Cannabidiol in Humans-The Quest for Therapeutic Targets.

“Cannabidiol (CBD), a major phytocannabinoid constituent of cannabis, is attracting growing attention in medicine for its anxiolytic, antipsychotic, antiemetic and anti-inflammatory properties.

However, up to this point, a comprehensive literature review of the effects of CBD in humans is lacking. The aim of the present systematic review is to examine the randomized and crossover studies that administered CBD to healthy controls and to clinical patients.

A systematic search was performed in the electronic databases PubMed and EMBASE using the key word “cannabidiol”. Both monotherapy and combination studies (e.g., CBD + ∆9-THC) were included. A total of 34 studies were identified: 16 of these were experimental studies, conducted in healthy subjects, and 18 were conducted in clinical populations, including multiple sclerosis (six studies), schizophrenia and bipolar mania (four studies), social anxiety disorder (two studies), neuropathic and cancer pain (two studies), cancer anorexia (one study), Huntington’s disease (one study), insomnia (one study), and epilepsy (one study).

Experimental studies indicate that a high-dose of inhaled/intravenous CBD is required to inhibit the effects of a lower dose of ∆9-THC. Moreover, some experimental and clinical studies suggest that oral/oromucosal CBD may prolong and/or intensify ∆9-THC-induced effects, whereas others suggest that it may inhibit ∆9-THC-induced effects.

Finally, preliminary clinical trials suggest that high-dose oral CBD  may exert a therapeutic effect for social anxiety disorder, insomnia and epilepsy, but also that it may cause mental sedation. Potential pharmacokinetic and pharmacodynamic explanations for these results are discussed.”

http://www.ncbi.nlm.nih.gov/pubmed/24281562

Therapeutic potential of cannabinoid medicines.

Drug Testing and Analysis

“Cannabis was extensively used as a medicine throughout the developed world in the nineteenth century but went into decline early in the twentieth century ahead of its emergence as the most widely used illicit recreational drug later that century. Recent advances in cannabinoid pharmacology alongside the discovery of the endocannabinoid system (ECS) have re-ignited interest in cannabis-based medicines.

The ECS has emerged as an important physiological system and plausible target for new medicines. Its receptors and endogenous ligands play a vital modulatory role in diverse functions including immune response, food intake, cognition, emotion, perception, behavioural reinforcement, motor co-ordination, body temperature, wake/sleep cycle, bone formation and resorption, and various aspects of hormonal control. In disease it may act as part of the physiological response or as a component of the underlying pathology.

In the forefront of clinical research are the cannabinoids delta-9-tetrahydrocannabinol and cannabidiol, and their contrasting pharmacology will be briefly outlined. The therapeutic potential and possible risks of drugs that inhibit the ECS will also be considered. This paper will then go on to review clinical research exploring the potential of cannabinoid medicines in the following indications: symptomatic relief in multiple sclerosis, chronic neuropathic pain, intractable nausea and vomiting, loss of appetite and weight in the context of cancer or AIDS, psychosis, epilepsy, addiction, and metabolic disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/24006213

http://onlinelibrary.wiley.com/doi/10.1002/dta.1529/abstract

Cannabis with high cannabidiol content is associated with fewer psychotic experiences.

“An increasing number of authors identify cannabidiol, another component of the cannabis plant, as an antipsychotic agent. The objective of the current study is to investigate the role of cannabidiol content in the association between cannabis use and psychiatric symptoms in a large non-clinical population of cannabis users…

CONCLUSION:

Although the observed effects are subtle, using high cannabidiol content cannabis was associated with significantly lower degrees of psychotic symptoms providing further support for the antipsychotic potential of cannabidiol.”

http://www.ncbi.nlm.nih.gov/pubmed/21592732

Cannabis users have higher premorbid IQ than other patients with first onset psychosis.

“A number of studies have reported that patients with psychosis who use cannabis have better cognitive performance than those who do not.

… we tested the hypothesis that patients who smoked cannabis would have a higher premorbid IQ than patients who did not.

Patients who had ever smoked cannabis had significantly higher current and premorbid IQ  compared to patients who had never used cannabis…”

 http://www.ncbi.nlm.nih.gov/pubmed/23958486

Cannabis abuse is associated with better emotional memory in schizophrenia: A functional magnetic resonance imaging study.

 “…we performed a functional magnetic resonance imaging study of emotional memory in schizophrenia patients with cannabis abuse…

  These results are consistent with previous findings showing that cannabis abuse is associated with fewer negative symptoms and better cognitive functioning in schizophrenia…”

http://www.ncbi.nlm.nih.gov/pubmed/23906663

Cannabis and psychosis: Have we found the missing links?

The association between cannabis and psychosis has long been a matter of debate, with cannabis widely perceived as a harmless recreational drug.

Heavy cannabis use at a n young age, in association with genetic liability to psychosis and exposure to environmental stressors like childhood trauma and urban upbringing increases the risk of psychotic outcome in later life.

Cannabis acts as a component cause of psychosis, that is, it increases the risk of psychosis in people with certain genetic or environmental vulnerabilities, though by itself, it is neither a sufficient nor a necessary cause of psychosis.”

http://www.ncbi.nlm.nih.gov/pubmed/23810133

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

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

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

http://articles.baltimoresun.com/2011-02-09/news/bs-ed-marijuana-letter-20110209_1_mental-illness-medical-marijuana-lower-rates

Doubt cast on cannabis, schizophrenia link – ABC Science

“A new study in the UK has cast doubt on the supposed link between cannabis use and schizophrenia.

This latest study, led by Dr Martin Frisher of Keele University, examined the records of 600,000 patients aged between 16 and 44, but failed to find a similar link.

“An important limitation of many studies is that they have failed to distinguish the direction of association between cannabis use and psychosis,” the authors write in the latest edition of the journal Schizophrenia Research.

Not as predicted

Frisher and colleagues compared the trends of cannabis use with general practitioner records of schizophrenia.

They argue if cannabis use does cause schizophrenia, then an increase in cannabis use should be followed by an increase in the incidence of schizophrenia.

According to the study, cannabis use in the UK between 1972 and 2002 has increased four-fold in the general population, and 18-fold among under-18s.

Based on the literature supporting the link, the authors argue that this should be followed by an increase in schizophrenia incidence of 29% between 1990 and 2010.

But the researchers found no increase in the diagnosis of schizophrenia or other psychotic disorders during that period. In fact some of the data suggested the incidence of these conditions had decreased.

“This study does not therefore support the specific causal link between cannabis use and the incidence of psychotic disorders,” the authors say”

http://www.abc.net.au/science/articles/2009/09/01/2673334.htm