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/

Impact of substance use disorder on gray matter volume in schizophrenia.

Psychiatry Research: Neuroimaging

“Substance use may confound the study of brain structure in schizophrenia. We used voxel-based morphometry (VBM) to examine whether differences in regional gray matter volumes exist between schizophrenia patients with (n = 92) and without (n = 66) clinically significant cannabis and/or alcohol use histories compared to 88 healthy control subjects.

Relative to controls, patients with schizophrenia had reduced gray matter volume in the bilateral precentral gyrus, right medial frontal cortex, right visual cortex, right occipital pole, right thalamus, bilateral amygdala, and bilateral cerebellum regardless of substance use history.

Within these regions, we found no volume differences between patients with schizophrenia and a history of cannabis and/or alcohol compared to patients with schizophrenia without a clinically significant substance use history.

Our data support the idea that a clinically meaningful history of alcohol or cannabis use does not significantly compound the gray matter deficits associated with schizophrenia.”

The Role of Cannabis within an Emerging Perspective on Schizophrenia.

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“Approximately 0.5% of the population is diagnosed with some form of schizophrenia, under the prevailing view that the pathology is best treated using pharmaceutical medications that act on monoamine receptors.

We briefly review evidence on the impact of environmental forces, particularly the effect of autoimmune activity, in the expression of schizophrenic profiles and the role of Cannabis therapy for regulating immunological functioning.

A review of the literature shows that phytocannabinoid consumption may be a safe and effective treatment option for schizophrenia as a primary or adjunctive therapy.

Conclusions: Emerging research suggests that Cannabis can be used as a treatment for schizophrenia within a broader etiological perspective that focuses on environmental, autoimmune, and neuroinflammatory causes of the disorder, offering a fresh start and newfound hope for those suffering from this debilitating and poorly understood disease.”

The endocannabinoid system in mental disorders: Evidence from human brain studies.

Biochemical Pharmacology

“Mental disorders have a high prevalence compared with many other health conditions and are the leading cause of disability worldwide. Several studies performed in the last years support the involvement of the endocannabinoid system in the etiopathogenesis of different mental disorders.

The present review will summarize the latest information on the role of the endocannabinoid system in psychiatric disorders, specifically depression, anxiety, and schizophrenia. We will focus on the findings from human brain studies regarding alterations in endocannabinoid levels, cannabinoid receptors and endocannabinoid metabolizing enzymes in patients suffering mental disorders.

Studies carried out in humans have consistently demonstrated that the endocannabinoid system is fundamental for emotional homeostasis and cognitive function. Thus, deregulation of the different elements that are part of the endocannabinoid system may contribute to the pathophysiology of several mental disorders. However, the results reported are controversial. In this sense, different alterations in gene and/or protein expression of CB1 receptors have been shown depending on the technical approach used or the brain region studied.

Despite the current discrepancies regarding cannabinoid receptors changes in depression and schizophrenia, present findings point to the endocannabinoid system as a pivotal neuromodulatory pathway relevant in the pathophysiology of mental disorders.

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

 

“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 does not display drug abuse potential in mice behavior.

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“Recent evidence suggests that cannabidiol (CBD) may be useful for the treatment of different neuropsychiatric disorders.

However, some controversy regarding its profile as a drug of abuse hampers the further development of basic and clinical studies.

In this study, the behavioral profile of CBD as a potential drug of abuse was evaluated in C57BL/6J mice.

Taken together, these results show that CBD lacks activity as a drug of abuse and should stimulate the development of the basic and clinical studies needed to elucidate its potential therapeutic use for the treatment of neuropsychiatric and drug use disorders.”

Evidence for the use of “medical marijuana” in psychiatric and neurologic disorders.

College of Psychiatric and Neurologic Pharmacists

“Cannabis is listed as a Schedule I substance under the Controlled Substances Act of 1970, meaning the US federal government defines it as an illegal drug that has high potential for abuse and no established medical use; however, half of the states in the nation have enacted “medical marijuana” (MM) laws. Clinicians must be aware of the evidence for and against the use of MM in their patients who may consider using this substance.

RESULTS:

Publications were identified that included patients with dementia, multiple sclerosis, Parkinson disease, Huntington disease, schizophrenia, social anxiety disorder, depression, tobacco use disorder, and neuropathic pain.

DISCUSSION:

There is great variety concerning which medical conditions are approved for treatment with MM for either palliative or therapeutic benefit, depending on the state law. It is important to keep an evidence-based approach in mind, even with substances considered to be illegal under US federal law. Clinicians must weigh risks and benefits of the use of MM in their patients and should ensure that patients have tried other treatment modalities with higher levels of evidence for use when available and appropriate.”

https://www.ncbi.nlm.nih.gov/pubmed/29955495

““Medical marijuana” encompasses everything from whole-plant cannabis to synthetic cannabinoids available for commercial use approved by regulatory agencies. In determining whether MM is of clinical utility to our patients, it is important to keep in mind chemical constituents, dose, delivery, and indication. Selection of the patient appropriate for MM must be carefully considered because clinical guidelines and treatment options with stronger levels of evidence should be exhausted first in most cases. There seems to be strongest evidence for the use of MM in patients with MS and in patients with neuropathic pain; moderate evidence exists to support further research in social anxiety disorder, schizophrenia, PD, and tobacco use disorder; evidence is limited for use in patients with dementia, Huntington disease, depression, and anorexia.”

http://mhc.cpnp.org/doi/10.9740/mhc.2017.01.029?code=cpnp-site

Probing the endocannabinoid system in healthy volunteers: Cannabidiol alters fronto-striatal resting-state connectivity.

European Neuropsychopharmacology Home

“Tetrahydrocannabinol (THC) and Cannabidiol (CBD) are two substances from cannabis sativa that have been implicated in the treatment of mental and neurological disorders.

We concentrated on a previously validated neuroimaging phenotype, fronto-striatal connectivity across different striatal seeds, because of this loop’s relevance to executive functioning, decision making, salience generation and motivation and its link to various neuropsychiatric conditions. Therefore, we studied the effect of THC and CBD on fronto-striatal circuitry by a seed-voxel connectivity approach using seeds from the caudate and the putamen.

We conducted a cross-over pharmaco-fMRI study in 16 healthy male volunteers with placebo, 10 mg oral THC and 600 mg oral CBD. Resting state was measured in a 3 T scanner. CBD lead to an increase of fronto-striatal connectivity in comparison to placebo.

In contrast to our expectation that THC and CBD show opposing effects, THC versus placebo did not show any significant effects, probably due to insufficient concentration of THC during scanning.

The effect of CBD on enhancing fronto-striatal connectivity is of interest because it might be a neural correlate of its anti-psychotic effect in patients.”

Cannabidiol effects on prepulse inhibition in nonhuman primates.

 

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“Prepulse inhibition (PPI) of acoustic startle reflex is a well-established behavior paradigm to measure sensorimotor gating deficits. PPI is disrupted in several neuropsychiatric disorders, including schizophrenia. PPI tests can be used to screen new drugs for treatment of such disorders.

In this review, we discuss how PPI paradigm can help in screening the therapeutic effects of cannabidiol (CBD).

We look into recent literature about CBD effects on PPI response in animal models, especially in nonhuman primates. CBD has been shown to modify PPI in N-methyl d-aspartate receptor antagonist models for schizophrenia, both in rodents and in nonhuman primates.

These results show CBD as a potential drug for the treatment of neurologic disorders that present alterations in sensorimotor system, such as schizophrenia. Moreover, the PPI paradigm seems to be a useful and relative simple paradigm to test the efficacy of CBD as a potential therapeutic drug.”

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