Title:An Agathokakological Tale of Δ9-THC: Exploration of Possible Biological Targets
VOLUME: 21
Author(s):Bijo Mathew*, Seetha Harilal, Arafa Musa, Rajesh Kumar, Della Grace Thomas Parambi, Jobin Jose, Md. Sahab Uddin, Muhammad Ajmal Shah, Tapan Behl and Mazhuvancherry Kesavan Unnikrishnan
Affiliation:Division of Drug Design and Medicinal Chemistry Research Lab, Department of Pharmaceutical Chemistry, Ahalia School of Pharmacy, Palakkad, 678557, Kerala, Department of Pharmacy, Kerala University of Health Sciences, Thrissur, Kerala, Department of Pharmacogonosy, College of Pharmacy, Jouf University, Sakaka, Al Jouf, 2014, Department of Pharmacy, Kerala University of Health Sciences, Thrissur, Kerala, Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka, Al Jouf, 2014, Department of Pharmaceutics, NGSM Institute of Pharmaceutical Science, NITTE Deemed to be University, Manglore, 575018, Department of Pharmacy, Southeast University, Dhaka, Department of Pharmacogonosy, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad, Department of Pharmacology, Chitkara College of Pharmacy, Chitkara University, Punjab, Department of Pharmaceutical Chemistry, National College of Pharmacy, Calicut
Keywords: ∆
9
-Tetrahydrocannabinol, tetrahydrocannabinol, epilepsy, atherogenesis, neuroinflammation, neurodegenerative diseases
Abstract:Δ9-Tetrahydrocannabinol (Δ9-THC), the active phytocannabinoid in cannabis, is virtually
an adjunct to the endogenous endocannabinoid signaling system. By interacting with G-protein--
coupled 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.
