CBG

The main cannabinoid receptor in the brain, responsible for THC’s intoxicating effects, binds CBG relatively weakly. One human-receptor study measured a CB1 Ki of 897 nM for CBG versus 35.6 nM for Delta-9-THC under the same conditions, meaning Delta-9-THC showed approximately 25x stronger CB1 binding affinity.

Functional studies indicate weak partial agonist activity, meaning CBG can activate CB1 but much less effectively than Delta-9-THC. Binding and signalling vary considerably between assays. A controlled human study found no meaningful intoxication after oral CBG, consistent with its weak CB1 activity.

The main cannabinoid receptor in the immune system, involved in regulating immune cell activity and inflammatory responses. The same receptor study measured a CB2 Ki of 153 nM for CBG versus 8.5 nM for Delta-9-THC, meaning Delta-9-THC showed approximately 18x stronger CB2 binding affinity. CBG nevertheless binds CB2 approximately 5.9x more strongly than CB1.

CBG acts as a partial CB2 agonist, although its strength varies between signalling pathways. CB2 activation could influence immune and inflammatory signalling, but specific CB2-mediated effects have not been established in humans.

Alpha2-adrenoceptors help regulate norepinephrine release, which influences alertness, stress responses, heart rate and blood pressure. CBG acted as a potent alpha2-adrenoceptor agonist, with an EC50 of 0.2 nM in a mouse brain signalling assay.

Activation of these receptors normally reduces norepinephrine release, so CBG could potentially influence alertness and reduce physical stress responses such as increased heart rate. This mechanism is well demonstrated experimentally, but its importance in humans has not been established.

Voltage-gated sodium channels help sensory nerves generate electrical signals, including those involved in transmitting pain. CBG inhibits several of these channels, including NaV1.7 and NaV1.8. Recent human-channel research measured an IC50 of approximately 3.3 µM at NaV1.7 and 0.9 µM at NaV1.8, showing particularly strong inhibition of NaV1.8.

Inhibiting these channels can make pain-sensing nerves less likely to become activated and transmit repeated pain signals. This could potentially contribute to reduced pain sensitivity and less persistent pain signalling, although these effects have not yet been confirmed clinically in humans.

TRP channels help sensory nerves detect temperature, irritation and pain-related signals. CBG activates TRPA1 at approximately 0.7 µM, TRPV1 at 1.3 µM and TRPV2 at 1.7 µM, followed by desensitisation. CBG also activates TRPV3 and TRPV4 at low concentrations.

CBG additionally blocks the cold-sensing TRPM8 channel with an IC50 of approximately 0.16 µM.

Together, these interactions could influence pain, temperature sensitivity and inflammatory responses, although their contribution to CBG’s effects in humans remains uncertain.

The 5-HT1A receptor helps regulate serotonin signalling involved in mood, stress and emotional processing. CBG acts as a 5-HT1A antagonist, with an apparent KB of 51.9 nM in animal brain tissue. This means it reduces activation caused by other molecules at this receptor rather than activating it itself.

Blocking 5-HT1A can have different effects depending on where the receptor is located. It may increase serotonin release in some brain areas, while also reducing some of serotonin’s calming effects elsewhere. CBG could therefore potentially influence mood, anxiety and stress responses, although its actual effects through this mechanism in humans remain unknown.

PPARα and PPARγ are receptors that regulate gene activity involved in inflammation, fat metabolism and energy balance. Experimental research identifies CBG as a dual PPARα and PPARγ agonist, meaning it can activate both receptors.

Activating PPARα can increase the breakdown and use of fats for energy, while PPARγ can influence fat storage and how cells respond to insulin. Activation of both receptors can also reduce some inflammatory activity. CBG could therefore potentially affect inflammation, fat metabolism and blood-sugar regulation, although these effects have not been established in humans.

Anandamide is an endocannabinoid naturally produced by the body that helps regulate pain, mood, stress and other cannabinoid-related processes. CBG inhibits the cellular uptake of anandamide, with a reported Ki of approximately 11.3 µM.

By slowing anandamide uptake into cells, CBG could keep it active for longer and strengthen its effects. This may potentially contribute to reduced pain perception, changes in mood and lower stress responses, although these effects have not been established in humans.

After oral administration, CBG is absorbed into human blood. In laboratory research using human liver enzymes, CBG is rapidly converted into several metabolites. The main identified metabolite is cyclo-CBG, while 6′,7′-epoxy-CBG is formed in much smaller amounts. Cyclo-CBG was produced approximately 100 times more than 6′,7′-epoxy-CBG under the tested conditions.

Human enzymes contribute to this metabolism. Both metabolites have shown biological activity in laboratory cell research, including effects on inflammatory responses, although their contribution to CBG’s effects in humans remains unknown.