A study published in the International Journal of Pharmaceutics suggests that combining cannabinoid and terpene nanoparticles could offer enhanced pain-relief effects while requiring lower doses.
For the study, researchers encapsulated cannabigerolic acid (CBGA) and three cannabis-derived terpenes—myrcene, nerolidol, and caryophyllene—into biodegradable nanoparticles, then tested them alone and in combination for their ability to activate the TRPV1 pain receptor.
Individually, nerolidol showed the strongest TRPV1 activation, followed by myrcene and caryophyllene, while CBGA was less potent on its own. However, when combined at their EC50 concentrations, the CBGA/nerolidol pairing produced a markedly stronger response than either compound alone, suggesting a synergistic effect. The CBGA/myrcene combo did not reach statistical significance over the additive baseline, but it still enhanced calcium influx and is considered worth further investigation due to myrcene’s known analgesic properties.
Nanoparticles measured between 152 and 297 nanometers, with high encapsulation efficiency for CBGA (98.6%) and moderate levels for the terpenes. The CBGA formulation showed a biphasic release pattern, offering both rapid onset and sustained delivery over 72 hours.
According to the study’s authors, one key advantage of these combinations is their ability to achieve therapeutic effects at lower doses, potentially reducing side effects.
The study’s “conclusion” section states:
Our findings demonstrate that combining CBGA-loaded NPs with terpene-loaded NPs leads to a marked enhancement in fluorescence intensity, attributed to increased intracellular calcium ion influx, compared to the effects of each component individually. This enhancement is linked to TRPV1 channel activation, indicating the potential of these nanoformulations for applications in pain management. Among the tested combinations, CBGA with NL exhibited the most pronounced effect, suggesting strong potential for pain management applications. Although the CBGA/MC combination did not show a statistically significant enhancement compared to calculated additive values, it still produced elevated responses and should be further explored, given the known analgesic properties of myrcene. A key advantage of these combinations is the ability to achieve therapeutic efficacy with lower nanoparticle doses, which may reduce potential side effects. Further in vivo studies in animal models are necessary to validate these findings and confirm their translational potential in pain-related conditions.
