Category Archives: Schizophrenia

Cannabidiol attenuates aggressive behavior induced by social isolation in mice: Involvement of 5-HT1A and CB1 receptors.

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Progress in Neuro-Psychopharmacology and Biological Psychiatry

“Long-term single housing increases aggressive behavior in mice, a condition named isolation-induced aggression or territorial aggression, which can be attenuated by anxiolytic, antidepressant, and antipsychotic drugs.

Preclinical and clinical findings indicate that cannabidiol (CBD), a non-psychotomimetic compound from Cannabis sativa, has anxiolytic, antidepressant, and antipsychotic properties. Few studies, however, have investigated the effects of CBD on aggressive behaviors.

Here, we investigated whether CBD (5, 15, 30, and 60 mg/kg; i.p.) could attenuate social isolation-induced aggressive behavior in the resident-intruder test.

Taken together, our findings suggest that CBD may be therapeutically useful to treat aggressive behaviors that are usually associated with psychiatric disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/31054943

https://www.sciencedirect.com/science/article/pii/S0278584618308340?via%3Dihub

“cannabidiol reduces aggressiveness, study concludes”  https://globalhealthnewswire.com/2019/07/31/cannabidiol-reduces-aggressiveness-study-concludes/

Dissociable effects of cannabis with and without cannabidiol on the human brain’s resting-state functional connectivity.

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“Two major constituents of cannabis are Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is the main psychoactive component; CBD may buffer the user against the harmful effects of THC.

AIMS:

We examined the effects of two strains of cannabis and placebo on the human brain’s resting-state networks using fMRI.

CONCLUSIONS:

THC disrupts the DMN, and the PCC is a key brain region involved in the subjective experience of THC intoxication. CBD restores disruption of the salience network by THC, which may explain its potential to treat disorders of salience such as psychosis and addiction.”

https://www.ncbi.nlm.nih.gov/pubmed/31013455

https://journals.sagepub.com/doi/abs/10.1177/0269881119841568?journalCode=jopa

“CBD in cannabis could reduce psychosis risk from high strength skunk, study shows. Buffer effect could point to a protective mechanism that may help ‘treat disorders like psychosis and addiction’. Cannabidiol (CBD), a chemical derived from the cannabis plant, can counteract the effects of high strength “skunk” strains and may help to reduce the risk of serious mental health conditions like psychosis, according to a new study.” https://www.independent.co.uk/news/health/cannabis-skunk-cbd-thc-psychosis-addiction-ucl-a8882991.html

Attenuation of Novelty-Induced Hyperactivity of Gria1-/- Mice by Cannabidiol and Hippocampal Inhibitory Chemogenetics.

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“Gene-targeted mice with deficient AMPA receptor GluA1 subunits (Gria1-/- mice) show robust hyperlocomotion in a novel environment, suggesting them to constitute a model for hyperactivity disorders such as mania, schizophrenia and attention deficit hyperactivity disorder. This behavioral alteration has been associated with increased neuronal activation in the hippocampus, and it can be attenuated by chronic treatment with antimanic drugs, such as lithium, valproic acid, and lamotrigine. Now we found that systemic cannabidiol strongly blunted the hyperactivity and the hippocampal c-Fos expression of the Gria1-/- mice, while not affecting the wild-type littermate controls. Acute bilateral intra-dorsal hippocampal infusion of cannabidiol partially blocked the hyperactivity of the Gria1-/- mice, but had no effect on wild-types. The activation of the inhibitory DREADD receptor hM4Gi in the dorsal hippocampus by clozapine-N-oxide robustly inhibited the hyperactivity of the Gria1-/- mice, but had no effect on the locomotion of wild-type mice. Our results show that enhanced neuronal excitability in the hippocampus is associated with pronounced novelty-induced hyperactivity of GluA1 subunit-deficient mice. When this enhanced response of hippocampal neurons to novel stimuli is specifically reduced in the hippocampus by pharmacological treatment or by chemogenetic inhibition, Gria1-/- mice recover from behavioral hyperactivity, suggesting a hippocampal dysfunction in hyperactive behaviors that can be treated with cannabidiol.”

https://www.ncbi.nlm.nih.gov/pubmed/30984001

https://www.frontiersin.org/articles/10.3389/fphar.2019.00309/full

Effect of cannabis on weight and metabolism in first-episode non-affective psychosis: Results from a three-year longitudinal study.

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“Recent evidence indicates a protective effect of cannabis on weight gain and related metabolic alterations. However, there are no previous studies on the long-term longitudinal effects of cannabis on first-episode drug-naïve patients, which would thereby avoid the confounding effects of chronicity and previous treatment exposure.

We aimed to explore the effect of cannabis smoking on weight and lipid/glycaemic metabolic measures in a sample of first-episode non-affective psychosis patients.

RESULTS::

Cannabis users at baseline presented a lower weight ( F=14.85, p<0.001), body mass index ( F=13.14, p<0.001), total cholesterol ( F=4.85, p=0.028) and low-density lipoprotein-cholesterol ( F=6.26, p=0.013) compared to non-users. These differences were also observed after three years: weight ( F=8.07, p=0.005), body mass index ( F=4.66, p=0.032) and low-density lipoprotein-cholesterol ( F=3.91, p=0.049). Moreover, those patients discontinuing cannabis use presented a higher increase in weight ( F=2.98, p=0.052), body mass index ( F=2.73, p=0.067) and triglyceride-high-density lipoprotein ratio ( F=2.72, p=0.067) than the ‘non-users’ and ‘continuers’.

CONCLUSIONS::

The study suggests that cannabis use may produce a protective effect against weight gain and related metabolic alterations in psychosis.”

https://www.ncbi.nlm.nih.gov/pubmed/30702972

https://doi.org/10.1177/0269881118822173

Opposite effects of cannabinoid CB1 and CB2 receptors on antipsychotic clozapine-induced cardiotoxicity.

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“Clozapine is an atypical antipsychotic drug that is very efficacious in treating psychosis but the risk of severe cardiotoxicity limits its clinical use.

The present study investigated the myocardial injury effects of clozapine and assessed the involvement of cannabinoid receptors in clozapine cardiotoxicity.

Our data provided evidence that cannabinoid CB1 and CB2 receptors had opposite effects and selective antagonists of CB1R or agonists of CB2R might confer protective effects against clozapine.”

https://www.ncbi.nlm.nih.gov/pubmed/30707759

https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bph.14591

How effective and safe is medical cannabis as a treatment of mental disorders? A systematic review.

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“We conducted a review of systematic reviews (SRs) and randomized-controlled trials (RCTs) to analyze efficacy and safety of cannabis-based medication in patients with mental disorders.

Five data bases were systematically searched (2006-August 2018); 4 SRs (of 11 RCTs) and 14 RCTs (1629 participants) were included. Diagnoses were: dementia, cannabis and opioid dependence, psychoses/schizophrenia, general social anxiety, posttraumatic stress disorder, anorexia nervosa, attention-deficit hyperactivity disorder, and Tourette`s disorder. Outcome variables were too heterogeneous to conduct a  meta-analysis. A narrative synthesis method was applied. The study quality was assessed using the risk-of-bias tool and SIGN-checklists.

THC- and CBD-based medicines, given as adjunct to pharmaco- and psychotherapy, were associated with improvements of several symptoms of mental disorders, but not with remission. Side effects occurred, but severe adverse effects were mentioned in single cases only. In order to provide reliable treatment recommendations, more and larger RCTs with follow-up assessments, consistent outcome measures and active comparisons are needed.”

https://www.ncbi.nlm.nih.gov/pubmed/30706168

https://link.springer.com/article/10.1007%2Fs00406-019-00984-4

Cannabidiol May Help Normalize Brain Function in Psychosis

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“Cannabidiol (CBD), the nonpsychoactive compound in cannabis, may help normalize function in brain regions associated with psychosis, found a study in JAMA Psychiatry.”

https://www.ncbi.nlm.nih.gov/pubmed/30694318
https://jamanetwork.com/journals/jama/article-abstract/2722769

“Effect of Cannabidiol on Medial Temporal, Midbrain, and Striatal Dysfunction in People at Clinical High Risk of Psychosis A Randomized Clinical Trial. Cannabidiol (CBD) has antipsychotic effects in humans. Cannabidiol may partially normalize alterations in parahippocampal, striatal, and midbrain function associated with the CHR state. As these regions are critical to the pathophysiology of psychosis, the influence of CBD at these sites could underlie its therapeutic effects on psychotic symptoms.” https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2697762

Assessing the impact of cannabis use on trends in diagnosed schizophrenia in the United Kingdom from 1996 to 2005.

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Schizophrenia Research

“The study cohort comprised almost 600,000 patients each year, representing approximately 2.3% of the UK population aged 16 to 44. Between 1996 and 2005 the incidence and prevalence of schizophrenia and psychoses were either stable or declining. Explanations other than a genuine stability or decline were considered, but appeared less plausible. In conclusion, this study did not find any evidence of increasing schizophrenia or psychoses in the general population from 1996 to 2005.”

https://www.ncbi.nlm.nih.gov/pubmed/19560900

https://www.sciencedirect.com/science/article/pii/S0920996409002692?via%3Dihub

“The incidence and prevalence of patients showing schizophrenic syndromes are unchanged or have even fallen while the use of cannabis has increased enormously. We must conclude that either previous schizophrenic illnesses have become much less common or that cannabis schizophrenia is rare and perhaps it may not even exist.” https://www.bmj.com/content/325/7374/1183/rapid-responses

“Cannabis use appears to be neither a sufficient nor a necessary cause for psychosis.”  https://www.ncbi.nlm.nih.gov/pubmed/14754822

“The current data do not support low to moderate lifetime cannabis use to be a major contributor to psychosis or poor social and role functioning in high-risk youth.”  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3459073/

“Multiple reports indicate no rise in psychosis accompanies increases in pot use rates” http://potfacts.ca/multiple-reports-indicate-no-rise-in-psychosis-accompanies-increases-in-pot-use-rates/

Peripubertal cannabidiol treatment rescued behavioral and neurochemical abnormalities in MAM model of schizophrenia.

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 Neuropharmacology

“In agreement with the neurodevelopmental hypothesis of schizophrenia, prenatal exposure of rats to the antimitotic agent methylazoxymethanol acetate (MAM) at gestational day 17 produced long-lasting behavioral alterations such as social withdrawal and cognitive impairment in the social interaction test and in the novel object recognition test, respectively. At molecular level, an increased cannabinoid receptor type-1 (CB1) mRNA and protein expression which might be due to a reduction in DNA methylation at gene promoter in the prefrontal cortex (PFC), coincided with deficits in the social interaction test and in the novel object recognition test in MAM rats. Both schizophrenia-like phenotype and altered transcriptional regulation of CB1 receptors were reversed by peripubertal treatment (from PND 19 to PND 39) with the non-psychotropic phytocannabinoid cannabidiol (30 mg/kg/day), or, in part, by treatment with the cannabinoid CB1 receptor antagonist/inverse agonist AM251 (0.5 mg/kg/day), but not with haloperidol (0.6 mg/kg/day). These results suggest that early treatment with cannabidiol may prevent both the appearance of schizophrenia-like deficits as well as CB1 alterations in the PFC at adulthood, supporting that peripubertal cannabidiol treatment might be protective against MAM insult.”

https://www.ncbi.nlm.nih.gov/pubmed/30496751

https://www.sciencedirect.com/science/article/pii/S0028390818308761?via%3Dihub

Translational Investigation of the Therapeutic Potential of Cannabidiol (CBD): Toward a New Age.

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“Among the many cannabinoids in the cannabis plant, cannabidiol (CBD) is a compound that does not produce the typical subjective effects of marijuana.

The aim of the present review is to describe the main advances in the development of the experimental and clinical use of cannabidiol CBD in neuropsychiatry.

CBD was shown to have anxiolytic, antipsychotic and neuroprotective properties. In addition, basic and clinical investigations on the effects of CBD have been carried out in the context of many other health conditions, including its potential use in epilepsy, substance abuse and dependence, schizophrenia, social phobia, post-traumatic stress, depression, bipolar disorder, sleep disorders, and Parkinson.

CBD is an useful and promising molecule that may help patients with a number of clinical conditions. Controlled clinical trials with different neuropsychiatric populations that are currently under investigation should bring important answers in the near future and support the translation of research findings to clinical settings.”

https://www.ncbi.nlm.nih.gov/pubmed/30298064

https://www.frontiersin.org/articles/10.3389/fimmu.2018.02009/full