Drug repurposing and emerging adjunctive treatments for schizophrenia.

“Schizophrenia is a frequent disorder, which substantially impairs patients’ quality of life. Moreover, the burden of illness for patients, their families and for the society, in general, is substantial.

Given the current failure of a number of mechanistically new drugs, repurposed compounds may serve as alternative and/or adjunctive agents for schizophrenic patients and for treatment refractory patients in particular. Anti-inflammatory drugs, as well as N-acetylcysteine, a precursor of the major antioxidant glutathione, hormones, glutamatergic and nicotinergic compounds, ‘nutraceuticals’ (e.g., ω-3 fatty acids) and cannabidiol, an endocannabinoid modulator, represent promising agents in this field.”


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Cannabis use does not cause schizophrenia

“According to a new report by a British government advisory body, the regular use of cannabis though it can have real and significant mental health effects it is unlikely to cause schizophrenia.

The Advisory Council on the Misuse of Drugs says that based on current evidence smoking cannabis was likely to increase the chances of developing schizophrenia by just one per cent.”

More: http://www.news-medical.net/news/2006/01/24/15577.aspx

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Marijuana’s Link to Schizophrenia Debated – American News report

“With the growing use of medical marijuana to treat chronic pain and other health problems, the debate over the medical effects of the drug on the human mind continue to make their way through the medical community.

The latest salvo comes from researchers in Australia and England.  At the center of the debate is the possible relationship between marijuana (cannabis) and mental illnesses such as schizophrenia.

Castle cites one study that indicated people with schizophrenia had a lifetime rate of cannabis exposure of 97 percent – meaning almost all of them have tried the drug.  Yet, he also notes that most people who use cannabis do not develop schizophrenia, and that many people diagnosed with schizophrenia have never used cannabis.

“Therefore, it is likely that cannabis exposure is a ‘component cause’ that interacts with other factors to ‘cause’ schizophrenia or other psychotic disorders, but is neither necessary nor sufficient to do so alone,” Castle wrote.

However, the authors of the accompanying article are not as convinced that the prevailing scientific evidence proves a relationship exists between pot use and schizophrenia.”

More: http://americannewsreport.com/marijuanas-link-to-schizophrenia-debated-8817482

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A false link between marijuana and mental illness

“The article published today in “Health News” makes the claim that smoking marijuana is “linked” to early onset of mental illness.

However, although the article implies some sort of cause and effect, that conclusion has no scientific basis. In fact, the authors of the study don’t even bother investigating whether marijuana use causes mental illness or if people with mental illness have a higher rate of smoking marijuana than the general public.

If marijuana caused mental illness, then cultures that have a higher rate of marijuana smoking than the U.S. should have a higher rate of mental illness. But in fact, the opposite is true. Cultures with higher rates of marijuana consumption have lower rates of mental illness than the United States. This would indicate that rather than marijuana causing mental illness, as your article implies, it is people with mental illness who are self medicating with marijuana in order to alleviate their symptoms.

This (more correct) reading of the data, however, does not fit the narrative being presented by the politicians who are making their careers by “getting tough” on marijuana smokers, nor does it fit the narrative of the manufacturers of the currently legal psychotropic drugs, like Prozac and Zoloft, who stand to lose billions of dollars if medical marijuana is legalized, and who funnel millions of dollars to those politicians who present their dubious science as fact.

Had your newspaper even taken the time to Google the Archive of General Psychiatry, you would have found that the “study” you cited was conducted by the “Genetic Risk and Outcome in Psychosis (GROUP) Investigators,” who publish only articles against medical marijuana. That alone should raise a red flag to anyone with a basic understanding of scientific research. When someone conducts numerous studies and publishes many articles that all draw the same conclusion, whether the evidence leads to that conclusion or not, the critical eye should suspect some ulterior motive at work. It’s not possible to keep an open mind when you have an axe to grind.”

William Smith, Baltimore


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Cannabis/schizophrenia link questioned

“The Swiss government is questioning the results of a study showing a link between marijuana use and schizophrenia.

The Zurich University study showed a higher incidence of schizophrenia in the 1990s in the age groups most likely to use cannabis, Swissinfo said Wednesday.

“We know from other experimental studies that cannabis can cause psychosis, but we have now established a clear link to schizophrenia for the first time,” study co-author Wulf Rossler said.

Swissinfo said the Federal Health Office is questioning the report, saying the patients’ drug histories and other medical details remained unknown.

“It does not uncover the medical history of the patients, for instance the consumption of psychotic substances or other factors that could lead to psychotic illnesses,” the health office in a statement.”


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Minimal Relationship Between Cannabis And Schizophrenia Or Psychosis Suggested By New UK Study

“Last year the UK government reclassified cannabis from a class C to a class B drug, partly out of concerns that cannabis, especially the more potent varieties, may increase the risk of schizophrenia in young people. But the evidence for the relationship between cannabis and schizophrenia or psychosis remains controversial. A new study has determined that it may be necessary to stop thousands of cannabis users in order to prevent a single case of schizophrenia.

Scientists from Bristol, Cambridge and the London School of Hygiene and Tropical Medicine took the latest information on numbers of cannabis users, the risk of developing schizophrenia, and the risk that cannabis use causes schizophrenia to estimate how many cannabis users may need to be stopped to prevent one case of schizophrenia. The study found it would be necessary to stop 2800 heavy cannabis users in young men and over 5000 heavy cannabis users in young women to prevent a single case of schizophrenia. Among light cannabis users, those numbers rise to over 10,000 young men and nearly 30,000 young women to prevent one case of schizophrenia.

That’s just part of the story. Interventions to prevent cannabis use typically do not succeed for every person who is treated. Depending on how effective an intervention is at preventing cannabis use, it would be necessary to treat even higher numbers of users to achieve the thousands of successful results necessary to prevent a very few cases of schizophrenia.

Matt Hickman, one of the authors of the report published last week in the scholarly journal Addiction, said that “preventing cannabis use is important for many reasons – including reducing tobacco and drug dependence and improving school performance. But our evidence suggests that focusing on schizophrenia may have been misguided. Our research cannot resolve the question whether cannabis causes schizophrenia, but does show that many people need to give up cannabis in order to have an impact on the number of people with schizophrenia. The likely impact of re-classifying cannabis in the UK on schizophrenia or psychosis incidence is very uncertain.”

Amy Molnar


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“Since the discovery of an endogenous cannabinoid system, research into the pharmacology and therapeutic potential of cannabinoids has steadily increased. Two subtypes of G-protein coupled cannabinoid receptors, CB(1) and CB(1), have been cloned and several putative endogenous ligands (endocannabinoids) have been detected during the past 15 years. The main endocannabinoids are arachidonoyl ethanolamide (anandamide) and 2-arachidonoyl glycerol (2-AG), derivatives of arachidonic acid, that are produced “on demand” by cleavage of membrane lipid precursors.

 Besides phytocannabinoids of the cannabis plant, modulators of the cannabinoid system comprise synthetic agonists and antagonists at the CB receptors and inhibitors of endocannabinoid degradation. Cannabinoid receptors are distributed in the central nervous system and many peripheral tissues, including immune system, reproductive and gastrointestinal tracts, sympathetic ganglia, endocrine glands, arteries, lung and heart. There is evidence for some non-receptor dependent mechanisms of cannabinoids and for endocannabinoid effects mediated by vanilloid receptors.

Properties of CB receptor agonists that are of therapeutic interest include analgesia, muscle relaxation, immunosuppression, anti-inflammation, antiallergic effects, improvement of mood, stimulation of appetite, antiemesis, lowering of intraocular pressure, bronchodilation, neuroprotection and antineoplastic effects. The current main focus of clinical research is their efficacy in chronic pain and neurological disorders. CB receptor antagonists are under investigation for medical use in obesity and nicotine addiction. Additional potential was proposed for the treatment of alcohol and heroine dependency, schizophrenia, conditions with lowered blood pressure, Parkinson’s disease and memory impairment in Alzheimer’s disease.”


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Targeting the endocannabinoid system in Alzheimer’s disease.

“The endocannabinoid system is rapidly emerging as a potential drug target for a variety of immune-mediated central nervous system diseases. There is a growing body of evidence suggesting that endocannabinoid interventions may have particular relevance to Alzheimer’s disease. Here we present a review of endocannabinoid physiology, the evidence that underscores its utility as a potential target for intervention in Alzheimer’s disease, and suggest future pathways of research.

Inflammation and oxidative stress are generally accepted as a critical risk factor for the development of AD, and interventions such as cannabinoids that attenuate these risks without arresting microglial activity and have innate neuroprotective benefits are attractive as potential preventative treatments for AD.

There is a potential for the development of CB1 interventions, whether agonists or antagonists, with applications for a variety of cognitive disorders including neurodegenerative disorders and schizophrenia. The recent discovery of a CB1 receptor Positron Emission Tomography tracer for clinical use may provide the opportunity to evaluate the impact of the regional distribution of CB1 receptors in brain on domain-specific cognitive performance (memory, executive function, praxis) in healthy individuals. Additionally, if AD is a disease of overproduction of eCBs, this may be visualized in case-control CB1receptor binding studies.

The emerging data suggest that the eCB system is a potential target for immune and/or cognitive intervention in AD. A wealth of available chemical compounds capable of intervening in the eCB system at a variety of levels and the success with which these compounds have been used in animal models suggest the potential for human drug development. What is missing is a clear direction for that development based on a concise conceptualization of eCB system function in both health and in neurodegenerative and inflammatory conditions such as AD. Focused experiments are now required to move the field forward.”


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Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia

“Cannabidiol is a component of marijuana that does not activate cannabinoid receptors, but moderately inhibits the degradation of the endocannabinoid anandamide. We previously reported that an elevation of anandamide levels in cerebrospinal fluid inversely correlated to psychotic symptoms. Furthermore, enhanced anandamide signaling let to a lower transition rate from initial prodromal states into frank psychosis as well as postponed transition. In our translational approach, we performed a double-blind, randomized clinical trial of cannabidiol vs amisulpride, a potent antipsychotic, in acute schizophrenia to evaluate the clinical relevance of our initial findings. Either treatment was safe and led to significant clinical improvement, but cannabidiol displayed a markedly superior side-effect profile. Moreover, cannabidiol treatment was accompanied by a significant increase in serum anandamide levels, which was significantly associated with clinical improvement. The results suggest that inhibition of anandamide deactivation may contribute to the antipsychotic effects of cannabidiol potentially representing a completely new mechanism in the treatment of schizophrenia.”

“Cannabidiol is a non-psychotropic component of marijuana that binds to CB1 receptors with only comparably very low affinity and is devoid of overt cannabimimetic or pro-psychotic properties. Biochemical studies indicate that cannabidiol may enhance endogenous anandamide signaling indirectly, by inhibiting the intracellular degradation of anandamide catalyzed by the enzyme fatty acid amide hydrolase (FAAH).Furthermore, preliminary clinical case reports suggest that cannabidiol might exert antipsychotic effects in schizophrenic patients. In addition, experimental studies show that cannabidiol reduces psychosis-like effects of Δ9-tetrahydrocannabinol and synthetic analogs.

Read more:: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3316151/

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Marijuana Compound Treats Schizophrenia with Few Side Effects:Clinical Trial

“A compound found in marijuana can treat schizophrenia as effectively as antipsychotic medications, with far fewer side effects, according to a preliminary clinical trial.

“Because it comes from marijuana, there are obvious political issues surrounding its use. Extracting it from the plant is also expensive. But the biggest barrier may be that CBD is a natural compound, and therefore can’t be patented the way new drugs are. That means that despite the possibility that it could outsell their current blockbuster antipsychotic drugs, pharmaceutical companies aren’t likely to develop it — a particularly striking fact when you consider that every major manufacturer of new generation antipsychotics in the U.S. has so far paid out hundreds of millions or billions of dollars in fines for mismarketing these drugs. Yet they still reaped huge profits.”

“For people with schizophrenia and their families, of course, it is likely to be infuriating that non-scientific issues like marijuana policy and patenting problems could stand in the way of a treatment that could potentially be so restorative. While it’s possible that these study results may not hold up or that researchers could discover problems related to long-term use of CBD,  it’s hard to imagine that they could be any worse than what patients already experience.”

Read more: http://healthland.time.com/2012/05/30/marijuana-compound-treats-schizophrenia-with-few-side-effects-clinical-trial/

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