Highly accomplished Pharmacist with a Master's and PhD in Biological Sciences (Biophysics), complemented by extensive postdoctoral training in Biophysics, Physiology, and Neurosciences. Over 15 years of dedicated experience in basic and translational scientific research, with a strong focus on pharmacology, physiology, biophysics, and neurosciences, particularly in the endocannabinoid system and the therapeutic use of Cannabis products. Proven expertise in leading research projects, coordinating scientific teams, mentoring students, and fostering national and international collaborations. Recognized for impactful scientific dissemination and active engagement in regulatory and professional discussions concerning medical cannabis.
RESEARCH, TEACHING, or OTHER INTERESTS
Pharmacology, Biophysics, Physiology
13
Scopus Publications
Scopus Publications
Oromucosal Administration of a Cannabidiol-Enriched Cannabis sp. Extract for 2 Weeks Moderately Reduces Cold Hyperalgesia in Rats With Neuropathic Pain Raquel Maria Pereira Campos, Luciana Conde, Andrey Aguiar, Luzia Sampaio, Ricardo Augusto de Melo Reis, Pedro Moreno Pimentel‐Coelho European Journal of Pain, 2026 Background Chronic neuropathic pain (CNP) involves complex interactions between resident and peripheral immune cells, as well as modulation of the endocannabinoid system. Cannabis‐based products have emerged as promising therapeutic options, but their effects on immune cells remain unclear. This study evaluated the effects of a cannabidiol (CBD)‐enriched Cannabis sp. extract administered via the oral mucosa in a CNP model. Methods Two‐month‐old Wistar rats of both sexes were randomly assigned to four groups. Two groups underwent chronic constriction injury (CCI) of the sciatic nerve, while the remaining groups underwent sham surgery (SHAM). Starting at Day 7 post‐CCI, rats received either the CBD‐enriched extract (10 mg/kg) or vehicle for 15 days. Mechanical and thermal sensitivity were assessed using the von Frey, acetone and hot plate tests. Ipsilateral spinal cord segments were analysed by flow cytometry, immunohistochemistry and western blotting. Results CCI induced thermal hyperalgesia and mechanical allodynia. Treatment with the CBD‐enriched extract modestly reduced cold sensitivity in CCI rats of both sexes but did not improve heat sensitivity and had a significant but minor effect on mechanical thresholds. CCI increased spinal cord microglial cell numbers, particularly in females, an effect not modulated by treatment. No significant changes were detected in immune cell infiltration or CB1R, CB2R, or TRPV1 protein expression across groups. Conclusion Oromucosal treatment with a CBD‐enriched extract modestly alleviates cold hypersensitivity in both sexes. Neuroimmune alterations in the spinal cord at 22 days post‐CCI indicate a predominance of microglia, with no detectable peripheral immune cell infiltration, regardless of treatment. Significance Statement This manuscript contributes to addressing gaps in the literature regarding preclinical models evaluating Cannabis sp. based products using treatment protocols that more closely reflect patient use, as commercially available cannabidiol‐enriched extract and the oromucosal route, consistent with the route commonly used by patients. In addition, all experiments were conducted in animals of both sexes, addressing a well‐recognised limitation of many preclinical studies in chronic pain research. Notably, the International Association for the Study of Pain has emphasised the need for further research in this area before endorsing the use of Cannabis sp. based products for the treatment of chronic pain.
Editorial: Insights on cannabinoid translational science and medicine: the endocannabinoidome as a target for clinical practice Luzia Sampaio, Raquel Maria Pereira Campos, Debra Karhson, Fabio Arturo Iannotti Frontiers in Neuroscience, 2024 In mammals and other vertebrates, the endocannabinoid system (ECS) is in a simplicistic manner formed by endocannabinoids, two cannabinoid receptors and large set of metabolic enzymes deputed to the synthesis and degradation of endocannabinoids. The ECS plays important physiological and homeostatic actions in the central nervous system (CNS), where it was discovered, but also in the majority (if not all) peripheral organs and tissue of the body especially those with endocrine, immune, gastrointestinal, reproductive functions. The identification of structure of the main phytocannabinoid present in Cannabis sativa, ∆ 9 -tetrahydrocannabinol (THC) and cannabidiol (CBD), led to the discovery of the cannabinoid receptors first, and then also using synthetic cannabinoids, to the deciphering of the entire system (Cristino et al., 2020;Maccarrone et al., 2023).The metabotropic cannabinoid receptor type 1 (CB1) and type 2 (CB2) are G protein coupled receptors (GPCR), with classically participation of Gi protein and inhibition of adenylate cyclase, but it can also be coupled to Gq/11 protein, leading to activation and modulation of activated kinases by mitogens (MAPKs) including extracellular signalregulated kinases (ERK1/2) (Ye et al., 2019). Pharmacological studies have revealed the existence of other receptors capable of interacting with cannabinoids, such as the transient potential vanilloid receptor, type 1 (TRPV1) (Cristino et al., 2020).Endocannabinoids are endogenous agonists of cannabinoid receptors, being classically derived from arachidonic acid and conjugated with an ethanolamine, dopamine or glycerol molecule. The first endocannabinoid discovered was Narachidonoylethanolamine or anandamide (AEA), extracted from pig brains. This discovery allowed the identification of cannabimetic properties in another already known bioactive lipid, 2-arachidonoylglycerol (2-AG), which became the second endocannabinoid, both in the CNS and in peripheral tissues. In the following years, other endocannabinoids and congeners were isolated, however the biological activity and pharmacological proprieties of AEA and 2-AG remain the most studied (Fezza et al., 2014). The biosynthesis of different endocannabinoids is driven by an extensive number of enzymes, creating complex canonical and non-canonical pathways. These mechanisms are responsible for a main ECS characteristic, the on-demand production of endocannabinoids (Iannotti et al., 2016). Among the main enzymes of the ECS, phospholipase D selective for N-acyl-phosphatidylethanolamine (NAPE-PLD), fatty acid amide hydrolase (FAAH), diacylglycerol lipase (DAGL) and monoacylglycerol lipase (MAGL) are responsible for the synthesis and degradation of AEA and 2-AG, respectively (Maccarrone et al., 2023).Recently, the new term endocannabinoidome, is started to be used to refer to the ECS in its expanded view, and thus encompass the new endocannabinoid and endocannabinoid-like mediators, signaling pathways, receptors and metabolic processes alternatives that can be modulated in health and disease. Therefore, the endocannabinoidome could be considered a valuable target in a pathological state. Considering all possible mechanisms for endocannabinoidome modulation, special attention is given to cannabinoids, substances capable of interacting with either receptors or other components of this system. Thus, scientific and medical efforts have sought to introduce synthetic and natural cannabinoids into clinical practice in order to improve patient's welfare (Cristino et al., 2020;Pacher et al., 2019).Cannabis sativa is one of the first plants in history to be used in medicine, its first use being described around 5000 years ago, although it intense use in the medicine for centuries. Despite its medicinal potential the use of Cannabis was prohibited in several countries in the twentieth century. Cannabinol (CBN) was the first phytocannabinoid to be isolated at the end of the 19th century. CBD was the second, although its chemical structure has not been correctly deciphered, while tetrahydrocannabinol was identified in 1942, but in a form of mixture of different tetrahydrocannabinols (Δ 8 -THC and Δ 9 -THC). Both CBD and THC, as other phytocannabinoids, are present in cannabis in acidic form, being decarboxylated when the plant is heated. Both the accurate structure, stereochemistry and synthesis of CBD and THC were complete elucidated by Professor Raphael Mechoulam in 1960and in 1964(Mechoulam et al., 2014;Pertwee, 2006). Mechoulam was a chemist, professor at the Faculty of Medicine of the Hebrew University of Jerusalem and his research opened door all over the word for a new era in the use of Cannabis in science and investigation of the potential in different pathological condition, including the fellowship with the Brazilian researcher professor Dr. Elisaldo Carlini to test CBD in epileptic patients (Cunha JM, 1980;Mechoulam R, 2023). Unfortunately, we lost Dr. Mechoulam in February of 2023, during the time this editorial was opened to receive manuscript, and we are honored to receive one of the last works he was involved.Currently, more than 520 active components extracted from Cannabis are known, including terpenes, flavonoids and more than 120 different phytocannabinoids, some of them acts as agonist and antagonists of CB1 and CB2 receptors (THC and Δ 9tetrahydrocannabivarin -THCV, respectively), and some have activity on the TRPV1 and TRPV2 receptor, such as CBD, THCV, cannabigerol (CBG), cannabigerovarin (CBGV) and cannabidivarin (CBDV) (Milay et al., 2020;Walsh et al., 2021). Phytocannabinoids can also exert important pharmacological effects by acting as ECS modulators, for instance, the acidic forms of phytocannabinoids can inhibit the AEA reuptake, while CBD which in addition to inhibiting AEA reuptake acts by inhibiting FAAH enzyme, in animal models, promoting an increase in intracellular levels of AEA (Di Marzo & Piscitelli, 2015). Although CBD has limited effects on cannabinoid receptors, it is known for antiinflammatory and immunosuppressive action and can also antagonize some important effects of THC, such as anxiety, sedation and increased appetite (Russo, 2011). THC is associated with the modulation of signals that include pain, sedation, appetite and mood, and is also described as a bronchodilator, antioxidant with neuroprotective and anti-inflammatory properties. The action of THC on the CB1 receptor causes 4 symptoms characteristic of its psychotropic effects (inhibition of locomotor activity, hypothermia, catalepsy and antinociception), while its action on CB2 is correlated with the antiinflammatory and relief action of pain (Keimpema et al., 2021).The therapeutic potential of cannabis-derived products has been the subject of much research in recent years. These products have been used to treat a variety of conditions, including cancer, neuropathic pain, dementia, schizophrenia, epilepsy, and autism spectrum disorders (Abrams et al., 2021;Aran et al., 2021;Campos et al., 2021;Cristino et al., 2020;Devinsky et al., 2024). While the evidence supporting their use is growing, further research is needed to fully understand the pharmacological basis and cellular actions of these compounds in different disease contexts. This special issue aims to compile and critically evaluate the current scientific evidence on the use of Cannabinoid for medical purposes, providing a comprehensive overview of the field and highlighting areas for future research.
Long-Term Treatment with Cannabidiol-Enriched Cannabis Extract Induces Synaptic Changes in the Adolescent Rat Hippocampus Andrey F. L. Aguiar, Raquel M. P. Campos, Alinny R. Isaac, Yolanda Paes-Colli, Virgínia M. Carvalho, Luzia S. Sampaio, Ricardo A. de Melo Reis International Journal of Molecular Sciences, 2023 The endocannabinoid system (eCS) is widely distributed in mammalian tissues and it is classically formed by cannabinoid receptors, endogenous bioactive lipids and its synthesis and degradation enzymes. Due to the modulatory role of eCS in synaptic activity in the Central Nervous System (CNS), phytocannabinoids have been increasingly used for the treatment of neurological disorders, even though little is known in terms of the long-term effect of these treatments on CNS development, mainly in the timeframe that comprises childhood and adolescence. Furthermore, an increased number of clinical trials using full-spectrum Cannabis extracts has been seen, rather than the isolated form of phytocannabinoids, when exploring the therapeutical benefits of the Cannabis plant. Thus, this study aims to evaluate the effect of cannabidiol (CBD)-enriched Cannabis extract on synaptic components in the hippocampus of rats from adolescence to early adulthood (postnatal day 45 to 60). Oral treatment of healthy male Wistar rats with a CBD-enriched Cannabis extract (3 mg/kg/day CBD) during 15 days did not affect food intake and water balance. There was also no negative impact on locomotor behaviour and cognitive performance. However, the hippocampal protein levels of GluA1 and GFAP were reduced in animals treated with the extract, whilst PSD95 levels were increased, which suggests rearrangement of glutamatergic synapses and modulation of astrocytic features. Microglial complexity was reduced in CA1 and CA3 regions, but no alterations in their phagocytic activity have been identified by Iba-1 and LAMP2 co-localization. Collectively, our data suggest that CBD-enriched Cannabis treatment may be safe and well-tolerated in healthy subjects, besides acting as a neuroprotective agent against hippocampal alterations related to the pathogenesis of excitatory and astrogliosis-mediated disorders in CNS.
Activation of cannabinoid type 1 receptor (CB1) modulates oligodendroglial process branching complexity in rat hippocampal cultures stimulated by olfactory ensheathing glia-conditioned medium Yolanda Paes-Colli, Priscila M. P. Trindade, Louise C. Vitorino, Fabiana Piscitelli, Fabio Arturo Iannotti, Raquel M. P. Campos, Alinny R. Isaac, Andrey Fabiano Lourenço de Aguiar, Silvana Allodi, Fernando G. de Mello, Marcelo Einicker-Lamas, Raphael de Siqueira-Santos, Vincenzo Di Marzo, Bakhos A. Tannous, Litia A. Carvalho, Ricardo A. De Melo Reis, Luzia S. Sampaio Frontiers in Cellular Neuroscience, 2023 The endocannabinoid system (ECS) refers to a complex cell-signaling system highly conserved among species formed by numerous receptors, lipid mediators (endocannabinoids) and synthetic and degradative enzymes. It is widely distributed throughout the body including the CNS, where it participates in synaptic signaling, plasticity and neurodevelopment. Besides, the olfactory ensheathing glia (OEG) present in the olfactory system is also known to play an important role in the promotion of axonal growth and/or myelination. Therefore, both OEG and the ECS promote neurogenesis and oligodendrogenesis in the CNS. Here, we investigated if the ECS is expressed in cultured OEG, by assessing the main markers of the ECS through immunofluorescence, western blotting and qRT-PCR and quantifying the content of endocannabinoids in the conditioned medium of these cells. After that, we investigated whether the production and release of endocannabinoids regulate the differentiation of oligodendrocytes co-cultured with hippocampal neurons, through Sholl analysis in oligodendrocytes expressing O4 and MBP markers. Additionally, we evaluated through western blotting the modulation of downstream pathways such as PI3K/Akt/mTOR and ERK/MAPK, being known to be involved in the proliferation and differentiation of oligodendrocytes and activated by CB1, which is the major endocannabinoid responsive receptor in the brain. Our data show that OEG expresses key genes of the ECS, including the CB1 receptor, FAAH and MAGL. Besides, we were able to identify AEA, 2-AG and AEA related mediators palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), in the conditioned medium of OEG cultures. These cultures were also treated with URB597 10-9 M, a FAAH selective inhibitor, or JZL184 10-9 M, a MAGL selective inhibitor, which led to the increase in the concentrations of OEA and 2-AG in the conditioned medium. Moreover, we found that the addition of OEG conditioned medium (OEGCM) enhanced the complexity of oligodendrocyte process branching in hippocampal mixed cell cultures and that this effect was inhibited by AM251 10-6 M, a CB1 receptor antagonist. However, treatment with the conditioned medium enriched with OEA or 2-AG did not alter the process branching complexity of premyelinating oligodendrocytes, while decreased the branching complexity in mature oligodendrocytes. We also observed no change in the phosphorylation of Akt and ERK 44/42 in any of the conditions used. In conclusion, our data show that the ECS modulates the number and maturation of oligodendrocytes in hippocampal mixed cell cultures.
Phytocannabinoids and Cannabis-Based Products as Alternative Pharmacotherapy in Neurodegenerative Diseases: From Hypothesis to Clinical Practice Yolanda Paes-Colli, Andrey F. L. Aguiar, Alinny Rosendo Isaac, Bruna K. Ferreira, Raquel Maria P. Campos, Priscila Martins Pinheiro Trindade, Ricardo Augusto de Melo Reis, Luzia S. Sampaio Frontiers in Cellular Neuroscience, 2022 Historically, Cannabis is one of the first plants to be domesticated and used in medicine, though only in the last years the amount of Cannabis-based products or medicines has increased worldwide. Previous preclinical studies and few published clinical trials have demonstrated the efficacy and safety of Cannabis-based medicines in humans. Indeed, Cannabis-related medicines are used to treat multiple pathological conditions, including neurodegenerative disorders. In clinical practice, Cannabis products have already been introduced to treatment regimens of Alzheimer’s disease, Parkinson’s disease and Multiple Sclerosis’s patients, and the mechanisms of action behind the reported improvement in the clinical outcome and disease progression are associated with their anti-inflammatory, immunosuppressive, antioxidant, and neuroprotective properties, due to the modulation of the endocannabinoid system. In this review, we describe the role played by the endocannabinoid system in the physiopathology of Alzheimer, Parkinson, and Multiple Sclerosis, mainly at the neuroimmunological level. We also discuss the evidence for the correlation between phytocannabinoids and their therapeutic effects in these disorders, thus describing the main clinical studies carried out so far on the therapeutic performance of Cannabis-based medicines.
Early Effects of Extracellular Vesicles Secreted by Adipose Tissue Mesenchymal Cells in Renal Ischemia Followed by Reperfusion: Mechanisms Rely on a Decrease in Mitochondrial Anion Superoxide Production Jarlene A. Lopes, Federica Collino, Clara Rodrigues-Ferreira, Luzia da Silva Sampaio, Glória Costa-Sarmento, Camila H. C. Wendt, Fernando P. Almeida, Kildare R. Miranda, Tais H. Kasai-Brunswick, Rafael S. Lindoso, Adalberto Vieyra International Journal of Molecular Sciences, 2022 Acute kidney injury (AKI) caused by ischemia followed by reperfusion (I/R) is characterized by intense anion superoxide (O2•−) production and oxidative damage. We investigated whether extracellular vesicles secreted by adipose tissue mesenchymal cells (EVs) administered during reperfusion can suppress the exacerbated mitochondrial O2•− formation after I/R. We used Wistar rats subjected to bilateral renal arterial clamping (30 min) followed by 24 h of reperfusion. The animals received EVs (I/R + EVs group) or saline (I/R group) in the kidney subcapsular space. The third group consisted of false-operated rats (SHAM). Mitochondria were isolated from proximal tubule cells and used immediately. Amplex Red™ was used to measure mitochondrial O2•− formation and MitoTracker™ Orange to evaluate inner mitochondrial membrane potential (Δψ). In vitro studies were carried out on human renal proximal tubular cells (HK-2) co-cultured or not with EVs under hypoxic conditions. Administration of EVs restored O2•− formation to SHAM levels in all mitochondrial functional conditions. The gene expression of catalase and superoxide dismutase-1 remained unmodified; transcription of heme oxygenase-1 (HO-1) was upregulated. The co-cultures of HK-2 cells with EVs revealed an intense decrease in apoptosis. We conclude that the mechanisms by which EVs favor long-term recovery of renal structures and functions after I/R rely on a decrease of mitochondrial O2•− formation with the aid of the upregulated antioxidant HO-1/Nuclear factor erythroid 2-related factor 2 system, thus opening new vistas for the treatment of AKI.
Cannabinoid Therapeutics in Chronic Neuropathic Pain: From Animal Research to Human Treatment Raquel Maria P. Campos, Andrey F. L. Aguiar, Yolanda Paes-Colli, Priscila Martins Pinheiro Trindade, Bruna K. Ferreira, Ricardo A. de Melo Reis, Luzia S. Sampaio Frontiers in Physiology, 2021 Despite the importance of pain as a warning physiological system, chronic neuropathic pain is frequently caused by damage in the nervous system, followed by persistence over a long period, even in the absence of dangerous stimuli or after healing of injuries. Chronic neuropathic pain affects hundreds of millions of adults worldwide, creating a direct impact on quality of life. This pathology has been extensively characterized concerning its cellular and molecular mechanisms, and the endocannabinoid system (eCS) is widely recognized as pivotal in the development of chronic neuropathic pain. Scientific evidence has supported that phyto-, synthetic and endocannabinoids are efficient for pain management, while strong data arise from the therapeutic use of Cannabis-derived products. The use of medicinal Cannabis products is directed toward not only relieving symptoms of chronic pain, but also improving several aspects of patients’ welfare. Here, we review the involvement of eCS, along with other cellular and molecular elements, in chronic neuropathic pain pathology and how this system can be targeted for pain management.
Neuro-glial cannabinoid receptors modulate signaling in the embryonic avian retina Regina C.C. Kubrusly, Alexander Günter, Luzia Sampaio, Roberta Silva Martins, Clarissa S. Schitine, Priscila Trindade, Arlete Fernandes, Rosa Borelli-Torres, Vivian Sayuri Miya-Coreixas, Anna Carolina Rego Costa, Hércules Rezende Freitas, Patrícia F. Gardino, Fernando G. de Mello, Karin Costa Calaza, Ricardo A.M. Reis Neurochemistry International, 2018
Bioactive lipids are altered in the kidney of chronic undernourished rats: Is there any correlation with the progression of prevalent nephropathies? Luzia S. Sampaio, Paulo A. da Silva, Valdilene S. Ribeiro, Carmem Castro-Chaves, Lucienne S. Lara, Adalberto Vieyra, M. Einicker-Lamas Lipids in Health and Disease, 2017 Undernutrition during childhood leads to chronic diseases in adult life including hypertension, diabetes and chronic kidney disease. Here we explore the hypothesis that physiological alterations in the bioactive lipids pattern within kidney tissue might be involved in the progression of chronic kidney disease. Membrane fractions from kidney homogenates of undernourished rats (RBD) were submitted to lipid extraction and analysis by thin layer chromatography and cholesterol determination. Kidneys from RBD rats had 25% lower cholesterol content, which disturb membrane microdomains, affecting Ca2+ homeostasis and the enzymes responsible for important lipid mediators such as phosphatidylinositol-4 kinase, sphingosine kinase, diacylglicerol kinase and phospholipase A2. We observed a decrease in phosphatidylinositol(4)-phosphate (8.8 ± 0.9 vs. 3.6 ± 0.7 pmol.mg−1.mim−1), and an increase in phosphatidic acid (2.2 ± 0.8 vs. 3.8 ± 1.3 pmol.mg−1.mim−1), being these lipid mediators involved in the regulation of key renal functions. Ceramide levels are augmented in kidney tissue from RBD rats (18.7 ± 1.4 vs. 21.7 ± 1.5 fmol.mg−1.min−1) indicating an ongoing renal lesion. Results point to an imbalance in the bioactive lipid generation with further consequences to key events related to kidney function, thus contributing to the establishment of chronic kidney disease.
