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Blunting of the HPA-axis underlies the lack of preventive efficacy of early post-stressor single-dose Delta-9-tetrahydrocannabinol (THC).
Pharmacol Biochem Behav. 2014 Jul; 122:307-18.PB

Abstract

The therapeutic value of Delta-9-tetrahydrocannabinol (Δ9-THC) in the aftermath of trauma has recently raised interest. A prospective animal model for posttraumatic stress disorder was employed to assess the behavioral effects of a single dose of Δ9-THC administered intraperitoneally following exposure to psychogenic stress. Animals were exposed to predator scent stress and treated 1h later with Δ9-THC (1, 5 and 10mg/kg) or vehicle. The outcome measures included behavior in an elevated plus-maze and acoustic startle response 1, 6 and 24 h or 7 days after exposure and freezing behavior upon exposure to a trauma cue on day 8. Pre-set cut-off behavioral criteria classified exposed animals as those with "extreme," "minimal" or "intermediate" (partial) response. Circulating corticosterone levels were assessed over 2h after exposure with and without Δ9-THC. The behavioral effects of a CB1 antagonist (AM251) administered systemically 1h post exposure were evaluated. In the short term (1-6 h), 5 mg/kg of Δ9-THC effectively attenuated anxiety-like behaviors. In the longer-term (7 days), it showed no effect in attenuating PTSD-like behavioral stress responses, or freezing response to trauma cue. Δ9-THC significantly decreased corticosterone levels. In contrast, administration of AM251 (a CB1 antagonist/inverse agonist) 1 h post exposure attenuated long-term behavioral stress responses through activation of the HPA-axis. The demonstrated lack of preventive efficacy of early Δ9-THC treatment and reports of its anxiogenic effects in many individuals raises doubts not only regarding its potential clinical value, but also the advisability of clinical trials. The endocannabinoids exert complex effects on behavioral responses mediating glucocorticoid effects on memory of traumatic experiences.

Authors+Show Affiliations

Soroka Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.Ministry of Health, Anxiety and Stress Research Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.Ministry of Health, Anxiety and Stress Research Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.Division of Psychiatry, The State of Israel Ministry of Health, The Chaim Sheba Medical Center, Sackler Medical School, Tel-Aviv University, Tel Hashomer, Israel.Ministry of Health, Anxiety and Stress Research Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel. Electronic address: hagitc@bgu.ac.il.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

24814135

Citation

Mayer, Tzur Alexander, et al. "Blunting of the HPA-axis Underlies the Lack of Preventive Efficacy of Early Post-stressor Single-dose Delta-9-tetrahydrocannabinol (THC)." Pharmacology, Biochemistry, and Behavior, vol. 122, 2014, pp. 307-18.
Mayer TA, Matar MA, Kaplan Z, et al. Blunting of the HPA-axis underlies the lack of preventive efficacy of early post-stressor single-dose Delta-9-tetrahydrocannabinol (THC). Pharmacol Biochem Behav. 2014;122:307-18.
Mayer, T. A., Matar, M. A., Kaplan, Z., Zohar, J., & Cohen, H. (2014). Blunting of the HPA-axis underlies the lack of preventive efficacy of early post-stressor single-dose Delta-9-tetrahydrocannabinol (THC). Pharmacology, Biochemistry, and Behavior, 122, 307-18. https://doi.org/10.1016/j.pbb.2014.04.014
Mayer TA, et al. Blunting of the HPA-axis Underlies the Lack of Preventive Efficacy of Early Post-stressor Single-dose Delta-9-tetrahydrocannabinol (THC). Pharmacol Biochem Behav. 2014;122:307-18. PubMed PMID: 24814135.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Blunting of the HPA-axis underlies the lack of preventive efficacy of early post-stressor single-dose Delta-9-tetrahydrocannabinol (THC). AU - Mayer,Tzur Alexander, AU - Matar,Michael Alex, AU - Kaplan,Zeev, AU - Zohar,Joseph, AU - Cohen,Hagit, Y1 - 2014/05/06/ PY - 2014/02/25/received PY - 2014/04/11/revised PY - 2014/04/26/accepted PY - 2014/5/13/entrez PY - 2014/5/13/pubmed PY - 2015/1/27/medline KW - Animal model KW - CB1 antagonist/inverse agonist KW - Delta-9-tetrahydrocannabinol (Δ9-THC) KW - Early drug intervention KW - Posttraumatic stress disorder KW - Secondary prevention SP - 307 EP - 18 JF - Pharmacology, biochemistry, and behavior JO - Pharmacol Biochem Behav VL - 122 N2 - The therapeutic value of Delta-9-tetrahydrocannabinol (Δ9-THC) in the aftermath of trauma has recently raised interest. A prospective animal model for posttraumatic stress disorder was employed to assess the behavioral effects of a single dose of Δ9-THC administered intraperitoneally following exposure to psychogenic stress. Animals were exposed to predator scent stress and treated 1h later with Δ9-THC (1, 5 and 10mg/kg) or vehicle. The outcome measures included behavior in an elevated plus-maze and acoustic startle response 1, 6 and 24 h or 7 days after exposure and freezing behavior upon exposure to a trauma cue on day 8. Pre-set cut-off behavioral criteria classified exposed animals as those with "extreme," "minimal" or "intermediate" (partial) response. Circulating corticosterone levels were assessed over 2h after exposure with and without Δ9-THC. The behavioral effects of a CB1 antagonist (AM251) administered systemically 1h post exposure were evaluated. In the short term (1-6 h), 5 mg/kg of Δ9-THC effectively attenuated anxiety-like behaviors. In the longer-term (7 days), it showed no effect in attenuating PTSD-like behavioral stress responses, or freezing response to trauma cue. Δ9-THC significantly decreased corticosterone levels. In contrast, administration of AM251 (a CB1 antagonist/inverse agonist) 1 h post exposure attenuated long-term behavioral stress responses through activation of the HPA-axis. The demonstrated lack of preventive efficacy of early Δ9-THC treatment and reports of its anxiogenic effects in many individuals raises doubts not only regarding its potential clinical value, but also the advisability of clinical trials. The endocannabinoids exert complex effects on behavioral responses mediating glucocorticoid effects on memory of traumatic experiences. SN - 1873-5177 UR - https://www.unboundmedicine.com/medline/citation/24814135/Blunting_of_the_HPA_axis_underlies_the_lack_of_preventive_efficacy_of_early_post_stressor_single_dose_Delta_9_tetrahydrocannabinol__THC__ DB - PRIME DP - Unbound Medicine ER -