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.”

http://phys.org/news104659898.html

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.”

Source:
Amy Molnar
Wiley-Blackwell”

http://www.medicalnewstoday.com/releases/168519.php

Alcohol and cannabis use and mortality in people with schizophrenia and related psychotic disorders.

“The impact of co-morbid substance use on mortality is not well studied in psychotic disorders. The objective of this study was to examine the impact of substance use on mortality in people with psychotic disorders and alcohol and/or drug use.

…In a Cox model, predicted mortality risk was higher in age group 35-55 compared to <35 years and in males, but reduced in cannabis users. Overall five- (3.1% vs 7.5%) and ten-year mortality risk (5.5% vs. 13.6%) was lower in cannabis users than in non-users with psychotic disorders (p = 0.005) in a survival model.

 We observed a lower mortality risk in cannabis-using psychotic disorder patients compared to cannabis non-users despite subjects having similar symptoms and treatments.

 Future research is warranted to replicate these findings and to shed light on the anti-inflammatory properties of the endocannabinoid system and its role in decreased mortality in people with psychotic disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/22595870

Cannabinoids and Schizophrenia: Therapeutic Prospects.

“Approximately one third of patients diagnosed with schizophrenia do not achieve adequate symptom control with standard antipsychotic drugs (APs).

The endocannabinoid system (ECS) in the brain plays an important role in maintaining normal mental health.

ECS modulates emotion, reward processing, sleep regulation, aversive memory extinction and HPA axis regulation…

The cannabis plant synthesises a large number of pharmacologically active compounds unique to it known as phytocannabinoids. In contrast to the euphoric and pro-psychotic effects of delta-9-tetrahydrocannabinol (THC), certain non-intoxicating phytocannabinoids have emerged in pre-clinical and clinical models as potential APs.

Since the likely mechanism of action does not rely upon dopamine D2 receptor antagonism, synergistic combinations with existing APs are plausible.

The anti-inflammatory and immunomodulatory effects of the non-intoxicating phytocannabinoid cannabidiol (CBD) are well established and are summarised below.

Preliminary data reviewed in this paper suggest that CBD in combination with a CB1 receptor neutral antagonist could not only augment the effects of standard APs but also target the metabolic, inflammatory and stress-related components of the schizophrenia phenotype.”

http://www.ncbi.nlm.nih.gov/pubmed/23829368

“6”-Azidohex-2″-yne-cannabidiol: a potential neutral, competitive cannabinoid CB1 receptor antagonist… 6″-azidohex-2″-yne-cannabidiol was as potent as cannabidiol in producing surmountable antagonism… it is a competitive cannabinoid CB(1) receptor antagonist…it may be a neutral cannabinoid CB(1) receptor antagonist.”  http://www.ncbi.nlm.nih.gov/pubmed/15033394

 

Could Marijuana Treat Schizophrenia?

“Researchers find cannabidiol is as effective as standard antipsychotic drugs—with fewer side effects.”

A compound found in marijuana can help treat schizophrenia as effectively as standard antipsychotic drugs—and with fewer side effects—according to the results of a new clinical trial, reports The Fix columnist Maia Szalavitz in Time. Researchers at University of Cologne in Germany studied 39 people with schizophrenia, all hospitalized for a psychotic episode. Twenty of the patients were given cannabidiol (CBD), a substance found in marijuana that is associated with its mellowing, anti-anxiety effects (not THC—the main ingredient in marijuana, which has been found to worsen schizophrenia). The other participants were given amisulpride, an antipsychotic medication. At the end of the four-week trial, both groups showed significant clinical improvement in their schizophrenic symptoms. “The results were amazing,” says Daniele Piomelli, professor of pharmacology at the University of California-Irvine and a co-author of the study. “Not only was [CBD] as effective as standard antipsychotics, but it was also essentially free of the typical side effects seen with antipsychotic drugs.” Antipsychotic medications can cause serious, sometimes permanent movement disorders and other side effects such as weight gain and movement problems. In the study, these side effects were observed in those taking amisulpride, but not in those taking CBD. “These exciting findings should stimulate a great deal of research,” says Dr. John Krystal, chair of psychiatry at Yale University School of Medicine, who was not associated with the study. He noted that CBD, in addition to having fewer side effects, also seemed to work better on schizophrenia’s negative symptoms, which are notoriously difficult to treat, including: social withdrawal, blunting of pleasure, and lack of motivation.”

http://www.thefix.com/content/pot-compound-treats-schizophrenia-few-side-effects91717

The endocannabinoid system and its therapeutic exploitation.

Image result for Nat Rev Drug Discov.

“The term ‘endocannabinoid’ – originally coined in the mid-1990s after the discovery of membrane receptors for the psychoactive principle in Cannabis, Delta9-tetrahydrocannabinol and their endogenous ligands – now indicates a whole signalling system that comprises cannabinoid receptors, endogenous ligands and enzymes for ligand biosynthesis and inactivation. This system seems to be involved in an ever-increasing number of pathological conditions. With novel products already being aimed at the pharmaceutical market little more than a decade since the discovery of cannabinoid receptors, the endocannabinoid system seems to hold even more promise for the future development of therapeutic drugs. We explore the conditions under which the potential of targeting the endocannabinoid system might be realized in the years to come.”  http://www.ncbi.nlm.nih.gov/pubmed/15340387

http://www.nature.com/nrd/journal/v3/n9/full/nrd1495.html

Cannabinoids ameliorate impairments induced by chronic stress to synaptic plasticity and short-term memory.

“Repeated stress is one of the environmental factors that precipitates and exacerbates mental illnesses like depression and anxiety as well as cognitive impairments. We have previously shown that cannabinoids can prevent the effects of acute stress on learning and memory.

Here we aimed to find whether chronic cannabinoid treatment would alleviate the long-term effects of exposure to chronic restraint stress on memory and plasticity as well as on behavioral and neuroendocrine measures of anxiety and depression. Late adolescence rats were exposed to chronic restraint stress for two weeks followed each day by systemic treatment with vehicle or with the CB1/2 receptor agonist WIN55,212-2 (1.2 mg/kg). Thirty days after the last exposure to stress, rats demonstrated impaired long-term potentiation (LTP) in the ventral subiculum (vSub)-nucleus accumbens (NAc) pathway, impaired performance in the prefrontal cortex (PFC)-dependent object recognition task and the hippocampal-dependent spatial version of this task, increased anxiety levels, and significantly reduced expression of glucocorticoid receptors (GRs) in the amygdala, hippocampus, PFC and NAc. Chronic WIN55,212-2 administration prevented the stress-induced impairment in LTP levels and in the spatial task, with no effect on stress-induced alterations in unconditioned anxiety levels or GR levels. The CB1 antagonist AM251 (0.3 mg/kg) prevented the ameliorating effects of WIN55,212-2 on LTP and short-term memory. Hence, the beneficial effects of WIN55,212-2 on memory and plasticity are mediated by CB1 receptors and are not mediated by alterations in GR levels in the brain areas tested.

 Our findings suggest that cannabinoid receptor activation could represent a novel approach to the treatment of cognitive deficits that accompany a variety of stress-related neuropsychiatric disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/23426383

Marijuana Compound May Beat Antipsychotics at Treating Schizophrenia

“A certain marijuana compound known as cannabidiol (CBD) can treat schizophrenia as well as antipsychotic drugs, with far fewer side effects, according to a preliminary clinical trial.”

Read more: http://psychcentral.com/news/2012/06/07/marijuana-compound-may-beat-antipsychotics-at-treating-schizophrenia/39803.html

New Study: Cannabidiol, a non- THC compound derived from Marijuana effectively treats schizophrenia.

“A certain marijuana compound known as cannabidiol (CBD) can treat schizophrenia as well as antipsychotic drugs, with far fewer side effects, according to a preliminary clinical trial. Cannabidiol differs from THC which is the much publicized intoxicating chemical in THC.”

 “The results were amazing,” said Daniel Piomelli, Ph.D., professor of pharmacology at the University of California-Irvine and a co-author of the study. “Not only was [CBD] as effective as standard antipsychotics, but it was also essentially free of the typical side effects seen with antipsychotic drugs.””

Read more: http://www.classicalmedicinejournal.com/the-classical-medicine-journal/2012/6/18/new-study-cannabidiol-a-non-thc-compound-derived-from-mariju.html

Cannabidiol Relieves Psychosis in Schizophrenia, Why is it Illegal?

“A molecule in cannabis (CBD) has shown to relieve anxiety and symptoms of psychosis in people diagnosed with schizophrenia, though many patients are denied or discouraged from this medicine with fewer side effects than pharmaceutical products because the DEA has deemed the cannabis plant to be “illegal”. The U.S. government needs to answer “why?” this medicine warrents time in prison when nobody is being harmed.

 Investigators concluded, “Our results provide evidence that the non-cannabimimetic constituent of marijuana, cannabidiol, exerts clinically relevant antipsychotic effects that are associated with marked tolerability and safety, when compared with current medications. … The results … potentially represent a completely new mechanism in the treatment of schizophrenia.”

 “Studies have suggested a wide range of possible therapeutic effects of cannabidiol on several conditions, including Parkinson’s disease, Alzheimer’s disease, cerebral ischemia, diabetes, rheumatoid arthritis, other inflammatory diseases, nausea and cancer,” Zuardi writes. Let’s look at a few of these in detail, shall we?

1. Antiepileptic action
“In 1973, a Brazilian group reported that CBD was active in … blocking convulsions produced in experimental animals.”

2. Sedative action
“In humans with insomnia, high doses of CBD increased sleep duration compared to placebo.”

3. Anxiolytic action
“CBD induce[s] a clear anxiolytic effect and a pattern of cerebral activity compatible with an anxiolytic activity.”

4. Antipsychcotic action
“[C]linical studies suggest that CBD is an effective, safe and well-tolerated alternative treatment for schizophrenic patients.”

5. Antidystonic action
“CBD … had antidystonic effects in humans when administered along with standard medication to five patients with dystonia, in an open study.”

6. Antioxidative action
“[I]t was demonstrated that CBD can reduce hydroperoxide-induced oxidative damage as well as or better than other antioxidants. CBD was more protective against glutamate neurotoxicity than either ascorbate or a-tocopherol, indicating that this drug is a potent antioxidant.”

7. Neuroprotective action
“A marked reduction in the cell survival was observed following exposure of cultured rat pheochromocytoma PC12 cells to beta-A peptide. Treatment of the cells with CBD prior to beta-A exposure significantly elevated the cell survival.”

8. Antiinflammatory action
“CBD, administered i.p. or orally, has blocked the progression of arthritis.”

9. Cardioprotective action
“CBD induces a substantial cardioprotective effect.”

10. Action on diabetes
“CBD treatment of NOD (non-obese diabetic) mice before the development of the disease reduced its incidence from 86% in the non-treated control mice to 30% in CBD-treated mice. … It was also observed that administration of CBD to 11-14 week old female NOD mice, which were either in a latent diabetes stage or had initial symptoms of diabetes, ameliorated the manifestations of the disease.”

11. Antiemetic action
“The expression of this conditioned retching reaction was completely suppressed by CBD and delta9-THC, but not by ondansetron, [an] antagonist that interferes with acute vomiting.”

12. Anticancer action
“A study of the effect of different cannabinoids on eight tumor cell lines, in vitro, has clearly indicated that, of the five natural compounds tested, CBD was the most potent inhibitor of cancer cell growth.”

In sum, the past 45 years of scientific study on CBD has revealed the compound to be non-toxic, non-psychoactive, and to possess a multitude of therapeutic properties. Yet, to this day it remains illegal to possess or use (and nearly impossible to study in US clinical trials) simply because it is associated with marijuana.

What possible advancements in medical treatment may have been achieved over the past decades had US government officials chosen to advance — rather than inhibit — clinical research into CBD (which, under federal law, remains a Schedule I drug defined as having “no currently accepted medical use”)? Perhaps it’s time someone asks John Walters or the DEA?” 

Read more: http://rinf.com/alt-news/latest-news/cannabidiol-relieves-psychosis-in-schizophrenia-why-is-it-illegal/17827/