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Long-Term Consequences of Adolescent Exposure to THC-Rich/CBD-Poor and CBD-Rich/THC-Poor Combinations: A Comparison with Pure THC Treatment in Female Rats

Cannabis is the most-used recreational drug worldwide, with a high prevalence of use among adolescents. In animal models, long-term adverse effects were reported following chronic adolescent exposure to the main psychotomimetic component of the plant, delta-9-tetrahydrocannabinol (THC). However, the...

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Autores principales: Gabaglio, Marina, Zamberletti, Erica, Manenti, Cristina, Parolaro, Daniela, Rubino, Tiziana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8396365/
https://www.ncbi.nlm.nih.gov/pubmed/34445602
http://dx.doi.org/10.3390/ijms22168899
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author Gabaglio, Marina
Zamberletti, Erica
Manenti, Cristina
Parolaro, Daniela
Rubino, Tiziana
author_facet Gabaglio, Marina
Zamberletti, Erica
Manenti, Cristina
Parolaro, Daniela
Rubino, Tiziana
author_sort Gabaglio, Marina
collection PubMed
description Cannabis is the most-used recreational drug worldwide, with a high prevalence of use among adolescents. In animal models, long-term adverse effects were reported following chronic adolescent exposure to the main psychotomimetic component of the plant, delta-9-tetrahydrocannabinol (THC). However, these studies investigated the effects of pure THC, without taking into account other cannabinoids present in the cannabis plant. Interestingly, cannabidiol (CBD) content seems to mitigate some of the side effects of THC, at least in adult animals. Thus, in female rats, we evaluated the long-term consequences of a co-administration of THC and CBD at a 3:1 ratio, chosen based on the analysis of recently confiscated illegal cannabis samples in Europe. CBD content is able to mitigate some of the long-term behavioral alterations induced by adolescent THC exposure as well as long-term changes in CB1 receptor and microglia activation in the prefrontal cortex (PFC). We also investigated, for the first time, possible long-term effects of chronic administration of a THC/CBD combination reminiscent of “light cannabis” (CBD:THC in a 33:1 ratio; total THC 0.3%). Repeated administration of this CBD:THC combination has long-term adverse effects on cognition and leads to anhedonia. Concomitantly, it boosts Glutamic Acid Decarboxylase-67 (GAD67) levels in the PFC, suggesting a possible lasting effect on GABAergic neurotransmission.
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spelling pubmed-83963652021-08-28 Long-Term Consequences of Adolescent Exposure to THC-Rich/CBD-Poor and CBD-Rich/THC-Poor Combinations: A Comparison with Pure THC Treatment in Female Rats Gabaglio, Marina Zamberletti, Erica Manenti, Cristina Parolaro, Daniela Rubino, Tiziana Int J Mol Sci Article Cannabis is the most-used recreational drug worldwide, with a high prevalence of use among adolescents. In animal models, long-term adverse effects were reported following chronic adolescent exposure to the main psychotomimetic component of the plant, delta-9-tetrahydrocannabinol (THC). However, these studies investigated the effects of pure THC, without taking into account other cannabinoids present in the cannabis plant. Interestingly, cannabidiol (CBD) content seems to mitigate some of the side effects of THC, at least in adult animals. Thus, in female rats, we evaluated the long-term consequences of a co-administration of THC and CBD at a 3:1 ratio, chosen based on the analysis of recently confiscated illegal cannabis samples in Europe. CBD content is able to mitigate some of the long-term behavioral alterations induced by adolescent THC exposure as well as long-term changes in CB1 receptor and microglia activation in the prefrontal cortex (PFC). We also investigated, for the first time, possible long-term effects of chronic administration of a THC/CBD combination reminiscent of “light cannabis” (CBD:THC in a 33:1 ratio; total THC 0.3%). Repeated administration of this CBD:THC combination has long-term adverse effects on cognition and leads to anhedonia. Concomitantly, it boosts Glutamic Acid Decarboxylase-67 (GAD67) levels in the PFC, suggesting a possible lasting effect on GABAergic neurotransmission. MDPI 2021-08-18 /pmc/articles/PMC8396365/ /pubmed/34445602 http://dx.doi.org/10.3390/ijms22168899 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gabaglio, Marina
Zamberletti, Erica
Manenti, Cristina
Parolaro, Daniela
Rubino, Tiziana
Long-Term Consequences of Adolescent Exposure to THC-Rich/CBD-Poor and CBD-Rich/THC-Poor Combinations: A Comparison with Pure THC Treatment in Female Rats
title Long-Term Consequences of Adolescent Exposure to THC-Rich/CBD-Poor and CBD-Rich/THC-Poor Combinations: A Comparison with Pure THC Treatment in Female Rats
title_full Long-Term Consequences of Adolescent Exposure to THC-Rich/CBD-Poor and CBD-Rich/THC-Poor Combinations: A Comparison with Pure THC Treatment in Female Rats
title_fullStr Long-Term Consequences of Adolescent Exposure to THC-Rich/CBD-Poor and CBD-Rich/THC-Poor Combinations: A Comparison with Pure THC Treatment in Female Rats
title_full_unstemmed Long-Term Consequences of Adolescent Exposure to THC-Rich/CBD-Poor and CBD-Rich/THC-Poor Combinations: A Comparison with Pure THC Treatment in Female Rats
title_short Long-Term Consequences of Adolescent Exposure to THC-Rich/CBD-Poor and CBD-Rich/THC-Poor Combinations: A Comparison with Pure THC Treatment in Female Rats
title_sort long-term consequences of adolescent exposure to thc-rich/cbd-poor and cbd-rich/thc-poor combinations: a comparison with pure thc treatment in female rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8396365/
https://www.ncbi.nlm.nih.gov/pubmed/34445602
http://dx.doi.org/10.3390/ijms22168899
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