Pre- and post-conditioning treatment with an ultra-low dose of Δ9-tetrahydrocannabinol (THC) protects against pentylenetetrazole (PTZ)-induced cognitive damage

Assaf, Fadi; Fishbein, Miriam; Gafni, Mikhal; Keren, Ora; Sarne, Yosef

doi:10.1016/j.bbr.2011.02.005

Cited by 35 publications

(32 citation statements)

References 52 publications

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“…However, Erdoğan et al have demonstrated impaired fear-related memory in rats one and two weeks after PTZ-induced seizures [89]. Later, Assaf et al further supported these findings by the demonstration of spatial and object memory deficits in mice that experienced episodes of PTZ-induced convulsions 3-5 weeks earlier [90]. Recently, we have performed a detailed long lasting behavioral study and demonstrated slowly developing impairments of short-term memory in rats after single PTZ-evoked seizure, appearing approximately 2 months after the seizure episode [91].…”

Section: Single Seizure and Cognition: Clinical And Translational Impsupporting

confidence: 54%

Single Seizure and Cognition: Clinical and Translational Implications

2016

ARC Journal of Neuroscience

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Section: Single Seizure and Cognition: Clinical And Translational Impsupporting

confidence: 54%

Single Seizure and Cognition: Clinical and Translational Implications

2016

ARC Journal of Neuroscience

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“…Previous animal studies have already demonstrated hepatoprotective effects of various cannabinoid drugs [6,7,8,9,10,11,12,25,26]. It should be noted, however, that these studies presented a common experimental features: the doses that were administrated intraperitonealy ranged between 3 and 20 mg/kg (the doses that also induce the conventional acute effects of cannabinoids).…”

Section: Discussionmentioning

confidence: 92%

“…This parameter might be of clinical importance. We previously showed that the same ultra-low dose of THC conferred a significant neuroprotection when applied to mice either 7 days before or 3 days after brain insult [10]. In addition we have demonstrated that a single ultra low dose of THC before ischemia is a safe and effective treatment that reduces myocardial ischemic damage when applied up to 48 hours before the insult [13].…”

Section: Discussionmentioning

confidence: 99%

“…Oxidative stress and inflammatory stimuli may trigger hepatic endocannabinoid production [6]. The protective effect of various cannabinoid agonists has previously been demonstrated in a well characterized mouse model of hepatic I/R injury [6,7,8,9,10,11,12]. All these cannabinoids has been applied at high doses (3-20 mg/kg) that also induce the conventional pharmacological effects of cannabinoids.…”

Section: Introductionmentioning

confidence: 99%

“…administration of Δ9- tetrahydrocannabiol (THC), the major psychoactive ingredient of marijuana, at an extremely low dose (0.002 mg/kg, which is 3-4orders of magnitude lower than doses that evoke the conventional acute effects of the drug), protected the mice and prevented the development of long-term cognitive deficits induced by the epileptogenic drug pentylenetetrazole, by pentobarbital deep anesthesia or by CO intoxication [10,11,12]. In addition we have demonstrated that a single ultra low dose of THC before ischemia is a safe and effective treatment that reduces myocardial ischemic damage [13].…”

Section: Introductionmentioning

confidence: 99%

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Ultra Low Dose Delta 9-Tetrahydrocannabinol Protects Mouse Liver from Ischemia Reperfusion Injury

Hochhauser

Lahat

Sultan

et al. 2015

Cell Physiol Biochem

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Background/Aims: Ischemia/reperfusion (I/R) injury is the main cause of both primary graft dysfunction and primary non-function of liver allografts. Cannabinoids has been reported to attenuate myocardial, cerebral and hepatic I/R oxidative injury. Delta-9-tetrahydrocannabinol (THC), a cannabinoid agonist, is the active components of marijuana. In this study we examined the role of ultralow dose THC (0.002mg/kg) in the protection of livers from I/R injury. This extremely low dose of THC was previously found by us to protect the mice brain and heart from a variety of insults. Methods: C57Bl Mice were studied in in vivo model of hepatic segmental (70%) ischemia for 60min followed by reperfusion for 6 hours. Results: THC administration 2h prior to the induction of hepatic I/R was associated with significant attenuated elevations of: serum liver transaminases ALT and AST, the hepatic oxidative stress (activation of the intracellular signaling CREB pathway), the acute proinflammatory response (TNF-α, IL-1α, IL-10 and c-FOS hepatic mRNA levels, and ERK signaling pathway activation). This was followed by cell death (the cleavage of the pro-apoptotic caspase 3, DNA fragmentation and TUNEL) after 6 hours of reperfusion. Significantly less hepatic injury was detected in the THC treated I/R mice and fewer apoptotic hepatocytes cells were identified by morphological criteria compared with untreated mice. Conclusion: A single ultralow dose THC can reduce the apoptotic, oxidative and inflammatory injury induced by hepatic I/R injury. THC may serve as a potential target for therapeutic intervention in hepatic I/R injury during liver transplantation, liver resection and trauma.

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Ultralow doses of cannabinoid drugs protect the mouse brain from inflammation‐induced cognitive damage

Fishbein-Kaminietsky

Gafni

Sarne

2014

J of Neuroscience Research

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In our previous studies, we found that a single ultralow dose of tetrahydrocannabinol (THC; 0.002 mg/kg, three to four orders of magnitude lower than the conventional doses) protects the brain from different insults that cause cognitive deficits. Because various insults may trigger a neuroinflammatory response that leads to secondary damage to the brain, the current study tested whether this extremely low dose of THC could protect the brain from inflammation-induced cognitive deficits. Mice received a single injection of THC (0.002 mg/kg) 48 hr before or 1-7 days after treatment with lipopolysccharide (LPS; 10 mg/kg) and were examined with the object recognition test 3 weeks later. LPS caused long-lasting cognitive deficits, whereas the application of THC before or after LPS protected the mice from this LPS-induced damage. The protective effect of THC was blocked by the cannabinoid (CB) 1 receptor antagonist SR14176A but not by the CB2 receptor antagonist SR141528 and was mimicked by the CB1 agonist ACEA but not by the CB2 agonist HU308. The protective effect of THC was also blocked by pretreatment with GW9662, indicating the involvement of peroxisome proliferator-activated receptor-γ. Biochemical examination of the brain revealed a long-term (at least 7 weeks) elevation of the prostaglandin-producing enzyme cyclooxygenase-2 in the hippocampus and in the frontal cortex following the injection of LPS. Pretreatment with the extremely low dose of THC tended to attenuate this elevation. Our results suggest that an ultralow dose of THC that lacks any psychotrophic activity protects the brain from neuroinflammation-induced cognitive damage and might be used as an effective drug for the treatment of neuroinflammatory conditions, including neurodegenerative diseases.

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Pre- and post-conditioning treatment with an ultra-low dose of Δ9-tetrahydrocannabinol (THC) protects against pentylenetetrazole (PTZ)-induced cognitive damage

Cited by 35 publications

References 52 publications

Single Seizure and Cognition: Clinical and Translational Implications

Single Seizure and Cognition: Clinical and Translational Implications

Ultra Low Dose Delta 9-Tetrahydrocannabinol Protects Mouse Liver from Ischemia Reperfusion Injury

Ultralow doses of cannabinoid drugs protect the mouse brain from inflammation‐induced cognitive damage

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