Tag Archives: antipsychotic

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

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

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

Cannabidiol prevents haloperidol-induced vacuos chewing movements and inflammatory changes in mice via PPARγ receptors.

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Brain, Behavior, and Immunity

“The chronic use of drugs that reduce the dopaminergic neurotransmission can cause a hyperkinetic movement disorder called tardive dyskinesia (TD). The pathophysiology of this disorder is not entirely understood but could involve oxidative and neuroinflammatory mechanisms.

Cannabidiol (CBD), the major non-psychotomimetic compound present in Cannabis sativa plant, could be a possible therapeutic alternative for TD. This phytocannabinoid shows antioxidant, anti-inflammatory and antipsychotic properties and decreases the acute motor effects of classical antipsychotics.

The present study investigated if CBD would attenuate orofacial dyskinesia, oxidative stress and inflammatory changes induced by chronic administration of haloperidol in mice. Furthermore, we verified in vivo and in vitro (in primary microglial culture) whether these effects would be mediated by PPARγ receptors.

The results showed that the male Swiss mice treated daily for 21 days with haloperidol develop orofacial dyskinesia. Daily CBD administration before each haloperidol injection prevented this effect.

Mice treated with haloperidol showed an increase in microglial activation and inflammatory mediators in the striatum. These changes were also reduced by CBD. On the other hand, the levels of the anti-inflammatory cytokine IL-10 increased in the striatum of animals that received CBD and haloperidol.

Regarding oxidative stress, haloperidol induced lipid peroxidation and reduced catalase activity. This latter effect was attenuated by CBD. The combination of CBD and haloperidol also increased PGC-1α mRNA expression, a co-activator of PPARγ receptors. Pretreatment with the PPARγ antagonist, GW9662, blocked the behavioural effect of CBD in our TD model. CBD also prevented LPS-stimulated microglial activation, an effect that was also antagonized by GW9662.

In conclusion, our results suggest that CBD could prevent haloperidol-induced orofacial dyskinesia by activating PPARγ receptors and attenuating neuroinflammatory changes in the striatum.”

https://www.ncbi.nlm.nih.gov/pubmed/30217539
https://www.sciencedirect.com/science/article/pii/S0889159118305828?via%3Dihub
“Haloperidol, marketed under the trade name Haldol among others, is a typical antipsychotic medication. Haloperidol is used in the treatment of schizophrenia, tics in Tourette syndrome, mania in bipolar disorder, nausea and vomiting, delirium, agitation, acute psychosis, and hallucinations in alcohol withdrawal”  https://en.wikipedia.org/wiki/Haloperidol

Cannabidiol Administered During Peri-Adolescence Prevents Behavioral Abnormalities in an Animal Model of Schizophrenia.

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“Schizophrenia is considered a debilitating neurodevelopmental psychiatric disorder and its pharmacotherapy remains problematic without recent major advances. The development of interventions able to prevent the emergence of schizophrenia would therefore represent an enormous progress.

Here, we investigated whether treatment with cannabidiol (CBD – a compound of Cannabis sativa that presents an antipsychotic profile in animals and humans) during peri-adolescence would prevent schizophrenia-like behavioral abnormalities in an animal model of schizophrenia: the spontaneously hypertensive rat (SHR) strain.

Treatment with CBD prevented the emergence of SHRs’ hyperlocomotor activity (a model for the positive symptoms of schizophrenia) and deficits in prepulse inhibition of startle and contextual fear conditioning (cognitive impairments). CBD did not induce any of the potential motor or metabolic side effects evaluated. Treatment with CBD increased the prefrontal cortex 5-HIAA/serotonin ratio and the levels of 5-HIAA on post-natal days 61 and 90, respectively.

Our data provide pre-clinical evidence for a safe and beneficial effect of peripubertal and treatment with CBD on preventing positive and cognitive symptoms of schizophrenia, and suggest the involvement of the serotoninergic system on this effect.”

https://www.ncbi.nlm.nih.gov/pubmed/30186164

https://www.frontiersin.org/articles/10.3389/fphar.2018.00901/full

Effect of Cannabidiol on Medial Temporal, Midbrain, and Striatal Dysfunction in People at Clinical High Risk of Psychosis: A Randomized Clinical Trial.

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“Cannabidiol (CBD) has antipsychotic effects in humans, but how these are mediated in the brain remains unclear.

OBJECTIVE:

To investigate the neurocognitive mechanisms that underlie the therapeutic effects of CBD in psychosis.

CONCLUSIONS AND RELEVANCE:

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://www.ncbi.nlm.nih.gov/pubmed/30167644

https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2697762

“Psychosis: Cannabis extract normalizes brain function” https://www.medicalnewstoday.com/articles/322926.php
“Cannabis extract helps reset brain function in psychosis” https://medicalxpress.com/news/2018-08-cannabis-reset-brain-function-psychosis.html
“Cannabis extract helps reset brain function in psychosis” https://www.eurekalert.org/pub_releases/2018-08/kcl-ceh082818.php
“Cannabidiol Reduces Symptoms of Psychosis. A new study found that the chemical extracted from cannabis has antipsychotic effects.” https://www.usnews.com/news/health-care-news/articles/2018-08-29/one-dose-of-cannabidiol-reduces-symptoms-of-psychosis
“MEDICAL MARIJUANA: CANNABIS EXTRACT CBD USED TO SUCCESSFULLY TREAT PSYCHOSIS.” https://www.newsweek.com/cannabidiol-cannabis-extract-could-treat-symptoms-psychosis-1094353

 “Single dose of the cannabis compound CBD reduces psychotic symptoms by normalising brain activity” http://www.dailymail.co.uk/health/article-6110591/Single-dose-cannabis-compound-CBD-reduces-psychotic-symptoms-normalising-brain-activity.html

“British scientists have unraveled how a non-intoxicating component of cannabis acts in key brain areas to reduce abnormal activity in patients at risk of psychosis, suggesting the ingredient could become a novel anti-psychotic medicine.” https://www.theglobeandmail.com/cannabis/article-scientists-unravel-how-cannabis-component-may-fight-psychosis/

“Science proves component in weed actually helps fight psychosis” https://nypost.com/2018/08/29/science-proves-component-in-weed-actually-helps-fight-psychosis/
“We Now Have Evidence That a Marijuana Compound Can Help People With Psychosis” https://futurism.com/cbd-psychosis/

Role of the Endocannabinoid System in the Pathophysiology of Schizophrenia: Implications for Pharmacological Intervention.

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“The term schizophrenia describes a group of multifaceted psychiatric conditions causing significant impairment of the quality of life of affected patients. Although multiple pharmacological treatment options exist, e.g. first- or second-generation antipsychotics, these therapeutics often cause disturbing side effects, such as extrapyramidal symptoms, prolactin increase, sexual dysfunction and/or metabolic syndrome. Furthermore, cognitive impairments and negative symptoms, two factors significantly influencing the course and outcome, are not sufficiently addressed by the available antipsychotics.

Since its discovery, multiple clinical and preclinical studies have linked the endocannabinoid system to schizophrenia.

Both the endocannabinoid anandamide and the cannabinoid CB1 receptor are deeply linked to underlying disease processes. Based hereon, clinical trials in schizophrenia have explored cannabidiol, a primary component of Cannabis sativa, and rimonabant, a partial antagonist to the CB1 receptor.

While the latter did not reveal positive results, cannabidiol significantly ameliorated psychotic symptoms, which was associated with an increase in anandamide serum levels. However, the exact mechanisms of the antipsychotic effects of cannabidiol are not fully understood, and, furthermore, only a limited number of clinical trials in humans have been concluded to date.

Thus, the level of proof of safety and efficacy required to approve the therapeutic use of cannabidiol in schizophrenia is currently lacking. However, cannabidiol is a promising candidate as an effective and mechanistically different antipsychotic treatment with a favourable side-effect profile. We therefore conclude that further studies are urgently needed to clarify the antipsychotic effects and safety profile of cannabidiol, and to fully explore its potential antipsychotic mechanism.”

https://www.ncbi.nlm.nih.gov/pubmed/30022465

https://link.springer.com/article/10.1007%2Fs40263-018-0539-z

Cannabidiol as a Promising Strategy to Treat and Prevent Movement Disorders?

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“Movement disorders such as Parkinson’s disease and dyskinesia are highly debilitating conditions linked to oxidative stress and neurodegeneration. When available, the pharmacological therapies for these disorders are still mainly symptomatic, do not benefit all patients and induce severe side effects. Cannabidiol is a non-psychotomimetic compound from Cannabis sativa that presents antipsychotic, anxiolytic, anti-inflammatory, and neuroprotective effects. Although the studies that investigate the effects of this compound on movement disorders are surprisingly few, cannabidiol emerges as a promising compound to treat and/or prevent them. Here, we review these clinical and pre-clinical studies and draw attention to the potential of cannabidiol in this field.”

https://www.ncbi.nlm.nih.gov/pubmed/29867488

https://www.frontiersin.org/articles/10.3389/fphar.2018.00482/full

Pharmacological properties of cannabidiol in the treatment of psychiatric disorders: a critical overview.

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“Cannabidiol (CBD) represents a new promising drug due to a wide spectrum of pharmacological actions. In order to relate CBD clinical efficacy to its pharmacological mechanisms of action, we performed a bibliographic search on PUBMED about all clinical studies investigating the use of CBD as a treatment of psychiatric symptoms.

Findings to date suggest that (a) CBD may exert antipsychotic effects in schizophrenia mainly through facilitation of endocannabinoid signalling and cannabinoid receptor type 1 antagonism; (b) CBD administration may exhibit acute anxiolytic effects in patients with generalised social anxiety disorder through modification of cerebral blood flow in specific brain sites and serotonin 1A receptor agonism; (c) CBD may reduce withdrawal symptoms and cannabis/tobacco dependence through modulation of endocannabinoid, serotoninergic and glutamatergic systems; (d) the preclinical pro-cognitive effects of CBD still lack significant results in psychiatric disorders.

In conclusion, current evidences suggest that CBD has the ability to reduce psychotic, anxiety and withdrawal symptoms by means of several hypothesised pharmacological properties. However, further studies should include larger randomised controlled samples and investigate the impact of CBD on biological measures in order to correlate CBD’s clinical effects to potential modifications of neurotransmitters signalling and structural and functional cerebral changes.”

https://www.ncbi.nlm.nih.gov/pubmed/29789034

https://www.cambridge.org/core/journals/epidemiology-and-psychiatric-sciences/article/pharmacological-properties-of-cannabidiol-in-the-treatment-of-psychiatric-disorders-a-critical-overview/D7FD68F40CF30CBB48A1025C66873F26

Cannabidiol to Improve Mobility in People with Multiple Sclerosis

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“Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) that affects an estimated 2.3 million people worldwide. The symptoms of MS are highly varied but frequently include pain, muscle spasticity, fatigue, inflammation, and depression. These symptoms often lead to reduced physical activity, negatively impact functional mobility, and have a detrimental impact on patients’ quality of life.

Although recent years have seen significant advances in disease modifying therapy, none of the current treatments halts or cures MS related symptoms. As a consequence, many people with MS (PwMS) look for alternative and complementary therapies such as cannabis.

The cannabis plant contains many biologically active chemicals, including ~60 cannabinoids. Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) are typically the most concentrated chemical components of cannabis and believed to primarily drive therapeutic benefit.

There is evidence that CBD has a number of beneficial pharmacological effects. It is anti-inflammatory, antioxidative, antiemetic, antipsychotic, and neuroprotective. The review of 132 original studies by Bergamaschi et al. describes the safety profile of CBD by highlighting that catalepsy is not induced and physiological parameters (heart rate, blood pressure, and body temperature) are not altered. Moreover, psychomotor and psychological functions are not negatively affected. High doses of up to 1,500 mg per day and chronic use have been repeatedly shown to be well tolerated by humans.

Additionally, there is also evidence that CBD may reduce the negative psychotropic effects, memory impairment, and appetite stimulation, anxiety and psychotic-like states of THC while enhancing its positive therapeutic actions.

 Anecdotal reports indicate that an increasing number of PwMS use cannabis (medical marijuana) as a supplement to improve their mobility.

Based on the following considerations, it is our opinion that CBD supplementation maybe advisable for PwMS to reduce fatigue, pain, spasticity, and ultimately improve mobility. “

https://www.frontiersin.org/articles/10.3389/fneur.2018.00183/full