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In addition to the effects of CBD, Dr. Perucca also discusses evidence of seizure inhibition by CBV, another non-intoxicating cannabinoid. The research on CBV is extremely limited but this cannabinoid also appears to act independently of CB1. Inter-estingly, there is also a case study in which a cannabis medication lost its efficacy when the terpene linalool was inadvertently removed from the formulation. [4, 5] Linalool has been shown to inhibit glutamate binding to CNS receptors, which may explain this activity. But to complicate matters, the patient in the linalool had been using both THC and THC-A as their primary cannabinoid. How CBD, THC, CBV, THC-A and the various terpenes modulate glutamate neuro-transmission in various comb-inations remains an unsolved puzzle.
While using multiple cannabinoids or whole plant medicines may be effective, the current FDA approach makes it very difficult to receive approval mixtures of compounds as new drug entities (NDEs). As the cannabinoid most effective as suppressing seizures, CBD is currently undergoing advanced clinical trials for Lennox-Gastaut and Dravet syndromes. [6] A recently completed Phase III study shows both the efficacy and safety of the plant-derived CBD product Epidiolex. In addition, GW Pharmaceuticals is developing a 1:1 THC:CBD product, Sativex. It has been approved for MS spasticity in sixteen countries and is currently undergoing clinical trials in the United States.
Looking back, humans have shaped cannabis chemistry for generations. We selectively grew strains with the most helpful properties, including – perhaps particularly – to combat seizures. The chemical production was guided towards the optimal overall effect; not necessarily the most singly potent compounds. The combinatorial (aka entourage) effect of cannabinoids may well be the most effective clinical approach. With more research we will better understand – and deliver to patients - the chemical compositions that best keep the ghosts away.