Is Delta-9-tetrahydrocannabinol (Delta-9-THC) the primary psychoactive component of cannabis?

From the Guidelines

Delta-9-tetrahydrocannabinol (Delta-9-THC) is indeed the primary psychoactive component of cannabis, acting as a cannabinoid receptor Type 1 (CB1) and Type 2 (CB2) partial agonist, as evidenced by recent research 1. The mechanism of action of Delta-9-THC involves binding to CB1 receptors in the brain, which affects perception, mood, consciousness, and other cognitive functions.

• The CB1 receptor is found in virtually all CNS tissues, making it a potential target of pharmacological intervention in pain pathways 1.
• The concentration of Delta-9-THC in cannabis products can vary widely, and its effects can be influenced by multiple variables, such as smoking technique and inspiratory effort 1.
• The clinical effects of cannabis, including those related to Delta-9-THC, can involve many organ systems, including the CNS, cardiovascular system, and respiratory system, and can be associated with various perioperative concerns 1. Key aspects of Delta-9-THC include its potential for developing into a reliable means of treating patients, particularly in the areas of chronic pain, chemotherapy-induced nausea and vomiting, and spasticity associated with multiple sclerosis, as suggested by recent studies 1.
• However, it is essential to consider the potential risks and interactions associated with Delta-9-THC, such as difficulty achieving adequate depth of anesthesia, increased cerebral blood flow, and cardiovascular concerns, including beta-adrenergic-mediated tachycardia and orthostatic hypotension 1.

From the Research

Delta-9-tetrahydrocannabinol (Delta-9-THC) as the Primary Psychoactive Component of Cannabis

• Delta-9-tetrahydrocannabinol (Delta-9-THC) is identified as the primary psychoactive component of cannabis in multiple studies 2, 3, 4, 5, 6
• The plant itself contains over 400 individual chemicals, many with unique pharmacological properties, but Delta-9-THC is the driving cannabinoid that produces its psychoactive effects 2
• Delta-9-THC is the main psychoactive ingredient of cannabis, and its variability in plant material leads to variability in tissue THC levels from smoking 3
• The pharmacokinetics of Delta-9-THC have been studied, and it is widely distributed, particularly to fatty tissues, but less than 1% of an administered dose reaches the brain 3
• Delta-9-THC is also used and prescribed medically for therapeutic qualities, but it is the primary compound that drives cannabis abuse potential 4

Pharmacokinetics and Effects of Delta-9-THC

• The pharmacokinetics of Delta-9-THC include a bioavailability of 30% when smoked, and a peak plasma level of 152±86.3 ng/mL approximately 10 min after inhalation 3
• Oral Delta-9-THC is only 4% to 12% bioavailable, and absorption is highly variable 3
• Delta-9-THC is eliminated from plasma in a multiphasic manner, with low amounts detectable for over one week after dosing 3
• A major active 11-hydroxy metabolite is formed after both inhalation and oral dosing of Delta-9-THC 3

Clinical and Preclinical Findings

• Cannabis use disorder and withdrawal symptoms are associated with the use of Delta-9-THC, and there are no efficacious treatments for these conditions 4
• The neurobiological mechanisms of cannabis use disorder and withdrawal symptoms are being studied, and the central action on the cannabinoid type-one receptor and downstream intracellular signaling related to the endogenous cannabinoid system are thought to play a role 4
• Delta-9-THC has been studied in clinical trials, and it has been found to produce less tachycardia and less euphoria than nabilone for a similar antiemetic response 3