Narrative review reveals limited evidence for phytochemical modulation of THC in humans, suggesting the entourage effect remains largely unproven.
Key Points
To critically review and synthesize empirical clinical and preclinical evidence regarding how non-THC cannabinoids and terpenes modulate the pharmacodynamic effects of delta-9-THC.
Conducted a systematic search of PubMed for controlled preclinical and clinical studies investigating interactions between delta-9-THC and other cannabis constituents.
Evaluated minor cannabinoids including CBD, CBN, THCV, CBG, and CBC, alongside common terpenes such as α-pinene, d-limonene, and β-myrcene.
Oral co-administration of CBD significantly exacerbates THC effects in humans, whereas inhaled CBD does not produce this interactive modulation.
THCV attenuates select cognitive and subjective effects of THC, while the terpene d-limonene selectively reduces adverse effects associated with high THC doses.
Most interactions between THC and minor phytochemicals identified in preclinical animal models fail to translate into observable clinical outcomes in humans.