Category Archives: Schizophrenia

Improved Social Interaction, Recognition and Working Memory with Cannabidiol Treatment in a Prenatal Infection (poly I:C) Rat Model.

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“Neuropsychiatric disorders such as schizophrenia are associated with cognitive impairment, including learning, memory and attention deficits. Antipsychotic drugs are limited in their efficacy to improve cognition; therefore, new therapeutic agents are required.

Cannabidiol (CBD), the non-intoxicating component of cannabis, has anti-inflammatory, neuroprotective and antipsychotic-like properties, however, its ability to improve the cognitive deficits of schizophrenia remains unclear. Using a prenatal infection model, we examined the effect of chronic CBD treatment on cognition and social interaction.

CBD treatment significantly improved recognition, working memory and social interaction deficits in the poly I:C model, did not affect total body weight gain, food or water intake, and had no effect in control animals.

In conclusion, chronic CBD administration can attenuate the social interaction and cognitive deficits induced by prenatal poly I:C infection.

These novel findings present interesting implications for potential use of CBD in treating the cognitive deficits and social withdrawal of schizophrenia.”

https://www.ncbi.nlm.nih.gov/pubmed/28230072

Pregnenolone blocks cannabinoid-induced acute psychotic-like states in mice.

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“Cannabis-induced acute psychotic-like states (CIAPS) represent a growing health issue, but their underlying neurobiological mechanisms are poorly understood.

The use of antipsychotics and benzodiazepines against CIAPS is limited by side effects and/or by their ability to tackle only certain aspects of psychosis. Thus, safer wide-spectrum treatments are currently needed.

Although the blockade of cannabinoid type-1 receptor (CB1) had been suggested as a therapeutical means against CIAPS, the use of orthosteric CB1 receptor full antagonists is strongly limited by undesired side effects and low efficacy.

The neurosteroid pregnenolone has been recently shown to act as a potent endogenous allosteric signal-specific inhibitor of CB1 receptors. Thus, we tested in mice the potential therapeutic use of pregnenolone against acute psychotic-like effects of Δ9-tetrahydrocannabinol (THC), the main psychoactive component of cannabis.

We found that pregnenolone blocks a wide spectrum of THC-induced endophenotypes typically associated with psychotic-like states, including impairments in cognitive functions, somatosensory gating and social interaction. Overall, this work reveals that signal-specific inhibitors mimicking pregnenolone effects can be considered as promising new therapeutic tools to treat CIAPS.”  https://www.ncbi.nlm.nih.gov/pubmed/28220044

“Pregnenolone can protect the brain from cannabis intoxication. The administration of the main active principle of Cannabis sativa (marijuana), Δ(9)-tetrahydrocannabinol (THC), substantially increases the synthesis of pregnenolone in the brain via activation of the type-1 cannabinoid (CB1) receptor. Pregnenolone then, acting as a signaling-specific inhibitor of the CB1 receptor, reduces several effects of THC. This negative feedback mediated by pregnenolone reveals a previously unknown paracrine/autocrine loop protecting the brain from CB1 receptor overactivation that could open an unforeseen approach for the treatment of cannabis intoxication and addiction.”  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4057431/

Neuronal and Molecular Effects of Cannabidiol on the Mesolimbic Dopamine System: Implications for Novel Schizophrenia Treatments.

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“Growing clinical and pre-clinical evidence points to a critical role for cannabidiol (CBD), the largest phytochemical component of cannabis, as a potential pharmacotherapy for various neuropsychiatric disorders.

In contrast to delta-9-tetrahydrocannabinol (THC), which is associated with acute and neurodevelopmental pro-psychotic side-effects, CBD possesses no known psychoactive or dependence-producing properties.

However, evidence has demonstrated that CBD strongly modulates the mesolimbic dopamine (DA) system and may possess promising anti-psychotic properties.

Despite the psychotropic differences between CBD and THC, little is known regarding their molecular and neuronal effects on the mesolimbic DA system, nor how these differential effects may relate to their potential pro vs. anti-psychotic properties.

This review summarizes clinical and pre-clinical evidence demonstrating CBD’s modulatory effects on DA activity states within the mesolimbic pathway, functional interactions with the serotonin 5-HT1A receptor system, and their downstream molecular signaling effects.

Together with clinical evidence showing that CBD may normalize affective and cognitive deficits associated with schizophrenia, CBD may represent a promising treatment for schizophrenia, acting through novel molecular and neuronal mesolimbic substrates.”

https://www.ncbi.nlm.nih.gov/pubmed/28185872

Cannabinoid receptors on peripheral leukocytes from patients with schizophrenia: Evidence for defective immunomodulatory mechanisms.

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“These results suggest a defective endocannabinoid system-mediated immunomodulation in patients with schizophrenia.”

https://www.ncbi.nlm.nih.gov/pubmed/28011441

http://www.thctotalhealthcare.com/category/schizophrenia/

Decreased CB receptor binding and cannabinoid signaling in three brain regions of a rat model of schizophrenia.

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“Schizophrenia is a serious mental health disorder characterized by several behavioral and biochemicel abnormalities.

In a previous study we have shown that mu-opioid (MOP) receptor signaling is impaired in specific brain regions of our three-hit animal model of schizophrenia. Since the cannabinoid system is significantly influenced in schizophrenic patients, in the present work we investigated cannabinoid (CB) receptor binding and G-protein activation in cortical, subcortical and cerebellar regions of control and ‘schizophrenic’ rats.

Taken together, in all three brain areas of model rats both cannabinoid receptor binding and cannabinoid agonist-mediated G-protein activation were regularly decreased.

Our results revealed that besides the opioids, the endocannabinoid – cannabis receptor system also shows impairment in our rat model, increasing its face validity and translational utility.”

https://www.ncbi.nlm.nih.gov/pubmed/27639959

A systematic review of the effect of cannabidiol on cognitive function: Relevance to schizophrenia.

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“Cognitive impairment is a core symptom domain of schizophrenia, neurological disorders and substance abuse. It is characterised by deficits in learning, memory, attention and executive functioning and can severely impact daily living.

Antipsychotic drugs prescribed to treat schizophrenia provide limited cognitive benefits and novel therapeutic targets are required. Cannabidiol (CBD), a component of the cannabis plant, has anti-inflammatory and antipsychotic-like properties; however, its ability to improve cognitive impairment has not been thoroughly explored. The aim of this systematic review was to evaluate preclinical and clinical literature on the effects of CBD in cognitive domains relevant to schizophrenia.

CBD improves cognition in multiple preclinical models of cognitive impairment, including models of neuropsychiatric (schizophrenia), neurodegenerative (Alzheimer’s disease), neuro-inflammatory (meningitis, sepsis and cerebral malaria) and neurological disorders (hepatic encephalopathy and brain ischemia). To-date, there is one clinical investigation into the effects of CBD on cognition in schizophrenia patients, with negative results for the stroop test. CBD attenuates Δ9-THC-induced cognitive deficits.

 

The efficacy of CBD to improve cognition in schizophrenia cannot be elucidated due to lack of clinical evidence; however, given the ability of CBD to restore cognition in multiple studies of impairment, further investigation into its efficacy in schizophrenia is warranted. Potential mechanisms underlying the efficacy of CBD to improve cognition are discussed.”

https://www.ncbi.nlm.nih.gov/pubmed/27884751

Cannabidiol as a Potential New Type of an Antipsychotic. A Critical Review of the Evidence

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“There is urgent need for the development of mechanistically different and less side-effect prone antipsychotic compounds.

The endocannabinoid system has been suggested to represent a potential new target in this indication.

Although, results from animal studies are inconsistent to a certain extent and seem to depend on behavioral paradigms, treatment duration and experimental conditions applied, cannabidiol has shown antipsychotic properties in both rodents and rhesus monkeys.

After some individual treatment attempts, the first randomized, double-blind controlled clinical trial demonstrated that in acute schizophrenia cannabidiol exerts antipsychotic properties comparable to the antipsychotic drug amisulpride while being accompanied by a superior, placebo-like side effect profile.

As the clinical improvement by cannabidiol was significantly associated with elevated anandamide levels, it appears likely that its antipsychotic action is based on mechanisms associated with increased anandamide concentrations.

The antipsychotic potential of cannabidiol has been investigated in various behavioral paradigms and different animal models of aspects of schizophrenia.

Although the results were partially inconsistent, they indicate that cannabidiol treatment ameliorates impairments of PPI, social interaction behavior and cognition in rodents and rhesus monkeys.

In addition, individual treatment attempts as well as one randomized, double-blind clinical study, demonstrated the antipsychotic potential of cannabidiol and its superior side effect profile compared to conventional antipsychotics. In addition, a recently conducted clinical trial investigating cannabidiol as an add-on medication showed promising results, although these have not yet been published in a peer reviewed process.

Obviously more clinical trials are needed to substantiate the current findings, and in particular to investigate long-term efficacy and safety in larger cohorts.

However, cannabidiol seems to represent a mechanistically different and less side-effect prone antipsychotic compound for the treatment of schizophrenia, even though the underlying pharmacological mechanisms are still under debate.

Nevertheless, the association between increased anandamide levels and reduced psychotic symptoms in schizophrenic patients treated with cannabidiol, points to a potentially new antipsychotic mechanism of action involving anandamide.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5099166/

Targeting the Endocannabinoid System in Psychiatric Illness.

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“Prevalence of psychiatric disorders continues to rise globally, yet remission rates and patient outcome remain less than ideal. As a result, novel treatment approaches for these disorders are necessary to decrease societal economic burden, as well as increase individual functioning.

The recent discovery of the endocannabinoid system has provided an outlet for further research into its role in psychiatric disorders, because efficacy of targeted treatments have been demonstrated in medical illnesses, including cancers, neuropathic pain, and multiple sclerosis.

The present review will investigate the role of the endocannabinoid system in psychiatric disorders, specifically schizophrenia, depressive, anxiety, and posttraumatic stress disorders, as well as attention-deficit hyperactivity disorder.

Controversy remains in prescribing medicinal cannabinoid treatments due to the fear of adverse effects. However, one must consider all potential limitations when determining the safety and tolerability of cannabinoid products, specifically cannabinoid content (ie, Δ-tetrahydrocannabinol vs cannabidiol) as well as study design.

The potential efficacy of cannabinoid treatments in the psychiatric population is an emerging topic of interest that provides potential value going forward in medicine.”

 https://www.ncbi.nlm.nih.gov/pubmed/27811555

Cannabidiol is a partial agonist at dopamine D2High receptors, predicting its antipsychotic clinical dose.

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“Although all current antipsychotics act by interfering with the action of dopamine at dopamine D2 receptors, two recent reports showed that 800 to 1000 mg of cannabidiol per day alleviated the signs and symptoms of schizophrenia, although cannabidiol is not known to act on dopamine receptors. Because these recent clinical findings may indicate an important exception to the general rule that all antipsychotics interfere with dopamine at dopamine D2 receptors, the present study examined whether cannabidiol acted directly on D2 receptors, using tritiated domperidone to label rat brain striatal D2 receptors. It was found that cannabidiol inhibited the binding of radio-domperidone with dissociation constants of 11 nm at dopamine D2High receptors and 2800 nm at dopamine D2Low receptors, in the same biphasic manner as a dopamine partial agonist antipsychotic drug such as aripiprazole. The clinical doses of cannabidiol are sufficient to occupy the functional D2High sites. it is concluded that the dopamine partial agonist action of cannabidiol may account for its clinical antipsychotic effects.”

https://www.ncbi.nlm.nih.gov/pubmed/27754480

Association of Anandamide with altered Binocular Depth Inversion Illusion in Schizophrenia.

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“Binocular depth inversion illusion (BDII) represents an illusion of visual perception that involves higher-order visual and cognitive processes. Its impairment has been linked to psychotic conditions and identified as a marker for at risk mental states.

The endogenous cannabinoid system (ECS) is involved in various neurophysiological processes. One of its key components, anandamide, is involved in the pathophysiology of schizophrenia.

Little is known about its impact on BDII alterations. Therefore, we explored associations between BDII and anandamide levels.

Conclusions These findings support the hypothesis of an involvement of anandamide in cognitive processes impaired in schizophrenia and are consistent with a protective effect of elevated anandamide levels herein.”

 https://www.ncbi.nlm.nih.gov/pubmed/27734750