophosphate and olivetolic acid, which is then enzymatically converted to tetrahydrocannabinolic acid. Heat and UV radiation decarboxylate the acid to THC.

Four stereoisomersof delta-9-tetrahydrocannabinol exist:

• (-)-Δ9-trans-tetrahydrocannabinol (dronabiol)
• (+)-Δ9-trans-tetrahydrocannabinol (THC)
• (-)-Δ9-cis-tetrahydrocannabinol (no psychoactivity)
• (+)-Δ9-cis-tetrahydrocannabinol (no psychoactivity).

The major psychoactively active isomer is the (-)-Δ9-trans-THC, also known as dronabinol, which is 6 to 100 times more potent than the (+)-Δ9-trans-THC. The cis-forms have no psychoactive effect, and there is varying information about their natural occurrence.

THC is metabolized predominantly in the liver Graefe KH et al. 2016In the process, still effective metabolites are formed, such as 11-hydroxy-THC. They are slowly excreted in the stool (70%) and urine 30%. Therefore, they are pharmacologically detectable even a long time after consumption, which can be of great importance forensically (Graefe KH et al. 2016).

Since 2017, cannabis can be prescribed at the expense of health insurance funds (see Cannabis as a prescription). Dosages, titration and the administration system are predominantly empirical and require further investigation (Temple LM et al. 2020).

The drugs used are, for example:

• Dronabinol (isomer of tetrahydrocannabinol (THC).
• Nabilone® (fully synthetic derivative of delta-9-tetrahydrocannabinol)
• Nabiximols (consists of plant-derived THC and cannabidiol and is approved as an oral spray for the treatment of spasticity in multiple sclerosis).
• THC is currently (2019) in clinical trials for the treatment of conditions such as: in glaucoma, Crohn's disease (Kafil TS et al. 2018), other inflammatory bowel diseases (Hoffenberg EJ et al. 2019) including ulcerative colitis (Kafil TS et al. 2018) or tic disorders.

The consumption can be done in different ways. The most common way of consumption is smoking hashish or marijuana pure or mixed with tobacco. Street names for marijuana are: Aunt Mary, BC Bud, Chronic, Dope, Gangster, Ganja, Grass, Hash, Herb, Joint, Mary Jane, Mota, Pot, Reefer, Sinsemilla, Skunk, Smoke, Weed, and Yerba.

Often, THC-containing material is also smoked with the help of special smoking accessories such as bongs and pipes or vaporized with a vaporizer and then inhaled.

In addition, THC is also incorporated into food and beverages. Since THC is lipophilic, it is often incorporated into high-fat foods such as milk, cakes, muffins, etc. THC-containing foods often have a stronger effect than the comparable smoked dose. However, they are much more difficult to dose and thus involve incalculable risks (Poyatos L et al. 2020).

Importantly, oral administration of CBD in a corn oil formulation does not bioconvert to THC in humans (Crippa JAS et al. 2020).

Note: The pure THC cannot be administered intravenously without an emulsifier due to its poor dissolution behavior caused by strong lipophilicity.

Tetrahydrocannabinol was subject to the provisions of the Narcotics Act in Germany until 2024.

Since 2024, only nabilone has been subject to the Narcotics Act.

Medical products containing THC and CBD in standardized form (finished products and special formulations) can be prescribed on a normal prescription.

1. Crippa JAS et al. (2020) Oral Cannabidiol Does Not Convert to Δ8-THC or Δ9-THC in Humans: A Pharmacokinetic Study in Healthy Subjects. Cannabis Cannabinoid Res 27: 89-98.
2. Graefe KH et al. (2016) Graefe KH et al. Cnetral Nervous System. In: Graefe KH et al (Eds) Pharmacology and toxicology. Georg Thieme Verlag Stuttgart SS 352-353.
3. Hoffenberg EJ et al (2019) Cannabis oil use by adolescents and young adults with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 68:348-352
4. Kafil TS et al (2018) Cannabis for the treatment of ulcerative colitis. Cochrane Database Syst Rev 11:CD012954
5. Kafil TS et al. (2018) Cannabis for the treatment of Crohn's disease. Cochrane Database Syst Rev 11:CD012853
6. Muecke M et al. (2018) Cannabis-based medicines for chronic neuropathic pain in adults. Cochrane Database Syst Rev 3:CD012182.
7. Poyatos L et al (2020) Oral administration of cannabis and Δ-9-tetrahydrocannabinol (THC) preparations: A Systematic Review. Medicina (Kaunas) 56:309.
8. Rong C et al. (2017) Cannabidiol in medical marijuana: Research vistas and potential opportunities. Pharmacol Res 121:213-218
9. Temple LM et al (2020) Tetrahydrocannabinol - friend or foe? - Debate Clin Toxicol (Phila) 58:75-81.
10. Tiwari J et al (2018) Tetrahydrocannabinol: a drug of interest. Panminerva Med 60:228-230.