A systematic review of minor phytocannabinoids with promising neuroprotective potential

Embase and PubMed were systematically searched for articles addressing the neuroprotective properties of phytocannabinoids, apart from cannabidiol and Δ(9)‐tetrahydrocannabinol, including Δ(9)‐tetrahydrocannabinolic acid, Δ(9)‐tetrahydrocannabivarin, cannabidiolic acid, cannabidivarin, cannabichromene, cannabichromenic acid, cannabichromevarin, cannabigerol, cannabigerolic acid, cannabigerivarin, cannabigerovarinic acid, cannabichromevarinic acid, cannabidivarinic acid, and cannabinol. Out of 2,341 studies, 31 articles met inclusion criteria. Cannabigerol (range 5 to 20 mg·kg(−1)) and cannabidivarin (range 0.2 to 400 mg·kg(−1)) displayed efficacy in models of Huntington's disease and epilepsy. Cannabichromene (10–75 mg·kg(−1)), Δ(9)‐tetrahydrocannabinolic acid (20 mg·kg(−1)), and tetrahydrocannabivarin (range 0.025–2.5 mg·kg(−1)) showed promise in models of seizure and hypomobility, Huntington's and Parkinson's disease. Limited mechanistic data showed cannabigerol, its derivatives VCE.003 and VCE.003.2, and Δ(9)‐tetrahydrocannabinolic acid mediated some of their effects through PPAR‐γ, but no other receptors were probed. Further studies with these phytocannabinoids, and their combinations, are warranted across a range of neurodegenerative disorders.