Background: The widespread use of cannabis, the increasing legalization of "medical" cannabis, the increasing potency of cannabis and the growing recreational use of synthetic cannabinoid 1 receptor (CB1R) full agonists underscores the importance of elucidating the effects of cannabinoids on the CB1R system. Exposure to cannabinoids is known to result in CB1R downregulation. However, the precise time course of changes in CB1R availability in cannabis dependent subjects (CDs) following short and intermediate term abstinence has not been determined.
Methods: Using High Resolution Research Tomography (HRRT) and [C]OMAR, CB1R availability as indexed by the volume of distribution () [C]OMAR was measured in male CDs (n=11) and matched healthy controls (HCs) (n=19). CDs were scanned at baseline (while they were neither intoxicated nor in withdrawal), and after 2 days and 28 days of monitored abstinence. HCs were scanned at baseline and a subset (n=4) was rescanned 28 days later.
Results: Compared to HCs, [C]OMAR was 15% lower in CDs (effect size Cohen's d=-1.11) at baseline in almost all brain regions. However, these group differences in CB1R availability were no longer evident after just 2 days of monitored abstinence from cannabis. There was a robust negative correlation between CB1R availability and withdrawal symptoms after 2 days of abstinence. Finally, there were no significant group differences in CB1R availability in CDs after 28 days of abstinence.
Conclusions: Cannabis dependence is associated with CB1R downregulation, which begins to reverse surprisingly rapidly upon termination of cannabis use and may continue to increase over time.
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http://dx.doi.org/10.1016/j.bpsc.2015.09.008 | DOI Listing |
Mov Disord
January 2025
Turku PET Centre, Turku University and Turku University Hospital, Turku, Finland.
Background: In Parkinson's disease (PD), postural instability and gait disorder (PIGD) symptoms are associated with a worse prognosis for an unknown reason.
Objective: The objective was to explore the relationship between cannabinoid receptor type 1 (CB1R) availability and motor symptoms in PD with [F]FMPEP-d positron emission tomography (PET).
Methods: Fifteen individuals with PD underwent [F]FMPEP-d PET to measure cerebral CB1R availability.
Int J Mol Sci
August 2024
Department of Life Sciences, School of Sciences, European University Cyprus, Nicosia 1516, Cyprus.
Alzheimer's disease (AD), a progressive neurodegenerative disorder, manifests through dysregulation of brain function and subsequent loss of bodily control, attributed to β-amyloid plaque deposition and TAU protein hyperphosphorylation and aggregation, leading to neuronal death. Concurrently, similar cannabinoids to the ones derived from are present in the endocannabinoid system, acting through receptors CBR and CBR and other related receptors such as Trpv-1 and GPR-55, and are being extensively investigated for AD therapy. Given the limited efficacy and adverse effects of current available treatments, alternative approaches are crucial.
View Article and Find Full Text PDFJ Chem Inf Model
September 2024
CNC─Center for Neuroscience and Cell Biology, Center for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-504 Coimbra, Portugal.
The increase in the available G protein-coupled receptor (GPCR) structures has been pivotal in helping to understand their activation process. However, the role of protonation-conformation coupling in GPCR activation still needs to be clarified. We studied the protonation behavior of the highly conserved Asp residue in five different class A GPCRs (active and inactive conformations) using a linear response approximation (LRA) p calculation protocol.
View Article and Find Full Text PDFDiabetologia
September 2024
Inserm UMR1190 - Translational Research for Diabetes, Université de Lille, CHU Lille, Institut Pasteur de Lille, Inserm, European Genomic Institute for Diabetes, Lille, France.
Aims/hypothesis: Insulitis, a hallmark of inflammation preceding autoimmune type 1 diabetes, leads to the eventual loss of functional beta cells. However, functional beta cells can persist even in the face of continuous insulitis. Despite advances in immunosuppressive treatments, maintaining functional beta cells to prevent insulitis progression and hyperglycaemia remains a challenge.
View Article and Find Full Text PDFFront Pharmacol
April 2024
Department of Pharmacy, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China.
Approximately 80% of all malignant brain tumors are gliomas, which are primary brain tumors. The most prevalent subtype of glioma, glioblastoma multiforme (GBM), is also the most deadly. Chemotherapy, immunotherapy, surgery, and conventional pharmacotherapy are currently available therapeutic options for GBM; unfortunately, these approaches only prolong the patient's life by 5 years at most.
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