Posts tagged cannabis
Articles and news from the latest research reports.
Brain imaging insight into cannabis as a pain killer
The pain relief offered by cannabis varies greatly between individuals, a brain imaging study carried out at the University of Oxford suggests.
The researchers found that an oral tablet of THC, the psychoactive ingredient in cannabis, tended to make the experience of pain more bearable, rather than actually reduce the intensity of the pain.
MRI brain imaging showed reduced activity in key areas of the brain that substantiated the pain relief the study participants experienced.
'We have revealed new information about the neural basis of cannabis-induced pain relief,' says lead researcher Dr Michael Lee of Oxford University's Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB).
'Cannabis does not seem to act like a conventional pain medicine. Some people respond really well, others not at all, or even poorly,' he says. 'Brain imaging shows little reduction in the brain regions that code for the sensation of pain, which is what we tend to see with drugs like opiates. Instead cannabis appears to mainly affect the emotional reaction to pain in a highly variable way.'
Long-term pain, often without clear cause, is a complex healthcare problem. Different approaches are often needed to help patient manage pain, and can include medications, physiotherapy and other forms of physical therapy, and psychological support.
For a few patients, cannabis or cannabis-based medications remain effective when other drugs have failed to control pain, while others report very little effect of the drug on their pain but experience side-effects.
'We know little about cannabis and what aspects of pain it affects, or which people might see benefits over the side-effects or potential harms in the long term. We carried out this study to try and get at what is happening when someone experiences pain relief using cannabis,' says Dr Lee.
He adds: ‘Our small-scale study, in a controlled setting, involved 12 healthy men and only one of many compounds that can be derived from cannabis. That’s quite different from doing a study with patients.
'My view is the findings are of interest scientifically but it remains to see how they impact the debate about use of cannabis-based medicines. Understanding cannabis' effects on clinical outcomes, or the quality of life of those suffering chronic pain, would need research in patients over long time periods.'
(The paper ‘Amygdala activity contributes to the dissociative effect of cannabis on pain perception' by Michael C. Lee, Markus Ploner, Katja Wiech, Ulrike Bingel, Vishvarani Wanigasekera, Jonathan Brooks, David K. Menon, Irene Tracey (DOI: 10.1016/j.pain.2012.09.017) will appear in PAIN®, Volume 154, Issue 1 (January 2013) published by Elsevier)
Study Confirms AKT1 Genotype Contributes to Risk of Cannabis Psychosis
The ability of cannabis to produce psychosis is an important public health concern. Some studies have suggested that cannabis exposure during adolescence may increase the risk of developing schizophrenia.
For these reasons, it would be valuable if a biological test could be developed that predicted the risk of developing psychosis in people who abuse cannabis or use marijuana as a medication.
A recent study has implicated a variation in the gene that codes for a protein called RAC-alpha serine/threonine-protein kinase in the risk for cannabis psychosis. However, independent verification of these finding is critical for genetic associations with complex genetic traits, like cannabis-related psychosis, because these findings are difficult to replicate.
Dr Forti’s team carried out a case control study to investigate variation in the AKT1 gene and cannabis use in increasing the risk of psychosis.
“We studied the AKT1 gene as this is involved in dopamine signaling which is known to be abnormal in psychosis. Our sample comprised 489 patients with their first episode of psychosis and 278 healthy controls,” explained Dr Forti, who, with colleagues, reports on the results in the journal Biological Psychiatry.
The endocannabinoid system in normal and pathological brain ageing
The role of endocannabinoids as inhibitory retrograde transmitters is now widely known and intensively studied. However, endocannabinoids also influence neuronal activity by exerting neuroprotective effects and regulating glial responses. This review centres around this less-studied area, focusing on the cellular and molecular mechanisms underlying the protective effect of the cannabinoid system in brain ageing. The progression of ageing is largely determined by the balance between detrimental, pro-ageing, largely stochastic processes, and the activity of the homeostatic defence system. Experimental evidence suggests that the cannabinoid system is part of the latter system. Cannabinoids as regulators of mitochondrial activity, as anti-oxidants and as modulators of clearance processes protect neurons on the molecular level. On the cellular level, the cannabinoid system regulates the expression of brain-derived neurotrophic factor and neurogenesis. Neuroinflammatory processes contributing to the progression of normal brain ageing and to the pathogenesis of neurodegenerative diseases are suppressed by cannabinoids, suggesting that they may also influence the ageing process on the system level. In good agreement with the hypothesized beneficial role of cannabinoid system activity against brain ageing, it was shown that animals lacking CB1 receptors show early onset of learning deficits associated with age-related histological and molecular changes. In preclinical models of neurodegenerative disorders, cannabinoids show beneficial effects, but the clinical evidence regarding their efficacy as therapeutic tools is either inconclusive or still missing.
A Gene Implicated In Schizophrenia Risk Is Also Associated With Risk for Cannabis Dependence
A paper by Shizhong Han and colleagues in the current issue of Biological Psychiatry implicates a new gene in the risk for cannabis dependence. This gene, NRG1, codes for the ErbB4 receptor, a protein implicated in synaptic development and function.
The researchers set out to investigate susceptibility genes for cannabis dependence, as research has already shown that it has a strong genetic component.
To do this, they employed a multi-stage design using genetic data from African American and European American families. In the first stage, a linkage analysis, the strongest signal was identified in African Americans on chromosome 8p21. Then using a genome-wide association study dataset, they identified one genetic variant at NRG1 that showed consistent evidence for association in both African Americans and European Americans. Finally, they replicated the association of that same variant in an independent sample of African-Americans.
All together, the findings suggest that NRG1 may be a susceptibility gene for cannabis dependence.
An interesting feature of this paper is that these findings may also suggest a link between the genetics of schizophrenia and the genetics of cannabis dependence. NRG1 emerged into public awareness after a series of genetic studies implicated it in the heritable risk for schizophrenia. Subsequent studies in post-mortem brain tissue also suggested that the regulation of NRG1 was altered in the brains of individuals diagnosed with schizophrenia.
Thus, the current findings may help to explain the already established link between cannabis use and the risk for developing schizophrenia. A number of epidemiologic studies have attributed the association of cannabis use and schizophrenia to the effects of cannabis on the brain rather than a common genetic link between these two conditions.
"The current data provide a potentially important insight into the heritable risk for schizophrenia and raise the possibility that there are some common genetic contributions to these two disorders," commented Dr. John Krystal, Editor of Biological Psychiatry.
However, further research will be necessary to further confirm the role that NRG1 plays in cannabis dependence and the potential link between cannabis use and psychosis.
(Source: alphagalileo.org)
Boosting natural marijuana-like brain chemicals treats fragile X syndrome symptoms
UCI study points to role endocannabinoids play in common genetic cause of autism
American and European scientists have found that increasing natural marijuana-like chemicals in the brain can help correct behavioral issues related to fragile X syndrome, the most common known genetic cause of autism.
The work indicates potential treatments for anxiety and cognitive defects in people with this condition. Results appear online in Nature Communications.
Daniele Piomelli of UC Irvine and Olivier Manzoni of INSERM, the French national research agency, led the study, which identified compounds that inhibit enzymes blocking endocannabinoid transmitters called 2-AG in the striatum and cortex regions of the brain.
These transmitters allow for the efficient transport of electrical signals at synapses, structures through which information passes between neurons. In fragile X syndrome, regional synapse communication is severely limited, giving rise to certain cognitive and behavioral problems.
Fragile X syndrome is caused by a mutation of the FMR1 gene on the X chromosome. People born with it are mentally disabled; generally experience crawling, walking and language delays; tend to avoid eye contact; may be hyperactive or impulsive; and have such notable physical characteristics as an elongated face, flat feet and large ears.
The researchers stress that their findings, while promising, do not point to a cure for the condition.
“What we hope is to one day increase the ability of people with fragile X syndrome to socialize and engage in normal cognitive functions,” said Piomelli, a UCI professor of anatomy & neurobiology and the Louise Turner Arnold Chair in the Neurosciences.
The study involved mice genetically altered with FMR1 mutations that exhibited symptoms of fragile X syndrome. Treated with novel compounds that correct 2-AG protein signaling in brain cells, these mice showed dramatic behavioral improvements in maze tests measuring anxiety and open-space acceptance.
While other work has focused on pharmacological treatments for behavioral issues associated with fragile X syndrome, Piomelli noted that this is the first to identify the role endocannabinoids play in the neurobiology of the condition.
About endocannabinoids
Endocannabinoid compounds are created naturally in the body and share a similar chemical structure with THC, the primary psychoactive component of the marijuana plant, Cannabis. Endocannabinoids are distinctive because they link with protein molecule receptors — called cannabinoid receptors — on the surface of cells. For instance, when a person smokes marijuana, the cannabinoid THC activates these receptors. Because the body’s natural cannabinoids control a variety of factors — such as pain, mood and appetite — they’re attractive targets for drug discovery and development. Piomelli is one of the world’s leading endocannabinoid researchers. His groundbreaking work is showing that this system can be exploited by new treatments to combat anxiety, pain, depression and obesity.
(Source: today.uci.edu)
Scientists at the University of Reading have demonstrated for the first time that a previously unstudied chemical in cannabis could lead to more effective treatments for people with epilepsy.
The team at the University’s Department of Pharmacy and School of Psychology have discovered that cannabidivarin (CBDV) - a largely ignored natural compound found in cannabis - has the potential to prevent more seizures, with few side effects such as uncontrollable shaking, caused by many existing anti-epileptic drugs.
In the study, carried out by the University of Reading in collaboration with GW Pharma and Otsuka Pharmaceuticals, cannabidivarin strongly suppressed seizures in six different experimental models commonly used in epilepsy drug discovery.
Cannabidivarin was also found to work when combined with drugs currently used to control epilepsy and, unlike other cannabinoids (unique components in cannabis) such as THC, is not psychoactive and therefore does not cause users to feel ‘high’.
The findings are reported in the British Journal of Pharmacology journal.
Cocaine-withdrawal emotion mechanism discovered
Washington State University researchers have found a cellular mechanism that contributes to the lack of motivation and negative emotions of a cocaine addict going through withdrawal. Their discovery, published in the latest Proceedings of the National Academy of Sciences, offers a deeper look into the cellular and behavioral implications of addiction.
Bradley Winters, lead author of the PNAS paper and a freshly minted WSU doctor of neuroscience, says he, his major advisor Yan Dong, and colleagues at WSU, the University of Pittsburgh and the European Neuroscience Institute focused on cells that produce a signaling molecule called cannabinoid receptor 1, or CB1. Its main function is regulating the communication between nerve cells related to the functions like memory, motor control, perception, mood and appetite. Those same functions are affected by THC, the cannabinoid in its namesake cannabis, or marijuana.
"These receptors are not here just to make marijuana fun,” says Winters. "Their main function is changes in how nerve cells communicate with each other.”
The researchers studied the CB1 cells by producing a line of mice in which the cells that make CB1 were labeled fluorescently. The researchers could then identify the cells and target them with glass pipettes 1/100th the width of a human hair and record electrical currents they use to communicate with other nerve cells.
The CB1 cells act like brakes, slowing down activity in a brain region called the nucleus accumbens, which governs emotion and motivation.
"Cocaine causes profound cellular changes in the nucleus accumbens, but no one has ever looked at this type of cell, and these cells are important because they help organize the output,” says Winters.
The researchers found that cocaine increases the excitability of the CB1 cells, in effect stepping on the brakes of emotion and motivation. When an addict is high on cocaine, the brakes are struggling to slow things down. The problem is, they stay on even when the cocaine has worn off.
"As you do cocaine, it speeds everything up, pushing you to a highly rewarding emotional state,” says Winters. "It is kind of like going down a steep hill so you have to start riding that brake really hard. But then after the cocaine wears off and the hill levels out, you’re still riding that brake just as hard. Now you’re going down a regular, low-grade hill but you’re going 2 mph because your foot is still jammed on the brake.”
The result is a drag on the emotions and motivation of an addict in withdrawal—a drag that could be linked to sluggish activation of the nucleus accumbens.
"That state is like, ‘I feel terrible and I don’t want to do anything,’” says Winters. "You have the high and the crashing low and this low that you feel is what brings you back to the drug because you want to feel better and the drug is the only thing you feel motivation for.”
(Source: news.wsu.edu)
Scientists find switch in the brain that could cause psychosis and addiction for cannabis users
(Source: Daily Mail)
Cannabis-based medications have been proved to relieve pain. This is the conclusion drawn by Franjo Grotenhermen and Kirsten Müller-Vahl in issue 29–30 of Deutsches Ärzteblatt International.
Cannabis medications can be used in patients whose symptoms are not adequately alleviated by conventional treatment. The indications are muscle spasms, nausea and vomiting as a result of chemotherapy, loss of appetite in HIV/Aids, and neuropathic pain.
The clinical effect of the various cannabis-based medications rests primarily on activation of endogenous cannabinoid receptors. Consumption of therapeutic amounts by adults does not lead to irreversible cognitive impairment. The risk is much greater, however, in children and adolescents (particularly before puberty), even at therapeutic doses.
Over 100 controlled trials of the effects of cannabinoids in various indications have been carried out since 1975. The positive results have led to official licensing of cannabis-based medications in many countries. In Germany, a cannabis extract was approved in 2011 for treatment of spasticity in multiple sclerosis. In June 2012 the Federal Joint Committee (the highest decision-making body for the joint self-government of physicians, dentists, hospitals and health insurance funds in Germany) pronounced that the cannabis extract showed a slight additional benefit for this indication and granted a temporary license until 2015.
U of S researchers have discovered the chemical pathway that Cannabis sativa uses to create bioactive compounds called cannabinoids, paving the way for the development of marijuana varieties to produce pharmaceuticals or cannabinoid-free industrial hemp.
"What cannabis has done is take a rare fatty acid with a simple, six-carbon chain and use it as a building block to make something chemically complex and pharmacologically active… Now that we know the pathway, we could develop ways to produce cannabinoids with yeast or other microorganisms, which could be a valuable alternative to chemical synthesis for producing cannabinoids for the pharmaceutical industry"
Read more: Cannabis ‘Pharma Factory’ Discovered