Cannabinoid Delivery Systems for Pain and Inflammation Treatment

Bruni, Natascia; Pepa, Carlo Della; Oliaro‐Bosso, Simonetta; Pessione, Enrica; Gastaldi, Daniela; Dosio, Franco

doi:10.3390/molecules23102478

Cited by 221 publications

(204 citation statements)

References 114 publications

(125 reference statements)

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“…Our results confirm that when entering keratinocytes, CBD-especially after exposure to UVA radiation-accumulates mainly in keratinocyte membranes, particularly in keratinocytes of patients with psoriasis. This is probably the result of the lipophilic nature of CBD and modification of the biomembrane structure under oxidative conditions [62]. The transportation of CBD through membranes can be facilitated by the action of membrane transporters (ABC transporters) shuttling endogenous and exogenous compounds [63].…”

Section: Redox Conditions In Psoriatic Patient Keratinocytes Treated mentioning

confidence: 99%

Cannabidiol Effects on Phospholipid Metabolism in Keratinocytes from Patients with Psoriasis Vulgaris

Jarocka-Karpowicz

Biernacki

Wroński³

et al. 2020

Biomolecules

101

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Psoriasis is a chronic inflammatory skin disease characterized by dysregulated keratinocyte differentiation, but oxidative stress also plays an important role in the pathogenesis of this disease. Here, we examined the effect of cannabidiol (CBD), a phytocannabinoid with antioxidant and anti-inflammatory properties, on the redox balance and phospholipid metabolism in UVA/UVB-irradiated keratinocytes isolated from the skin of psoriatic patients or healthy volunteers. CBD accumulates mainly in membrane keratinocytes, especially from patients with psoriasis. This phytocannabinoid reduces the redox imbalance observed in the UV-irradiated keratinocytes of healthy subjects. It does so by decreasing reactive oxygen species (ROS) generation, increasing the Trx-dependent system efficiency, and increasing vitamin A and E levels. Consequently, a reduction in lipid peroxidation products, such as 8-isoprostanes and 4-hydroxynonenal, was also observed. Moreover, CBD modifies redox balance and lipid peroxidation in psoriatic patient keratinocytes following UV-irradiation. Interestingly, these changes are largely in the opposite direction to the case of keratinocytes from healthy subjects. CBD also regulates metabolic changes by modulating the endocannabinoid system that is disturbed by psoriasis development and UV irradiation. We observed a decrease in anandamide level in the UV-irradiated keratinocytes of healthy controls following CBD treatment, while in keratinocytes from patients treated with CBD, anandamide level was increased. However, the level of palmitoylethanolamide (PEA) was decreased in both groups treated with CBD. We further demonstrate that CBD increases CB1 receptor expression, primarily in the keratinocytes of patients, and increases CB2 receptor expression in both the psoriatic and control groups. However, CBD decreases CB2 receptor expression in UV-irradiated keratinocytes taken from patients. The UV- and psoriasis-induced activity of transmembrane transporters (Multidrug-Resistance (MDR) and breast cancer resistance protein (BCRP)) is normalized after CBD treatment. We conclude that CBD partially reduces oxidative stress in the keratinocytes of healthy individuals, while showing a tendency to increase the oxidative and inflammatory state in the keratinocytes of patients with psoriasis, especially following UV-irradiation.

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Section: Redox Conditions In Psoriatic Patient Keratinocytes Treated mentioning

confidence: 99%

Cannabidiol Effects on Phospholipid Metabolism in Keratinocytes from Patients with Psoriasis Vulgaris

Jarocka-Karpowicz

Biernacki

Wroński³

et al. 2020

Biomolecules

101

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“…3 These differences are not surprising given that pharmacokinetics varies as a function of the route of absorption. 38 Specifically, oral absorption of cannabinoids is slow and variable with maximal plasma concentrations occurring 60-120 min postingestion but can be delayed upward of 6 h. 38 Cannabinoids are subjective to significant first-pass liver metabolism, which further reduces the bioavailability. 39 Utilizing transdermal, inhaled, or oral transmucosal formulations allows for direct plasma uptake and avoidance of the first-pass effect.…”

Section: Discussionmentioning

confidence: 99%

Cannabinoids in the Management of Acute Pain: A Systematic Review and Meta-analysis

Gazendam

Nucci

Gouveia

et al. 2020

Cannabis and Cannabinoid Research

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Objective: To synthesize the best evidence surrounding the efficacy of cannabinoids for acute pain in the clinical setting based on subjective pain scores and observed adverse effects. Design: Systematic review with meta-analysis. Data Sources: PubMed, Embase, Cochrane Databases, and Google Scholar. Eligibility Criteria: English-language randomized-controlled clinical trials comparing cannabinoids with placebo in patients with acute pain. Data Extraction and Synthesis: Study quality was assessed using the Cochrane risk of bias tool. All stages were conducted independently by a team of three reviewers. Data were pooled through meta-analysis and stratified by route of administration. Primary Outcomes and Measures: Patient-reported pain and adverse events (AEs). Results: Six trials (678 participants) were included examining oral (5 trials) and intramuscular (1 trial) cannabinoids. Overall, there was a small but statistically significant treatment effect favoring the use of cannabinoids over placebo (À0.90, 95% confidence interval [CI] À1.69 toÀ0.1, i 2 = 65%, p = 0.03). When stratified by route of administration, intramuscular cannabinoids were found to have a significant reduction in pain relative to placebo (À2.98, 95% CIÀ4.09 toÀ1.87, i 2 = 0%, p < 0.0001). No difference in effect was observed between oral cannabinoids and placebo (À0.21, 95% CI À0.64 to 0.22, i 2 = 3%, p = 0.34). Serious AEs were rare, and similar across the cannabinoid (14/374, 3.7%) and placebo groups (8/304, 2.6%). Conclusions: There is low-quality evidence indicating that cannabinoids may be a safe alternative for a small but significant reduction in subjective pain score when treating acute pain, with intramuscular administration resulting in a greater reduction relative to oral. Higher quality, long-term randomized-controlled trials examining whether there may be a role for cannabinoids in treating acute pain are required.

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“…A localized increase of endocannabinoids caused by applying degrading enzyme inhibitors can suppress the action of these inflammatory cells and thereby contribute to attenuation of neuropathic pain symptoms. The possible interaction of endocannabinoids with inflammatory and glial cells described above has been evidenced in neuropathic and inflammatory pain models of areas outside the orofacial regions [272][273][274].…”

Section: Route Of Administrationmentioning

confidence: 95%

Targeting Peripherally Restricted Cannabinoid Receptor 1, Cannabinoid Receptor 2, and Endocannabinoid-Degrading Enzymes for the Treatment of Neuropathic Pain Including Neuropathic Orofacial Pain

Hossain

Ando

Unno

2020

IJMS

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Neuropathic pain conditions including neuropathic orofacial pain (NOP) are difficult to treat. Contemporary therapeutic agents for neuropathic pain are often ineffective in relieving pain and are associated with various adverse effects. Finding new options for treating neuropathic pain is a major priority in pain-related research. Cannabinoid-based therapeutic strategies have emerged as promising new options. Cannabinoids mainly act on cannabinoid 1 (CB1) and 2 (CB2) receptors, and the former is widely distributed in the brain. The therapeutic significance of cannabinoids is masked by their adverse effects including sedation, motor impairment, addiction and cognitive impairment, which are thought to be mediated by CB1 receptors in the brain. Alternative approaches have been developed to overcome this problem by selectively targeting CB2 receptors, peripherally restricted CB1 receptors and endocannabinoids that may be locally synthesized on demand at sites where their actions are pertinent. Many preclinical studies have reported that these strategies are effective for treating neuropathic pain and produce no or minimal side effects. Recently, we observed that inhibition of degradation of a major endocannabinoid, 2-arachydonoylglycerol, can attenuate NOP following trigeminal nerve injury in mice. This review will discuss the above-mentioned alternative approaches that show potential for treating neuropathic pain including NOP.

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Cannabinoid Delivery Systems for Pain and Inflammation Treatment

Cited by 221 publications

References 114 publications

Cannabidiol Effects on Phospholipid Metabolism in Keratinocytes from Patients with Psoriasis Vulgaris

Cannabidiol Effects on Phospholipid Metabolism in Keratinocytes from Patients with Psoriasis Vulgaris

Cannabinoids in the Management of Acute Pain: A Systematic Review and Meta-analysis

Targeting Peripherally Restricted Cannabinoid Receptor 1, Cannabinoid Receptor 2, and Endocannabinoid-Degrading Enzymes for the Treatment of Neuropathic Pain Including Neuropathic Orofacial Pain

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