Cannabinoids inhibit the synaptic uptake of adenosine and dopamine in the rat and mouse striatum

Pandolfo, Pablo; Silveirinha, Vasco de Casimiro Lousada; Santos-Rodrigues, Alexandre dos; Venance, Laurent; Ledent, Catherine; Takahashi, Reinaldo Ν.; Cunha, Rodrigo A.; Köfalvi, Attila

doi:10.1016/j.ejphar.2011.01.013

Cited by 74 publications

(66 citation statements)

References 50 publications

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“…With regard to dopamine transport, further studies showed a dose-dependent reduction in dopamine uptake following application of CBD (0.5-100.0 μM; IC 50 = 16.2 μM) in rat striatal synaptosomes, consistent with a previous study (Table 4) [105]. Glutamate uptake was again inhibited in a dose-dependent manner following application of CBD (1-100 μM) to rat striatal synaptosomes.…”

Section: Neurotransmitter Transporterssupporting

confidence: 89%

“…Glutamate uptake was again inhibited in a dose-dependent manner following application of CBD (1-100 μM) to rat striatal synaptosomes. However, unlike CBD's effect on dopamine uptake, half maximal inhibition was achieved at the higher concentration of 43.8 μM [105]. These studies indicate that CBD can inhibit uptake of adenosine, dopamine, and glutamate in vitro, but with variable potency.…”

Section: Neurotransmitter Transportersmentioning

confidence: 72%

“…CBD inhibits the uptake of glutamate, dopamine, and adenosine, but only at high micromolar concentrations [105]. Impaired glutamate uptake has been reported in transgenic rodent models of HD, but the effect of this on motor function has not been determined [176].…”

Section: Cbd Transporter Targets In Movement Disordersmentioning

confidence: 99%

“…CBD can inhibit both dopamine and glutamate uptake [105]. The dopaminergic system is involved in some stages of AD, for instance its degeneration can result in apathy and although its precise role is still debated, agonists can be of some benefit [242].…”

Section: Cbd Transporter Targets In Neurodegenerationmentioning

confidence: 99%

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Molecular Targets of Cannabidiol in Neurological Disorders

Bih

Chen

Nunn³

et al. 2015

Neurotherapeutics

447

323

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Cannabis has a long history of anecdotal medicinal use and limited licensed medicinal use. Until recently, alleged clinical effects from anecdotal reports and the use of licensed cannabinoid medicines are most likely mediated by tetrahydrocannabinol by virtue of: 1) this cannabinoid being present in the most significant quantities in these preparations; and b) the proportion:potency relationship between tetrahydrocannabinol and other plant cannabinoids derived from cannabis. However, there has recently been considerable interest in the therapeutic potential for the plant cannabinoid, cannabidiol (CBD), in neurological disorders but the current evidence suggests that CBD does not directly interact with the endocannabinoid system except in vitro at supraphysiological concentrations. Thus, as further evidence for CBD's beneficial effects in neurological disease emerges, there remains an urgent need to establish the molecular targets through which it exerts its therapeutic effects. Here, we conducted a systematic search of the extant literature for original articles describing the molecular pharmacology of CBD. We critically appraised the results for the validity of the molecular targets proposed. Thereafter, we considered whether the molecular targets of CBD identified hold therapeutic potential in relevant neurological diseases. The molecular targets identified include numerous classical ion channels, receptors, transporters, and enzymes. Some CBD effects at these targets in in vitro assays only manifest at high concentrations, which may be difficult to achieve in vivo, particularly given CBD's relatively poor bioavailability. Moreover, several targets were asserted through experimental designs that demonstrate only correlation with a given target rather than a causal proof. When the molecular targets of CBD that were physiologically plausible were considered for their potential for exploitation in neurological therapeutics, the results were variable. In some cases, the targets identified had little or no established link to the diseases considered. In others, molecular targets of CBD were entirely consistent with those already actively exploited in relevant, clinically used, neurological treatments. Finally, CBD was found to act upon a number of targets that are linked to neurological therapeutics but that its actions were not consistent withmodulation of such targets that would derive a therapeutically beneficial outcome. Overall, we find that while >65 discrete molecular targets have been reported in the literature for CBD, a relatively limited number represent plausible targets for the drug's action in neurological disorders when judged by the criteria we set. We conclude that CBD is very unlikely to exert effects in neurological diseases through modulation of the endocannabinoid system. Moreover, a number of other molecular targets of CBD reported in the literature are unlikely to be of relevance owing to effects only being observed at supraphysiological concentrations. Of interest and after excludin...

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Section: Neurotransmitter Transporterssupporting

confidence: 89%

Section: Neurotransmitter Transportersmentioning

confidence: 72%

Section: Cbd Transporter Targets In Movement Disordersmentioning

confidence: 99%

Section: Cbd Transporter Targets In Neurodegenerationmentioning

confidence: 99%

See 2 more Smart Citations

Molecular Targets of Cannabidiol in Neurological Disorders

Bih

Chen

Nunn³

et al. 2015

Neurotherapeutics

447

323

View full text Add to dashboard Cite

show abstract

“…CBD inhibits uptake of adenosine by blocking the equilibrative nucleoside transporter [118,119]. Increased levels of adenosine activate A2 receptors, which regulate striatal CB 1 Rs [120].…”

Section: Cbdmentioning

confidence: 99%

Cannabinoids and Epilepsy

et al. 2015

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Cannabis has been used for centuries to treat seizures. Recent anecdotal reports, accumulating animal model data, and mechanistic insights have raised interest in cannabisbased antiepileptic therapies. In this study, we review current understanding of the endocannabinoid system, characterize the pro-and anticonvulsive effects of cannabinoids [e.g., Δ9-tetrahydrocannabinol and cannabidiol (CBD)], and highlight scientific evidence from pre-clinical and clinical trials of cannabinoids in epilepsy. These studies suggest that CBD avoids the psychoactive effects of the endocannabinoid system to provide a well-tolerated, promising therapeutic for the treatment of seizures, while whole-plant cannabis can both contribute to and reduce seizures. Finally, we discuss results from a new multicenter, open-label study using CBD in a population with treatment-resistant epilepsy. In all, we seek to evaluate our current understanding of cannabinoids in epilepsy and guide future basic science and clinical studies.

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Impact of cannabidiol on brain glucose metabolism of C57Bl/6 male mice previously exposed to cocaine

Spelta,

Real,

Bruno

et al. 2024

J of Neuroscience Research

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Despite evidence of the beneficial effects of cannabidiol (CBD) in animal models of cocaine use disorder (CUD), CBD neuronal mechanisms remain poorly understood. This study investigated the effects of CBD treatment on brain glucose metabolism, in a CUD animal model, using [18F]FDG positron emission tomography (PET). Male C57Bl/6 mice were injected with cocaine (20 mg/kg, i.p.) every other day for 9 days, followed by 8 days of CBD administration (30 mg/kg, i.p.). After 48 h, animals were challenged with cocaine. Control animals received saline/vehicle. [18F]FDG PET was performed at four time points: baseline, last day of sensitization, last day of withdrawal/CBD treatment, and challenge. Subsequently, the animals were euthanized and immunohistochemistry was performed on the hippocampus and amygdala to assess the CB1 receptors, neuronal nuclear protein, microglia (Iba1), and astrocytes (GFAP). Results showed that cocaine administration increased [18F]FDG uptake following sensitization. CBD treatment also increased [18F]FDG uptake in both saline and cocaine groups. However, animals that were sensitized and challenged with cocaine, and those receiving only an acute cocaine injection during the challenge phase, did not exhibit increased [18F]FDG uptake when treated with CBD. Furthermore, CBD induced modifications in the integrated density of NeuN, Iba, GFAP, and CB1R in the hippocampus and amygdala. This is the first study addressing the impact of CBD on brain glucose metabolism in a preclinical model of CUD using PET. Our findings suggest that CBD disrupts cocaine‐induced changes in brain energy consumption and activity, which might be correlated with alterations in neuronal and glial function.

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Cannabinoids inhibit the synaptic uptake of adenosine and dopamine in the rat and mouse striatum

Cited by 74 publications

References 50 publications

Molecular Targets of Cannabidiol in Neurological Disorders

Molecular Targets of Cannabidiol in Neurological Disorders

Cannabinoids and Epilepsy

Impact of cannabidiol on brain glucose metabolism of C57Bl/6 male mice previously exposed to cocaine

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