Reversal of cannabinoids (delta9-THC) by the benzoflavone moiety from methanol extract of Passiflora incarnata Linneaus in mice: a possible therapy for cannabinoid addiction.
The newly reported benzoflavone moiety from the plant Passiflora incarnata Linneaus has been evaluated in light of traditional reports on the use of P. incarnata in breaking down cannabis addiction. In the modern or allopathic system of therapeutics, there has been no suitable remedy to combat the severe withdrawal effects of various cannabis products, including marihuana, marijuana, bhang, hashish, ganja, etc., the world-wide consumption of which has attained alarming proportions especially among the younger generation. Mice were given a 10-mg-kg(-1) twice-daily dose of delta9-tetrahydrocannabinol (delta9-THC) by mouth for six days to make them dependent upon cannabinoids. Concurrently, other groups of mice were administered delta9-THC along with a 10- or 20-mg-kg(-1) twice-daily dose of the benzoflavone moiety from P. incarnata orally for 6 days. Upon measuring locomotor activity during the treatment regimen, it was noticed that the mice receiving the P. incarnata extract and delta9-THC together developed significantly less tolerance and dependence, relative to the mice receiving delta9-THC alone. Upon administration of SR-141716A, a selective cannabinoid-receptor antagonist (10 mg kg(-1), p.o.) to all the groups of mice on the 7th day, an artificial withdrawal was produced due to an abrupt decline of delta9-THC levels in mouse brain. However, the typical withdrawal effects like paw tremors and head shakes were significantly less in the mice given delta9-THC+P. incarnata benzoflavone moiety for 6 days. Upon administration of 20 mg kg(-1) of the P. incarnata benzoflavone moiety to mice showing severe symptoms of withdrawal due to administration of SR-141716A, there was a marked attenuation of withdrawal effects, thereby suggesting the usefulness of the benzoflavone moiety in delta9-THC withdrawal. Thus, the benzoflavone moiety of P. incarnata, when administered concurrently with delta9-THC, prevented the development of tolerance and dependence of cannabinoids in mice. Even an acute administration of the benzoflavone moiety (20 mg kg(-1), p.o.) significantly blocked the expression of withdrawal effects in delta9-THC-dependent mice.
Dhawan
Kamaldeep
K
Pharmacognosy Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Kumar
Suresh
S
Sharma
Anupam
A
D000284:Administration, Oral; D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology*; D004361:Drug Tolerance; D006213:Hallucinogens / Q000494:pharmacology*; D000432:Methanol; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D029598:Passiflora; D010880:Piperidines / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D011720:Pyrazoles / Q000494:pharmacology; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000037:antagonists & inhibitors; D000077285:Rimonabant; D012997:Solvents; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy
D001571:Benzoflavones; D006213:Hallucinogens; D010880:Piperidines; D010936:Plant Extracts; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D012997:Solvents; D013759:Dronabinol; D000077285:Rimonabant; D000432:Methanol