Cannabinoids

Cannabinoids are unique compounds that are essentially only found in cannabis. They are technically “terpenophenolic” compounds, having properties of terpenes and phenols.

The cannabis plant produces over 100 cannabinoids through complex enzymatic processes. First, the plant combines olivetolic acid and geranyl pyrophosphate to produce cannabigerolic acid (CBGA), the “mother cannabinoid.” Specialized enzymes then convert CBGA to all other cannabinoids. For example, THCA synthase converts CBGA to THCA, and CBDA synthase converts CBGA to CBDA. A plant’s genetics and environment influence the expression of these synthase enzymes.

These acidic cannabinoids convert to their neutral forms after exposure to heat. Therefore, THCA becomes THC, and CBDA becomes CBD. In the medical cannabis world, the heated, neutral cannabinoids are far more prevalent than acidic cannabinoids, although their value is being increasingly recognized.

Short descriptions of all the major phytocannabinoids are found below.

THC

THC is the primary psychotropic cannabinoid in cannabis. It’s essentially the only one that cause a strong “high”. THC works by activating CB1 and CB2 cannabinoid receptors on the surfaces of cells throughout the body, leading to analgesic, anti-stress, anti-anxiety, and anti-spasmodic activity. The ability to cause a high is directly related to CB1 activation in the brain.

THC is one of the most potent cannabinoids, and many patients get good results from small doses. Those new to cannabis may want to start with as little as 1 mg, and increase by only 1 – 5 mg/day until reaching a dose that provides therapeutic relief.

In exchange for THC’s power, it also has the most potential for negative side effects of any cannabinoid. Taking too much can lead to anxiety, paranoia, nausea, and overall discomfort. Side effects can be largely avoided by slow dosing and potentially combining THC with other cannabinoids.

THC

CBD

CBD is the primary non-psychotropic cannabinoid in cannabis. It doesn’t have strong activity at the CB1 receptor, so doesn’t cause a high, although some studies indicate benefits do come from CB1/CB2 interactions. Most of CBD’s benefits appear to come from interactions with other receptors, like TRPV1, TRPV2, PPAR-gamma, and 5-HT1A (serotonin) receptors.

Patients report CBD helping with a very wide variety of ailments, including pain, sleep, anxiety, nausea, and seizures. The “therapeutic window” is quite wide, with patients using as little as 5-10 mg/day, and others needing upwards of 500 mg/day. Generally, the more severe one’s condition, the more CBD they need.

Combining small amounts of THC, or other cannabinoids, with CBD may lower the total amount of CBD needed. CBD may also reduce the psychoactivity of THC for some patients, by reducing THC’s action at CB1 receptors (through receptor antagonism and negative allosteric modulation, if you’re interested!)

CBG

CBG is the neutral version of the “mother cannabinoid”, CBGA. CBG is arguably the third-most popular cannabinoid, often appearing in formulations with CBD.

Some research suggests CBG may have stronger anti-inflammatory properties than CBD, and some patients report it works better for pain, sleep, and stress. Initial research suggests it may be able to replace THC for certain conditions, which decreases the risk of THC-related adverse effects.

For now, CBG tends to be used at lower doses than CBD. Many people may find doses between 10 – 100 mg/day may provide benefits.

CBG

CBC

CBC is a far less-studied cannabinoid, but early research suggests it may be especially good for anxiety and depression.

One unique element of CBC is its particularly potent activation of TRPA1 receptors, which may convey efficacy for improving blood flow, enhancing insulin sensitivity, and reducing pain.

Dosing with CBC is quite uncertain right now, but it’s reasonable to explore doses of 5 – 50 mg/day to see if it works for you.

CBN

CBN is most associated with helping improve sleep, with some clinical evidence supporting this efficacy. CBN likely works best for sleep when combined with at least some THC.

Interestingly, CBN is not produced by the cannabis plant – it emerges when THC degrades via oxidation caused by air, light, and heat.

In terms of dosing, one double-blind, placebo-controlled trial found that between 25 – 100 mg/day CBN was a “safe and effective” alternative for improving sleep.

CBN

THCV

THCV is the “varin counterpart” of THC, with a shorter side-chain on the molecule. This different shape causes it to behave differently, including having overall less psychoactivity than THC.

The compound shows special promise with metabolic health, potentially helping reduce appetite and weight. Mentally, it has been reported to improve focus.

CBDV

CBDV is the “varin counterpart” of CBD. It may be a particularly powerful anti-inflammatory compound – this study specifically called out CBDV as reducing numerous protein associated with inflammation.

Emerging reports also suggest CBDV may help reduce seizures. For some patients who don’t respond to CBD, CBDV may be worth trying.