Tetrahydrocannabinol [THC]

Tetrahydrocannabinol (THC) is the principal psychoactive constituent of cannabis, identified as one of at least 113 cannabinoids found in the plant. The chemical formula for THC is C21H30O2, and it primarily refers to the delta-9-THC isomer, known chemically as (−)-trans-Δ9-tetrahydrocannabinol. THC functions as a terpenoid and is believed to play a role in the plant’s defense mechanisms against insect predation, ultraviolet light, and environmental stress. Discovered and isolated in 1964 by Israeli chemist Raphael Mechoulam, THC acts by binding to endocannabinoid receptors in the brain, affecting areas responsible for thinking, memory, pleasure, coordination, and movement. It is one of the few cannabinoids scheduled by the UN Convention on Psychotropic Substances, reflecting its psychoactive properties and potential for abuse and dependence, albeit at a relatively low to moderate level compared to other controlled substances.

Medical Uses and Regulation:

• THC is an active ingredient in nabiximols, approved for multiple sclerosis symptoms.
• Nabiximols (Sativex) is a prescription drug in Canada and was approved for medical use in Ukraine in 2021.
• 38 states in the U.S. allow medical cannabis use.
• Dronabinol is classified differently from cannabis by the U.S. federal government.
• Canada legalized recreational cannabis use in October 2018.
• Approved dietary supplements in Canada contain up to 10 parts per million of THC extract.
• Legalization in Canada has led to an increase in approved THC-containing products.

Pharmacology and Mechanism of Action:

• Delta-9-THC acts as a partial agonist at cannabinoid receptors, mediating psychoactive effects.
• THC has antioxidant properties protecting neurons and is a partial autotaxin inhibitor.
• THC activates cannabinoid receptors in the CNS and immune system, decreasing cAMP concentration.
• THC has lower receptor affinity compared to endocannabinoids and binds to various entities in the brain and body.

Toxicity and Drug Testing:

• Lethal dose of THC in humans is uncertain, with conflicting evidence on lethal doses in animals.
• THC and its metabolites can be detected in blood, urine, hair, oral fluid, or sweat.
• Ongoing research aims to detect THC in breath for drug testing purposes.
• Prolonged exposure to high doses of THC may interfere with chromosomal stability and carcinogenicity in heavy users is uncertain.
• Various methods are used for drug testing programs, including immunoassay and chromatographic techniques.

Legal Aspects and International Legislation:

• Cannabis is classified as a Schedule I controlled substance in the U.S.
• Drug scheduling impacts the legal status and research opportunities of cannabis.
• International legal developments include the 2018 Cannabis Act in Canada and Uruguay’s Law No. 19172 on cannabis regulation.
• Landmark legal cases like Gonzales v. Raich in the U.S. have influenced cannabis laws.
• International treaty laws have impacted the rescheduling of cannabis and other substances in drug laws.

Research and Chemistry:

• THC was first isolated in 1964 and has medical uses with low abuse potential.
• Research on cannabinoids’ pharmacokinetics, pharmacodynamics, and metabolism is crucial for safe medical use.
• Studies on acute oral toxicity of cannabinoids in animals are essential for determining safe dosages.
• Evolution of cannabis chemistry research includes studies on cannabinoid and terpene content during growth.
• Medical marijuana research focuses on cannabinoids for various medical conditions and the legal status of cannabis under U.S. law.

Tetrahydrocannabinol Data Sources