Aalysis of THC-induced depression mechanism focused on the molecular clock

• Project/Area Number: 25893282
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Environmental and hygienic pharmacy
• Research Institution: Daiichi University, College of Pharmaceutical Sciences
• Principal Investigator: KOHRO ERIKO 第一薬科大学, 薬学部, 助教 (10708431)
• Project Period (FY): 2013-08-30 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 大麻 / 体内時計

Outline of Final Research Achievements

Tetrahydrocannabinol (THC), a major component of the Cannabis Sativa, exhibits a variety of pharmacological effects. Previous studies have suggested that THC use may be a contributory cause of depression and suicidal behaviours.The alteration of clock genes expression in striatum has been suggested to be an underlying cause of drug-induced depression and addiction, in the psychoactive drugs such as cocaine and amphetamine. However, the physiological role of the clock genes in THC-induced depression has not yet been understood.
Here, we examined whether the alteration of circadian clock function might occur by chronic administration of THC in mice. THC-treated mice altered the circadian rhythm of clock genes expression in striatum. THC-treated mice exhibited alteration of locomotor activity and prolonged immobility time in forced swim test. These results suggest that disruption in circadian clock system may be an underlying cause of THC-induced depression.

Research Products

• [Journal Article] Bongkrekic acid as a selective activator of the peroxisome proliferator-activated receptor γ (PPARγ) isoform (2015)
  • Author(s): Okazaki H, Takeda S, Ikeda E, Fukunishi Y, Ishii H, Taniguchi A, Tokuyasu M, Himeno T, Kakizoe K, Matsumoto K, Shindo M, Aramaki H.
  • Journal Title: J. Toxicol. Sci. Volume: 40 Issue: 2 Pages: 223-233
  • DOI: 10.2131/jts.40.223
  • NAID: 130004904039
  • ISSN: 0388-1350, 1880-3989
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Δ(9)-THC modulation of fatty acid 2-hydroxylase (FA2H) gene expression: possible involvement of induced levels of PPARα in MDA-MB-231 breast cancer cells. (2014)
  • Author(s): Takeda, S., Ikeda, E., Su, S., Harada, M., Okazaki, H., Yoshioka, Y., Nishimura, H., Ishii, H., Kakizoe, K., Taniguchi, A., Tokuyasu, M., Himeno, T., Watanabe, K., Omiecinski, C.J., and Aramaki, H.
  • Journal Title: Toxicology. Volume: 326 Pages: 18-24
  • DOI: 10.1016/j.tox.2014.09.011
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Down-regulation of cyclooxygenase-2 (COX-2) by cannabidiolic acid in human breast cancer cells. (2014)
  • Author(s): Takeda S, Okazaki H, Ikeda E, Abe S, Yoshioka Y, Watanabe K, Aramaki H.
  • Journal Title: J Toxicol Sci. Volume: 39 Pages: 711-716
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 大麻主成分Δ9-THCのマウス概日時計機構に与える影響 (2014)
  • Author(s): 池田恵理子1、 岡崎裕之1、竹田修三2、 渡辺和人3、 荒牧弘範1
  • Organizer: 時間生物学会
  • Place of Presentation: 福岡県 九州大学
  • Year and Date: 2014-11-07 – 2014-11-09