Category: Marijuana

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 recently published in the 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."

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Journal Reference:

1. Hickman et al. If cannabis caused schizophrenia-how many cannabis users may need to be prevented in order to prevent one case of schizophrenia? England and Wales calculations. Addiction, 2009; 104 (11): 1856 DOI: 10.1111/j.1360-0443.2009.02736.

New research by Weill Cornell Medical College researchers looks at the specific ways parents and peers influence teenagers to smoke, drink and use marijuana in combination. Among their findings: attitudes toward smoking influenced teenagers' use of multiple drugs (smoking, drinking and marijuana), and that this manifested itself differently in boys and girls.

For girls, friends were shown to be central. Ambivalent or permissive attitudes within their social group toward smoking were associated with poly-drug use — defined as two or more of the following behaviors: smoking, drinking and marijuana use. This wasn't the case with boys, whose poly-drug use was instead predicted by the extent to which they perceived smoking to be prevalent in their larger age group — not just among their friends.

"If a teenager feels smoking is socially acceptable and widely practiced, they are much more likely not only to smoke, but to also drink and possibly use marijuana," says lead author Dr. Jennifer A. Epstein, assistant professor of public health in the Division of Prevention and Health Behavior at Weill Cornell Medical College. "While the differences between how boys and girls are influenced by these social factors are subtle, they could help us develop new gender-specific educational tactics for preventing these behaviors."

The study also revealed several factors that were the same for boys and girls. When their friends drank alcohol or smoked or when their parents had permissive or ambivalent attitudes toward drinking, both teenage boys and girls were more likely to report poly-drug use. Other major variables included teenagers' inability to refuse drugs and achieve goals through their own efforts.

"A parent's opinion matters. Moms and dads are critical role models and should let their attitudes against drug use be known. It's also important to keep an eye on their child's social circle, since, especially for girls, it's their friends who are so central to influencing their behavior," says Dr. Epstein. "At the same time, parents can do things that reduce their child's risk for using drugs, such as teaching them to set goals and assert themselves."

Researchers analyzed confidential surveys taken by 2,400 sixth- and seventh-graders in inner-city schools in New York City. Questions dealt with substance use and several psychological factors that previous research suggests may be related to drug use. The majority of the schools serve youths from families with incomes averaged well below the federal poverty level.

The current study is one of the first to look at the relationships between smoking, drinking and marijuana use. The vast majority of research in this area has focused on a single substance in isolation, especially among white middle-class suburban populations. The importance of Dr. Epstein's approach is backed up by evidence suggesting that teenage poly-drug use is a significant risk factor for adult poly-drug use.

One implication of these findings, according to Dr. Epstein, is that "comprehensive prevention programs focusing on multiple gateway drugs (alcohol, cigarettes and marijuana) may prove to be more valuable than programs focusing on a single drug."

Study co-authors included Dr. Gilbert J. Botvin, chief of the Public Health Department's Division of Prevention and Health Behavior and professor of psychology in public health and psychology in psychiatry at Weill Cornell Medical College; and Margaret Doyle, formerly of Weill Cornell.

The study appears online in the July 1 issue of the Journal of Child and Adolescent Substance Abuse. The research was supported by a grant to Dr. Epstein from the National Institute on Drug Abuse (NIDA) to analyze data previously collected under a grant to Dr. Botvin from the National Cancer Institute (NCI). Some students in the NCI study received a prevention program called Life Skills Training (LST), while others did not. Dr. Botvin receives income from sales of the LST program. The data used by Dr. Epstein for the current NIDA study were from students who did not receive the LST program.

 In this week's PLoS Medicine, a team of researchers from Australia and the US, led by Louisa Degenhardt at the University of New South Wales, Sydney, makes the case for estimating the role that cannabis has worldwide as a risk factor for psychosis.

This estimation, says the team, will give an idea of how much impact cannabis has upon public health globally. The information in turn could be valuable for guiding health policymakers in deciding about health policies, services, and research.

The global impact of different diseases and risk factors upon population health is estimated by a high profile international research initiative called the Global Burden of Disease Project (http://www.globalburden.org/). Some of the risk factors that the project assesses are smoking, high blood pressure, obesity, and alcohol use. But in the past the project has not examined cannabis as a risk factor, say Degenhardt and colleagues, because of concerns that the evidence linking cannabis use to psychosis is too weak.

Degenhardt and colleagues examine the studies that have shown a link between using cannabis and developing psychotic illnesses such as schizophrenia. Based on the strength of this evidence, and on the fact that cannabis use is a potentially preventable exposure, they argue that the Global Burden of Disease Project should include cannabis as a risk factor. The authors review lines of evidence which suggest that cannabis may be a particular risk for those vulnerable to developing the illness. They propose to model multiple possible relationships between cannabis and psychosis, including models of poorer outcomes for those who have developed the disorder.

Researchers in Australia, for example, included cannabis in their national study of the impact of risk factors and diseases upon population health. In estimating the impact of cannabis, the researchers assumed that the evidence was good enough to show a link between cannabis use and psychosis, suicide, and car crashes. "Even after assuming that these relationships were causal," say Degenhardt and colleagues, "cannabis was not a major contributor to disease burden in Australia, accounting for 0.2% of all disease burden, which amounted to 10% of the total burden attributable to all illicit drugs."

"These estimates are important for public policy purposes," they say, "because failure to make them allows untested estimates to be offered in public policy debate."

The authors argue that if the international community does not estimate the global impact of cannabis use, there will be important consequences. "There will be a reduced public health, policy, or research imperative, since there will be no estimated burden."

On the other hand, they say that "if we do attempt to estimate burden, future work will examine the accuracy of our estimates and refine them as evidence accumulates. Debates may emerge and (hopefully) improvements made as new evidence supports or challenges the assumptions made.''

This work was given funding support from the Australian Government Department of Health and Ageing. LD is the recipient of an Australian National Health and Medical Research Council (NHMRC) Senior 

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Journal Reference:

1. Degenhardt L, Hall WD, Lynskey M, McGrath J, McLaren J, et al. Should Burden of Disease Estimates Include Cannabis Use as a Risk Factor for Psychosis?PLoS Med, 2009; 6(9): e1000133 DOI: 10.1371/journal.pmed.1000133

Scientists investigating the effects of cannabis on bone health have found that its impact varies dramatically with age.

The study has found that although cannabis could reduce bone strength in young people, it may protect against osteoporosis, a weakening of the bones, in later life.

The team at the University of Edinburgh has shown that a molecule found naturally in the body, which can be activated by cannabis – called the type 1 cannabinoid receptor (CB1) – is key to the development of osteoporosis.

It is known that when CB1 comes into contact with cannabis it has an impact on bone regeneration, but until now it was not clear whether the drug had a positive or negative effect.

Researchers, funded by the Arthritis Research Campaign, investigated this by studying mice that lacked the CB1 receptor. The scientists then used compounds – similar to those in cannabis – that activated the CB1 receptor. They found that compounds increased the rate at which bone tissue was destroyed in the young.

The study also showed, however, that the same compounds decreased bone loss in older mice and prevented the accumulation of fat in the bones, which is known to occur in humans with osteoporosis. The results are published in Cell Metabolism.

Osteoporosis affects up to 30 per cent of women and 12 per cent of men at some point in life.

Stuart Ralston, the Arthritis Research Campaign Professor of Rheumatology at the University of Edinburgh, who led the study, said: "This is an exciting step forward, but we must recognise that these are early results and more tests are needed on the effects of cannabis in humans to determine how the effects differ with age in people.

"We plan to conduct further trials soon and hope the results will help to deliver new treatments that will be of value in the fight against osteoporosis."

 Memory loss associated with marijuana use is caused by the drug’s interference with the brain’s natural protein synthesis machinery, according to a study published in Nature Neuroscience.

Though it has been documented that marijuana impairs memory, the precise mechanism for this memory impairment was previously unknown. Andrés Ozaita, of the Universitat Pompeu Fabra in Spain, along with colleagues in France and Germany, focused on THC, the main psychoactive chemical compound in marijuana, which acts on a specific class of receptors known as cannabinoid receptors. These receptors are known to affect the connection strength between neurons.

The scientists found that THC increases the activity of a pathway that promotes protein synthesis in the mouse brain. This transient increase of protein synthesis was mediated specifically by cannabinoid receptors expressed on the brain’s inhibitory neurons, and correlated with long-term memory deficits in mice. Interestingly, the authors also found that inhibition of this signaling pathway by rapamycin, an immunosuppressant drug used to prevent organ rejection following transplantation, prevents THC-induced amnesia in mice.

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Journal Reference:

1. Emma Puighermanal, Giovanni Marsicano, Arnau Busquets-Garcia, Beat Lutz, Rafael Maldonado & Andrés Ozaita. Cannabinoid modulation of hippocampal long-term memory is mediated by mTOR signaling. Nature Neuroscience, 2009; DOI: 10.1038/nn.2369

 Those in the United States living with HIV/AIDS are more likely to use marijuana than those in Kenya, South Africa or Puerto Rica to alleviate their symptoms, according to a new study published in Clinical Nursing Research, published by SAGE. Those who did use marijuana rate it as effective as prescribed or over the counter (OTC) medicines for the majority of common symptoms, once again raising the issue that therapeutic marijuana use merits further study and consideration among policy makers.

A significant percentage of those with HIV/AIDS use marijuana as a symptom management approach for anxiety, depression, fatigue, diarrhoea, nausea, and peripheral neuropathy. Members of the University of California, San Francisco (UCSF) International HIV/AIDS Nursing Research Network examined symptom management and quality of life experiences among those with HIV/AIDS in the US, Africa, and Puerto Rico, to gain a fuller picture of marijuana’s effectiveness and use in this population.

With data from a longitudinal, multi-country, multi-site, randomised control clinical trial, the researchers used four different evaluation tools to survey demographics, self-care management strategies for six common symptoms experienced by those living with HIV/AIDS, quality of life instrument and reasons for non-adherence to medications.

Either marijuana use for symptom management is vastly higher in the US, or participants elsewhere chose not to disclose that they use it: nine tenths of study participants who said they used marijuana live in the US. No African participants said they used it, and the remaining ten percent were from Puerto Rico.

The researchers found no differences between marijuana users and nonusers in age, race, and education level, income adequacy, having an AIDS diagnosis, taking ARV medications, or years on ARV medications. But the two groups did differ in that marijuana users had been HIV positive longer, and were more likely to have other medical conditions. Transgender participants were also more likely to use marijuana.

Participants using marijuana as a management strategy were spread fairly consistent across all six symptoms, ranging from a low of 20% for fatigue to a high of 27% for nausea. Prescribed medications were used by 45% of those with fatigue, ranging down to almost 18% of those with neuropathy.

The findings contained nuances when comparing marijuana to other medications. Those who used marijuana rated their anxiety significantly lower than those who did not, and women who used marijuana had more intense nausea symptoms. For those who use both marijuana and medications for symptom management, antidepressants were considered more effective than marijuana for anxiety and depression, but marijuana was rated more highly than anti-anxiety medications. Immodium was better for diarrhoea than marijuana, as were prescribed medications for fatigue. However, marijuana was perceived to be more effective than either prescribed or OTC medications for nausea and neuropathy. However, the differenced in perceived efficacy in all these results were slight.

As found in previous studies, those who used marijuana were less likely to comply with their regime of ARV medications. But perhaps counter-intuitively of the many reasons given for skipping pills, ‘forgetfulness’ was no different in this group than among those who did not use marijuana. Marijuana use is known to contribute to patients’ lack of compliance with ARV drugs, however those who use marijuana to target a particular symptom are actually more likely to stick closely to their ARV regimen too. The researchers point out that of those who used marijuana for their symptoms, it is not known whether they also used the drug for recreation. Patterns of how marijuana use interferes with patients’ adherence to medication regimens, along with other drugs, warrant further study.

The 775 participants were recruited from Kenya, South Africa, two sites in Puerto Rico, and ten sites in the United States. They had on average been diagnosed for a decade – the majority (70%) were taking anti-retroviral (ARV) medications and more than half had other medical conditions alongside HIV/AIDS. It is hard to pinpoint the marijuana use targeted to alleviate symptoms of those other illnesses as distinct from those relating solely to HIV/AIDS.

Data suggest that marijuana is a trigger among those susceptible to psychosis, and is also associated with the risk of suicidal thoughts. However it is not linked to an increased risk of lung cancer (over and above risks associated with smoking it along with tobacco).

The question of the use of marijuana for symptom management when legal drugs are available remains a practice and policy issue.

“Given that marijuana may have other pleasant side effects and may be less costly than prescribed or OTC drugs, is there a reason to make it available?” asks study leader Inge Corless.  “These are the political ramifications of our findings. Our data indicate that the use of marijuana merits further inquiry.”

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Journal Reference:

1. Corless et al. Marijuana Effectiveness as an HIV Self-Care Strategy. Clinical Nursing Research, 2009; 18 (2): 172 DOI: 10.1177/1054773809334958

When legal therapies let them down, some teens turn to cannabis. A new study, published in BioMed Central's open access journal Substance Abuse, Treatment, Prevention and Policy suggests that around a third of teens who smoke cannabis on a regular basis use it as a medication, rather than as a means of getting high.

Joan Bottorff worked with a team of researchers from the University of British Columbia, funded by the Canadian Institutes of Health Research, to conduct in-depth interviews with 63 cannabis-using adolescents. Of these, 20 claimed that they used cannabis to relieve or manage health problems. Bottorff said, "Marijuana is perceived by some teens to be the only available alternative for those experiencing difficult health problems when legitimate medical treatments have failed or when they lack access to appropriate health care".

The most common complaints recorded were emotional problems (including depression, anxiety and stress), sleep difficulties, problems with concentration and physical pain. The teens' experiences with the medical system were uniformly negative. The authors said, "Youth who reported they had been prescribed drugs such as Ritalin, Prozac or sleeping pills, stopped using them because they did not like how these drugs made them feel or found them ineffective. For these kids, the purpose of smoking marijuana was not specifically about getting high or stoned".

The authors emphasize that the unmet medical needs of these teens are of key importance in these findings. In contrast to the unpleasant side effects of prescribed medications and long, ineffective legal therapies, cannabis provided these adolescents with immediate relief for a variety of health concerns. Of course, cannabis isn't completely harmless, but as one of the respondents noted, "It's not good for you, but then again, neither is McDonald's and a lot of other things".

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Journal Reference:

1. Joan L Bottorff, Joy L Johnson, Barbara M Moffat and Tasmin Mulvogue. Relief oriented use of marijuana by teens. Substance Abuse Treatment, Prevention, and Policy, 2009;

U.S. and Brazilian scientists have discovered that the brain manufactures proteins that act like marijuana at specific receptors in the brain itself. This discovery may lead to new marijuana-like drugs for managing pain, stimulating appetite, and preventing marijuana abuse.

"Ideally, this development will lead to drugs that bind to and activate the THC receptor, but are devoid of the side effects that limit the usefulness of marijuana," said Lakshmi A. Devi of the Department of Pharmacology and Systems Therapeutics at Mount Sinai School of Medicine in New York and one of the senior researchers involved in the study. "It would be helpful to have a drug that activated or blocked the THC receptor, and our findings raise the possibility that this will lead to effective drugs with fewer side effects."

Scientists made their discovery by first extracting several small proteins, called peptides, from the brains of mice and determining their amino acid sequence. The extracted proteins were then compared with another peptide previously known to bind to, but not activate, the receptor (THC) affected by marijuana. Out of the extracted proteins, several not only bound to the brain's THC receptors, but activated them as well.

"The War on Drugs has hit very close to home," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "Last year, scientists found that our skin makes its own marijuana-like substance. Now, we see that our brain has been making proteins that act directly on the marijuana receptors in our head. The next step is for scientists to come up with new medicines that eliminate the nasty side of pot—a better joint, so to speak."

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Journal Reference:

1. Ivone Gomes, Julia S. Grushko, Urszula Golebiewska, Sascha Hoogendoorn, Achla Gupta, Andrea S. Heimann, Emer S. Ferro, Suzanne Scarlata, Lloyd D. Fricker, and Lakshmi A. Devi. Novel endogenous peptide agonists of cannabinoid receptors. FASEB J, DOI: 10.1096/fj.09-132142

— In earlier studies, researchers at Louisiana State University had found that estrogen – or more precisely, having ovaries – made adult rats exposed for the first time to THC, the primary ingredient in marijuana and hashish, less sensitive to THC's negative effects on tests of learning and memory.

A new study, reported at the Experimental Biology 2009 meeting in New Orleans, finds that when rats are first exposed to THC during the equivalent of adolescence, however, estrogen loses its protective effect. When these rats were again exposed to THC as adults, they performed more poorly on tests of learning and memory – diminished response time, increase in errors — than did similar rats that had not been exposed to THC when younger.

Dr. Peter Winsauer says these results indicate that the effects of THC and estrogen are different, depending on age, and, even more important, that THC use during adolescence, a critical period of development, has lasting effects on cognitive processes such as learning and memory. He believes that illicit use of THC during adolescence produces persistent changes in the brain that sensitize females to the negative effects of THC later in life.

Jessie Sutton, a research associate in the laboratory of Dr. Peter Winsauer, presented the findings April 19 at Experimental Biology 2009 as part of the scientific program of the American Society for Pharmacology and Experimental Therapeutics.

When a group of 12 female rats were 35 days old, an age equivalent to that of human teenagers about to undergo puberty, they began to be exposed to THC chronically for 40 days. Half had had their ovaries removed when they were 30 days old, half retained their ovaries. The day after the 12 females finished the period of exposure, they underwent an extensive training process consisting of pressing colored keys in a specific sequence in order to obtain food pellets. Then, as adults, they were challenged with different dosages of THC and tested with a learning task.

Also being trained in the learning and memory tasks was another group of 12 female rats, half with ovaries, half not, which had never been exposed to THC as adolescents.

All rats given THC did worse on tests than did similar animals receiving saline, and all showed a dose-dependent reaction: the more THC, the worse they performed. However, the rats that had been exposed to THC earlier in life performed significantly worse at the varying doses of THC than did the rats for which the adult exposure to THC was their first. This was true whether the animals had ovaries or not. Because of their earlier THC exposure, having ovaries did not bestow any benefit when exposed to THC as adults.

The study by Dr. Winsauer is funded by a grant from the National Institutes of Health. The grant focuses on the interaction between gonadal hormones and cannabinoid abuse and the subsequent effects this interaction has on development as it relates to learning and memory. The investigators suspect that this interaction could se the stage for a lifetime of mental health issues such as drug taking or drug abuse. Medical student Jerielle Hulst also was a co-author on the paper, in addition to Ms. Sutton and Dr. Winsauer.

 Patients with schizophrenia are able to correctly see through an illusion known as the ‘hollow mask’ illusion, probably because their brain disconnects ‘what the eyes see’ from what ‘the brain thinks it is seeing’, according to a joint UK and German study published in the journal NeuroImage. The findings shed light on why cannabis users may also be less deceived by the illusion whilst on the drug.

People with schizophrenia, a mental illness affecting about one per cent of the population, are known to be immune to certain vision illusions. The latest study confirms that patients with schizophrenia are not fooled by the ‘hollow mask’ illusion, and that this may relate to a difference in the way two parts of their brains communicate with each other – the ‘bottom-up’ process of collecting incoming visual information from the eyes, and the ‘top-down’ process of interpreting this information.

Illusions occur when the brain interprets incoming sensory information on the basis of its context and a person’s previous experience, so called top-down processing. Sometimes this process can mean that people’s perception of an object is quite different to reality – a phenomenon often exploited by magicians. The new study, by scientists at the Hannover Medical School in Germany and UCL Institute of Cognitive Neuroscience in the UK, suggests that patients with schizophrenia rely considerably less on top-down processing during perception.

The study used a variation on the three-dimensional ‘hollow mask’ illusion. In this illusion, a hollow mask of a face (pointing inwards, or concave) appears as a normal face (pointing outwards, or convex). During the experiment, 3D normal faces and hollow faces were shown to patients with schizophrenia and control volunteers while they lay inside an fMRI brain scanner, which monitored their brain responses.

As expected, all 16 control volunteers perceived the hollow mask as a normal face – mis-categorising the illusion faces 99 percent of the time. By contrast, all 13 patients with schizophrenia could routinely distinguish between hollow and normal faces, with an average of only six percent mis-categorisation errors for illusion faces.

The results of the brain imaging analysis suggested that in the healthy volunteers, connectivity between two parts of the brain, the parietal cortex involved in top-down control, particularly spatial attention, and the lateral occipital cortex involved in bottom-up processing of visual information, increased when the hollow faces were presented. In the patients with schizophrenia, this connectivity change did not occur. These results suggest that patients with schizophrenia have difficulty coordinating responses between different brain areas, also known as ‘dysconnectivity’, and that this may contribute to their immunity to visual illusions. The research group is now investigating dysconnectivity in schizophrenia further, which will hopefully advance our understanding of this disorder.

Danai Dima, Hannover Medical School, says: “The term ‘schizophrenia’ was coined almost a century ago to mean the splitting of different mental domains, but the idea has now shifted more towards connectivity between brain areas. The prevailing theory is that perception principally comprises three components: firstly, sensory input (bottom-up); secondly, the internal production of concepts (top-down); and thirdly, a control (a ‘censor’ component), which covers interaction between the two first components. Our study provides further evidence of ‘dysconnectivity’ between these components in the brains of people with schizophrenia.”

Dr Jonathan Roiser, UCL Institute of Cognitive Neuroscience, says: “Our findings also shed light on studies of visual illusions which have used psychomimetics – drugs that mimic the symptoms of psychosis. Studies using natural or synthetic tetrahydrocannabinol (THC), the ingredient of cannabis resin responsible for its psychotic-like effects, have found that people under the influence of cannabis are also less deceived by the hollow mask illusion. It may be that THC causes a temporary “disconnection” between brain areas, similar to that seen in patients with schizophrenia, though this hypothesis needs to be tested in further research.”

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Journal Reference:

1. Dima et al. Understanding why patients with schizophrenia do not perceive the hollow-mask illusion using dynamic causal modelling. NeuroImage, 2009; DOI: 10.1016/j.neuroimage.2009.03.033