Mouse study finds stronger effects for THCP than for delta-8 THC or CBN

Δ9-Tetrahydrocannabinol (Δ9-THC), along with the non-intoxicating cannabinoid cannabidiol (CBD), is one of the most-abundant phytocannabinoids in the Cannabis sativa plant after decarboxylation of its acid form. Other phytocannabinoids present in limited quantities that may also be psychotropic, specifically Δ9-tetrahydrocannabiphorol (THCP), Δ8-tetrahydrocannabinol (Δ8-THC), and cannabinol (CBN). Compared to Δ9-THC, relatively little is known about their properties, yet these compounds are increasingly available in cannabis products. There is a pressing need to better understand the pharmacology of these phytocannabinoids and their potential health risks. In the present study, male and female mice were treated with THCP, Δ8-THC, or CBN via tail vein intravenous injection, intraperitoneal injection, or oral gavage and their levels were measured in whole-blood to estimate pharmacokinetic parameters while also measuring catalepsy, body temperature, and nociception. Catalepsy, body temperature, nociception, and locomotion were further assessed in male and female mice receiving Δ8-THC or CBN by intracranial injection. THCP levels were relatively high in blood and rapidly eliminated, whereas Δ8-THC and CBN pharmacokinetics were similar, compared to past studies using Δ9-THC. When accounting for circulating compound levels and ED50 responses, THCP was a highly potent and efficacious inducer of catalepsy, hypothermia, and reduced nociception, while Δ8-THC and CBN displayed limited activity, consistent with others' findings. Intracranial administration of Δ8-THC or CBN produced significant catalepsy or reduced nociception, respectively. This study presents the relative potencies and pharmacokinetic properties of THCP, Δ8-THC, and CBN in mice, that suggest that compared to Δ9-THC, THCP is more intoxicating, whereas Δ8-THC and CBN may be less-so.