Intoxicação de cães por maconha: sinais clínicos e tratamento / Marijuana poisoning in dogs: clinical signs and treatment

Intoxicações por drogas recreativas como Cannabissativa, comumente conhecida como maconha, estão cada vez mais presentes nas clínicas de atendimento veterinário. A Cannabis contém mais de 500 compostos diferentes e mais de 80 canabinoides conhecidos; destes, o delta-9 tetrahidrocanabinol (THC) é o mais psicoativo e responsável pela maioria dos sintomas de intoxicação. Os canabinoides são substâncias exógenas extraídas da Cannabis e se ligam aos receptores CB1 e CB2 do sistema endocanabinoide. Em cães, dentre os sinais clínicos de intoxicação mais presentes destacam-se: agitação, ataxia, midríase, aumento da sensibilidade ao som, hiperestesia, sialorreia, distúrbios neurológicos, espasmos musculares e início agudo de incontinência urinária. Muitas vezes o diagnóstico de intoxicação por maconha é difícil, principalmente porque os tutores resistem em admitir a exposição a drogas ilícitas com receio das implicações legais. O médico-veterinário deve ganhar a confiança do tutor do animal para que o diagnóstico possa ser realizado precocemente e iniciado o tratamento mais adequado para a situação. O tratamento inclui monitoramento clínico, cuidados de suporte, administração de fluidos intravenosos, administração de carvão ativado, indução de vômitos, administração de antieméticos, suporte térmico (aquecimento/resfriamento) e monitoramento da pressão arterial. Os médicos-veterinários são os principais responsáveis pela educação dos tutores nessas circunstâncias, sendo de grande importância enfatizar para os tutores manterem agentes tóxicos fora do acesso dos animais.(AU)

Intoxications by recreational drugs such as Cannabissativa, commonly known as marijuana, are increasingly present in veterinary care clinics. Cannabis contains over 500 different compounds and over 80 known cannabinoids; of these, delta-9 tetrahydrocannabinol (THC) is the most psychoactive and responsible for most symptoms of intoxication. Cannabinoids are exogenous substances extracted from Cannabis and bind to the CB1 and CB2 receptors of the endocannabinoid system. Among the most common clinical signs of intoxication in dogs are: agitation, ataxia, mydriasis, increased sensitivity to sound, hyperesthesia, drooling, neurological disorders, muscle spasms and acute onset of urinary incontinence. The diagnosis of marijuana intoxication is often difficult, mainly because tutors resist in admitting exposure to illicit drugs for fear of the legal implications. The Veterinarian must gain the trust of the animal's tutor so that the diagnosis can be carried out early and the most appropriate treatment for the situation can be initiated. Treatment includes: clinical monitoring, supportive care, administration of intravenous fluids, administration of activated charcoal, induction of vomiting, administration of antiemetics, thermal support (warming/cooling), and blood pressure monitoring. Veterinarians are primarily responsible for the education of tutors in these circumstances, and it is of great importance to emphasize that tutors must keep toxic agents away from animal's acess.(AU)

Perspectives in veterinary medicine on the use of cannabinoids as complementary palliative therapy for pain in cancer patients / Perspectivas sobre o uso de canabinoides como terapêutica paliativa complementar da dor em pacientes oncológicos na medicina veterinária

Pain in the cancer patient is an important clinical manifestation that results in low life expectancy and poor prognosis. Pain may be related to tumor type, invasion of adjacent tissues, metastasis, and diagnostic and therapeutic procedures with variable response to analgesic therapy. Many studies have called attention due to their potential therapeutic effect in the modulation of pain and inflammation. Cannabinoid derivatives are chemical compounds obtained from Cannabis that act on specific receptors.Several commercial products have already been approved in Europe and the USA for use in human patients. The present study aimed to review articles on the use of cannabinoids in the control of pain contributing to the well-being and quality of life in cancer patients undergoing palliative care. Although, there are few reports in the veterinary medical literature on the use of cannabinoids in the control of pain in dogs, it is believed that such patients can benefit from this therapeutic modality.(AU)

A dor no paciente com câncer é uma manifestação clínica importante que resulta em baixa perspectiva de vida e pior prognóstico. Esta dor pode estar relacionada ao tipo de tumor, à invasão em tecidos adjacentes, metástases, procedimentos diagnósticos e terapêuticos, com resposta variável à terapêutica analgésica. Muitos estudos têm chamado atenção para os derivados canabinoides, substâncias químicas obtidas a partir da Canabis que atuam em receptores específicos, por seu potencial efeito terapêutico na modulação da dor e da inflamação. Vários produtos comerciais já tiveram seu uso aprovado na Europa e EUA para uso em pacientes humanos. Objetivou-se pesquisar artigos sobre o uso de canabinoides no controle da dor no intuito de que os mesmos possam contribuir para o bem-estar e a qualidade de vida em pacientes oncológicos sob cuidado paliativo. Apesar de ainda serem escassos os relatos na medicina veterinária sobre o uso de canabinoides no controle da dor em cães, acredita-se que tais pacientes podem ser beneficiados por esta modalidade terapêutica.(AU)

Involvement of Gaba and Cannabinoid Receptors in Central Food Intake Regulation in Neonatal Layer Chicks: Role of CB1 and Gabaa Receptors

Feeding behavior is regulated via a complex network which interacts via diverse signals from central and peripheral tissues. Endocannabinoids modulate release of GABA in a variety of regions of the central nervous system. Endocannabinoids and GABAergic system have an important role in the central regulation of appetite. Thus, the present study examines the possible interaction of central canabinoidergic and GABAergic systems on food intake in 3-h food-deprived (FD3) neonatal layer-type chicks. The results of this study showed that intracerebroventricular (ICV) injection of 2-AG (2-Arachidonoylglycerol, selective CB1 receptors agonist, 2µg) significantly increased food intake and this effect of 2-AG was attenuated by Picrotoxin (GABAA antagonist, 0.5µg) (P 0.001); but 21ng CGP54626 (GABAB antagonist) had no effect (p>0.05). Also, hyperphagic effect of CB65 (CB2 receptors agonist, 1.25µg) was not affected by Picrotoxin or CGP54626 (p>0.05). Moreover, the food intake of chicks was significantly increased by ICV injection of GABAA agonist (Gaboxadol, 0.2 µg) and SR141716A (CB1 receptors antagonist, 6.25µg) significantly decreased Gaboxadol-induced hyperphagia (P 0.001) but CB2 receptors antagonist (AM630, 1.25µg) had no effect. In contrast, co-injection of SR141716A or AM630 with GABAB agonist (baclofen, 0.2µg) had no effect on the hyperphagia induced by baclofen (p>0.05). These data showed there might be an interaction between central cannabinoidergic and GABAergic systems via CB1 and GABAA receptors in control of food intake in neonatal layer chicks.(AU)

Involvement of Gaba and Cannabinoid Receptors in Central Food Intake Regulation in Neonatal Layer Chicks: Role of CB1 and Gabaa Receptors

Feeding behavior is regulated via a complex network which interacts via diverse signals from central and peripheral tissues. Endocannabinoids modulate release of GABA in a variety of regions of the central nervous system. Endocannabinoids and GABAergic system have an important role in the central regulation of appetite. Thus, the present study examines the possible interaction of central canabinoidergic and GABAergic systems on food intake in 3-h food-deprived (FD3) neonatal layer-type chicks. The results of this study showed that intracerebroventricular (ICV) injection of 2-AG (2-Arachidonoylglycerol, selective CB1 receptors agonist, 2µg) significantly increased food intake and this effect of 2-AG was attenuated by Picrotoxin (GABAA antagonist, 0.5µg) (P 0.001); but 21ng CGP54626 (GABAB antagonist) had no effect (p>0.05). Also, hyperphagic effect of CB65 (CB2 receptors agonist, 1.25µg) was not affected by Picrotoxin or CGP54626 (p>0.05). Moreover, the food intake of chicks was significantly increased by ICV injection of GABAA agonist (Gaboxadol, 0.2 µg) and SR141716A (CB1 receptors antagonist, 6.25µg) significantly decreased Gaboxadol-induced hyperphagia (P 0.001) but CB2 receptors antagonist (AM630, 1.25µg) had no effect. In contrast, co-injection of SR141716A or AM630 with GABAB agonist (baclofen, 0.2µg) had no effect on the hyperphagia induced by baclofen (p>0.05). These data showed there might be an interaction between central cannabinoidergic and GABAergic systems via CB1 and GABAA receptors in control of food intake in neonatal layer chicks.

A spider derived peptide, PnPP-19, induces central antinociception mediated by opioid and cannabinoid systems

Background: Some peptides purified from the venom of the spider Phoneutria nigriventer have been identified as potential sources of drugs for pain treatment. In this study, we characterized the antinociceptive effect of the peptide PnPP-19 on the central nervous system and investigated the possible involvement of opioid and cannabinoid systems in its action mechanism. Methods: Nociceptive threshold to thermal stimulation was measured according to the tail-flick test in Swiss mice. All drugs were administered by the intracerebroventricular route.Results: PnPP-19 induced central antinociception in mice in the doses of 0.5 and 1 µg. The non-selective opioid receptor antagonist naloxone (2.5 and 5 µg), µ-opioid receptor antagonist clocinnamox (2 and 4 µg), δ-opioid receptor antagonist naltrindole (6 and 12 µg) and CB1 receptor antagonist AM251 (2 and 4 µg) partially inhibited the antinociceptive effect of PnPP-19 (1 µg). Additionally, the anandamide amidase inhibitor MAFP (0.2 µg), the anandamide uptake inhibitor VDM11 (4 µg) and the aminopeptidase inhibitor bestatin (20 µg) significantly enhanced the antinociception induced by a low dose of PnPP-19 (0.5 µg). In contrast, the κ-opioid receptor antagonist nor-binaltorphimine (10 µg and 20 µg) and the CB2 receptor antagonist AM630 (2 and 4 µg) do not appear to be involved in this effect. Conclusions: PnPP-19-induced central antinociception involves the activation of CB1 cannabinoid, µ- and δ-opioid receptors. Mobilization of endogenous opioids and cannabinoids might be required for the activation of those receptors, since inhibitors of endogenous substances potentiate the effect of PnPP-19. Our results contribute to elucidating the action of the peptide PnPP-19 in the antinociceptive pathway.(AU)

Developmental changes in the gubernaculum and anogenital distance of male rat offspring exposed in utero to WIN 55, 212-2 as a candidate of the endocannabinoid system

Cannabinoids can inhibit the release of androgens locally or centrally. For this reason, this study was designed to assess the effect of WIN 55, 212-2, a CB1 receptor agonist, on gubernacular development histologically. Sprague-Dawley female rats were time-mated and divided into treatment and control groups. For prenatal exposures, the groups received injections subcutaneously of 0.5 mg/kg WIN 55, 212-2 (WIN) or vehicle on gestational days 13.520.5. Five to 13 male offspring were collected at time points E19 (embryonic), P0 (postnatal), P2, and P8. The body weight and anogenital distance (AGD) of postnatal male pups were recorded at birth. The inguino-perineal region of all the samples after fixing in 4% paraformaldehyde were sectioned oblique-sagittally and stained with Hematoxilin and Eosin (HE) or Masson's trichrome. Measured Factors in this study were based on previous studies and included gubernacular cone height (GCH), gubernacular cone width (GCW), distance from gubernaculum to scrotum (G-S), and pubic symphysis-to-anus distance (PS-A). The former two factors were measured bilaterally and the latter two only on the left side. The gubernaculum at P0 appeared more bulky than that of controls. Failure of eversion at P2 and remaining bulb of gubernaculum at P8 were important findings in WIN-treated group. The mean distance from gubernaculum to scrotum increased significantly only atP2 compared to controls. AGD as a bioassay of fetal androgen action also showed a significant 16% reduction as compared with the control group at birth. These data propose that prenatal exposure to WIN can affect gubernacular development probably due to androgen-disruptive action.

Developmental changes in the gubernaculum and anogenital distance of male rat offspring exposed in utero to WIN 55, 212-2 as a candidate of the endocannabinoid system

Cannabinoids can inhibit the release of androgens locally or centrally. For this reason, this study was designed to assess the effect of WIN 55, 212-2, a CB1 receptor agonist, on gubernacular development histologically. Sprague-Dawley female rats were time-mated and divided into treatment and control groups. For prenatal exposures, the groups received injections subcutaneously of 0.5 mg/kg WIN 55, 212-2 (WIN) or vehicle on gestational days 13.520.5. Five to 13 male offspring were collected at time points E19 (embryonic), P0 (postnatal), P2, and P8. The body weight and anogenital distance (AGD) of postnatal male pups were recorded at birth. The inguino-perineal region of all the samples after fixing in 4% paraformaldehyde were sectioned oblique-sagittally and stained with Hematoxilin and Eosin (HE) or Masson's trichrome. Measured Factors in this study were based on previous studies and included gubernacular cone height (GCH), gubernacular cone width (GCW), distance from gubernaculum to scrotum (G-S), and pubic symphysis-to-anus distance (PS-A). The former two factors were measured bilaterally and the latter two only on the left side. The gubernaculum at P0 appeared more bulky than that of controls. Failure of eversion at P2 and remaining bulb of gubernaculum at P8 were important findings in WIN-treated group. The mean distance from gubernaculum to scrotum increased significantly only atP2 compared to controls. AGD as a bioassay of fetal androgen action also showed a significant 16% reduction as compared with the control group at birth. These data propose that prenatal exposure to WIN can affect gubernacular development probably due to androgen-disruptive action.(AU)

A spider derived peptide, PnPP-19, induces central antinociception mediated by opioid and cannabinoid systems

Some peptides purified from the venom of the spider Phoneutria nigriventer have been identified as potential sources of drugs for pain treatment. In this study, we characterized the antinociceptive effect of the peptide PnPP-19 on the central nervous system and investigated the possible involvement of opioid and cannabinoid systems in its action mechanism. Methods Nociceptive threshold to thermal stimulation was measured according to the tail-flick test in Swiss mice. All drugs were administered by the intracerebroventricular route. Results PnPP-19 induced central antinociception in mice in the doses of 0.5 and 1 g. The non-selective opioid receptor antagonist naloxone (2.5 and 5 g), -opioid receptor antagonist clocinnamox (2 and 4 g), -opioid receptor antagonist naltrindole (6 and 12 g) and CB1 receptor antagonist AM251 (2 and 4 g) partially inhibited the antinociceptive effect of PnPP-19 (1 g). Additionally, the anandamide amidase inhibitor MAFP (0.2 g), the anandamide uptake inhibitor VDM11 (4 g) and the aminopeptidase inhibitor bestatin (20 g) significantly enhanced the antinociception induced by a low dose of PnPP-19 (0.5 g). In contrast, the -opioid receptor antagonist nor-binaltorphimine (10 g and 20 g) and the CB2 receptor antagonist AM630 (2 and 4 g) do not appear to be involved in this effect. Conclusions PnPP-19-induced central antinociception involves the activation of CB1 cannabinoid, - and -opioid receptors. Mobilization of endogenous opioids and cannabinoids might be required for the activation of those receptors, since inhibitors of endogenous substances potentiate the effect of PnPP-19. Our results contribute to elucidating the action of the peptide PnPP-19 in the antinociceptive pathway.(AU)

A spider derived peptide, PnPP-19, induces central antinociception mediated by opioid and cannabinoid systems

Some peptides purified from the venom of the spider Phoneutria nigriventer have been identified as potential sources of drugs for pain treatment. In this study, we characterized the antinociceptive effect of the peptide PnPP-19 on the central nervous system and investigated the possible involvement of opioid and cannabinoid systems in its action mechanism. Methods Nociceptive threshold to thermal stimulation was measured according to the tail-flick test in Swiss mice. All drugs were administered by the intracerebroventricular route. Results PnPP-19 induced central antinociception in mice in the doses of 0.5 and 1 g. The non-selective opioid receptor antagonist naloxone (2.5 and 5 g), -opioid receptor antagonist clocinnamox (2 and 4 g), -opioid receptor antagonist naltrindole (6 and 12 g) and CB1 receptor antagonist AM251 (2 and 4 g) partially inhibited the antinociceptive effect of PnPP-19 (1 g). Additionally, the anandamide amidase inhibitor MAFP (0.2 g), the anandamide uptake inhibitor VDM11 (4 g) and the aminopeptidase inhibitor bestatin (20 g) significantly enhanced the antinociception induced by a low dose of PnPP-19 (0.5 g). In contrast, the -opioid receptor antagonist nor-binaltorphimine (10 g and 20 g) and the CB2 receptor antagonist AM630 (2 and 4 g) do not appear to be involved in this effect. Conclusions PnPP-19-induced central antinociception involves the activation of CB1 cannabinoid, - and -opioid receptors. Mobilization of endogenous opioids and cannabinoids might be required for the activation of those receptors, since inhibitors of endogenous substances potentiate the effect of PnPP-19. Our results contribute to elucidating the action of the peptide PnPP-19 in the antinociceptive pathway.

Efeitos da fumaça da Cannabis sativa e de compostos canabinóides: uma avaliação in vivo e in

Os efeitos do uso materno da maconha sobre o desenvolvimento do sistema nervoso central da prole não são bem esclarecidos. Neste estudo foram investigados os efeitos da inalação materna da fumaça da Cannabis sativa sobre o desenvolvimento cerebral e os efeitos de exo e endocanabinóides e do extrato da fumaça da maconha sobre a função mitocondrial em cultura celular. Camundongas grávidas (n=20) foram expostas diariamente durante 5 minutos à fumaça decorrente da queima de maconha (0,2 g de Cannabis), ou ao ar filtrado, a partir do 5,5° dia gestacional (DG) ao 17,5° DG. No 18,5° DG metade dos fetos foram eutanasiados e a outra metade foi eutanasiada com 20 e 60 dias pós-natal (DPN) para análises estereológicas, imunohistoquímicas e de Western blotting. Cultura de neurônios primários corticais de ratos e células PC12 diferenciadas foram tratados com AEA, THC e CBD para avaliação da viabilidade celular e da função mitocondrial (produção de estresse oxidativo, potencial de membrana e dinâmica mitocondrial). A caracterização de HPAs, da composição elementar e de canabinóides foram realizados no material particulado e na droga, respectivamente. Animais expostos à fumaça da maconha no período gestacional tiveram alteração no volume encefálico, no tálamo, no hipotálamo e cerebelo com 60DPN. Houve alteração do volume do bulbo olfatório e do diencéfalo em fetos. A espessura das camadas corticais foi alterada em animais com 20 e 60DPN. Houve aumento de BDNF no córtex de animais adultos e alteração na expressão das proteínas BDNF (18DPC e 60DPN), CB1 e NeuN (60DPN). Além disso, diferenças específicas ligadas ao sexo foram observadas. Diminuição da viabilidade celular e no potencial de membrana, aumento na produção de EROs e inibição da dinâmica mitocondrial foram observadas nas culturas celulares. Os resultados desse estudo demonstram que a exposição in vivo e in vitro à fumaça da Cannabis causa alterações morfológicas cerebrais em camundongos e na função da mitocondrial neuronal.

The effects of maternal marijuana use on the development of central nervous system in offsprings are not completely understood. In this study, we have investigated the effects of maternal Cannabis smoke inhalation on the brain development and the effects of cannabinoids and Cannabis smoke extracts on in vitro mitochondrial function. Pregnant mice (n = 20) were exposed daily for 5 minutes to marijuana smoke (0.2 g of Cannabis), or filtered air from gestational day (GD) 5.5 to 17.5 GD. On GD 18.5 half of the dams (n=10) were euthanized and the other half (n=10) were euthanized at postnatal day (PND) 20 and 60 for stereological, immunohistochemical, and Western blotting analysis. Neurons culture from rats and differentiated PC12 cells were treated with AEA, THC, and CBD to assess cell viability and mitochondrial function (reactive oxygen species production i.e. ROS), membrane potential, and mitochondrial dynamic). PHAs, elemental composition, and cannabinoids characterization were carried out by using the particulate material and the drug, respectively. The animals exposed to marijuana smoke during gestation presented changes in encephalon total volume, thalamus, hypothalamus, and cerebellum at PND 60. There was an alteration in the volume of the olfactory bulb and the diencephalon in fetuses. The thickness of the cortical layers changed in animals with PND 20 and 60. There was an increase in BDNF in the cortex of adult animals and a change in the expression of BDNF proteins (GD18 and PND60), CB1, and NeuN (PND60). Also, sex- specific differences were found. Cell viability and membrane potential were decreased. On the other hand, increased ROS production was found, and inhibition of mitochondrial dynamics was observed in cell cultures. In summary, this study points out that smoke Cannabis exposure in vivo and in vitro may cause brain damage in mice and in neuronal mitochondrial function.

Intoxicação por Cannabis sativa em um cão - relato de caso / Cannabis sativa intoxication in a dog - a case report / Intoxicación con Cannabis sativa en un perro - relato de caso

A maconha consiste na mistura feita a partir de folhas e flores secas da planta Cannabis sativa. Normalmente, os animais se intoxicam por meio de ingestão acidental. Os efeitos da planta são associados aos canabinoides, que não são encontrados em outras espécies vegetais. Em alguns estados dos Estados Unidos, vem sendo observado um aumento de casos de intoxicação em cães. No Brasil, os relatos são escassos. O objetivo deste trabalho é relatar um caso clínico em canino intoxicado por maconha. O cão deu entrada no hospital apresentando incoordenação motora, depressão, midríase, diminuição de reflexo pupilar, nistagmo horizontal, opistótono, bradicardia e estado de obnubilação. O paciente foi internado e submetido a um tratamento de suporte, uma vez que não há antídoto para essa intoxicação.A recuperação se deu em torno de 36 horas.

Marijuana consists of a mixture of dried leaves and flowers of the plant Cannabis sativa. Animals are usually poisoned by accidental ingestion. The effects of the plant are associated with cannabinoids, which are not found in other plant species. An increase in poisoning cases in dogs was observed in some states of the USA. In Brazil, reports are scarce. The objective of this study is to report a case of a dog intoxicated by marijuana. The animal was admitted to the hospital with incoordination, depression, mydriasis, decreased pupillary reflex, horizontal nystagmus, opisthotonos, bradycardia, and obnubilation. The patient was hospitalized and subjected to supportive treatment, since there is no antidote for this kind of poisoning. Patient recovery took approximately 36 hours.

La marihuana es una mezcla que se hace a partir de hojas y flores secas de la planta Cannabis sativa. Normalmente los animales se intoxican por ingestión accidental del producto. Los efectos de la planta están relacionados a los cannabinoides, que no se encuentran en otras especies vegetales. En algunos estados de los Estados Unidos de Norteamérica se ha observado un aumento de los casos de intoxicación en perros. En Brasil son pocos los casos registrados. El objetivo del presente trabajo es relatar el caso de un canino intoxicado con marihuana. El paciente se presentó en el hospital con incoordinación motora, depresión, midriasis, disminución del reflejo pupilar, nistagmo horizontal, opistótonos, bradicardia y obnubilación. El paciente fue internado y sometido a un tratamiento de soporte, ya que no existe antídoto para este tipo de intoxicación. La recuperación del paciente se produjo aproximadamente 36 horas después.

Intoxicação por Cannabis sativa em um cão - relato de caso / Cannabis sativa intoxication in a dog - a case report / Intoxicación con Cannabis sativa en un perro - relato de caso

A maconha consiste na mistura feita a partir de folhas e flores secas da planta Cannabis sativa. Normalmente, os animais se intoxicam por meio de ingestão acidental. Os efeitos da planta são associados aos canabinoides, que não são encontrados em outras espécies vegetais. Em alguns estados dos Estados Unidos, vem sendo observado um aumento de casos de intoxicação em cães. No Brasil, os relatos são escassos. O objetivo deste trabalho é relatar um caso clínico em canino intoxicado por maconha. O cão deu entrada no hospital apresentando incoordenação motora, depressão, midríase, diminuição de reflexo pupilar, nistagmo horizontal, opistótono, bradicardia e estado de obnubilação. O paciente foi internado e submetido a um tratamento de suporte, uma vez que não há antídoto para essa intoxicação.A recuperação se deu em torno de 36 horas.(AU)

Marijuana consists of a mixture of dried leaves and flowers of the plant Cannabis sativa. Animals are usually poisoned by accidental ingestion. The effects of the plant are associated with cannabinoids, which are not found in other plant species. An increase in poisoning cases in dogs was observed in some states of the USA. In Brazil, reports are scarce. The objective of this study is to report a case of a dog intoxicated by marijuana. The animal was admitted to the hospital with incoordination, depression, mydriasis, decreased pupillary reflex, horizontal nystagmus, opisthotonos, bradycardia, and obnubilation. The patient was hospitalized and subjected to supportive treatment, since there is no antidote for this kind of poisoning. Patient recovery took approximately 36 hours.(AU)

La marihuana es una mezcla que se hace a partir de hojas y flores secas de la planta Cannabis sativa. Normalmente los animales se intoxican por ingestión accidental del producto. Los efectos de la planta están relacionados a los cannabinoides, que no se encuentran en otras especies vegetales. En algunos estados de los Estados Unidos de Norteamérica se ha observado un aumento de los casos de intoxicación en perros. En Brasil son pocos los casos registrados. El objetivo del presente trabajo es relatar el caso de un canino intoxicado con marihuana. El paciente se presentó en el hospital con incoordinación motora, depresión, midriasis, disminución del reflejo pupilar, nistagmo horizontal, opistótonos, bradicardia y obnubilación. El paciente fue internado y sometido a un tratamiento de soporte, ya que no existe antídoto para este tipo de intoxicación. La recuperación del paciente se produjo aproximadamente 36 horas después.(AU)

Efeitos da Anandamida sobre a esfera neuroimune de camundongos: avaliação comportamental, endócrina e de parâmetros da atividade imune adquirida / Anandamide effects on neuroimmune interactions in mice: Behavioral, endocrine, and parameters of adaptative immune activity evaluation

A neuroimunomodulação é um ramo da ciência que estuda as inter-relações existentes entre o SNC e o SI. O termo inter-relações foi empregado porque, sabe-se hoje serem estas relações bidirecionais. Conhecendo-se a existência desta comunicação, não é difícil de se supor que substâncias que atuem no sistema neuro-endócrino tenham a capacidade de influenciar as respostas imunes seja por uma ação neuroimune indireta ou por outra que se faça diretamente nas células imunes. Os canabinóides (endógenos, derivados da planta e sintéticos) apresentam um amplo espectro de ações, dentre as quais cabe destacar aquelas sobre o comportamento (ansiedade e medo), o sistema neuro-endócrino (ativação do eixo HHA) e imune (resposta imune inata e adquirida). Estes efeitos são geralmente atribuídos à ligação dos canabinóides a receptores específicos presentes no SNC (receptores CB1) e na periferia (receptores CB2). Neste sentido, buscamos neste trabalho avaliar os efeitos da Anandamida (AEA), uma agonista canabinóide endógeno, sobre o comportamento, a ativação do eixo HHA e alguns parâmetros de atividade imune adquirida, e o fizemos à luz de mecanismos neuroimunomodulatórios. Nossos resultados mostraram que os efeitos da AEA sobre o comportamento são dependentes da dose e, também, do tempo de latência para as observações. Neste sentido, 10 minutos após a administração de doses crescentes de AEA observou-se, tanto no campo aberto como no LCE, um efeito que seguiu um padrão de curva em U invertido dependente da dose. Nossos resultados mostraram, também, que a AEA na dose de 0,1mg/kg administrada 90 minutos antes das observações, aumentou o tempo gasto pelos animais em movimento na zona periférica e diminui o tempo gasto em movimento na zona central do campo aberto. Mostrou-se, ainda, que a AEA na dose de 0,1mg/kg aumentou acentuadamente os níveis séricos de corticosterona nos animais medidos 45 e 90 minutos após a administração. Finalmente, mostrou-se que uma dose de 0,1mg/kg de AEA previamente a uma imunização com OVA promoveu um aumento da reposta de hipersensibilidade do tipo tardia (DTH) e um aumento na porcentagem de proliferação de células T CD4+. Estes resultados em seu conjunto permitem sugerir que a AEA (0,1mg/kg) administrada 90 minutos antes das observações tenha se comportado como um estressor químico, promovendo efeito semelhante ao de ansiogênicos no campo aberto e aumentando os níveis séricos de corticosterona; esses níveis aumentados de corticosterona teriam sido os responsáveis pelo aumento da resposta imune celular (Th1) observada

Neuroimmunomodulation is a field of research concerned with the relationships between the CNS and the IS. The term relationship is frequently employed because it is assumed that such communication is bidirectional. In this regard, if we consider that this communication exists, it should be accetable that substances acting on the neuroendocrine system are able of modifying immune responses, either acting via a neuroimmune indirect pathway, or acting directly on immune cells. Cannabinoids (endogenous, plant derived, and synthetic) show a large spectrum of actions over the body. We emphasize here, behavioral (anxiety and fear), endocrine (HPA axis activation), and immune (innate and adaptative immunity) effects. These effects are generally attributed to cannabinoid bind to specific receptors present on CNS (CB1 receptors) and in the periphery (CB2 receptors). In this sense, we evaluated Anandamide (AEA, an endogenous cannabinoid agonist) effects, on behavior, HPA axis activation, and parameters of adaptative immunity, particularly neuroimmune relationships. Briefly, our results show that the AEA effects on behavior are dependent on the dose and time. Thus, 10 minutes after injection of growing increasing doses of AEA, we found in the open field and plus maze an inverted U-shape dose-response for AEA which is characteristic of cannabinoids in this type of behavioral evaluation. Additionally we show, that AEA 0,1mg/kg after 90 minutes of administration increased the time spent in the peripheral zone, and decreased the time spent in the central zone of the open field. Furthermore, we found that AEA 0.1mg/kg strongly increased the serum levels of corticosterone after 45 and 90 minutes of administration. Finally, we show that AEA 0.1mg/kg prior to immunization promoted an increase of delayed-type hypersensitivity (DTH) and an increase in the percentage of CD4+ T cell proliferation. These results allow us to suggest that AEA 0.1mg/kg 90 minutes after administration acted as a chemical stressor, promoting an anxiogenic-like effect in the open field, and increasing the serum levels of corticosterone. Additionally, the increased levels of corticosterone at the moment of antigenic exposition could be responsible for the increased cell-mediated immunity (Th1) observed