scholarly journals Cannabidiol as a potential treatment for psychosis

2019 ◽  
Vol 9 ◽  
pp. 204512531988191 ◽  
Author(s):  
Cathy Davies ◽  
Sagnik Bhattacharyya
Keyword(s):  
Mechanism Of Action ◽  
Psychotic Disorders ◽  
Dopamine D2 Receptor ◽  
Significant Proportion ◽  
D2 Receptor ◽  
Current Evidence ◽  
Novel Treatment ◽  
D2 Antagonist ◽  
Unique Mechanism ◽  
Preclinical Work

Psychotic disorders such as schizophrenia are heterogeneous and often debilitating conditions that contribute substantially to the global burden of disease. The introduction of dopamine D2 receptor antagonists in the 1950s revolutionised the treatment of psychotic disorders and they remain the mainstay of our treatment arsenal for psychosis. However, traditional antipsychotics are associated with a number of side effects and a significant proportion of patients do not achieve an adequate remission of symptoms. There is therefore a need for novel interventions, particularly those with a non-D2 antagonist mechanism of action. Cannabidiol (CBD), a non-intoxicating constituent of the cannabis plant, has emerged as a potential novel class of antipsychotic with a unique mechanism of action. In this review, we set out the prospects of CBD as a potential novel treatment for psychotic disorders. We first review the evidence from the perspective of preclinical work and human experimental and neuroimaging studies. We then synthesise the current evidence regarding the clinical efficacy of CBD in terms of positive, negative and cognitive symptoms, safety and tolerability, and potential mechanisms by which CBD may have antipsychotic effects.

The Effect of PAOPA, a Novel Allosteric Modulator of Dopamine D2 Receptors, on Select Signaling Proteins Following Sub-Chronic Administration in the Rat

2020 ◽  
Vol 13 ◽  
Author(s):  
Ritesh Daya ◽  
Joella Ho ◽  
Sharon Thomson ◽  
Jayant Bhandari ◽  
Ram K. Mishra
Keyword(s):  
Frontal Cortex ◽  
Mechanism Of Action ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Dorsal Striatum ◽  
D2 Receptors ◽  
Dopamine D2 ◽  
Therapeutic Mechanism ◽  
Clinical Models ◽  
G Protein Coupled

Background: Allosteric modulators of G-protein coupled receptors regulate receptor activity by binding to sites other than the active site and have emerged as a new and highly desirable class of drugs. PAOPA (3(R)-[(2(S)- pyrrolidinylcarbonyl)amino]-2-oxo-1-pyrrolidineacetamide), a peptidomimetic analog of Prolyl-Leucyl-Glycinamide, is a potent dopamine D2 receptor allosteric modulator. PAOPA has shown therapeutic effects in pre-clinical models of schizophrenia and extrapyramidal dysfunction. Objective: in this study, we sought to examine the biomolecular underpinnings of PAOPA‘s therapeutic outcomes in preclinical models of schizophrenia. Method: Following sub-chronic (daily for 7 days) administration of PAOPA, we assessed levels of dopamine D2 receptors, receptor kinases (GRK2 (G protein-coupled receptor kinase 2) and Arrestin-3), and phosphorylated mitogenactivated protein kinase (MAPKs), namely, extracellular signal-regulated kinases (ERK1/2) in the hippocampus, medial pre-frontal cortex, nucleus accumbens, pre-frontal cortex, and dorsal striatum via protein quantification. Results: Following 7 days of daily PAOPA treatment, we observed decreased GRK2 and increased dopamine D2 receptor expression in the dorsal striatum. These findings potentially underscore PAOPA’s therapeutic mechanism of action for the positive-like symptoms of schizophrenia in pre-clinical animal models. Additionally, we observed a decline in GRK2 in the hippocampus and an increase in phosphorylated ERK1 in the pre-frontal cortex, suggestive of a role for PAOPA in treating cognitive and/or affective dysfunction in pre-clinical models. Conclusion: While further studies are required to elucidate PAOPA’s mechanism of action, this study builds on prior investigations and develops an early framework to describe the therapeutic mechanism of action of PAOPA.

scholarly journals Exercise and Worsening of Extrapyramidal Symptoms during Treatment with Long-Acting Injectable Antipsychotics

Pharmacy ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 123
Author(s):  
David D. Kim ◽  
Donna J. Lang ◽  
Darren E. R. Warburton ◽  
Alasdair M. Barr ◽  
Randall F. White ◽  
...  
Keyword(s):  
Antipsychotic Medication ◽  
Psychotic Disorders ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Exercise Program ◽  
Extrapyramidal Symptoms ◽  
Antipsychotic Treatment ◽  
Antipsychotic Medications ◽  
Treatment Regimens ◽  
Long Acting

Second-generation antipsychotic medications are used to treat schizophrenia and a range of other psychotic disorders, although adverse effects, including cardiovascular and metabolic abnormalities and extrapyramidal symptoms, are often inevitable. Studies have shown that exercise, as an adjunct therapy, can be effective in reducing the core symptoms of schizophrenia as well as ameliorating intrinsic and antipsychotic-induced cardiometabolic abnormalities. However, it is noteworthy that exercise may need to be implemented with caution in some individuals receiving certain antipsychotic treatment regimens. We report here two cases of exercise-associated worsening of extrapyramidal symptoms in two individuals with schizoaffective disorder treated with a long-acting injectable antipsychotic medication over the course of a 12-week exercise program. This worsening of extrapyramidal symptoms can be attributed to an increase in blood flow to the site of injection during exercise, accelerating the rate of absorption and bioavailability of the antipsychotic medication and subsequently increasing dopamine D2 receptor blockade. When monitoring drug therapy for patients receiving long-acting injectable antipsychotic medications, pharmacists and other healthcare professionals need to consider exercise as a contributing factor for the emergence of extrapyramidal symptoms.

Mechanism of action of antipsychotic drugs: From dopamine D2 receptor antagonism to glutamate NMDA facilitation

2005 ◽  
Vol 27 ◽  
pp. S16-S24 ◽  
Author(s):  
Marc Laruelle ◽  
W. Gordon Frankle ◽  
Rajesh Narendran ◽  
Lawrence S. Kegeles ◽  
Anissa Abi-Dargham
Keyword(s):  
Mechanism Of Action ◽  
Antipsychotic Drugs ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Receptor Antagonism ◽  
Dopamine D2

Novel Approaches for Treating Psychotic Disorders

2017 ◽  
Author(s):  
Tiago Reis Marques ◽  
Shitij Kapur
Keyword(s):  
Psychotic Disorders ◽  
Dopamine D2 Receptor ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
D2 Receptor ◽  
Cognitive Remediation ◽  
Mechanisms Of Action ◽  
Serotoninergic System ◽  
Antipsychotic Medications ◽  
Alpha7 Nicotinic Acetylcholine Receptor ◽  
New Treatments

Current antipsychotic medications have been the mainstay in the treatment of schizophrenia since chlorpromazine was introduced in 1952. However, all antipsychotics share the same mechanism of action, which involves a blockade of the dopamine D2-receptor. This chapter covers recent attempts to develop new treatments for psychotic disorders. These include new approaches to the delivery of existing antipsychotic medications and the most recent and promising mechanisms of action that are distinct from existing antipsychotics. Some of the new mechanisms of action include drugs targeting the glutamatergic system, the alpha7 nicotinic acetylcholine receptor, the phosphodiesterase 10A enzyme, or the muscarinic and serotoninergic system. Finally, we have reviewed a number of alternative nonpharmacological pathways, such as avatar therapy, repetitive transcranial magnetic stimulation, or cognitive remediation. The chapter ends by discussing some of the major challenges facing the development of new treatments for psychotic disorders.

Effect of amphetamine on dopamine D2 receptor binding in the primate brain with the agonist ligand [11C]MNPA

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S646-S646
Author(s):  
Nicholas Seneca ◽  
Sjoerd Finnema ◽  
Masanori Ichise ◽  
Balazs Gulyas ◽  
Håkan Wikstrom ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Dopamine D2 ◽  
Primate Brain

Assessment of endocrine disorders of the hypothalamicpituitary axis by nuclear medicine techniques

2002 ◽  
Vol 41 (02) ◽  
pp. 80-90 ◽  
Author(s):  
F. Jockenhövel ◽  
P. Theissen ◽  
M. Dietlein ◽  
W. Krone ◽  
H. Schicha ◽  
...  
Keyword(s):  
Nuclear Medicine ◽  
Pituitary Adenomas ◽  
Dopamine D2 Receptor ◽  
Somatostatin Receptor ◽  
D2 Receptor ◽  
Ectopic Acth Syndrome ◽  
Endocrine Disorders ◽  
Ectopic Acth ◽  
Number Of Patients ◽  
Hypothalamic Pituitary Axis

SummaryThe following article reviews nuclear medicine techniques which can be used for assessment of endocrine disorders of the hypothalamic-pituitary axis. For planar and SPECT imaging somatostatin-receptor- and dopamine- D2-receptor-scintigraphy are the most widely distributed techniques. These nuclear medicine techniques may be indicated in selected cases to answer differential diagnostic problems. They can be helpful to search for presence and localization of receptor positive tissue. Furthermore they can detect metastasis in the rare cases of a pituitary carcinoma. Scintigraphy with Gallium-67 is suitable for further diagnostic evaluation in suspected hypophysitis. Other SPECT radiopharmaca do not have relevant clinical significance. F-18-FDG as PET radiopharmacon is not ideal because obvious pituitary adenomas could not be visualized. Other PET radiopharmaca including C-11-methionine, C-11-tyrosine, F-18-fluoroethylspiperone, C-11-methylspiperone, and C-11-raclopride are available in specialized centers only. Overall indications for nuclear medicine in studies for the assessment of endocrine disorders of the hypothalamic-pituitary-axis are rare. Original studies often report only about a small number of patients. According to the authors’ opinion the relevance of nuclear medicine in studies of clinically important endocrinologic fields, e. g. localization of small ACTH-producing pituitary adenomas, tumor localization in ectopic ACTH syndrome, localization of recurrent pituitary tissue, assessment of small incidentalomas, can not be definitely given yet.

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