Cannabinoids for the Treatment of Schizophrenia? A Balanced Neurochemical Framework for Both Adverse and Therapeutic Effects of Cannabis Use

Recent studies have found that cannabinoids may improve neuropsychological performance, ameliorate negative symptoms, and have antipsychotic properties for a subgroup of the schizophrenia population. These findings are in contrast to the longstanding history of adverse consequences of cannabis use, predominantly on the positive symptoms, and a balanced neurochemical basis for these opposing views is lacking. This paper details a review of the neurobiological substrates of schizophrenia and the neurochemical effects of cannabis use in the normal population, in both cortical (in particular prefrontal) and subcortical brain regions. The aim of this paper is to provide a holistic neurochemical framework in which to understand how cannabinoids may impair, or indeed, serve to ameliorate the positive and negative symptoms as well as cognitive impairment. Directions in which future research can proceed to resolve the discrepancies are briefly discussed.

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Conceptual disorganization and redistribution of resting state cortical hubs in untreated first episode psychosis: A 7T MRI study

10.31234/osf.io/rzvby ◽

2020 ◽

Author(s):

Avyarthana Dey ◽

Kara Dempster ◽

Michael Mackinley ◽

Peter Jeon ◽

Tushar Das ◽

...

Keyword(s):

Negative Symptoms ◽

Superior Temporal Gyrus ◽

Brain Regions ◽

First Episode Psychosis ◽

Cortical Reorganization ◽

First Episode ◽

Formal Thought Disorder ◽

Whole Brain ◽

Episode Psychosis ◽

Positive And Negative Symptoms

Background:Network level dysconnectivity has been studied in positive and negative symptoms of schizophrenia. Conceptual disorganization (CD) is a symptom subtype which predicts impaired real-world functioning in psychosis. Systematic reviews have reported aberrant connectivity in formal thought disorder, a construct related to CD. However, no studies have investigated whole-brain functional correlates of CD in psychosis. We sought to investigate brain regions explaining the severity of CD in patients with first-episode psychosis (FEPs) compared with healthy controls (HCs).Methods:We computed whole-brain binarized degree centrality maps of 31 FEPs, 25 HCs and characterized the patterns of network connectivity in the two groups. In FEPs, we related these findings to the severity of CD. We also studied the effect of positive and negative symptoms on altered network connectivity.Results:Compared to HCs, reduced hubness of a right superior temporal gyrus (rSTG) cluster was observed in the FEPs. In patients exhibiting high CD, increased hubness of a medial superior parietal (mSPL) cluster was observed, compared to patients exhibiting low CD. These two regions were strongly correlated with CD scores but not with other symptom scores.Discussion:Our observations are congruent with previous findings of reduced but not increased hubness. We observed increased hubness of mSPL suggesting that cortical reorganization occurs to provide alternate routes for information transfer.Conclusion:These findings provide insight into the underlying neural processes mediating the presentation of symptoms in untreated FEP. A longitudinal tracking of the symptom course will be useful to assess the mechanisms underlying these compensatory changes.

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An Atypical Case of Catatonia, Abnormal Gait and Psychosis in an Adolescent with Chronic Cannabis Use

10.47363/jdat/2021(2)114 ◽

2021 ◽

pp. 1-3

Author(s):

Pooja Palkar ◽

◽

Sagarika Ray ◽

Keyword(s):

Cannabinoid Receptors ◽

Oral Intake ◽

Brain Regions ◽

Cannabis Use ◽

Unique Case ◽

Open Chain ◽

Walking Gait ◽

The Past ◽

Abnormal Gait ◽

History Of

An association between cannabis and psychosis is well established. Cannabis use is known to precipitate schizophrenia in vulnerable individuals and it can exacerbate existing psychosis. However, there is a paucity of knowledge about the emergence of catatonia and abnormal gait associated with cannabis use. History of cannabis use is associated with long-lasting changes in open-chain elements of walking gait. Cannabinoid receptors are located in movement-related brain regions and cannabis use is suggested to affect gait. This report is a unique case of a 16-year-old male with no known past medical history, no past psychiatric history, with family history significant for psychosis who presented to the hospital for bizarre, disorganized behavior, and decreased oral intake following heavy cannabis use over the past three months in the context of a break-up. Upon arrival, he was found to be in a catatonic state with an impaired gait. As catatonia resolved with treatment, he was able to speak and the psychosis surfaced which was addressed with antipsychotics. This case report highlights an atypical but serious clinical picture observed to be precipitated by chronic, heavy cannabis use.

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0089 ALCOHOL AND CANNABIS USE IN URBAN, AFRICAN AMERICAN, FIRST-EPISODE PSYCHOSIS PATIENTS: ASSOCIATIONS WITH POSITIVE AND NEGATIVE SYMPTOMS

Schizophrenia Research ◽

10.1016/s0920-9964(06)70296-1 ◽

2006 ◽

Vol 86 ◽

pp. S99

Author(s):

M.T. Compton ◽

N.E. Whicker ◽

K. Hochman

Keyword(s):

African American ◽

Negative Symptoms ◽

First Episode Psychosis ◽

Cannabis Use ◽

First Episode ◽

Episode Psychosis ◽

Positive And Negative Symptoms

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CANNABIS USE AMONG MILITARY VETERANS: A GREAT DEAL TO GAIN OR LOSE?

10.31234/osf.io/b7jcf ◽

2020 ◽

Author(s):

James MacKillop ◽

Jasmine Turna

Keyword(s):

Substance Use ◽

Health Outcomes ◽

The United States ◽

Cannabis Use ◽

Future Research ◽

Therapeutic Effects ◽

Medical Cannabis ◽

Cross Sectional ◽

Physical Health Outcomes ◽

Male Veterans

Policy changes have resulted in dramatic increases in access to cannabis for medical purposes. Veterans are disproportionately affected by conditions for which medical cannabis is often pursued, making an evidence-based perspective on risks versus benefits of high priority. The current review sought to examine the state of the evidence on consequences and correlates of cannabis use among veterans. Using a comprehensive search strategy, 501 articles were identified and 86 studies met criteria for inclusion. The literature was predominated by cross-sectional studies (67%) of male veterans (71.4%-100% male) from the United States (93.0%). Three overarching themes emerged, comprising cannabis associations with other substance use, mental health, and physical health outcomes. The balance of the evidence associated cannabis use with negative health outcomes, with consistent positive associations with other substance use, psychiatric disorders, and self-harm/suicidality. Few studies examined the therapeutic effects of cannabis, thus limiting the potential to evaluate evidence of efficacy. Priority areas for future research are studies using designs that can examine the directionality of links between cannabis and health in veterans more conclusively, and studies directly examining therapeutic efficacy of cannabis-based therapies in veterans. Methodologically rigorous design will be essential to inform clinical recommendations and practices guidelines in an era of burgeoning access to cannabis.

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Schizophrenia phenomenology revisited: positive and negative symptoms are strongly related reflective manifestations of an underlying single trait indicating overall severity of schizophrenia

CNS Spectrums ◽

10.1017/s1092852920001182 ◽

2020 ◽

pp. 1-10 ◽

Cited By ~ 4

Author(s):

Abbas F. Almulla ◽

Hussein K. Al-Hakeim ◽

Michael Maes

Keyword(s):

Convergent Validity ◽

Negative Symptoms ◽

Discriminant Validity ◽

Psychomotor Retardation ◽

Future Research ◽

Stable Phase ◽

Deficit Schizophrenia ◽

Latent Vector ◽

Thought Disorders ◽

Positive And Negative Symptoms

Abstract Background. To examine whether negative symptoms, psychosis, hostility, excitation, and mannerism (PHEM symptoms), formal thought disorders (FTD) and psychomotor retardation (PMR) are interrelated phenomena in major neurocognitive psychosis (MNP) or deficit schizophrenia and whether those domains belong to an underlying latent vector reflecting general psychopathology. Methods. In this study, we recruited 120 patients with MNP or deficit schizophrenia and 54 healthy subjects and measured the above-mentioned symptom domains. Results. In MNP, there were significant associations between negative and PHEM symptoms, FTD and PMR. A single latent trait, which is essentially unidimensional, underlies these key domains of schizophrenia and MNP and additionally shows excellent internal consistency reliability, convergent validity, and predictive relevance. Confirmatory Tedrad Analysis indicates that this latent vector fits a reflective model. The lack of discriminant validity shows that positive (and PHEM or psychotic) and negative symptoms greatly overlap and probably measure the same latent construct. Soft independent modeling of class analogy (SIMCA) shows that MNP (diagnosis based on negative symptoms) is better modeled using PHEM symptoms, FTD, and PMR than negative symptoms. Conclusions. In stable phase MNP, which is a restricted sample of the schizophrenia population, negative and PHEM symptoms, FTD and PMR belong to one underlying latent vector reflecting overall severity of schizophrenia (OSOS). The bi-dimensional concept of “positive” and “negative” symptoms cannot be validated and, therefore, future research in stable phase schizophrenia should consider that the latent phenomenon OSOS as well as its reflective manifestations are the key factors of schizophrenia phenomenology.

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Central 5-HT2 antagonists: A preclinical evaluation of a therapeutic potential

Acta Neuropsychiatrica ◽

10.1017/s0924270800034517 ◽

1990 ◽

Vol 2 (4) ◽

pp. 101-109 ◽

Cited By ~ 2

Author(s):

T.F. Meert ◽

F. Awouters

Keyword(s):

Animal Models ◽

Negative Symptoms ◽

Tricyclic Antidepressants ◽

Therapeutic Potential ◽

Test Procedure ◽

Therapeutic Effects ◽

Preclinical Evaluation ◽

Animal Models Of Depression ◽

Animal Models Of Anxiety ◽

Positive And Negative Symptoms

SummaryA preclinical evaluation is presented of the serotonin 5-HT2 antagonists ritanserin and risperidone. Whereas ritanserin is a relative selective 5-HT2 antagonist, risperidone is a potent 5-HT2 and catecholamine antagonist. The pharmacological differences between both drugs are also observed in the drug discrimination test procedure. Using DOM, d-amphetamine and cocaine. Ritanserin was found active in animal models of anxiety using natural aversive stimuli; and in animal models of depression. Clear differences were observed between ritanserin and the benzodiazepines and between ritanserin and the tricyclic antidepressants. Risperidone was active in animal models of psychosis. Risperidone has, as opposed to classical neuroleptics such as haloperidol, less risks of inducing a dopamine D2 overblockade. Clinically, ritanserin is described as a thymostenic agent.Risperidone is an antipsychotic with therapeutic effects on both the positive and negative symptoms of schizophrenia and with a reduced risk of extrapyramidal side-effects.

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The impact of a family history of psychosis on age-at-onset and positive and negative symptoms of schizophrenia: A meta-analysis

Schizophrenia Research ◽

10.1016/j.schres.2010.01.011 ◽

2010 ◽

Vol 120 (1-3) ◽

pp. 121-130 ◽

Cited By ~ 68

Author(s):

Michelle L. Esterberg ◽

Hanan D. Trotman ◽

Carrie Holtzman ◽

Michael T. Compton ◽

Elaine F. Walker

Keyword(s):

Family History ◽

Negative Symptoms ◽

Meta Analysis ◽

Age At Onset ◽

History Of ◽

The Impact ◽

Positive And Negative Symptoms

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Neuropsychological Outcomes of U.S. Veterans with Report of Remote Blast-Related Concussion and Current Psychopathology

Journal of the International Neuropsychological Society ◽

10.1017/s1355617712000616 ◽

2012 ◽

Vol 18 (5) ◽

pp. 845-855 ◽

Cited By ~ 33

Author(s):

Nathaniel W. Nelson ◽

James B. Hoelzle ◽

Bridget M. Doane ◽

Kathryn A. McGuire ◽

Amanda G. Ferrier-Auerbach ◽

...

Keyword(s):

Future Research ◽

Control Group ◽

Neuropsychological Performance ◽

Structured Interviews ◽

Psychological Conditions ◽

Main Effect ◽

Current Axis ◽

History Of ◽

Axis I ◽

Neuropsychological Outcomes

AbstractThis study explored whether remote blast-related MTBI and/or current Axis I psychopathology contribute to neuropsychological outcomes among OEF/OIF veterans with varied combat histories. OEF/OIF veterans underwent structured interviews to evaluate history of blast-related MTBI and psychopathology and were assigned to MTBI (n = 18), Axis I (n = 24), Co-morbid MTBI/Axis I (n = 34), or post-deployment control (n = 28) groups. A main effect for Axis I diagnosis on overall neuropsychological performance was identified (F(3,100) = 4.81; p = .004), with large effect sizes noted for the Axis I only (d = .98) and Co-morbid MTBI/Axis I (d = .95) groups relative to the control group. The latter groups demonstrated primary limitations on measures of learning/memory and processing speed. The MTBI only group demonstrated performances that were not significantly different from the remaining three groups. These findings suggest that a remote history of blast-related MTBI does not contribute to objective cognitive impairment in the late stage of injury. Impairments, when present, are subtle and most likely attributable to PTSD and other psychological conditions. Implications for clinical neuropsychologists and future research are discussed. (JINS, 2012, 18, 1–11)

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Schizophrenia Phenomenology Revisited: Positive and Negative Symptoms are Strongly Related Reflective Manifestations of an Underlying Single Trait Indicating Overall Severity of Schizophrenia

10.20944/preprints201907.0147.v1 ◽

2019 ◽

Cited By ~ 1

Author(s):

Abbas Almulla ◽

Hussein Al-Hakeim ◽

Michael Maes

Keyword(s):

Convergent Validity ◽

Negative Symptoms ◽

Discriminant Validity ◽

Psychomotor Retardation ◽

Future Research ◽

Stable Phase ◽

Latent Vector ◽

Thought Disorders ◽

Symptom Domains ◽

Positive And Negative Symptoms

Schizophrenia comprises various symptom domains, including positive and negative symptoms. Machine learning showed that a) negative symptoms are significantly interrelated with PHEM (psychosis, hostility, excitation, and mannerism) symptoms, formal thought disorders (FTD) and psychomotor retardation (PMR); and b) stable phase schizophrenia comprises two distinct classes, namely Major Neuro-Cognitive Psychosis (MNP, largely overlapping with deficit schizophrenia) and Simple NP (SNP). In this study, we recruited 120 MNP patients and 54 healthy subjects and measured the above-mentioned symptom domains. In MNP, there were significant associations between negative and PHEM symptoms, FTD and PMR. A single latent trait, which is essentially unidimensional, underlies these key domains of schizophrenia and MNP and additionally shows excellent internal consistency reliability, convergent validity, and predictive relevance. Confirmatory Tedrad Analysis indicates that this latent vector fits a reflective model. The lack of discriminant validity shows that PHEM and negative symptoms greatly overlap and probably measure the same construct. Soft Independent Modeling of Class Analogy (SIMCA) shows that MNP (diagnosis based on negative symptoms) is better modeled using PHEM symptoms, FTD, and PMR than negative symptoms. In conclusion, in stable phase MNP, a restricted sample of the schizophrenia population, negative and PHEM symptoms, FTD and PMR belong to one underlying latent vector reflecting overall severity of schizophrenia (OSOS). The bi-dimensional concept of “positive” and “negative” symptoms cannot be validated and, therefore, future research in stable phase schizophrenia should consider that the latent phenomenon OSOS as well as its 8 reflective manifestations are the key factors of schizophrenia phenomenology.

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Chemical Structures and Pharmacological Profiles of Ginseng Saponins

Molecules ◽

10.3390/molecules24132443 ◽

2019 ◽

Vol 24 (13) ◽

pp. 2443 ◽

Cited By ~ 15

Author(s):

Ze-Yu Shi ◽

Jin-Zhang Zeng ◽

Alice Sze Tsai Wong

Keyword(s):

Future Research ◽

Therapeutic Effects ◽

Bioactive Constituents ◽

Chemical Structures ◽

Anticancer Effects ◽

Steroid Glycosides ◽

History Of ◽

Regulatory Effects ◽

History Of Use

Ginseng is a group of cosmopolitan plants with more than a dozen species belonging to the genus Panax in the family Araliaceae that has a long history of use in traditional Chinese medicine (TCM). Among the bioactive constituents extracted from ginseng, ginseng saponins are a group of natural steroid glycosides and triterpene saponins found exclusively throughout the plant. Studies have shown that these ginseng saponins play a significant role in exerting multiple therapeutic effects. This review covers their chemical structure and classification, as well as their pharmacological activities, including their regulatory effects on immunomodulation, their anticancer effects, and their functions in the central nervous and cardiovascular systems. The general benefits of ginseng saponins for boosting physical vitality and improving quality of life are also discussed. The review concludes with fruitful directions for future research in the use of ginseng saponins as effective therapeutic agents.

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