Opposite Cannabis-Cognition Associations in Psychotic Patients Depending on Family History.

Posted on August 13, 2016 by David

“The objective of this study is to investigate cognitive performance in a first-episode psychosis sample, when stratifying the interaction by cannabis use and familial or non-familial psychosis.

We found that cannabis use was associated with worse working memory, regardless of family history. However, cannabis use was clearly associated with worse cognitive performance in patients with no family history of psychosis, in cognitive domains including verbal memory, executive function and global cognitive index, whereas cannabis users with a family history of psychosis performed better in these domains.

The main finding of the study is that there is an interaction between cannabis use and a family history of psychosis in the areas of verbal memory, executive function and global cognition: that is, cannabis use is associated with a better performance in patients with a family history of psychosis and a worse performance in those with no family history of psychosis.

In order to confirm this hypothesis, future research should explore the actual expression of the endocannabinoid system in patients with and without a family history of psychosis.”

http://www.ncbi.nlm.nih.gov/pubmed/27513670

Medical Marijuana-Opportunities and Challenges

Posted on August 11, 2016 by David

“Over the recent years, public and political opinions have demonstrated increasing support for the legalization of medical marijuana.

To date, 24 states as well as the District of Columbia have legalized cannabis for medical use, 4 states have legalized the recreational use of Marijuana.

Marijuana is derived from the hemp plant Cannabis sativa. Δ-9-tetrahydrocannabinol (THC) is the major psychoactive constituent of cannabis, while cannabidiol (CBD) is the major non-psychoactive constituent. THC is a partial agonist at CB1 and CB2 receptors, while CBD at high levels is an antagonist CB1 and CB2.

CB1 is abundantly expressed in the brain, and CB2 is expressed on immune cells (expression of CB2 on neurons remains controversial). The brain also produces endogenous cannabis-like substances (endocannabinoids) that bind and activate the CB1/CB2 receptors.

There is tremendous interest in harnessing the therapeutic potential of plant-derived and synthetic cannabinoids.

This Editorial provides an overview of diseases that may be treated by cannabinoids.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4948749/

A new antipsychotic mechanism of action for cannabidiol

Posted on August 10, 2016 by David

Totally dope! – A new antipsychotic mechanism of action for cannabidiol, by Anand Gururajan

“The pharmacological strategy for the treatment of schizophrenia has not changed in the six decades since chlorpromazine was introduced in 1952. Although several newer agents have recently gained approval, the mechanism of action of antipsychotics is still largely based on normalising dopaminergic neurotransmission which does not adequately address the symptomatology of a very complex disorder. Moreover, they cause side effects such as extrapyramidal motor symptoms and metabolic syndrome which can worsen the patient condition.

In this regard, preclinical and clinical studies since the ’90s have demonstrated the antipsychotic potential of cannabidiol (CBD), a derivative of the cannabis sativa plant which does not have the adverse psychoactive properties of tetrahydrocannabinol.

In particular, CBD has been shown to be effective in attenuating the positive symptoms of schizophrenia with a negligible side-effect profile.

Accumulating evidence implicates dysfunction of the mammalian target of rapamycin (mTOR) signaling cascade in the pathophysiology of schizophrenia. Thus, in a recent paper, Renard et al. (2016) used the amphetamine (AMPH)-sensitisation protocol in rats to investigate whether the antipsychotic effects of CBD were mediated by its effects on the mTOR cascade. Specifically, they focused on the nucleus accumbens shell (NASh) which has been implicated as a therapeutically relevant ‘hot-spot’ for antipsychotic action and is one of the brain regions targeted by CBD.

Thus, together with the fact that CBD alone had no behavioural effects, the behavioural findings reinforce the potential utility of this cannabinoid as an antipsychotic for the treatment of the positive symptoms of schizophrenia.”

http://medicalxpress.com/news/2016-08-antipsychotic-mechanism-action-cannabidiol.html

Fluorinated Cannabidiol Derivatives: Enhancement of Activity in Mice Models Predictive of Anxiolytic, Antidepressant and Antipsychotic Effects.

Posted on July 16, 2016 by David

“Cannabidiol (CBD) is a major Cannabis sativa constituent, which does not cause the typical marijuana psychoactivity. However, it has been shown to be active in a numerous pharmacological assays, including mice tests for anxiety, obsessive-compulsive disorder, depression and schizophrenia. In human trials the doses of CBD needed to achieve effects in anxiety and schizophrenia are high. We report now the synthesis of 3 fluorinated CBD derivatives, one of which, 4′-F-CBD (HUF-101) (1), is considerably more potent than CBD in behavioral assays in mice predictive of anxiolytic, antidepressant, antipsychotic and anti-compulsive activity. Similar to CBD, the anti-compulsive effects of HUF-101 depend on cannabinoid receptors.”

http://www.ncbi.nlm.nih.gov/pubmed/27416026

Does cannabidiol have a role in the treatment of schizophrenia?

Posted on July 6, 2016 by David

“Schizophrenia is a debilitating psychiatric disorder which places a significant emotional and economic strain on the individual and society-at-large. Unfortunately, currently available therapeutic strategies do not provide adequate relief and some patients are treatment-resistant.

In this regard, cannabidiol (CBD), a non-psychoactive constituent of Cannabis sativa, has shown significant promise as a potential antipsychotic for the treatment of schizophrenia.

However, there is still considerable uncertainty about the mechanism of action of CBD as well as the brain regions which are thought to mediate its putative antipsychotic effects. We argue that further research on CBD is required to fast-track its progress to the clinic and in doing so, we may generate novel insights into the neurobiology of schizophrenia.”

http://www.ncbi.nlm.nih.gov/pubmed/27374322

Cannabidiol monotherapy for treatment-resistant schizophrenia

Posted on June 21, 2016 by David

SJO banner

“Cannabidiol (CBD), one of the major products of the marijuana plant, is devoid of marijuana’s typical psychological effects. In contrast, potential antipsychotic efficacy has been suggested based on preclinical and clinical data.

In this report, we further investigated the efficacy and safety of CBD monotherapy in three patients with treatment-resistant schizophrenia (TRS).

Efficacy, tolerability and side effects were assessed.

All patients tolerated CBD very well and no side effects were reported.

These preliminary data suggest that CBD monotherapy may not be effective for TRS.”

http://jop.sagepub.com/content/20/5/683.short

Could cannabidiol be used as an alternative to antipsychotics?

Posted on June 10, 2016 by David

“Schizophrenia is a mental disorder that affects close to 1% of the population. Individuals with this disorder often present signs such as hallucination, anxiety, reduced attention, and social withdrawal. Although antipsychotic drugs remain the cornerstone of schizophrenia treatment, they are associated with severe side effects.

Recently, the endocannabinoid system (ECS) has emerged as a potential therapeutic target for pharmacotherapy that is involved in a wide range of disorders, including schizophrenia.

Since its discovery, a lot of effort has been devoted to the study of compounds that can modulate its activity for therapeutic purposes.

Among them, cannabidiol (CBD), a non-psychoactive component of cannabis, shows great promise for the treatment of psychosis, and is associated with fewer extrapyramidal side effects than conventional antipsychotic drugs.

The overarching goal of this review is to provide current available knowledge on the role of the dopamine system and the ECS in schizophrenia, and to discuss key findings from animal studies and clinical trials investigating the antipsychotic potential of CBD.”

http://www.ncbi.nlm.nih.gov/pubmed/27267317

ABC transporters P-gp and Bcrp do not limit the brain uptake of the novel antipsychotic and anticonvulsant drug cannabidiol in mice.

Posted on June 4, 2016 by David

“Cannabidiol (CBD) is currently being investigated as a novel therapeutic for the treatment of CNS disorders like schizophrenia and epilepsy.

These results suggest that CBD is not a substrate of P-gp or Bcrp and may be free from the complication of reduced brain uptake by these transporters.

Such findings provide favorable evidence for the therapeutic development of CBD in the treatment of various CNS disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/27257556

Cannabidiol Counteracts Amphetamine-Induced Neuronal and Behavioral Sensitization of the Mesolimbic Dopamine Pathway through a Novel mTOR/p70S6 Kinase Signaling Pathway.

Posted on May 6, 2016 by David

“Schizophrenia-related psychosis is associated with disturbances in mesolimbic dopamine (DA) transmission, characterized by hyperdopaminergic activity in the mesolimbic pathway. Currently, the only clinically effective treatment for schizophrenia involves the use of antipsychotic medications that block DA receptor transmission. However, these medications produce serious side effects leading to poor compliance and treatment outcomes.

Emerging evidence points to the involvement of a specific phytochemical component of marijuana called cannabidiol (CBD), which possesses promising therapeutic properties for the treatment of schizophrenia-related psychoses.

Our findings demonstrate a novel mechanism for the putative antipsychotic-like properties of CBD in the mesolimbic circuitry. We identify the molecular signaling pathways through which CBD may functionally reduce schizophrenia-like neuropsychopathology.

SIGNIFICANCE STATEMENT:

The cannabis-derived phytochemical, cannabidiol (CBD), has been shown to have pharmacotherapeutic efficacy for the treatment of schizophrenia.

However, the mechanisms by which CBD may produce antipsychotic effects are entirely unknown. Using preclinical behavioral procedures combined with molecular analyses and in vivo neuronal electrophysiology, our findings identify a functional role for the nucleus accumbens as a critical brain region whereby CBD can produce effects similar to antipsychotic medications by triggering molecular signaling pathways associated with the effects of classic antipsychotic medications.

Specifically, we report that CBD can attenuate both behavioral and dopaminergic neuronal correlates of mesolimbic dopaminergic sensitization, via a direct interaction with mTOR/p70S6 kinase signaling within the mesolimbic pathway.”

http://www.ncbi.nlm.nih.gov/pubmed/27147666

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

Neuroscientists discover previously unknown function of cannabinoid receptor

Posted on May 2, 2016 by David

“Previously Unknown Function of a Cannabinoid Receptor Identified. Study could improve our insights into brain diseases.” http://neurosciencenews.com/cb2-cannabinoid-receptor-hippocampus-4147/

“In the brain, there is a delicate interplay of signaling substances and cellular activity. Scientists have now identified another key player within this ensemble. In a laboratory study they found that the ‘cannabinoid type 2 receptor’ influences information processing inside the hippocampus. The research results might help advance our understanding of schizophrenia and Alzheimer’s, say the authors.” https://www.sciencedaily.com/releases/2016/05/160502111228.htm

“The cannabinoid type 2 receptor – also called “CB2 receptor” – is a special membrane protein. Its function is to receive chemical signals that control cellular activity. “Until now, this receptor was considered part of the immune system without function in nerve cells. However, our study shows that it also plays an important role in the signal processing of the brain,” explains Professor Dietmar Schmitz, Speaker for the DZNE-Site Berlin and Director of the Neuroscience Research Center of the Charité (NWFZ/NeuroCure).” https://scienceblog.com/483935/neuroscientists-discover-previously-unknown-function-cannabinoid-receptor/