Abstract
Δ9-Tetrahydrocannabinol (Δ9-THC), the active phytocannabinoid in cannabis, is virtually
an adjunct to the endogenous endocannabinoid signaling system. By interacting with G-proteincoupled
receptors CB1 and CB2, Δ9-THC affects peripheral and central circulation by lowering
sympathetic activity, altering gene expression, cell proliferation, and differentiation, decreasing
leukocyte migration, modulating neurotransmitter release, thereby modulating cardiovascular functioning,
tumorigenesis, immune responses, behavioral and locomotory activities. Δ9-THC effectively
suppresses chemotherapy-induced vomiting, retards malignant tumor growth, inhibits metastasis,
and promotes apoptosis. Other mechanisms involved are targeting cell cycle at the G2-M phase
in human breast cancer, downregulation of E2F transcription factor 1 (E2F1) in human glioblastoma
multiforme, and stimulation of ER stress-induced autophagy. Δ9-THC also plays a role in ameliorating
neuroinflammation, excitotoxicity, neuroplasticity, trauma, and stroke and is associated
with reliving childhood epilepsy, brain trauma, and neurodegenerative diseases. Δ9-THC via CB1
receptors affects nociception, emotion, memory, and reduces neuronal excitability and excitotoxicity
in epilepsy. It also increases renal blood flow, reduces intraocular pressure via a sympathetic
pathway, and modulates hormonal release, thereby decreasing the reproductive function and increasing
glucose metabolism. Versatile medical marijuana has stimulated abundant research demonstrating
substantial therapeutic promise, suggesting the possibilities of first-in-class drugs in diverse
therapeutic segments. This review represents the current pharmacological status of the phytocannabinoid,
Δ9-THC, and synthetic analogs in cancer, cardiovascular, and neurodegenerative disorders.