Marijuana may lead non-smokers to cigarettes

Former smokers who use cannabis are also more likely to relapse, and current smokers who use cannabis are less likely to quit

March 27, 2018

Science Daily/Columbia University's Mailman School of Public Health

While cigarette smoking has long been on the decline, marijuana use is on the rise and, disproportionately, marijuana users also smoke cigarettes. A new study by researchers at Columbia University's Mailman School of Public Health and the City University of New York reports that cannabis use was associated with an increased initiation of cigarette smoking among non-cigarette smokers. They also found adults who smoke cigarettes and use cannabis are less likely to quit smoking cigarettes than those who do not use cannabis. Former smokers who use cannabis are also more likely to relapse to cigarette smoking. Results are published online in the Journal of Clinical Psychiatry.

Until now, little was known about the association between cannabis use and smoking cessation or relapse over time in the general adult population.

The analyses were based on data from the National Epidemiologic Survey on Alcohol and Related Conditions in 2001-2002 and 2004-2005, and responses from 34,639 individuals to questions about cannabis use and smoking status.

"Developing a better understanding of the relationship between marijuana use and cigarette use transitions is critical and timely as cigarette smoking remains the leading preventable cause of premature death and disease, and use of cannabis is on the rise in the U.S.," said Renee Goodwin, PhD, in the Department of Epidemiology at the Mailman School of Public Health, and senior author.

The study suggests that marijuana use -- even in the absence of cannabis use disorder (characterized by problematic use of cannabis due to impairment in functioning or difficulty quitting or cutting down on use) -- is associated with increased odds of smoking onset, relapse, and persistence. As cannabis use is much more common than cannabis use disorder, its potential impact on cigarette use in the general community may be greater than estimates based on studies of cannabis use disorder alone, according to the researchers.

An earlier study by Goodwin and colleagues showed that the use of cannabis by cigarette smokers had increased dramatically over the past two decades to the point where smokers are more than 5 times as likely as nonsmokers to use marijuana daily.

Goodwin advises that additional attention to cannabis use in tobacco control efforts and in clinical settings aimed at reducing cigarette smoking and smoking related negative consequences may be warranted. She also points out that understanding the potential links between cannabis use and cigarette initiation in youth is needed given that recent data suggest cannabis use is more common among adolescents than cigarette use.

https://www.sciencedaily.com/releases/2018/03/180327111032.htm

Non-psychoactive cannabis ingredient could help addicts stay clean

Preclinical study using rats shows that Cannabidiol can reduce the risk of relapse

March 23, 2018

Science Daily/Springer

A preclinical study in rats has shown that there might be value in using a non-psychoactive and non-addictive ingredient of the Cannabis sativa plant to reduce the risk of relapse among recovering drug and alcohol addicts. The study's findings inform the ongoing debate about the possible medical benefits of non-psychoactive cannabinoids, and the way that these may be used as therapeutics. So says Friedbert Weiss, leader of an investigative team at the Scripps Research Institute in La Jolla, California, in Neuropsychopharmacology published by Springer Nature.

Staying drug-free is a constant battle for abstinent addicts. This struggle is made more difficult when former-addicts find themselves in drug-related settings, experience stress or higher levels of anxiousness. Many struggle to control their impulses when offered an addictive drug like alcohol or cocaine.

Weiss and his research associate Gustavo Gonzalez-Cuevas set out to test the effect of Cannabidiol (CBD) on drug relapse in a rat model. CBD is the major non-psychoactive ingredient of Cannabis sativa, a plant that is used to make marijuana. CBD has been considered for some time as a possible treatment for various neurological and psychiatric disorders, and more recently also for the treatment of drug and alcohol addiction.

The researchers applied a gel containing CBD once per day for a week to the skin of the rats in the current study. These animals had a history of voluntary daily alcohol or cocaine self-administration, leading to addiction-like behaviour. Various tests were performed to see how they reacted to stressful and anxiety-provoking situations and behavior in tests of impulsivity, a psychological trait associated with drug addiction. The researchers reported that CBD effectively reduced relapse provoked by stress and drug cues; CBD also reduced anxiety and impulsivity in the drug-experienced rats.

Further studies showed that CBD was completely cleared from the brain and plasma of the rats three days after the therapy was completed. Quite unexpectedly though, five months later, experimental animals that had been treated with CBD still showed a reduced relapse induced by stress or drug cues. The authors of the study believe that insight into the mechanisms by which CBD exerts these effects in future research may open new vistas for the pharmacotherapeutic prevention of relapse to drug use.

"The efficacy of the cannabinoid [CBD] to reduce reinstatement in rats with both alcohol and cocaine -- and, as previously reported, heroin -- histories predicts therapeutic potential for addiction treatment across several classes of abused drugs," says Weiss. "The results provide proof of principle supporting the potential of CBD in relapse prevention along two dimensions: beneficial actions across several vulnerability states, and long-lasting effects with only brief treatment." He goes on to say that "Drug addicts enter relapse vulnerability states for multiple reasons. Therefore, effects such as these observed with CBD that concurrently ameliorate several of these are likely to be more effective in preventing relapse than treatments targeting only a single state."

https://www.sciencedaily.com/releases/2018/03/180323104821.htm

Millions of Americans seek and find illicit marijuana online

A new study explores the online marketplace for mail-order marijuana in the United States

March 22, 2018

Science Daily/San Diego State University

Researchers found marijuana shopping searches nearly tripled in the United States from 2005 to 2017, peaking between 1.4 and 2.4 million searches each month. Mail-order marijuana retailers occupied half of the first-page results, and three out of every four searches resulted in a mail-order marijuana retailer as the very first suggested link.

These days, Americans shop for nearly everything online -- including marijuana. That's the conclusion of a new study published today in the American Journal of Preventive Medicine led by San Diego State University Graduate School of Public Health associate research professor John W. Ayers. Millions are searching for and finding online marijuana retailers across the country, the researchers find.

The team monitored Google searches in the United States between January 2005 and June 2017, including all searches with the terms marijuana, weed, pot, or cannabis combined with the terms buy, shop, or order (for example., "buy marijuana"). They omitted similar but irrelevant searches like "buy weed killer." The team then replicated the relevant searches and checked to see whether the resulting websites advertised mail-order marijuana.

"By studying anonymized, aggregate Internet searches and search results, we were able to directly observe the online marijuana marketplace," said study coauthor Mark Dredze, the John C. Malone Associate Professor of Computer Science at Johns Hopkins University.

The team found marijuana shopping searches nearly tripled in the United States from 2005 to 2017, peaking between 1.4 and 2.4 million searches each month.

Marijuana shopping searches were highest in Washington, Oregon, Colorado, and Nevada. However, the annual growth rate in searching for these terms increased in all but two states, Alabama and Mississippi, suggesting demand is accelerating across the nation. (The six least populated states were excluded from the study.)

Forty-one percent of all search results linked to retailers advertising mail-order marijuana, promising delivery using a variety of methods including the United State Postal Service, commercial parcel companies such as UPS, or private courier. Moreover, mail-order marijuana retailers occupied half of the first-page results, and three out of every four searches resulted in a mail-order marijuana retailer as the very first suggested link.

"Anyone, including teenagers, can search for and buy marijuana from their smartphone regardless of what state they live in," Ayers said.

Such online sales of marijuana are prohibited in the United States, even in states that have legalized or partially legalized the drug, "but clearly these regulations are failing," said coauthor Eric Leas, a research fellow at Stanford University.

Public health leaders must immediately take action to curtail online marijuana sales, urged Theodore Caputi, the study's lead author and George J. Mitchell Scholar at University College Cork.

"Children could obtain marijuana online without safeguards to protect them," he said. "States that have legalized marijuana might not be able to collect taxes to offset the public health costs of legal marijuana from online retailers, and the instant online availability of marijuana could increase marijuana dependence among all age groups."

One solution could be for public safety officials to work with internet service providers to purge marijuana retailers from major search engine results, said Ayers. Such a move would "effectively close off illicit retailers from consumers," he said.

https://www.sciencedaily.com/releases/2018/03/180322103233.htm

LSD blurs boundaries between the experience of self and other

March 19, 2018

Science Daily/University of Zurich

LSD reduces the borders between the experience of our own self and others, and thereby affects social interactions. Researchers at the University of Zurich have now found that the serotonin 2A receptor in the human brain is critically involved in these intertwined psychological mechanisms. This knowledge could help develop new therapies for psychiatric disorders such as schizophrenia or depression.

Virtually all mental health disorders come with difficulties in interpersonal relations that in the long run negatively affect the progression of the disease. The associated health and social restrictions can only be marginally improved by current forms of therapy. One of the reasons for this is that there has been very little research into the basic neurobiological principles and in particular the neurochemical mechanisms of these kinds of disorders. A further symptom of various psychiatric disorders is distortions of self-experience. People suffering from mental disorders often show either an inflated or weakened sense of self.

Researchers at the University Hospital of Psychiatry Zurich have now investigated the links between changes in the sense of self and changes in social interaction, and the pharmacological mechanisms that play a role in these processes.

LSD impacts self-boundaries

"LSD blurs the boundaries between one's own self and others during a social interactions ," explains Katrin Preller. She led the research team of the Neuropsychology and Brain Imaging group together with Prof. Franz Vollenweider and cooperated with the Max Planck Institute of Psychiatry in Munich on the study. While lying in an MRI scanner, study participants communicated with a virtual avatar by means of eye movements after having been administered a placebo, LSD, or LSD in combination with ketanserin.

Changes in social interaction

"This allowed us to show that brain regions which are important for distinguishing between self and others were less active under the influence of LSD," says Preller. "And this also changed social interactions." The researchers were also able to show that the LSD-induced changes were blocked by ketanserin indicating that the serotonin 2A receptor (5-HT2A receptor) plays a critical role in this mechanism.

Approaches for new drugs

These findings demonstrate that self-experience and social interaction are closely linked. Varying impairments of these intertwined processes could be the result of an impaired transfer of information mediated by the 5-HT2A receptor system. This could be important for the development of new pharmacological therapies. For example, blocking this receptor in patients suffering from an incoherent sense of self such as schizophrenia could improve their symptoms as well as their social abilities. On the other hand, stimulating this receptor could help patients who suffer from an increased self-focus, as is the case with depression, for example.

https://www.sciencedaily.com/releases/2018/03/180319155948.htm

Coffee affects cannabis and steroid systems

March 15, 2018

Science Daily/Northwestern University

Coffee affects your metabolism in dozens of other ways besides waking you up, including your metabolism of neurotransmitters typically linked to cannabis, a study reports. The neurotransmitters related to the endocannabinoid system -- the same ones affected by cannabis -- decreased after drinking four to eight cups of coffee in a day. That's the opposite of what occurs after someone uses cannabis. The study also gives possible insight in the cause of munchies. Coffee may also increase the elimination of steroids.

It's well known that a morning cup of joe jolts you awake. But scientists have discovered coffee affects your metabolism in dozens of other ways, including your metabolism of steroids and the neurotransmitters typically linked to cannabis, reports a new study from Northwestern Medicine.

In a study of coffee consumption, Northwestern scientists were surprised to discover coffee changed many more metabolites in the blood than previously known. Metabolites are chemicals in the blood that change after we eat and drink or for a variety of other reasons.

The neurotransmitters related to the endocannabinoid system -- the same ones affected by cannabis -- decreased after drinking four to eight cups of coffee in a day. That's the opposite of what occurs after someone uses cannabis. Neurotransmitters are the chemicals that deliver messages between nerve cells.

Cannabinoids are the chemicals that give the cannabis plant its medical and recreational properties. The body also naturally produces endocannabinoids, which mimic cannabinoid activity.

In addition, certain metabolites related to the androsteroid system increased after drinking four to eight cups of coffee in a day, which suggests coffee might facilitate the excretion or elimination of steroids. Because the steroid pathway is a focus for certain diseases including cancers, coffee may have an effect on these diseases as well.

"These are entirely new pathways by which coffee might affect health," said lead author Marilyn Cornelis, assistant professor of preventive medicine at Northwestern University Feinberg School of Medicine. "Now we want to delve deeper and study how these changes affect the body."

Little is known about how coffee directly impacts health. In the new study, Northwestern scientists applied advanced technology that enabled them to measure hundreds of metabolites in human blood samples from a coffee trial for the first time. The study generates new hypotheses about coffee's link to health and new directions for coffee research.

The paper will be published March 15 in the Journal of Internal Medicine.

Drinking lots of coffee for science

 In the three-month trial based in Finland, 47 people abstained from coffee for one month, consumed four cups a day for the second month and eight cups a day for the third month. Cornelis and colleagues used advanced profiling techniques to examine more than 800 metabolites in the blood collected after each stage of the study.

Blood metabolites of the endocannabinoid system decreased with coffee consumption, particularly with eight cups per day, the study found.

The endocannabinoid metabolic pathway is an important regulator of our stress response, Cornelis said, and some endocannabinoids decrease in the presence of chronic stress.

"The increased coffee consumption over the two-month span of the trial may have created enough stress to trigger a decrease in metabolites in this system," she said. "It could be our bodies' adaptation to try to get stress levels back to equilibrium."

The endocannabinoid system also regulates a wide range of functions: cognition, blood pressure, immunity, addiction, sleep, appetite, energy and glucose metabolism.

"The endocannabinoid pathways might impact eating behaviors," suggested Cornelis, "the classic case being the link between cannabis use and the munchies."

Coffee also has been linked to aiding weight management and reducing risk of type 2 diabetes.

"This is often thought to be due to caffeine's ability to boost fat metabolism or the glucose-regulating effects of polyphenols (plant-derived chemicals)," Cornelis said. "Our new findings linking coffee to endocannabinoids offer alternative explanations worthy of further study."

It's not known if caffeine or other substances in coffee trigger the change in metabolites.

Although Cornelis studies the effects of coffee, she didn't drink it growing up in Toronto or later living in Boston.

"I didn't like the taste of it," Cornelis said. But when she moved to join Northwestern in 2014, she began to enjoy several cups a day. "Maybe it's the Chicago water," she mused, "but I do have to add cream and sweetener."

The study was supported by the American Diabetes Association, the German Federal Ministry of Health and other sources.

https://www.sciencedaily.com/releases/2018/03/180315091253.htm

How does resolving cannabis problems differ from problems with alcohol or other drugs?

Those resolving cannabis problems do so at younger ages, with less assistance than those resolving other substance-use problems

March 5, 2018

Science Daily/Massachusetts General Hospital

Individuals who report having resolved a problem with cannabis use appear to have done so at younger ages than those who resolved problems with alcohol or other drugs, report investigators from the Recovery Research Institute at Massachusetts General Hospital (MGH). While study participants also were much less likely to use any formal sources of assistance or support in resolving problems with cannabis than those whose problems were with other substances, that finding was less common in those who resolved a cannabis problem more recently, which may reflect the increased availability and potency of cannabis in recent years.

"Very little has been known about recovery from cannabis use problems, and this is the first study to examine that on a national basis," says John Kelly, PhD, director of the Recovery Research Institute, who led the study published in the March issue of the International Journal of Drug Policy. "Compared with alcohol and other drugs, cannabis holds a unique place in federal and state policies -- continuing to be illegal federally but with medical and recreational use legalized at the state level. Due to this increased availability and the proliferation of a for-profit cannabis industry, understanding the needs of individuals with cannabis problems will be increasingly important."

The current study analyzes data from the National Recovery Survey, conducted by Kelly's team. A nationally representative sample of nearly 40,000 U.S. adults who participate in the Knowledge Panel of the market research company GfK were asked "Did you used to have a problem with drugs or alcohol, but no longer do?" Of more than 25,000 respondents, a little over 2,000 indicated they had resolved such a problem and were sent a link to the full study survey, which asked a variety of questions such as the specific problem substances and details regarding how and when they had resolved their problem. As reported in a paper published last year in Drug and Alcohol Dependence, more than half of all respondents reported resolving their problem with no assistance.

The current study focused on participants who indicated having resolved a cannabis problem, who made up around 11 percent of respondents, reflecting around 2.4 million U.S. adults. Compared with those resolving problems with alcohol or other drugs, those resolving cannabis problems reported starting regular use -- once a week or more -- at younger ages but also resolving the problem at younger ages, an average of 29 compared with 38 for alcohol and 33 for other drugs.

Cannabis-primary respondents were even less likely to have used formal treatment or support services than were those resolving problems with illicit drugs -- 18 percent versus 42 percent -- but were more likely to have participated in drug courts than those who had resolved alcohol problems -- 24 percent versus 8 percent. Cannabis users also reported "addiction careers" -- the years between their first use and problem resolution -- that were significantly shorter than those of the alcohol group -- 12 years versus 18 years, which may reflect the greater physical and mental health impairment associated with alcohol and the continuing illegality of cannabis.

"We did expect that the cannabis-primary individuals would be less likely than the illicit drug group to use formal treatment; but very little is known about the magnitude or nature of such differences, " says Kelly. "That may be due to fewer physiological and other life consequences compared with the impairments caused by drugs like alcohol or opioids. For example, while there is a documented withdrawal syndrome related to cannabis dependence, withdrawal from opioids or alcohol is notoriously more severe and often requires medically-managed detoxification."

Given the increased levels of THC -- the psychoactive component of cannabis -- in products available today, the team investigated whether the use of formal support services had changed over time. Indeed, they found that utilization of outpatient services was more common in those resolving their problems within the past 5.5 years, while use of inpatient services was actually more common in those who resolved their problem around 20 years previously.

The Spallin Associate Professor of Psychiatry in Addiction Medicine at Harvard Medical School, Kelly explains that brain changes caused by the higher THC content in marijuana today -- 15 to 20 percent, versus 1 to 5 percent 10 or 20 years ago -- could make it harder for individuals using this more potent cannabis to stop on their own. While inpatient treatment was considered first-line treatment for addiction two decades ago, it is much less common today, and insurance companies often require attendance at outpatient treatment first.

"In the current landscape of higher potency cannabis and the greater availability and variety of cannabis products, it is more likely that individuals will need to seek help in resolving problems with cannabis," he says. "Now it will be important to determine whether the recovery timeline from high-potency cannabis will be different and more challenging. And since so many of the cannabis-primary group resolved their problem without either formal treatment or mutual help organizations like Marijuana Anonymous or Narcotics Anonymous, it will be critical to understand the changes in their lives that helped make recovery possible."

https://www.sciencedaily.com/releases/2018/03/180305160204.htm

No link between current or previous marijuana use and kidney disease

March 1, 2018

Science Daily/Elsevier

Marijuana is the most commonly used illicit drug in the United States, with an increasing trend of use among middle-aged and older individuals. However, potential health effects of marijuana use in the general population have not been extensively studied, and little is known about potential effects on kidney function. According to a new cross-sectional study of adults aged 18-59 in the US, there is no association between current or previous marijuana use and kidney function. The results are reported in The American Journal of Medicine.

Marijuana use among people aged 12 years or older in the US has increased from 7.5 percent to 8.3 percent from 2013 to 2015. From 2002 to 2015, the increase in percentage of adult users 26 years or older is even greater than the increase among those aged 18 to 25 years during the same period. Health effects of acute and chronic marijuana use remain controversial and the US Food and Drug Administration (FDA) has not officially approved marijuana as a medicine, nor has it been extensively studied within the general population. Little is known about its potential effects on kidney function.

Investigators analyzed a nationally representative sample of nearly 14,000 predominantly healthy adults aged 18-59 years living in the US who participated in the National Health and Nutrition Examination Survey from 2007 to 2014. Participants used an audio computer-assisted self-interview system to answer several questions. Questionnaires were administered at a mobile examination center. Participants were classified as never users, past users, and current users of marijuana. Nearly 5,500 users said they had smoked marijuana at least once, but not in the past 30 days, and over 2,000 users had smoked marijuana at least once within the last 30 days. Serum creatinine concentration was measured after blood collection at the mobile examination center.

The investigators did not find any association between current or past marijuana use and impaired kidney function. There was no statistically significant association between history of marijuana use and the likelihood of developing stage 2 or greater chronic kidney disease. Likewise, they did not observe a statistically significant association between the history of marijuana use and the incidence of microalbuminuria, a moderate increase in the level of urine albumin and a marker of kidney disease.

"Our research provides some reassuring evidence suggesting that there is no determinantal effect of infrequent, relatively light use of marijuana on kidney function among healthy adults under age 60," commented lead investigator Murray A. Mittleman, MD, DrPH, Professor of Epidemiology at the Harvard T.H. Chan School of Public Health, Associate Professor of Medicine at Harvard Medical School, and a practicing preventive cardiologist at Beth Israel Deaconess Medical Center. "However, our research does not address heavy users, the elderly, or those with preexisting chronic kidney disease. Research is needed to evaluate the impact of marijuana use in adults 60 and over, and among those with existing or at risk of developing kidney disease."

Under US Federal law it is illegal to possess, use, buy, sell, or cultivate marijuana, although it is legal in some US states. As of January 2018, medical marijuana is legal in 30 states and the District of Columbia (DC); in eight states and DC, it is also legal for recreational use. Other states have taken steps to decriminalize marijuana to some degree.

https://www.sciencedaily.com/releases/2018/03/180301125051.htm

Why are some mushrooms 'magic?'

Study offers evolutionary explanation, could pave way for neurological treatments

February 27, 2018

Science Daily/Ohio State University

The work helps explain a biological mystery and could open scientific doors to studies of novel treatments for neurological disease, said lead researcher Jason Slot, an assistant professor of fungal evolutionary genomics at The Ohio State University.

Mushrooms that contain the brain-altering compound psilocybin vary widely in terms of their biological lineage and, on the surface, don't appear to have a whole lot in common, he said.

From an evolutionary biology perspective, that is intriguing and points to a phenomenon in which genetic material hops from one species to another -- a process called horizontal gene transfer, Slot said. When it happens in nature, it's typically in response to stressors or opportunities in the environment.

He and his co-authors examined three species of psychedelic mushrooms -- and related fungi that don't cause hallucinations -- and found a cluster of five genes that seem to explain what the psychedelic mushrooms have in common.

"But our main question is, 'How did it evolve?'" Slot said. "What is the role of psilocybin in nature?"

Slot and his co-authors found an evolutionary clue to why the mushrooms gained the ability to send human users into a state of altered consciousness. The genes responsible for making psilocybin appear to have been exchanged in an environment with a lot of fungus-eating insects, namely animal manure.

Psilocybin allows fungi to interfere with a neurotransmitter in humans and also insects, which are probably their bigger foe. In flies, suppression of this neurotransmitter is known to decrease appetite.

"We speculate that mushrooms evolved to be hallucinogenic because it lowered the chances of the fungi getting eaten by insects," Slot said. The study appears online in the journal Evolution Letters.

"The psilocybin probably doesn't just poison predators or taste bad. These mushrooms are altering the insects' 'mind' -- if they have minds -- to meet their own needs."

And the reason that unrelated species have the same genetic protection probably comes down to the fact that they commonly grow in the same insect-rich mediums: animal feces and rotten wood.

This work could guide medical science by pointing researchers in the direction of other molecules that could be used to treat disorders of the brain, Slot said.

Psilocybin has been studied for the treatment of a variety of mental disorders, including treatment-resistant depression, addiction and end-of-life anxiety. A handful of researchers in the U.S. are looking at potential treatment applications, and much of the work is happening abroad. Strict drug laws have delayed those types of studies for decades, Slot said.

https://www.sciencedaily.com/releases/2018/02/180227115548.htm

New guideline warns pain benefits of medical cannabis overstated

University of Alberta led guideline warns health risks may outweigh benefits, provides guidance on when (and when not to) prescribe.

February 15, 2018

Science Daily/University of Alberta Faculty of Medicine & Dentistry

A new medical guideline published today suggests Canada's family physicians should take a sober second thought before prescribing medical cannabis to most patients.

Published in Canadian Family Physician, "Simplified Guideline for Prescribing Medical Cannabinoids in Primary Care" states there is limited evidence to support the reputed benefits of medical marijuana for many conditions, and what benefits do exist may be balanced out or even outweighed by the harms.

"While enthusiasm for medical marijuana is very strong among some people, good-quality research has not caught up," said Mike Allan, director of evidence-based medicine at the University of Alberta and project lead for the guideline.

The guideline was created after an in-depth review of clinical trials involving medical cannabis and will be distributed to roughly 30,000 clinicians across Canada. It was overseen by a committee of 10 individuals, supported by 10 other contributors, and peer reviewed by 40 others, each a mixture of doctors, pharmacists, nurse practitioners, nurses and patients. The review examined cannabinoids for the treatment of pain, spasticity, nausea and vomiting, as well as their side-effects and harms.

Researchers found that in most cases the number of randomized studies involving medical cannabis is extremely limited or entirely absent. The size and duration of the studies that do exist are also very narrow in scope.

"In general we're talking about one study, and often very poorly done," said Allan. "For example, there are no studies for the treatment of depression. For anxiety, there is one study of 24 patients with social anxiety in which half received a single dose of cannabis derivative and scored their anxiety doing a simulated presentation. This is hardly adequate to determine if lifelong treatment of conditions like general anxiety disorders is reasonable."

According to the guideline, there is acceptable research for the use of medical cannabinoids to treat a handful of very specific medical conditions. They include chronic neuropathic (nerve) pain, palliative cancer pain, spasticity associated with multiple sclerosis or spinal cord injury, and nausea and vomiting from chemotherapy. Even in those specific cases, the benefits were found to be generally minor.

For nerve pain, 30 per cent of patients given a placebo saw a moderate improvement in their pain while 39 per cent experienced the same effect while on medical cannabinoids. In patients with muscle spasticity, 25 per cent of those taking a placebo saw a moderate improvement compared to 35 per cent on medical cannabis. The use of medical cannabis was best supported in its use for chemotherapy patients experiencing nausea and vomiting. Just under half of patients using cannabinoids for their symptoms had an absence of nausea and vomiting compared to 13 per cent on placebo.

"Medical cannabinoids should normally only be considered in the small handful of conditions with adequate evidence and only after a patient has tried of number of standard therapies," said Allan. "Given the inconsistent nature of medical marijuana dosing and possible risks of smoking, we also recommend that pharmaceutical cannabinoids be tried first before smoked medical marijuana."

While the researchers found evidence supporting the use of medical cannabinoids to be limited, side-effects were both common and consistent. About 11 per cent of patients were not able to tolerate medical cannabinoids, versus three per cent of those taking placebo. Common effects included sedation (50 per cent versus 30 per cent), dizziness (32 per cent versus 11 per cent) and confusion (nine per cent versus two per cent).

"This guideline may be unsatisfactory for some, particularly those with polarized views regarding medical cannabinoids," said Allan.

He added that those who oppose the use of cannabinoids for medical therapy may be disappointed that the guideline considers medical cannabinoids in specific cases. Others, who feel cannabinoids are highly effective and don't pose any risk, may be frustrated that the guideline doesn't advocate their use sooner or for a broader range of conditions.

"Better research is definitely needed -- randomized control trials that follow a large number of patients for longer periods of time. If we had that, it could change how we approach this issue and help guide our recommendations."

https://www.sciencedaily.com/releases/2018/02/180215153923.htm

Risk of fatal traffic crash higher during annual 4/20 cannabis celebration

Over 25 years, 142 additional deaths

February 12, 2018

Science Daily/University of British Columbia

US drivers are more likely to be in a fatal traffic crash during the annual April 20 cannabis celebration. Twenty-five years' worth of data from the National Highway Traffic Safety Administration shows the number of drivers involved in fatal crashes after 4:20 pm on April 20 is higher compared to the same time intervals on control days one week earlier and one week later.

"One-fifth of Americans now live in states that have legalized recreational cannabis, and legalization is set to occur for all Canadians in July 2018," said lead researcher Dr. John Staples, a clinical assistant professor of medicine and scientist at UBC's Centre for Health Evaluation and Outcome Sciences. "We hope that legalization doesn't lead to more people driving while high."

Along with University of Toronto professor Dr. Donald Redelmeier, Staples examined 25 years of National Highway Traffic Safety Administration data on all fatal traffic crashes in the United States. They compared the number of drivers involved in fatal crashes after 4:20 p.m. on April 20 with the number of drivers involved in fatal crashes during the same time intervals on control days one week earlier and one week later.

The investigators found that April 20 was associated with a 12 per cent increase in the risk of a fatal traffic crash. Among drivers younger than 21 years of age, the risk was 38 per cent higher than on control days. The overall increase amounted to 142 additional deaths over the 25-year study period.

Since the 4/20 holiday was first popularized in 1991, annual events in Denver, San Francisco, Vancouver, and other cities have grown to include tens of thousands of attendees. It isn't known how commonly drivers get behind the wheel while high on 4/20, but a 2011 study of U.S. college freshmen found 44 per cent of cannabis users drove soon after consuming marijuana in the month prior to the survey. Only half of cannabis users in the 2017 Canadian Cannabis Survey thought cannabis use affected driving.

"Assuming fewer than 10 per cent of Americans drive while high on April 20, our results suggest that drug use at 4/20 celebrations more than doubles the risk of a fatal crash," said Redelmeier.

Staples and Redelmeier hope that authorities will respond to these results by encouraging safer 4/20 travel options, including public transit, rideshares, taxis and designated drivers. The investigators also note that cannabis retailers and 4/20 event organizers have an opportunity to serve their customers and save lives by warning users not to drive while high.

As Canada and other places move toward legalization, Staples says it's also important to employ multiple strategies to reduce driving under the influence of drugs throughout the year.

"Driving is a potentially dangerous activity," Staples said. "Improving road safety requires both policymakers and drivers to make smart decisions. If you're going to get behind the wheel, buckle up, put the phone away, don't speed, stay sober and don't drive high."

The study was published today in JAMA Internal Medicine. The research was supported by Vancouver Coastal Health Research Institute, the Canadian Institutes for Health Research, and the Canada Research Chair in Medical Decision Science.

https://www.sciencedaily.com/releases/2018/02/180212112005.htm

New cannabis products highly potent, pose mental health risks

Cannabis can activate latent psychiatric issues, physician counsel is recommended before use, according to comprehensive research

February 12, 2018

Science Daily/American Osteopathic Association

With states rapidly legalizing cannabis for medicinal and recreational use, physicians will be increasingly pressed to counsel patients on their frequency of use and dosage, as well as associated risks.

Schizophrenia and other psychiatric issues may be triggered by marijuana use, according to a research analysis in the Journal of the American Osteopathic Association.

With states rapidly legalizing cannabis for medicinal and recreational use, physicians will be increasingly pressed to counsel patients on their frequency of use and dosage, as well as associated risks. The special report in the JAOA aggregates what is known to help physicians give the best evidence-based recommendations.

"We have a special concern for young people in their late teens and early twenties, whose brains are still developing," says Jeramy Peters, DO, lead study author and psychiatrist at Oregon Health and Science University in Portland.

Dr. Peters adds that while there is no simple way to predict which young people might develop mental health issues as a result of marijuana use, a family history of mental illness could suggest potential risk.

"Pediatricians should be aware of this, especially for patients who have exhibited symptoms of anxiety and depression, and be willing to have candid discussions about cannabis," says Dr. Peters.

Some longer-term effects associated with cannabis use include impaired memory and concentration, and decreased motivation. Researchers say when cannabis use starts to impair an individual's health status or social or occupational functioning, he or she should be counseled to stop using cannabis or referred to substance abuse treatment providers.

Patients without mental health or substance abuse problems, who use cannabis recreationally or medicinally, can still benefit from physician counsel.

Know your cannabinoid

The main pharmacologically active chemicals in cannabis are the cannabinoids Tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is responsible for the "high" people experience and there is moderate-quality evidence that THC may help chronic neuropathic or cancer pain. However, it has also been shown to induce symptoms of psychosis among healthy study volunteers and is thought to be a risk factor in developing psychosis.

Conversely, CBD is theorized to have antipsychotic and anxiolytic properties. Currently, CBD is being studied for its possible antiseizure and anti-inflammatory properties.

Many new products contain varied ratios of THC and CBD in order to create specific euphoric and medicinal effects. Researchers recommend physicians be aware of what products their patients are using -- as well as how much and how often -- in order to best advise them on dosing and risks.

"It is very difficult to tell someone what effect they can expect without knowing the specifics of the product," says Walter Prozialeck, Ph.D., professor and chair of the Department of Pharmacology, Chicago College of Osteopathic Medicine at Midwestern University. "How much THC is in the product, how it's consumed -- and, of course, the individual's physiology -- all play a role in determining their experience."

Dosing not always straightforward

The strength of cannabis has been increasing over the past half century. During the 1960s, cannabis was typically about 1% to 5% THC by weight. Many strains available today range from 15% to 25% THC by weight, with some strains reaching 30% or higher. When smoked, about 25% of the cannabinoids present in herbal cannabis get absorbed.

However, when inhaling cannabis via a vaporizer, the user absorbs up to 33% of the total cannabinoids. People who smoke or vape also experience the effects quickly, with intoxication setting in within 2 minutes and lasting 2-4 hours. The near immediate onset of the high allows users to titrate their dosing more effectively.

By comparison, when cannabis products are ingested orally, THC is absorbed inconsistently. Users typically experience the effects of THC about 2 to 4 hours after ingestion, and its effects last for 6 to 8 hours. Persons who ingest cannabis products often experience a more intense and longer-lasting effect. Given the significant delay of intoxication, it is much easier to overdose and experience negative effects.

"The best advice we can give is start low and go slow," says Prozialeck. He adds that more research is needed from the medical community to create specific protocols that physicians can use to better counsel patients.

https://www.sciencedaily.com/releases/2018/02/180212125804.htm

Study questions link between medical marijuana and fewer opioid deaths

Association appears to be changing as medical marijuana laws and opioid epidemic change

February 7, 2018

Science Daily/RAND Corporation

The association between medical marijuana and lower levels of opioid overdose deaths -- identified previously in several studies -- is more complex than previously described and appears to be changing as both medical marijuana laws and the opioid crisis evolve, according to a new RAND Corporation study.

The report -- the most-detailed examination of medical marijuana and opioid deaths conducted to date -- found that legalizing medical marijuana was associated with lower levels of opioid deaths only in states that had provisions for dispensaries that made medical marijuana easily available to patients. Opioid death rates were not lower in states that just provided legal protections to patients and caregivers, allowing them to grow their own marijuana.

In addition, the association between medical marijuana dispensaries and fewer opioid deaths appears to have declined sharply after 2010, when states began to tighten requirements on sales by dispensaries.

"Our findings are consistent with previous studies showing an association between the legalization of medical marijuana and lower deaths from overdoses of opioids," said Rosalie Liccardo Pacula, co-author of the study and co-director of the RAND Drug Policy Research Center.

"However, our findings show that the mechanism for this was loosely regulated medical marijuana dispensaries, and that the association between these laws and opioid mortality has declined over time as state laws have more tightly regulated medical dispensaries and the opioid crisis shifted from prescription opioids to heroin and fentanyl," Pacula said. "This is a sign that medical marijuana, by itself, will not be the solution to the nation's opioid crisis today."

The study was published online by the Journal of Health Economics.

Researchers from RAND and the University of California, Irvine analyzed information about treatment admissions for addiction to pain medications from 1999 to 2012 and state-level overdose deaths from opioids from 1999 to 2013. They also identified state laws legalizing medical marijuana, examining provisions such as whether the regulations made marijuana easily accessible to patients by allowing dispensaries.

When the researchers narrowly focused on the time period from 1999 to 2010 and replicated a model used by other researchers, they obtained results similar to those previously published, showing an approximately 20 percent decline in opioid overdose deaths associated with the passage of any state medical marijuana law. However, these general findings were driven by states that had laws allowing for loosely regulated marijuana dispensary systems.

When researchers extended their analysis through 2013, they found that the association between having any medical marijuana law and lower rates of opioid deaths completely disappeared. Moreover, the association between states with medical marijuana dispensaries and opioid mortality fell substantially as well.

The researchers provide two explanations for the decline in the association between medical marijuana dispensaries and opioid harm. First, states that more recently adopted laws with medical marijuana dispensaries more tightly regulated them, in response to a U.S. Justice Department memo saying it would not challenge state-level medical marijuana laws so long as dispensary sales were in full compliance with state regulations. Second, beginning in 2010, the primary driver of the opioid crisis and related deaths became illicit opioids, mainly heroin and then fentanyl, not prescription opioids.

The study also found no evidence that states with medical marijuana laws experience reductions in the volume of legally distributed opioid analgesics used to treat pain. Even if medical marijuana patients were substituting medical marijuana for opioids in medical marijuana states, these patients did not represent a measurable part of the medical opioid analgesic market.

"While our study finds that medical marijuana dispensaries reduce some of the harms associated with the misuse of opioids, there is little evidence that this is happening because a large number of patients suffering from pain are using marijuana instead of opioid medications," Pacula said. "Either the patients are continuing to use their opioid pain medications in addition to marijuana, or this patient group represents a small share of the overall medical opioid using population."

The RAND study was conducted before any any states had begun to allow retail sales of recreational marijuana.

"Our research suggests that the overall story between medical marijuana and opioid deaths is complicated," Pacula said. "Before we embrace marijuana as a strategy to combat the opioid epidemic, we need to fully understand the mechanism through which these laws may be helping and see if that mechanism still matters in today's changing opioid crisis."

Support for the study was provided by the National Institute on Drug Abuse. Other authors of the study are David Powell of RAND and Mireille Jacobson of UC Irvine.

https://www.sciencedaily.com/releases/2018/02/180207090111.htm#

Developing a roadside test for marijuana intoxication isn't as easy as it sounds

January 25, 2018

Science Daily/Cell Press

As the movement to legalize marijuana in the United States gains momentum, researchers worry about keeping the public safe, particularly on the roads. Recent studies in which marijuana users took controlled doses of cannabis in the lab have identified new biomarkers that can be used to estimate a person's recent cannabinoid intake. But, using those markers to judge cognitive and behavioral impairment is complex, say toxicologists in a commentary published on January 25 in a special issue of the journal Trends in Molecular Medicine on biomarkers of substance abuse.

"There is no one blood or oral fluid concentration that can differentiate impaired and not impaired," says Marilyn Huestis, who spent over 20 years leading cannabinoid-related research projects at the National Institute on Drug Abuse. "It's not like we need to say, 'Oh, let's do some more research and give you an answer.' We already know. We've done the research."

Alcohol can impair a user more than cannabis, and indeed, the risk of an accident while driving increases in proportion with blood alcohol concentrations. But pot is different: many variables can affect how impaired someone is at any given concentration of ?9-tetrahydrocannabinol (THC), the primary psychoactive agent in cannabinoids. Whether it is inhaled or consumed, or whether the user titrates their own dose, can affect the level of impairment. And pairing cannabis with alcohol makes the high higher, and the alcohol buzz last longer.

Another problem is that THC quickly leaves the bloodstream. Previous research by Huestis has shown that while an occasional user is impaired for 6 to 8 hours, blood THC concentrations can be effectively zero after 2.5 hours. And on average in the United States, it takes from 1.4-4 hours after a crash or traffic stop to administer a blood test. "If someone is driving impaired, by the time you get their blood sample, you've lost 90% or more of the drug. So, we have to change what we do at the roadside," says Huestis.

Long-term daily cannabis users, like those who use marijuana for medical reasons, also present a challenge for developing roadside protocols. THC accumulates in the tissues of the body and then slowly releases over time, meaning that chronic users can test positive for cannabis even after 30 days of abstinence. Psychomotor impairment can be observed three weeks after the last dose. "You want people to be taking medicinal cannabinoids and now you know that their driving is going to be impacted," says Huestis. "So how do you handle that problem?"

Huestis, like most researchers, doesn't support a legal driving limit for cannabis like the one in place for blood alcohol concentrations. Instead, she advocates for well-trained police officers who can identify the behavioral signs of impairment and less invasive biological marker tests, which could be immediately performed at the roadside to confirm the presence of a cannabinoid. To that end, recent research has identified new blood and urine markers, and tests using breath and saliva markers are being developed.

The implications go beyond driving. These new markers and tests could also be used to assist in treating drug dependence, in determining appropriate therapeutic levels of medical marijuana, and for monitoring women who want to stop using cannabinoids during pregnancy.

Huestis, who also owns a toxicology consulting company with her co-author, Michael Smith, isn't opposed to legalization. But she does want to make sure that marijuana's status as a legal drug and a medicine doesn't make us complacent. "Cannabis probably is less dangerous to use than alcohol," she says. "There's less morbidity and mortality associated with it, but there's still a lot of problems. And we as a public are not recognizing this."

The Intramural Research Program of the National Institute on Drug Abuse, and the National Institutes of Health funded this research.

https://www.sciencedaily.com/releases/2018/01/180125135606.htm

Cannabidiol may help to reduce seizures for people with treatment-resistant form of epilepsy

January 25, 2018

Science Daily/The Lancet

Treatment with a pharmaceutical formulation of cannabidiol alongside other anti-epilepsy treatments helped to reduce the number of drop seizures -- seizures which involve sudden falls due to loss of muscle tone -- in people with Lennox-Gastaut syndrome who did not respond to previous treatment, according to a phase 3 randomised clinical trial published in The Lancet.

Around 1-4% of childhood epilepsy cases are caused by Lennox-Gastaut syndrome -- a lifelong, severe form of epilepsy involving multiple seizure types and cognitive impairment. While there are a range of drug and non-pharmacological treatments (such as ketogenic diet, nerve stimulation, and brain surgery) available, these only help 10% of patients become seizure free.

The 14-week trial reduced the frequency of seizures, but the long-term efficacy and safety of the pharmaceutical formulation of cannabidiol, as well as the drug's interaction with other epilepsy drugs, now needs to be confirmed.

"There is an urgent need for novel treatment options for patients with Lennox-Gastaut syndrome, and we are pleased that our study has potentially found an additional option to add to patients' existing treatment to reduce drop seizures," says lead author Dr Elizabeth Thiele, Massachusetts General Hospital, USA. "Our results suggest that the use of cannabidiol as an add-on therapy with other anti-epilepsy drugs might significantly reduce the frequency of drop seizures in patients with Lennox-Gastaut syndrome, which is positive news for these patients, who often do not respond to treatment."

She notes: "It's important to highlight that the drug used in this trial is a pharmaceutical formulation, and not medical marijuana."

The 14-week trial involved 171 participants aged 2-55 years from the USA, the Netherlands or Poland, who had had a variety of seizures over the past six months (including two or more drop seizures per week during the four week baseline period).

All participants were highly treatment resistant. Before the trial began, participants had not responded to an average of six anti-epilepsy drugs, were taking three anti-epilepsy drugs, and had 73.8 drop seizures every 28 days, on average.

Participants were given a daily dose of a pharmaceutical formulation of cannabidiol (86 people) or placebo (85 people), alongside their usual treatment, for 14 weeks. During this time participants or their caregivers recorded the number and types of seizures each day, as well as medication use and adverse events.

At the end of the trial, drop seizures reduced by 43.9% for the cannabidiol group (from an average of 71.4 drop seizures per month at the start of the trial, to 31.4 per month at the end), compared with a 21.8% reduction for those taking the placebo (from 74.7 seizures per month to 56.3 per month at the end).

Participants in the cannabidiol group also had a greater reduction in their levels of other seizures, and monthly frequency of all seizures decreased by 41.2% (from an average of 144.6 seizures per month at the start of the trial, to 83.8 per month at the end), compared with a 13.7% reduction for the placebo group (from 176.7 seizures per month to 128.7 at the end of the trial).

62% (53/86) participants in the cannabidiol group experienced side effects related to the treatment, compared with 34% (29/85) participants in the placebo group. The most common adverse events in the cannabidiol group were diarrhoea, drowsiness, fever, decreased appetite and vomiting. Serious adverse events were reported in 20 participants in the cannabidiol group, the most common of which were increases in liver enzymes that showed no signs of lasting damage in four participants.

For 61% of participants in the cannabidiol group and 64% in the placebo group, adverse events resolved during the trial. However, some participants withdrew from the study due to side effects (14% [12/86] participants in the cannabidiol group and one participant in the placebo group). These withdrawals included the four participants with temporary liver enzyme elevations, and other participants who experienced multiple other side-effects.

There were no instances of abuse or misuse of the study drug throughout the trial.

The authors note that potential drug interactions between cannabidiol and an epilepsy drug called clobazam need to be explored further. They also note that different doses of cannabidiol should be explored as this study only trialled one dose, and that the long-term efficacy and safety of the treatment needs to be confirmed. The treatment also needs to be tested in a more ethnically diverse group as 90% of participants in this trial were white.

Writing in a linked Comment, Dr Sophia Varadkar, Great Ormond Street Hospital for Children NHS Foundation Trust, UK, says: "After many years without promise of new treatments in Lennox-Gastaut syndrome, this is an exciting time for patients and clinicians. More data and clinical experience of cannabidiol in Lennox-Gastaut syndrome is expected… Clinical trials with cannabidiol are underway in tuberous sclerosis complex… and infantile spasms… and future studies are expected in the other pharmacoresistant epilepsy syndromes."

https://www.sciencedaily.com/releases/2018/01/180125110804.htm

Marijuana use does not lower chances of getting pregnant

January 22, 2018

Science Daily/Boston University School of Medicine

Marijuana use -- by either men or women -- does not appear to lower a couple's chances of getting pregnant, according to a new study led by Boston University School of Public Health (BUSPH) researchers.

The study, published in the Journal of Epidemiology and Community Health (JECH), was the first to evaluate the link between fecundability -- the average per-cycle probability of conception -- and marijuana use.

About 15 percent of couples experience infertility. Infertility costs the US healthcare system more than $5 billion per year, and thus identifying modifiable risk factors for infertility, including recreational drug use, is of public health importance. Marijuana is one of the most widely used recreational drugs among individuals of reproductive age. Previous studies have examined the effects of marijuana use on reproductive hormones and semen quality, with conflicting results.

"Given the increasing number of states legalizing recreational marijuana across the nation, we thought it was an opportune time to investigate the association between marijuana use and fertility," says lead author Lauren Wise, professor of epidemiology.

In Pregnancy Study Online (PRESTO), a web-based prospective cohort study of North American couples, the researchers surveyed 4,194 women aged 21 to 45 living in the United States or Canada. The study specifically targeted women in stable relationships who were not using contraception or fertility treatment. Female participants were given the option to invite their male partners to participate; 1,125 of their male partners enrolled.

The researchers found that during the period from 2013 through 2017, approximately 12 percent of female participants and 14 percent of male participants reported marijuana use in the two months before completing the baseline survey. After 12 cycles of follow-up, conception probabilities were similar among couples that used marijuana and those that did not.

The researchers stressed that questions about the effects of marijuana use remain. As one example, they said, classifying people correctly according to the amount of marijuana used, especially when relying on self-reported data, is challenging. "Future studies with day-specific data on marijuana use might better be able to distinguish acute from chronic effects of marijuana use, and evaluate whether effects depend on other factors," they wrote.

https://www.sciencedaily.com/releases/2018/01/180122150813.htm

Light-sensitive THC: Intoxicatingly light-sensitive

January 10, 2018

Science Daily/ETH Zurich

Chemists have synthesized several variants of THC, the active ingredient in cannabis. Its structure can be altered with light, and the researchers have used this to create a new tool that can be used to more effectively study the body's own cannabinoid system.

When many people hear the abbreviation THC (tetrahydrocannabinol), they immediately think of smoking marijuana and intoxication. But the substance is also of interest to medicine -- when given to people suffering from serious illnesses, it relieves muscle cramps, pain, loss of appetite and nausea.

THC works by binding to the corresponding cannabinoid-1 (CB1) receptors, which are located in the cell membrane and are present in large numbers in the central and peripheral nervous system. CB1 receptors play a major role in memory, motor coordination, mood and cognitive processes.

Receptors key to signal transmission

When a THC molecule binds to one of these CB1 receptors, it changes form, triggering a cascade of various signals inside the cell. However, it is still hard to study CB1 receptors and their manifold functions, because cannabinoids such as THC are highly lipophilic, so they frequently embed themselves in the membranes made of fat molecules in an uncontrolled manner. To be able to use THC or variants of it more precisely for pharmaceutical and medical applications, it is therefore important to gain a better understanding of CB1 receptors.

To study the diverse interactions between CB1 receptors and cannabinoids, a group of chemists headed by ETH professor Erick Carreira synthesised THC molecules. Their structure can be altered with light. The researchers published their findings in the latest issue of the Journal of the American Chemical Society.

Light-sensitive THC derivatives

The scientists synthesised four variants, or derivatives, of THC by attaching a light-sensitive "antenna" to the THC molecule. This antenna makes it possible to use light of a specific wavelength to precisely manipulate the altered molecule. Ultraviolet light changes the spatial structure of the antenna, and this change can be reversed again with blue light.

The researchers tested two of these derivatives in a living cell culture. The derivatives docked with CB1 receptors in the same way as naturally occurring THC. When the researchers irradiated the THC derivative with ultraviolet light, its structure altered just as the researchers expected, consequently activating the CB1 receptor. This triggers reactions such as the opening of the potassium ion channels located in the cell membrane, which causes potassium ions to flow out of the cell. The researchers were able to measure this with an electrode inserted into the cell.

When irradiated with blue light, the THC derivative returned to its original form, disabling the CB1 receptor as a result. The ion channels closed and the flow of potassium stopped. The researchers were able to activate and deactivate these processes using the corresponding coloured pulses of light.

A basis for light-controlled applications

"This work is our successful proof of principle: light-sensitive THC variants are a suitable tool for controlling and influencing CB1 receptors," says Michael Schafroth, a doctoral student with ETH professor Carreira and major contributor to the study. He added that they have now laid an important foundation for further projects that are already in progress; for example, another doctoral student in Carreira's group, Roman Sarott, is working on synthesising additional THC derivatives that react to long-wavelength red light. "Red light penetrates deeper into tissue than blue light," says Sarott. "If we want to study CB1 receptors in a living organism, we need molecules that are sensitive to red light."

In addition to the researchers from Carreira's group, leading scientists from New York University (NYU), the Indiana University Bloomington (IUB) and the University of Southern California (USC) as well as the Ludwig-Maximilian University in Munich were involved in the interdisciplinary project. The biological experiments were conducted by James Frank and Dirk Trauner.

A starting point for medicine

Many cultures have long known of the intoxicating and therapeutic effect of THC. The identification of THC eventually led to the discovery of the endocannabinoid system, which involves the body's native as well as exogenous substances in the cannabinoids class as well as their receptors in the body.

The pharmaceutical industry is also interested in gaining a better understanding of the endocannabinoid system so that it can better use specific components for pharmaceutical purposes. The system is considered a possible starting point for treatments for addiction, obesity, depression and even Alzheimer's and Parkinson's.

https://www.sciencedaily.com/releases/2018/01/180110112944.htm

Cigarette smoking is increasing among Americans with drug problems

Odds of smoking among Americans with a substance use disorder are more than five times greater than the overall population

December 19, 2017

Science Daily/Columbia University's Mailman School of Public Health

While cigarette smoking has declined in the U.S. for the past several decades, since 2002 the prevalence of smoking has increased significantly among people with an illicit substance use disorder, according to a new study by researchers at Columbia University's Mailman School of Public Health and the City University of New York. Until now, little was known about whether the decline in smoking was also occurring among individuals with illicit substance use disorders. The findings are published online in the journal Addiction.

The data show that smoking rates increased among those with substance use disorders, including hallucinogens, inhalants, tranquilizers, cocaine, heroin, pain relievers, simulants, and sedatives, while cigarette smoking decreased among individuals with cannabis use disorders, as well as among those without any substance use disorders.

The researchers analyzed data from 725,010 Americans ages 12 and older in the National Survey on Drug Use and Health for 2002 to 2014. They found more than half of individuals with a substance use disorder (56 percent) reported cigarette use in the past month, compared with 18 percent of those without a substance use disorder. When cannabis use disorders were excluded, smoking rates for those with a substance use disorder climbed to 64 percent; among those with cannabis use disorder, 51 percent reported past month cigarette use.

"We found that cigarette use was not only disproportionately common among those with a substance use disorder, but that the odds of smoking were five times greater than that of the general population," said Renee Goodwin, PhD, in the Department of Epidemiology at the Mailman School of Public Health, and senior author. "And individuals with a substance use disorder other than cannabis were 7.5 times more likely to be smokers."

"Given the extremely elevated rates of smoking among persons with substance use disorders, it seems that neither population-based tobacco control efforts nor clinical smoking cessation strategies have reached or been as effective among persons with substance use disorders," noted Goodwin. "New and innovative public health strategies are needed if we are to reach those with substance use disorders and bring down the smoking rates among this vulnerable group of individuals."

"An increasing number of substance-use treatment programs are offering smoking cessation services, presenting an important opportunity for smoking cessation," observed Goodwin. "How substance disorder treatment programs can integrate smoking treatments into their service delivery most effectively, however, still remains an open question."

https://www.sciencedaily.com/releases/2017/12/171219091306.htm

All politics -- and cannabis marketing -- are local

Washington, Colorado provide insight for California

December 14, 2017

Science Daily/University of California - Davis

California's legal cannabis market, opening for business on Jan. 1, is expected to quickly grow to be the largest in the nation and worth more than $5 billion a year.

County voting on Proposition 64 that led the state here -- to legalizing sales for recreational use -- can offer insight into how medical marijuana dispensaries will now market themselves, according to research from the University of California, Davis.

"The way that communities vote and the values they have are going to have an impact on how this industry's going to evolve over time," said Greta Hsu, a professor at the UC Davis Graduate School of Management and lead author on the paper, soon to be published in the journal Organizational Science.

Hsu draws her conclusions from the experiences of Washington and Colorado. She and her co-authors from Yale and Emory universities examined county voting patterns in the 2012 referendums that legalized marijuana sales in the two states and how medical marijuana dispensaries responded.

In communities where the majority voted against such initiatives, medical marijuana dispensaries maintained a more traditional approach, accentuating the therapeutic benefits of marijuana as an alternative medicine.

However, where the majority voted in favor of legalizing recreational marijuana sales, medical marijuana dispensaries adopted marketing strategies that de-emphasized the medical orientation and sought to attract recreational customers.

Analysis of dispensary reviews, descriptions

The researchers analyzed information, reviews and descriptions of more than 1,000 medical cannabis businesses, using WeedMaps.com, a crowdsourcing website that is considered the "Yelp of cannabis" for dispensaries and other retailers. The researchers developed a coding system for the language in order to track trends across the two states.

"Some of these dispensaries, when you look at them, they emphasize medicine a lot, and they emphasize their ties to the local community," said Hsu. "Others just emphasize convenience and price."

Marketing recreational vs. medical marijuana

Some clusters of dispensaries were more conservative in their marketing, with statements like: "We aim to educate our patients about cannabis treatments and other alternative health approaches to supplement their medicine."

Despite legalization's substantial disruption to their industry, these businesses continued with their original identity focused on therapy and the patients, said Hsu. They tended to be in counties where the majority voted against legalizing recreational marijuana.

Dispensaries that embraced the new recreational market took more risk by advertising to a broader, emerging consumer class, which has been bolstered by a growing tourism industry.

Supporters for these cannabis businesses emphasized the benefits to the local economy, public health and social justice, casting marijuana as less harmful than alcohol. Dispensaries with this more recreational-oriented marketing tended to be in counties that voted in favor of legalizing recreational use.

Legalization and regulation in California

Communities hold a great deal of power in affecting how dispensaries decide to market themselves, according to Hsu.

In 2009, California was the first state to legalize medicinal marijuana, and Proposition 64 legalized recreational marijuana in the state beginning on Jan. 1, 2018. The state has unveiled a new licensing process for the cultivation, manufacturing and sale of marijuana, which is divided into both medicinal and recreational (or adult use) branches.

However, the law gives local municipalities flexibility in deciding how easily dispensaries can operate within their boundaries. Some counties have chosen to ban all dispensaries. Others are carefully regulating sales and businesses through zoning and taxes.

While 57 percent statewide voted in favor of Proposition 64 in 2016, a majority of voters in 18 counties did not. This included Kern County, which recently announced a ban on all marijuana businesses, including existing medicinal dispensaries.

Other applications for research

Hsu said the research contributes to understanding about how local conditions or cultural changes drive dynamics in a broad range of markets including rise of organic agriculture and the growth of energy and wind power.

"Organizations in these changing markets have to think very carefully about how they want to position themselves and about the strategic choices they make," said Hsu.

The paper is titled "Co-opt or Co-exist? A Study of Medical Cannabis Dispensaries' Identity-based Responses to Recreation-use Legalization in Colorado and Washington." The co-authors are Balázs Kovács, assistant professor of organizational behavior at Yale, and Özgecan Koçak, associate professor of organization and management at Emory.

Hsu, who is an expert in organizational behavior and theory, is continuing related research. She is also studying how cannabis dispensaries in several states are adjusting to changing markets.

Link to video: https://www.youtube.com/watch?v=Mdg6js_BwT8&feature=youtu.be

Link to paper: https://gsm.ucdavis.edu/sites/main/files/file-attachments/cannabis_os_final.pdf

https://www.sciencedaily.com/releases/2017/12/171214153334.htm

Marijuana may help HIV patients keep mental stamina longer

December 12, 2017

Science Daily/Michigan State University

A chemical found in marijuana, known as tetrahydrocannabinol, or THC, has been found to potentially slow the process in which mental decline can occur in up to 50 percent of HIV patients, says a new Michigan State University study.

"It's believed that cognitive function decreases in many of those with HIV partly due to chronic inflammation that occurs in the brain," said Norbert Kaminski, lead author of the study, now published in the journal AIDS. "This happens because the immune system is constantly being stimulated to fight off disease."

Kaminski and his co-author, Mike Rizzo, a graduate student in toxicology, discovered that the compounds in marijuana were able to act as anti-inflammatory agents, reducing the number of inflammatory white blood cells, called monocytes, and decreasing the proteins they release in the body.

"This decrease of cells could slow down, or maybe even stop, the inflammatory process, potentially helping patients maintain their cognitive function longer," Rizzo said.

The two researchers took blood samples from 40 HIV patients who reported whether or not they used marijuana. Then, they isolated the white blood cells from each donor and studied inflammatory cell levels and the effect marijuana had on the cells.

"The patients who didn't smoke marijuana had a very high level of inflammatory cells compared to those who did use," Kaminski said. "In fact, those who used marijuana had levels pretty close to a healthy person not infected with HIV."

Kaminski, director of MSU's Institute for Integrative Toxicology, has studied the effects of marijuana on the immune system since 1990. His lab was the first to identify the proteins that can bind marijuana compounds on the surface of immune cells. Up until then, it was unclear how these compounds, also known as cannabinoids, affected the immune system.

HIV, which stands for human immunodeficiency virus, infects and can destroy or change the functions of immune cells that defend the body. With antiretroviral therapy -- a standard form of treatment that includes a cocktail of drugs to ward off the virus -- these cells have a better chance of staying intact.

Yet, even with this therapy, certain white blood cells can still be overly stimulated and eventually become inflammatory.

"We'll continue investigating these cells and how they interact and cause inflammation specifically in the brain," Rizzo said. "What we learn from this could also have implications to other brain-related diseases like Alzheimer's and Parkinson's since the same inflammatory cells have been found to be involved."

Knowing more about this interaction could ultimately lead to new therapeutic agents that could help HIV patients specifically maintain their mental function.

"It might not be people smoking marijuana," Kaminski said. "It might be people taking a pill that has some of the key compounds found in the marijuana plant that could help."

https://www.sciencedaily.com/releases/2017/12/171212092100.htm

Marijuana use may not aid patients in opioid addiction treatment

Symptoms harder to manage

December 4, 2017

Science Daily/Washington State University

New research finds that frequent marijuana use seems to strengthen the relationship between pain and depression and anxiety, not ease it.

Many patients who are being treated for opioid addiction in a medication-assisted treatment clinic use marijuana to help manage their pain and mood symptoms.

But new research led by Marian Wilson, Ph.D., of the Washington State University College of Nursing found that frequent marijuana use seems to strengthen the relationship between pain and depression and anxiety, not ease it.

"For people who are using cannabis the most, they have a very strong relationship between pain and mood symptoms, and that's not necessarily the pattern you'd want to see," Wilson said. "You would hope, if cannabis is helpful, the more they use it the fewer symptoms they'd see."

The research, recently published in the journal Addictive Behaviors, involved 150 patients being seen at an opioid treatment clinic. Previous studies have shown that nearly two-thirds of patients receiving medication-assisted treatment for opioid addiction also have chronic pain, and many experience depression and anxiety.

About 67 percent of the clinic patients surveyed by Wilson and her team said they had used marijuana in the past month.

"Some are admitting they use it just for recreation purposes, but a large number are saying they use it to help with pain, sleep, and their mood," Wilson said. "We don't have evidence with this study that cannabis is helping with those issues." In fact, the relationship between pain and depression and anxiety increased with the frequency of marijuana use.

In most cases, people reported they were self-medicating with marijuana, Wilson noted, yet only a small number had a medical marijuana card.

The study noted that opioid overdose rates have more than tripled in the past two decades and are now the second-leading cause of accidental death in the United States. There are many questions about the relationship between marijuana use and opioid addiction and treatment -- such as why opioid death rates are 25 percent lower in states that have legalized medical marijuana -- but the primary purpose of Wilson's study was to see whether cannabis use affects the relationship between pain and depression and anxiety.

Patients believe using marijuana helps them with their symptoms, but the study's results could indicate the opposite is true for those in addiction treatment -- that by strengthening the connection between feelings of pain and emotional distress, it makes it harder for them to manage their symptoms.

"The effectiveness of cannabis for relieving distressing symptoms remains mixed and requires further research," the study concludes.

https://www.sciencedaily.com/releases/2017/12/171204091144.htm