Phytocannabinoids are produced in Cannabis sativa L. in acidic form and are decarboxylated upon heating, processing, and storage. While the biological effects of decarboxylated cannabinoids such as Δ9-tetrahydrocannabinol have been extensively investigated, the bioactivity of Δ9-tetahydrocannabinol acid (Δ9-THCA) is largely unknown, despite its occurrence in different cannabis preparations. Here we have assessed possible neuroprotective actions of Δ9-THCA through modulation of PPARγ pathways. The effects of six phytocannabinoids on PPARγ binding and transcriptional activity were investigated. The effect of Δ9-THCA on mitochondrial biogenesis and PPARγ coactivator 1-α expression was investigated in Neuro-2a (N2a) cells. The neuroprotective effect was analysed in STHdhQ111/Q111 cells expressing a mutated form of the huntingtin protein and in N2a cells infected with an adenovirus carrying human huntingtin containing 94 polyQ repeats (mHtt-q94). The in vivo neuroprotective activity of Δ9-THCA was investigated in mice intoxicated with the mitochondrial toxin 3-nitropropionic acid (3-NPA).