ABSTRACT
Cannabis is the most used illicit substance for recreational purposes around the world. However, it has become increasingly common to witness the use of approved cannabis preparations for symptoms management in various diseases. The aim of this study was to investigate the effects of cannabis nano emulsion in the liver of Wistar rats, with different proportions of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). For this, a total of 40 male Wistar rats were distributed into 5 groups, as follows (n = 8 per group): Control: G1, Experimental group (G2): treated with cannabis nano emulsion (THC and CBD) at a dose of 2.5 mg/kg, Experimental group (G3): treated with cannabis nano emulsion (THC and CBD) at a dose of 5 mg/kg, Experimental group (G4): treated with cannabis nano emulsion (CBD) at a dose of 2.5 mg/kg; Experimental group (G5): treated with cannabis nano emulsion (CBD) at a dose of 5 mg/kg. Exposure to the nano emulsion was carried out for 21 days, once a day, orally (gavage). Our results showed that cannabis nano emulsions at higher doses (5 mg/kg), regardless of the composition, induced histopathologic changes in the liver (G3 and G5) in comparison with the control group. In line with that, placental glutathione S-transferase (GST-P) positive foci increased in both G3 and G5 (p < 0.05), as well as the immune expression of Ki-67, vascular endothelial growth factor (VEGF) and p53 (p < 0.05). Also, the nano emulsion intake induced an increase in the number of micronucleated hepatocytes in G5 (p < 0.05) whereas G3 showed an increase in binucleated cells (p < 0.05). As for metanuclear alterations, karyolysis and pyknosis had an increased frequency in G3 (p < 0.05). Taken together, the results show that intake of cannabis nano emulsion may induce degenerative changes and genotoxicity in the liver in higher doses, demonstrating a clear dose-response relationship.
Subject(s)
Cannabidiol , Cannabis , Dose-Response Relationship, Drug , Emulsions , Liver , Rats, Wistar , Animals , Male , Liver/drug effects , Liver/pathology , Liver/metabolism , Cannabidiol/toxicity , Cannabidiol/administration & dosage , Cannabis/chemistry , Dronabinol/toxicity , Dronabinol/administration & dosage , Rats , Nanoparticles/toxicity , Chemical and Drug Induced Liver Injury/pathology , Chemical and Drug Induced Liver Injury/etiologyABSTRACT
As a consequence of the Presidential Decree that reforms and additions the General Statute of Health with regard to medicinal and scientific use of tetrahydrocannabinol, its isomers and stereochemical variants, the National Academy of Medicine of Mexico declares its position in favor of regulating investigation and national production thereof.
Como consecuencia del decreto presidencial que reforma y adiciona la Ley General de Salud respecto al uso medicinal y científico del tetrahidrocannabinol, sus isómeros y variantes estereoquímicas, la Academia Nacional de Medicina de México declara su posición para normar la investigación y producción nacional de los mismos.
Subject(s)
Cannabis/chemistry , Dronabinol/administration & dosage , Health Policy , Medical Marijuana/administration & dosage , Academies and Institutes , Dronabinol/chemistry , Humans , Isomerism , MexicoABSTRACT
RATIONALE: Delta(9)-Tetrahydrocannabinol (Delta(9)-THC) disrupts working memory. The prefrontal cortex (PFC) is involved in the processing of working memory, and its medial portion (mPFC) is part of a brain reward circuit as constituted by the mesocorticolimbic dopaminergic system. OBJECTIVE: This study examined the involvement of the mPFC in the effects of Delta(9)-THC on spatial working memory. METHODS: Ten male Wistar rats well-trained in a radial arm maze and with bilateral cannula implanted in the mPFC received Delta(9)-THC intra-cortically (Delta(9)-THC IC) at doses of 0 (VEH), 32, 100 or 180 microg, 5 min before a 5-s or a 1-h delayed task in order to measure a short- or long-term spatial working memory, respectively. By contrast, 11 other animals received Delta(9)-THC intraperitoneally (Delta(9)-THC IP) at doses of 0 (VEH), 0.32, 1 or 1.8 mg/kg, 30 min before a 5-s or a 1-h delayed task. Additionally, after a 15-day washout, the effect of an IP or IC pre-exposure of Delta(9)-THC was examined by repeating both dose-effect curves in a crossover order for the routes of administration. RESULTS: Delta(9)-THC IP produced significantly larger number of errors at doses of 0.32 or 1 mg/kg as compared to VEH in the 1-h post-delay performance. Delta(9)-THC 100 microg IC also produced significantly larger number of errors as compared to VEH and also to the other doses (32 or 180 microg) IC in the 1-h post-delay performance. Previous exposure to Delta(9)-THC IP or IC did not significantly affect the disruptive effect of this cannabinoid. CONCLUSIONS: Delta(9)-THC administered directly in the mPFC impaired 1-h delayed task in the radial arm maze in a manner similar to that observed for its systemic administration, suggesting that the mPFC is involved in the disruptive effects of Delta(9)-THC on spatial working memory.
Subject(s)
Dronabinol/pharmacology , Memory/drug effects , Prefrontal Cortex/drug effects , Psychotropic Drugs/pharmacology , Animals , Dose-Response Relationship, Drug , Dronabinol/administration & dosage , Injections, Intraventricular , Male , Maze Learning/drug effects , Prefrontal Cortex/physiology , Psychotropic Drugs/administration & dosage , Rats , Rats, Wistar , Time FactorsABSTRACT
To investigate the effects of the cannabinoids on learning and on scopolamine-induced disruptions in learning, delta9-tetrahydrocannabinol (delta9-THC), SR 141716A (an antagonist at CB1 receptors) and scopolamine were administered to squirrel monkeys responding in a repeated-acquisition task. In this task, monkeys acquired a different three-response sequence each session and responding was maintained by food presentation under a second-order fixed-ratio 5 schedule. When either delta9-THC (0.1-0.56 mg/kg, i.m.) or SR 141716A (1-10 mg/kg, i.m.) was administered alone, 60 and 75 min before the session, respectively, both cannabinoid ligands dose-dependently decreased the overall rate of responding and increased the overall percentage of errors. However, at a dose that had little or no effect alone (i.e. 1 mg/kg), SR 141716A antagonized the disruptive effects of delta9-THC (0.18-1.8 mg/kg) on acquisition, shifting the dose-effect curves for rate of responding and percentage of errors at least 1/2 log unit to the right. Finally, when either delta9-THC (0.001-1 mg/kg) or SR 141716A (0.32-10 mg/kg) was administered with scopolamine (0.01 or 0.032 mg/kg, 15 min before the session), greater rate-decreasing and error-increasing effects were obtained than with scopolamine alone. These results suggest that while low doses of SR 141716A can antagonize the effects of delta9-THC in squirrel monkeys, high doses can also disrupt acquisition when administered alone and potentiate the disruptive effects of scopolamine on acquisition.
Subject(s)
Dronabinol/pharmacology , Hallucinogens/pharmacology , Learning/drug effects , Muscarinic Antagonists/pharmacology , Piperidines/pharmacology , Pyrazoles/pharmacology , Scopolamine/pharmacology , Animals , Dose-Response Relationship, Drug , Dronabinol/administration & dosage , Female , Hallucinogens/administration & dosage , Ligands , Muscarinic Antagonists/administration & dosage , Piperidines/administration & dosage , Pyrazoles/administration & dosage , Rimonabant , Saimiri , Scopolamine/administration & dosageABSTRACT
1. Schedule-induced intravenous self-injection of delta 9-tetrahydrocannabinol (delta 9-THC) and d-amphetamine was investigated in the same animals. 2. Rats self-injected significantly more amphetamine than delta 9-THC. However, the results suggested that delta 9-THC did not play a predisposing role to the increased amphetamine intake. When delta 9-THC was reinstated after amphetamine response rates were drastically reduced. 3. It is concluded that the reinforcing effects of delta 9-THC may be unrelated to its stimulant effects. The small number of responses for delta 9-THC is in agreement with reports of the poor reinforcing capability of cannabis compounds in rats.
Subject(s)
Dextroamphetamine/administration & dosage , Dronabinol/administration & dosage , Rats, Wistar/physiology , Reinforcement, Psychology , Substance-Related Disorders/physiopathology , Animals , Injections, Intravenous , Male , Rats , Self AdministrationABSTRACT
1. Schedule-induced intravenous self-injection of delta9 - tetrahydrocannabinol (delta9 -THC) and d-amphetamine was investigated in the same animals. 2. /rats self-injected significantly more amphetamine than delta9 -THC. However, the results suggested that delta9 -THC did not play a predisposing role to the increased amphetamine intake. When delta 9 -THC was reinstated after amphetamine response rates were drastically reduced. 3. It is conclued that the reinforcing effects of delta- -THC may be unrelated to its stimulant effects. The small number of responses for delta9 -THC is in agreement with reports of the poor reinforcing capability of cannabis compounds in rats