Despite strong behavioral disruption, Δ9-tetrahydrocannabinol does not affect cell proliferation in the adult mouse dentate gyrus

Kochman, Linda J.; Amâncio-dos-Santos, Ângela; Fornal, Casimir A.; Jacobs, Barry L.

doi:10.1016/j.brainres.2006.07.080

Cited by 34 publications

(23 citation statements)

References 39 publications

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“…Although HU210 studies in rats have shown increased hippocampal neurogenesis following treatment [11], studies with tetrahydrocannabinol (THC) in mice could not reproduce these findings [37] despite neurogenesis problems seen in CB1 knockout mice [9]. To investigate whether HU210 had any effect on neurogenesis in AD model mice, we first treated WT mice with high and low doses of HU210, and found that treatment did not increase hippocampal neurogenesis compared to vehicle controls (data not shown).…”

Section: Discussionmentioning

confidence: 82%

Effect of Synthetic Cannabinoid HU210 on Memory Deficits and Neuropathology in Alzheimers Disease Mouse Model

Chen

Bromley-Brits²,

et al. 2010

CAR

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Cannabinoids have been shown to increase neurogenesis in adult brain, as well as protect neurons from excitotoxicity, calcium influx, inflammation, and ischemia. Recent studies have shown that synthetic cannabinoids can alleviate water maze impairments in rats treated with intracranial amyloid beta protein (Abeta); however it is unknown whether this effect is due to the cannabinoids' anti-inflammatory properties or whether it affects Abeta processing. Here we investigate whether cannabinoids have any effect on Alzheimer's disease in vivo. We found that HU210, a potent synthetic cannabinoid, did not improve water maze performance or a contextual fear conditioning task in an APP23/PS45 double transgenic mouse model of AD. HU210 had no effect on APP processing and Abeta generation, as well as neuritic plaque formation in the brains of AD transgenic mice. Our study showed that synthetic cannabinoid HU210 had no beneficial effects on AD neuropathology and behavioral deficits of AD model mice, which advises caution of such drug's application in AD therapies.

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Section: Discussionmentioning

confidence: 82%

Effect of Synthetic Cannabinoid HU210 on Memory Deficits and Neuropathology in Alzheimers Disease Mouse Model

Chen

Bromley-Brits²,

et al. 2010

CAR

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“…However, some discrepancies exist in the literature regarding cannabinoids and alcohol. A recent study using D 9 -tetrahydrocannabinol (THC), the principal agent responsible for most of the psychopharmacological effects of marijuana, showed that this cannabinoid (CB) agonist did not alter cell proliferation in the mouse dentate gyrus, even at high, toxic, doses [80]. Morever, Jiang et al [81] found that chronic treatment with the CB1 receptor agonist, HU210, promoted cell proliferation, an effect which could be blocked by irradiation of the hippocampus.…”

Section: Neurogenesis and Mood Disordersmentioning

confidence: 98%

Life-Long Hippocampal Neurogenesis: Environmental, Pharmacological and Neurochemical Modulations

et al. 2007

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It is now well documented that active neurogenesis does exist throughout the life span in the brain of various species including human. Two discrete brain regions contain progenitor cells that are capable of differentiating into neurons or glia, the subventricular zone and the dentate gyrus of the hippocampal formation. Recent studies have shown that neurogenesis can be modulated by a variety of factors, including stress and neurohormones, growth factors, neurotransmitters, drugs of abuse, and also strokes and traumatic brain injuries. In particular, the hippocampal neurogenesis may play a role in neuroadaptation associated with pathologies, such as cognitive disorders and depression. The increased neurogenesis at sites of injury may represent an attempt by the central nervous system to regenerate after damage. We herein review the most significant data on hippocampal neurogenesis in brain under various pathological conditions, with a special attention to mood disorders including depression and addiction.

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“…per day p.o. for 21 days) had significant effects on hippocampal neurogenesis (Kochman et al, 2006). A paper by Downer et al reported that the brain is more sensitive to Δ 9 -THC during development than in adult life (Downer et al, 2007).…”

Section: Neurotoxicitymentioning

confidence: 99%

“…i.p. suppressed spontaneous locomotion (Kochman et al, 2006). Chronic administration in adults (1 mg/kg b.w.…”

Section: Neurotoxicitymentioning

confidence: 99%

Scientific Opinion on the risks for human health related to the presence of tetrahydrocannabinol (THC) in milk and other food of animal origin

2015

EFS2

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The European Food Safety Authority (EFSA) was asked to deliver a scientific opinion on the risks for human health related to the presence of tetrahydrocannabinol (THC) in milk and other food of animal origin. THC, more precisely delta-9-tetrahydrocannabinol (Δ 9 -THC) is derived from the hemp plant Cannabis sativa. In fresh plant material, up to 90 % of total Δ 9 -THC is present as the non-psychoactive precursor Δ 9 -THC acid. Since few data on ∆ 9 -THC levels in foods of animal origin were available, the Panel on Contaminants in the Food Chain (CONTAM Panel) estimated acute human dietary exposure to ∆ 9 -THC combining different scenarios for the presence of ∆ 9 -THC in hemp seed-derived feed materials. Acute exposure to ∆ 9 -THC from the consumption of milk and dairy products ranged between 0.001 and 0.03 µg/kg body weight (b.w.) per day in adults, and 0.006 and 0.13 µg/kg b.w. per day in toddlers. From human data, the CONTAM Panel concluded that 2.5 mg Δ 9 -THC/day, corresponding to 0.036 mg Δ 9 -THC/kg b.w. per day, represents the lowest observed adverse effect level. By applying an overall uncertainty factor of 30, an acute reference dose (ARfD) of 1 μg Δ 9 -THC/kg b.w. was derived. The exposure estimates are at most 3 % and 13 % the ARfD, in adults and toddlers, respectively. The CONTAM Panel concluded that exposure to ∆ 9 -THC via consumption of milk and dairy products, resulting from the use of hemp seed-derived feed materials at the reported concentrations, is unlikely to pose a health concern. A risk assessment resulting from the use of whole hemp plant-derived feed materials is currently not feasible due to a lack of occurrence data. The CONTAM Panel could also not conclude on the possible risks to public health from exposure to ∆ 9 -THC via consumption of animal tissues and eggs, due to a lack of data on the potential transfer and fate of ∆ 9 -THC. Tetrahydrocannabinol, more precisely delta-9-tetrahydrocannabinol (Δ 9 -THC) is the most relevant constituent derived from the hemp plant Cannabis sativa. Four stereoisomers of Δ 9 -THC are possible, with (-)-trans-Δ 9 -THC being the only naturally occurring isomer. Delta-9-tetrahydrocannabinolic acid, which is found in the growing and harvested plant, is the biosynthetic precursor of Δ 9 -THC. Besides 2-COOH-Δ 9 -THC, which in this opinion is referred to as Δ 9 -THCA-A, another positional isomer, 4-COOH-Δ 9 -THC, denoted as Δ 9-THCA-B, may also occur in the hemp plant. In fresh plant material of C. sativa, up to 90 % of the 'total' Δ 9 -THC is present as the non-psychoactive precursor Δ 9 -THCA-A. The rate and extent of transformation of the precursor acids into Δ 9 -THC in the plant material is dependent on physical effects, in particular temperature. In addition to Δ 9 -THC, C. sativa preparations may contain at least 60 other cannabinoids, several of which are biologically active. This risk assessment does not evaluate the exposure and associated risks of cannabis used as a medicinal drug or for recreational purposes, but as requested in the ter...

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Despite strong behavioral disruption, Δ9-tetrahydrocannabinol does not affect cell proliferation in the adult mouse dentate gyrus

Cited by 34 publications

References 39 publications

Effect of Synthetic Cannabinoid HU210 on Memory Deficits and Neuropathology in Alzheimers Disease Mouse Model

Effect of Synthetic Cannabinoid HU210 on Memory Deficits and Neuropathology in Alzheimers Disease Mouse Model

Life-Long Hippocampal Neurogenesis: Environmental, Pharmacological and Neurochemical Modulations

Scientific Opinion on the risks for human health related to the presence of tetrahydrocannabinol (THC) in milk and other food of animal origin

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