Among 10 lesser-known cannabinoids tested on pain-sensing neurons, THCP and CBC showed the strongest ability to reduce pain signaling — with THCP active at very low concentrations — expanding the potential toolkit beyond THC and CBD.
Read this if you're interested in the next generation of cannabinoid pain research — beyond THC and CBD, there are at least 10 other cannabinoids with measurable effects on pain-sensing neurons.
What the researchers found
Cannabis produces over 100 cannabinoids, but research has focused almost exclusively on THC and CBD. This study tested 10 'minor' cannabinoids for their effects on pain-sensing neurons — and found that some of them are surprisingly potent.
The researchers used an established model of neuropathic pain: cultured rat dorsal root ganglion (DRG) neurons sensitized with nerve growth factor and GDNF, then challenged with capsaicin (the compound that makes chili peppers burn). This model mimics the neuronal hypersensitivity that underlies chronic neuropathic pain.
The 10 cannabinoids tested — THCC, CBT, CBDV, CBN, CBC, CBCV, CBCT, CBGM, THCB, and THCP — showed differential, dose-related effects on pain signaling. THCP (tetrahydrocannabiphorol) stood out for its potency at very low concentrations, consistent with its known high affinity for CB1 receptors. CBC (cannabichromene) also showed strong analgesic activity.
Other cannabinoids like CBN and CBDV showed moderate effects, while some had minimal impact. Importantly, the effects were dose-related — at certain concentrations some cannabinoids reduced pain signaling, while at higher concentrations the effects sometimes changed direction.
This matters because neuropathic pain affects millions of people and remains inadequately treated. Current options — opioids, anticonvulsants, antidepressants — have significant side effects and limited efficacy. If minor cannabinoids like THCP or CBC can modulate pain at the neuronal level, they represent entirely new pharmacological targets.
Why it matters
Neuropathic pain is one of the greatest unmet clinical needs in medicine. Current treatments fail about 50% of patients. Minor cannabinoids represent a largely unexplored pharmacological frontier. This systematic comparison of 10 cannabinoids on pain-sensing neurons provides the foundational data needed to identify which minor cannabinoids are most worth pursuing in animal models and eventually human trials.
The numbers in context
10 minor cannabinoids tested: THCC, CBT, CBDV, CBN, CBC, CBCV, CBCT, CBGM, THCB, THCP. Concentration range: 0.001-100 μM. THCP showed potency at very low concentrations. CBC showed strong analgesic activity. Effects were dose-related and varied by cannabinoid. Model: sensitized rat DRG neurons challenged with capsaicin.
How the study worked
In vitro study using adult rat DRG neurons cultured with nerve growth factor (100 ng/mL) and GDNF (50 ng/mL) for 48 hours to sensitize nociceptors. Calcium imaging measured neuronal responses to capsaicin stimulation, and the modulatory effects of 10 minor cannabinoids at concentrations of 0.001-100 μM were assessed in individual neurons.
Who was studied
Adult rat dorsal root ganglion neurons cultured in vitro.
What this study cannot tell us
In vitro study using rat neurons — several steps removed from human clinical relevance. The capsaicin challenge model assesses one type of pain signaling (TRPV1-mediated) and may not represent all neuropathic pain mechanisms. Dose-response relationships in isolated neurons don't predict effective doses in living animals or humans. No comparison to THC or CBD in the same assay, making it hard to benchmark the minor cannabinoids. Cannabinoid metabolism, distribution, and brain penetration — critical for clinical efficacy — aren't addressed.
How to read the evidence
In vitro study on rat neurons. Provides systematic comparison data that's valuable for prioritizing which minor cannabinoids to advance into animal studies, but is very early-stage evidence with no direct clinical applicability.
When this study was published
Published in 2025. Minor cannabinoid research is a rapidly expanding field as interest moves beyond THC and CBD.
The bigger picture
This study expands the cannabinoid toolkit beyond the two compounds (THC and CBD) that dominate research and commerce. The CBG research in RTHC-00097 (rheumatoid arthritis) and the CBD immune work in RTHC-00098 have already shown that non-THC cannabinoids have biological activity. This study goes further by systematically comparing 10 minor cannabinoids head-to-head for pain-relevant activity. THCP's potency at low concentrations is particularly interesting because it could potentially provide pain relief at doses below the threshold for psychoactive effects.
Replication
Not stated in abstract.
Funding
Not reported in abstract.
Conflicts of interest
Not reported in abstract.
Questions still open
- Would THCP or CBC reduce neuropathic pain in animal models? Can THCP's pain-modulating effects be achieved at doses below the psychoactive threshold? Could combinations of minor cannabinoids produce synergistic analgesic effects? Would any of these minor cannabinoids work topically for localized neuropathic pain?
Read the original research
Modulatory Effects of "Minor" Cannabinoids in an in vitro Model of Neuronal Hypersensitivity.
Journal of pain research, 18, 6259-6274
The Journal of Pain Research is a peer-reviewed journal focusing on pain management and research.
Citation
Anand, Uma; Anand, Praveen; Sodergren, Mikael H. (2025). Modulatory Effects of "Minor" Cannabinoids in an in vitro Model of Neuronal Hypersensitivity.. Journal of pain research, 18, 6259-6274. https://doi.org/10.2147/JPR.S547613
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