Effects of Cannabidiol on Locomotor Activity

Calapai, Fabrizio; Cardia, Luigi; Calapai, Gioacchino; Mauro, Debora Di; Trimarchi, Fabio; Ammendolia, Ilaria; Mannucci, Carmen

doi:10.3390/life12050652

Cited by 12 publications

(15 citation statements)

References 87 publications

(100 reference statements)

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“…Besides chronic pain as a common comorbidity among PLWH, individuals also exhibit motor deficits, including impaired gait, multitasking, motor strength, and motor coordination, all correlated with HAND status ( Schleicher et al, 2019 ; Florensa-Zanuy et al, 2021 ). As a result of these motor difficulties, physical activity often suffers, and a majority of PLWH exhibit inadequate levels of daily physical activity, even lower than most other chronic disease populations ( Calapai et al, 2022 ). These lower levels of activity have been associated with depression, physical pain, and worse cardio-respiratory fitness ( Magen et al, 2010 ; Calapai et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Effects of acute cannabidiol on behavior and the endocannabinoid system in HIV-1 Tat transgenic female and male mice

Yadav-Samudrala,

Gorman,

Barmada

et al. 2024

Front. Neurosci.

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BackgroundSome evidence suggests that cannabidiol (CBD) has potential to help alleviate HIV symptoms due to its antioxidant and anti-inflammatory properties. Here we examined acute CBD effects on various behaviors and the endocannabinoid system in HIV Tat transgenic mice.MethodsTat transgenic mice (female/male) were injected with CBD (3, 10, 30 mg/kg) and assessed for antinociception, activity, coordination, anxiety-like behavior, and recognition memory. Brains were taken to quantify endocannabinoids, cannabinoid receptors, and cannabinoid catabolic enzymes. Additionally, CBD and metabolite 7-hydroxy-CBD were quantified in the plasma and cortex.ResultsTat decreased supraspinal-related nociception and locomotion. CBD and sex had little to no effects on any of the behavioral measures. For the endocannabinoid system male sex was associated with elevated concentration of the proinflammatory metabolite arachidonic acid in various CNS regions, including the cerebellum that also showed higher FAAH expression levels for Tat(+) males. GPR55 expression levels in the striatum and cerebellum were higher for females compared to males. CBD metabolism was altered by sex and Tat expression.ConclusionFindings indicate that acute CBD effects are not altered by HIV Tat, and acute CBD has no to minimal effects on behavior and the endocannabinoid system.

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Section: Discussionmentioning

confidence: 99%

Effects of acute cannabidiol on behavior and the endocannabinoid system in HIV-1 Tat transgenic female and male mice

Yadav-Samudrala,

Gorman,

Barmada

et al. 2024

Front. Neurosci.

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“…However, it is worth noting that other studies report no effect at low doses or an increase or a decrease in locomotor activity after high doses in mice [ 55 , 56 ]. Whereas rats treated with CBD show hyperlocomotive effects after 10 and 30 mg/kg but only after 240–360 min post-administration [ 50 , 57 ]. Thus, CBD's action on locomotor activity seems to depend on experimental settings and species, and probably reflects the activation of distinct pathways in the different settings, as if CBD was at the crossroads of multiple circuits.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the biochemical and behavioral effects of cannabidiol: implications for migraine

Greco¹,

Francavilla

Demartini

et al. 2023

J Headache Pain

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Cannabidiol (CBD) is the main pharmacologically active phytocannabinoid. CBD exerts an analgesic effect in several pain models, does not have side effects and has low toxicity. The data about CBD mechanisms of action in pain and its therapeutic potential in this area are limited. Here, we tested CBD effects in animal models specific for migraine. We assayed CBD distribution in plasma and in cranial areas related to migraine pain in male Sprague Dawley rats treated chronically (5 days). Successively, we tested CBD activity on the behavioral and biochemical effects induced in the acute and the chronic migraine animal models by nitroglycerin (NTG) administration. In the acute migraine model, rats received CBD (15 mg or 30 mg/kg, i.p) 3 h after NTG (10 mg/kg i.p.) or vehicle injection. In the chronic migraine model, rats were treated with CBD and NTG every other day over nine days with the following doses: CBD 30 mg/kg i.p., NTG 10 mg/kg i.p. We evaluated behavioral parameters with the open field and the orofacial formalin tests. We explored the fatty acid amide hydrolase gene expression, cytokines mRNA and protein levels in selected brain areas and CGRP serum level. CBD levels in the meninges, trigeminal ganglia, cervical spinal cord, medulla pons, and plasma were higher 1 h after the last treatment than after 24 h, suggesting that CBD penetrates but does not accumulate in these tissues. In the acute model, CBD significantly reduced NTG-induced trigeminal hyperalgesia and CGRP and cytokine mRNA levels in peripheral and central sites. In the chronic model, CBD caused a significant decrease in NTG-induced IL-6 protein levels in the medulla–pons, and trigeminal ganglion. It also reduced CGRP serum levels. By contrast, CBD did not modulate TNF-alpha protein levels and fatty acid amide hydrolase (FAAH) gene expression in any of investigated areas. In both experimental conditions, there was no modulation of anxiety, motor/exploratory behavior, or grooming. These findings show that CBD reaches brain areas involved in migraine pain after systemic administration. They also show for the first time that CBD modulates migraine-related nociceptive transmission, likely via a complex signaling mechanism involving different pathways.

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“…These results are consistent with previous studies showing that CBD can block the effects of MK‐801 (Kruk‐Slomka & Biala, 2021). While CBD or CBDA alone does not seem to affect locomotor activity (Calapai et al, 2022), its regulation of NDMAR via CB1Rs and 5‐HT1ARs is likely one of the mechanisms that reverses MK‐801‐indcued hyperlocomotion (Rodríguez‐Muñoz et al, 2016; Yuen et al, 2005). Previous research showed that NMDAR antagonism can induce immobility in the FST (Langen et al, 2012), and our study corroborates the findings that compounds such as CBD and HU‐580 can significantly reduce immobility behaviour (Dlugosz et al, 2023; Sales et al, 2019, 2020).…”

Section: Discussionmentioning

confidence: 99%

Therapeutic‐like activity of cannabidiolic acid methyl ester in the MK‐801 mouse model of schizophrenia: Role for cannabinoid CB1 and serotonin‐1A receptors

Richardson,

Clarke,

Blundell

et al. 2024

Eur J of Neuroscience

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Schizophrenia is a psychotic disorder with an increasing prevalence and incidence over the last two decades. The condition presents with a diverse array of positive, negative, and cognitive impairments. Conventional treatments often yield unsatisfactory outcomes, especially with negative symptoms. We investigated the role of prefrontocortical (PFC) N‐methyl‐D‐aspartate receptors (NMDARs) in the pathophysiology and development of schizophrenia. We explored the potential therapeutic effects of cannabidiolic acid (CBDA) methyl ester (HU‐580), an analogue of CBDA known to act as an agonist of the serotonin‐1A receptor (5‐HT1AR) and an antagonist of cannabinoid type 1 receptor (CB1R). C57BL/6 mice were intraperitoneally administered the NMDAR antagonist, dizocilpine (MK‐801, .3 mg/kg) once daily for 17 days. After 7 days, they were concurrently given HU‐580 (.01 or .05 μg/kg) for 10 days. Behavioural deficits were assessed at two time points. We conducted enzyme‐linked immunosorbent assays to measure the concentration of PFC 5‐HT1AR and CB1R. We found that MK‐801 effectively induced schizophrenia‐related behaviours including hyperactivity, social withdrawal, increased forced swim immobility, and cognitive deficits. We discovered that low‐dose HU‐580 (.01 μg/kg), but not the high dose (.05 μg/kg), attenuated hyperactivity, forced swim immobility and cognitive deficits, particularly in female mice. Our results revealed that MK‐801 downregulated both CB1R and 5‐HT1AR, an effect that was blocked by both low‐ and high‐dose HU‐580. This study sheds light on the potential antipsychotic properties of HU‐580, particularly in the context of NMDAR‐induced dysfunction. Our findings could contribute significantly to our understanding of schizophrenia pathophysiology and offer a promising avenue for exploring the therapeutic potential of HU‐580 and related compounds in alleviating symptoms.

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Effects of Cannabidiol on Locomotor Activity

Cited by 12 publications

References 87 publications

Effects of acute cannabidiol on behavior and the endocannabinoid system in HIV-1 Tat transgenic female and male mice

Effects of acute cannabidiol on behavior and the endocannabinoid system in HIV-1 Tat transgenic female and male mice

Characterization of the biochemical and behavioral effects of cannabidiol: implications for migraine

Therapeutic‐like activity of cannabidiolic acid methyl ester in the MK‐801 mouse model of schizophrenia: Role for cannabinoid CB1 and serotonin‐1A receptors

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