Now that you have an understanding of the endocannabinoid system and how CBD interacts with it, let us consider the next major phytocannabinoid of the more than 100 identified so far.

Phytocannabinoid: ∆-9-THC

First isolated from cannabis in 1964 by Dr. Raphael Mechoulam, Tetrahydrocannabinol (THC) is one of the best studied, most widely known and most often maligned plant derived cannabinoid. It is the only cannabinoid considered to have psychoactive effects; however, that is not quite accurate. A more proper way to consider THC is it is the only cannabinoid producing euphoric effects. As with the other cannabinoids and terpenes, the effects of THC on the endocannabinoid system are complex and only partially understood.

Tetrahydrocannabinol comes in different varieties based on chemical structure. The different structures cause the drug to produce different effects. The native form produced by the plant is an acidic version of the chemical known as THCA. The "A" addition designates the acidic version and applies to the other cannabinoids like CBDA/CBD, etc. The acidic versions are considered inactive. Heating cannabis, referred to as decarboxylation, changes cannabinoids from the inactive acidic forms into the active chemical structure, which will interact with the endocannabinoid system. When THC is mentioned, I am referring specifically to the most prominent, active (through decarboxylation) delta-9-THC (∆-9-THC) variant of THC. Other versions of tetrahydrocannabinol, including the way the body changes ∆-9-THC to the more potent and longer lasting 11-OH-THC species, will be discussed separately.

The endocannabinoids are made by the individual nerve as needed for a very precise effect. The phytocannabinoids (cannabinoids derived from plants) are much less specific as they effect all the receptors exposed to them, not just those along a unique pathway. They are also less effective than the endocannabinoids at stimulating the receptors, which classifies them as "partial agonists."

Phytocannabinoids like THC, interact with the endocannabinoid system similar to the endocannabinoids. Andandemide (AEA) works primarily at the CB1 receptor centrally and has CB2 activity peripherally. 2-Arachidonoylglycerol (2-AG) is a full agonist (activates) at CB1 and CB2.

THC acts as a partial agonist (partially activates) at cannabinoid receptors CB1 and CB2. It has a stronger action at CB1, making it more like AEA than 2-AG. It is through the activation of these receptors that THC's wide variety of medical benefits are realized. Nausea, poor appetite, pain, inflammation, anxiety, depression and anticancer properties are some conditions for which medical cannabis has been shown to be of benefit. THC’s activities on the endocannabinoid system are a major component of medical cannabis’ efficacy in treating many of these conditions.

Back to the Big Picture

THC, like CBD, is just one piece of the cannabinoid puzzle. For some patients, such as those with nausea, poor appetite or cachexia, THC alone can be very effective. For most conditions, THC alone will offer only a partial response. It is the combination of and relative ratios of the individual cannabinoids and terpenes working together that produce the desired response.

Enter the Chemovar

The primary cannabinoid players in medical cannabis, THC and CBD, are the first to consider in choosing a particular chemovar rather than just a cultivar. A chemovar refers to the specific chemical composition of cannabinoids and terpenes present in a particular cannabis specimen while cultivar is a specific cannabis strain. Achieving the optimal response in using medical cannabis as treatment for you and your conditions requires thinking of cannabis a bit differently than just the strain name, indica, sativa, hybrid... Your understanding of the endocannabinoid system, phytocannabinoids, terpenes and their interactions will help you in selecting the most appropriate chemovar(s) for the best possible response.

Brian Nichol MD
Cannabis Expert