Psychedelic drugs may reduce criminal behavior

Illicit substances may be effective interventions to crime

October 23, 2017

Science Daily/University of British Columbia Okanagan campus

Newly published research suggests that common psychedelic drugs -- such as magic mushrooms, LSD and mescaline (a substance derived from the peyote cactus) -- may reduce criminal offences.

The new study, co-authored by UBC Okanagan's Associate Professor of Psychology Zach Walsh, found that psychedelic drugs are associated with a decreased likelihood of antisocial criminal behaviour.

"These findings add to a growing body of research suggesting that use of classic psychedelics may have positive effects for reducing antisocial behaviour," said Walsh, a p. "They certainly highlight the need for further research into the potentially beneficial effects of these stigmatized substances for both individual and public health."

Lead author, University of Alabama Assoc. Prof. Peter Hendricks, used data obtained by the National Survey on Drug Use and Health, which is administered by the U.S. Department of Health and Human Services, to explore the connection between the use of classic psychedelic substances and criminal behaviour among more than 480,000 American adult respondents from the past 13 years.

Key findings of the study are that respondents who have used psychedelic drugs had 27 per cent decreased odds of larceny or theft, and 22 per cent decreased odds of arrest for a violent crime in the past year. At the same time, lifetime use of other illicit substances was generally associated with increased odds of criminal behaviour.

Hendricks says that psilocybin and related compounds could revolutionize the mental health field.

"The development of innovative and effective interventions to prevent criminal behaviour is an obvious priority," Hendricks adds. "Our findings suggest the protective effects of classic psychedelic use are attributable to genuine reductions in antisocial behaviour rather than reflecting improved evasion of arrest. Simply put, the positive effects associated with classic psychedelic use appear to be reliable. Given the costs of criminal behaviour, the potential represented by this treatment paradigm is significant."

Walsh points out that research on the benefits of psychedelic drugs started decades ago, primarily to treat mental illness. However, it was stopped due to the reclassification of the drugs to controlled substances in the mid-1970s. Recent years have seen a resurgence of interest in psychedelic medicine.

"More research is needed to figure out what factors underlie these effects," Walsh says. "But the experiences of unity, positivity and transcendence that characterize the psychedelic experience may have lasting benefits that translate into real-world consequences."

The research was recently published by the Journal of Psychopharmacology.

https://www.sciencedaily.com/releases/2017/10/171023101753.htm

Marijuana's hidden price: Environmental impact

October 19, 2016

Science Daily/Ithaca College

A new survey of marijuana grow sites in California demonstrates the potential environmental impact of marijuana farming and provides an example of the survey and analysis needed as farming expands.

"It's just a plant" is a common refrain from those who want to legalize the leaf, but a recent study of cannabis production argues that the environmental impact of marijuana farming must be considered -- especially as more states move toward further legalization this election season.

The study was conducted by Jake Brenner, an assistant professor in the Department of Environmental Studies and Sciences at Ithaca College, and Van Bustic, a specialist at the University of California Cooperative Extension. It was published earlier this year in the journal Environmental Research Letters.

The study also highlights the lack of published, peer-reviewed empirical research on all aspects of cannabis agriculture, which is already a multi-billion dollar industry in the United States despite still being listed as a Schedule 1 drug by the federal government.

Location, location

The amount of land and water used for growing cannabis has not traditionally been a concern, especially when compared to other agricultural products grown in California. But where the cannabis is grown has potential ecological consequences.

Brenner and Bustic examined grow sites in three northern California counties and found that their usual placement had potentially negative impacts on two threatened fish species.

That's because the sites are typically placed on remote plots of land in forested areas, many on steep slopes. Access roads need to be created and swaths of land cleared for production, regardless of whether the cannabis is grown outdoors or in a greenhouse; that increases potential for soil erosion and chemical run-off into streams in which the Chinook salmon and steelhead trout live.

The fish are also susceptible to harm from a decrease in water flow as a result of the cannabis agriculture.

"Siting grows in areas with better access to roads, gentler slopes, and ample water resources could significantly reduce threats to the environment," Brenner and Bustic write. "Future cannabis policy should take into consideration the potential for mitigating environmental impacts through land-use planning."

Know before you grow

Brenner and Bustic say their study, which covers the watersheds of northern California's Humbolt County, is an example of the sort of survey and analysis that could be done -- and is necessary -- anywhere cannabis agriculture takes place.

And while California is taking efforts to encourage local governments to create land-use policies for cannabis agriculture, they argue that more research on marijuana farming needs to be done.

"Land-use science on cannabis agriculture lags behind research on other crops, but advances in the field will be crucial for predicting future cannabis expansion and moderating its impacts," they write.

That multi-billion marijuana production industry is only going to grow: This November, voters in Arizona, California, Maine, Massachusetts and Nevada will decide whether to allow their states to legalize and tax recreational marijuana; while voters in Arkansas, Florida, Montana and North Dakota will head to the polls to determine whether their states will allow medicinal uses of marijuana, joining the 25 other states that already do so.

https://www.sciencedaily.com/releases/2016/10/161019173110.htm

A new target for marijuana

October 16, 2017

Science Daily/Society for Neuroscience

Cellular-level changes to a part of the brain's reward system induced by chronic exposure to the psychoactive component of marijuana may contribute to the drug's pleasurable and potentially addictive qualities, suggests a study in young mice published in JNeurosci. The results could advance our understanding of marijuana's effects on the developing brain as the drug's rapidly changing legal status increases its recreational and medical use in the United States.

Drugs of abuse impact the ventral tegmental area (VTA) of the brain, which is rich in dopamine neurons. Using juvenile and adolescent mice, Jeffrey Edwards and colleagues investigated the effects of tetrahydrocannabinol (THC), the chemical in marijuana responsible for its effects on cognition and behavior, on VTA GABA cells, an understudied inhibitory cell type in the reward system that regulates dopamine levels.

The authors found that a week of daily THC injections, but not a single injection, blocked the recovery of synapses onto VTA GABA cells in the mice. This finding suggests that persistent THC may alter the inhibitory function of these cells, increasing dopamine levels and the rewarding features of marijuana. These GABA neurons may represent a promising new target for treatment of cannabis use disorder, a common condition on the rise in the United States.

https://www.sciencedaily.com/releases/2017/10/171016132754.htm

'Magic mushrooms' may 'reset' the brains of depressed patients

October 13, 2017

Science Daily/Imperial College London

Patients taking psilocybin to treat depression show reduced symptoms weeks after treatment following a 'reset' of their brain activity.

The findings come from a study in which researchers from Imperial College London used psilocybin -- the psychoactive compound that occurs naturally in magic mushrooms -- to treat a small number of patients with depression in whom conventional treatment had failed.

In a paper, published today in the journal Scientific Reports, the researchers describe patient-reported benefits lasting up to five weeks after treatment, and believe the psychedelic compound may effectively reset the activity of key brain circuits known to play a role in depression.

Comparison of images of patients' brains before and one day after they received the drug treatment revealed changes in brain activity that were associated with marked and lasting reductions in depressive symptoms.

The authors note that while the initial results of the experimental therapy are exciting, they are limited by the small sample size as well as the absence of a control group -- such as a placebo group -- to directly contrast with the patients.

Dr Robin Carhart-Harris, Head of Psychedelic Research at Imperial, who led the study, said: "We have shown for the first time clear changes in brain activity in depressed people treated with psilocybin after failing to respond to conventional treatments.

"Several of our patients described feeling 'reset' after the treatment and often used computer analogies. For example, one said he felt like his brain had been 'defragged' like a computer hard drive, and another said he felt 'rebooted'. Psilocybin may be giving these individuals the temporary 'kick start' they need to break out of their depressive states and these imaging results do tentatively support a 'reset' analogy. Similar brain effects to these have been seen with electroconvulsive therapy."

Over the last decade or so, a number of clinical trials have been conducted into the safety and effectiveness of psychedelics in patients with conditions such as depression and addictions, yielding promising results.

In the recent Imperial trial, the first with psilocybin in depression, 20 patients with treatment-resistant form of the disorder were given two doses of psilocybin (10 mg and 25 mg), with the second dose a week after the first.

Nineteen of these underwent initial brain imaging and then a second scan one day after the high dose treatment. Carhart-Harris and team used two main brain imaging methods to measure changes in blood flow and the crosstalk between brain regions, with patients reporting their depressive symptoms through completing clinical questionnaires.

Immediately following treatment with psilocybin, patients reported a decrease in depressive symptoms -- corresponding with anecdotal reports of an 'after-glow' effect characterised by improvements in mood and stress relief.

Functional MRI imaging revealed reduced blood flow in areas of the brain, including the amygdala, a small, almond-shaped region of the brain known to be involved in processing emotional responses, stress and fear. They also found increased stability in another brain network, previously linked to psilocybin's immediate effects as well as to depression itself.

These findings provide a new window into what happens in the brains of people after they have 'come down' from a psychedelic, where an initial disintegration of brain networks during the drug 'trip', is followed by a re-integration afterwards.

Dr Carhart-Harris explained: "Through collecting these imaging data we have been able to provide a window into the after effects of psilocybin treatment in the brains of patients with chronic depression. Based on what we know from various brain imaging studies with psychedelics, as well as taking heed of what people say about their experiences, it may be that psychedelics do indeed 'reset' the brain networks associated with depression, effectively enabling them to be lifted from the depressed state.

The authors warn that while the initial findings are encouraging, the research is at an early stage and that patients with depression should not attempt to self-medicate, as the team provided a special therapeutic context for the drug experience and things may go awry if the extensive psychological component of the treatment is neglected. They add that future studies will include more robust designs and currently plan to test psilocybin against a leading antidepressant in a trial set to start early next year.

Professor David Nutt, Edmond J. Safra Professor of Neuropsychopharmacology and director of the Neuropsychopharmacology Unit in the Division of Brain Sciences, and senior author of the paper, added: "Larger studies are needed to see if this positive effect can be reproduced in more patients. But these initial findings are exciting and provide another treatment avenue to explore."

https://www.sciencedaily.com/releases/2017/10/171013091018.htm

Don't dispense of cannabis dispensaries, caution researchers

Recent publication states 'store-front' system has elements that work well

October 12, 2017

Science Daily/University of British Columbia Okanagan campus

UBC researchers are cautioning policy makers not to alter a cannabis distribution system that -- while not legal yet -- works well.

Associate professor Zach Walsh, who teaches psychology at UBC's Okanagan campus, and PhD candidate Rielle Capler, say store-front dispensaries -- often under fire by law enforcement and city governments -- are a tried and true method of selling cannabis. The pair recently published a study on medicinal cannabis dispensaries and determined customers prefer the independent storefront as opposed to growing their own, or getting it from a dealer.

In Canada, dispensaries are not an authorized source for cannabis, although many operate as 'compassion clubs' selling cannabis for medical -- not recreational -- purposes. Their research suggests that when recreational marijuana use becomes legal in 2018, the current system of dispensaries should remain.

"Dispensaries do serve a role in our society, especially for some people with chronic illnesses who use cannabis for medicinal purposes," says Walsh. "There is a self-regulatory model that already exists and improvements can be made in a legalized environment."

The study is one of the first to specifically look at the experience of dispensary users. It compared their experiences to those who purchase cannabis through other sources including self-production, and illegal sources, such as friends or street dealers.

"Our study shows there are people who have preferences for dispensaries especially compared to other illegal sources," says Capler. "Our study also provides insight into some of the aspects of dispensaries that the government may want to emulate in the legal framework for both medical and recreational use."

Recently, the Ontario government announced that once restrictions come off next year, it will sell marijuana in dedicated stores run by the province's liquor control board.

While operating under the shadows of provincial laws and city bylaws, dispensaries have thrived in neighbourhoods across Canada. Capler calls the current method a 'natural experiment' that's been underway for decades and says law makers should this keep in mind when addressing regulation policies.

"Dispensaries are not new and they provide a proven, valuable service," she says. "While some are thought of as a nuisance, in reality many of these dispensaries are small, independent, long-standing businesses who serve a dedicated clientele."

For their research, more than 440 people who use cannabis for therapeutic purposes were asked to compare different methods of purchasing cannabis on a number of factors such as quality of product, safety, availability, efficiency and feeling respected. Study participants rated dispensaries highly across most categories with the only prominent negative being that the cost of dispensary product is often higher than from a street dealer.

"Clearly dispensaries are already playing a big role in cannabis access in Canada," Capler adds. "The provincial and municipal governments will have to either look at including them in a legal framework -- or drawing on what's working in dispensaries as they build a new model. We want to think this paper may, in some way, guide policy to create a system that works."

https://www.sciencedaily.com/releases/2017/10/171012111452.htm

Cannabis excess linked to bone disease, fractures

October 12, 2016

Science Daily/University of Edinburgh

People who regularly smoke large amounts of cannabis have reduced bone density and are more prone to fractures, research has found.

The study also found that heavy cannabis users have a lower body weight and a reduced body mass index (BMI), which could contribute to thinning of their bones.

Researchers say this could mean heavy users of the drug are at greater risk of osteoporosis in later life.

Scientists at the University of Edinburgh assessed 170 people who smoke cannabis regularly for recreational purposes and 114 non-users.

The team used a specialised x-ray technique called a DEXA scan to measure the bone density of study participants. They found that the bone density of heavy cannabis users was about five per cent lower than cigarette smokers who did not use cannabis.

Fractures were more common in heavy users compared to non-users, the study found. Moderate users, however, showed no difference from non-users.

The researchers defined heavy users as those who reported smoking cannabis on 5000 or more occasions in their lifetime. In this study, however, the average heavy cannabis user had taken the drug more than 47,000 times. Moderate users had, on average, taken the drug about 1000 times.

Smoking cannabis is often associated with increased appetite so the researchers were surprised to find that heavy cannabis users had a lower body weight and BMI than non-users. This could be because cannabis may reduce appetite when taken in large amounts over a long period of time, the team says.

The study is the first to investigate bone health amongst cannabis users. Researchers say further studies are needed to better understand the link between use of the drug and thinning of the bones.

The study -- funded by Arthritis Research UK -- is published in the American Journal of Medicine.

Lead researcher Professor Stuart Ralston, of the University of Edinburgh's Centre for Genomic and Experimental Medicine, said: "We have known for a while that the components of cannabis can affect bone cell function but we had no idea up until now of what this might mean to people who use cannabis on a regular basis.

"Our research has shown that heavy users of cannabis have quite a large reduction in bone density compared with non-users and there is a real concern that this may put them at increased risk of developing osteoporosis and fractures later in life."

https://www.sciencedaily.com/releases/2016/10/161012132657.htm

Human minibrains reveal effects of psychedelic substance

Study brings first evidence that psychedelics interfere with molecular signaling related to learning and memory in the human brain tissue. Minibrains, also known as cerebral organoids, have been considered a breakthrough in neuroscience studies

https://www.sciencedaily.com/images/2017/10/171009084404_1_540x360.jpg

October 9, 2017

Science Daily/D'Or Institute for Research and Education

A Brazilian study, published in Scientific Reports on October 09, 2017, has identified changes in signaling pathways associated with neural plasticity, inflammation and neurodegeneration triggered by a compound from the family of dimethyltryptamine known as 5-MeO-DMT.

"For the first time we could describe psychedelic related changes in the molecular functioning of human neural tissue," states Stevens Rehen, study leader, Professor of Federal University of Rio de Janeiro (UFRJ) and Head of Research at D'Or Institute for Research and Education (IDOR).

Though recent studies have demonstrated that psychedelic substances, such as LSD (Lysergic acid diethylamide), MDMA (Methylenedioxymethamphetamine) and ayahuasca brew which contains DMT, hold therapeutic potential with possible anti-inflammatory and antidepressant effects, the lack of appropriate biological tools has been shown as a critical limitation for the identification of molecular pathways targeted by psychedelics in the brain.

In order to unveil the effects of 5-MeO-DMT, Vanja Dakic (IDOR) and Juliana Minardi Nascimento (IDOR and University of Campinas) have exposed cerebral organoids, which are 3D cultures of neural cells that mimic a developing human brain, to a single dose of the psychedelic.

By employing mass spectrometry-based proteomics to analyze cerebral organoids, they identified that 5-MeO-DMT altered the expression of nearly thousand proteins. Then, they mapped which proteins were impacted by the psychedelic substance and their role in the human brain.

Researchers found that proteins important for synaptic formation and maintenance were upregulated. Among them, proteins related to cellular mechanisms of learning and memory, key components of brain functioning.

On the other hand, proteins involved in inflammation, degeneration and brain lesion were downregulated, suggesting a potential neuroprotective role for the psychedelic substance.

"Results suggest that classic psychedelics are powerful inducers of neuroplasticity, a tool of psychobiological transformation that we know very little about," states Sidarta Ribeiro, Director of the Brain Institute of Federal University of Rio Grande do Norte (UFRN) and coauthor of the study.

According to Professor Draulio Araujo (UFRN) and coauthor of the study, ""The study suggests possible mechanisms by which these substances exert their antidepressant effects that we have been observing in our studies."

"Our study reinforces the hidden clinical potential of substances that are under legal restrictions, but which deserve attention of medical and scientific communities," Dr. Rehen said.

https://www.sciencedaily.com/releases/2017/10/171009084404.htm

Antidote to synthetic cannabis ‘Spice’ intoxication could be found in slimming drug

October 4, 2017

Science Daily/Queen Mary University of London

Early research from Queen Mary University of London has potentially found an antidote that can rapidly stop the intoxicating effects of cannabis and synthetic cannabinoids.

Synthetic cannabinoids, such as 'Spice' and 'Black Mamba', are becoming an increasing problem, especially with youths game to experiment and within the homeless and prison populations, due to their cheapness and odourless properties. Their super strength compared to cannabis is leading to an increasing number of severe adverse reactions and an increasing number of deaths.

The study, published in the British Journal of Pharmacology, looked at mice that were experiencing the effects of synthetic cannabinoid intoxication, to see the effects of treating them with a molecule known as AM251.

AM251 blocked the action of the synthetic cannabinoid on one of the brain receptors and led to a loss of the cannabinoid-related behavioural effects within a few minutes. This included a significant loss of sedation within 20 minutes, and a loss of the associated hypothermia within 40 minutes.

The researchers say that the most rapid way to develop an antidote would be to re-develop one of the slimming drugs, known as rimonabant, which also blocks the cannabinoid system on which marijuana acts.

https://www.sciencedaily.com/releases/2017/10/171004132517.htm

Cancerous toxins linked to cannabis extract

September 26, 2017

Science Daily/Portland State University

Researchers at Portland State University found benzene and other potentially cancer-causing chemicals in the vapor produced by butane hash oil, a cannabis extract.

Their study raises health concerns about dabbing, or vaporizing hash oil -- a practice that is growing in popularity, especially in states that have legalized medical or recreational marijuana.

Dabbing is already controversial. The practice consists of placing a small amount of cannabis extract -- a dab -- on a heated surface and inhaling the resulting vapor. The practice has raised concerns because it produces extremely high levels of cannabinoids -- the active ingredients in marijuana.

The process of making hash oil also is dangerous because it uses highly flammable and potentially explosive butane as a solvent to extract active ingredients from marijuana leaves and flowers. In July, two people in Portland, OR, died in an explosion and fire at a home where butane hash oil was being manufactured.

"Given the widespread legalization of marijuana in the USA, it is imperative to study the full toxicology of its consumption to guide future policy," said Rob Strongin, a Portland State professor who led the study. "The results of these studies clearly indicate that dabbing, while considered a form of vaporization, may in fact deliver significant amounts of toxins."

Strongin and his team analyzed the chemical profile of terpenes -- the fragrant oils in marijuana and other plants -- by vaporizing them in much the same way as a user would vaporize hash oil.

Terpenes are also used in e-cigarette liquids. Previous experiments by Strongin and his colleagues at Portland State found toxic chemicals in e-cigarette vapor when the devices were used at high temperature settings.

The dabbing experiments produced benzene -- a known carcinogen -- at levels many times higher than the ambient air, Strongin said. It also produced high levels of methacrolein, a chemical similar to acrolein, another carcinogen.

Their findings were published in the Sept. 22 issue of ACS Omega, a journal of the American Chemical Society.

https://www.sciencedaily.com/releases/2017/09/170926162306.htm

Up to one-quarter of cancer patients use marijuana

September 25, 2017

Science Daily/Wiley

A new study conducted in a cancer center in a state with legalized medicinal and recreational marijuana found that approximately one-quarter of surveyed patients used marijuana in the past year, mostly for physical and psychological symptoms. Published early online in CANCER, a peer-reviewed journal of the American Cancer Society, the study also revealed that legalization increased the likelihood for use among patients.

Eight states and the District of Columbia have legalized recreational marijuana, and over half the states in the U.S. have passed laws allowing for medical marijuana in some form. As availability and acceptance of marijuana use continue to increase, many cancer patients will have greater access to marijuana during their cancer treatment.

Marijuana is purported to alleviate symptoms related to cancer treatment, but patterns of use among cancer patients are not well known. To investigate, Steven Pergam, MD, MPH, of the Fred Hutchinson Cancer Research Center and his colleagues surveyed 926 patients at the Seattle Cancer Center Alliance.

The team found that most patients had a strong interest in learning about marijuana during treatment and 74 percent wanted information from cancer care providers. Sixty-six percent had used marijuana in the past, 24 percent used in the last year, and 21 percent used in the last month. Most current users smoked or consumed marijuana primarily for physical symptoms (such as pain and nausea) or psychological reasons (such as coping with stress, depression, and insomnia).

The study reports that random analysis of patient urine samples showed that 14 percent had evidence of recent cannabis use, similar to the 18 percent of users who reported use within the past week.

Although nearly all respondents wanted more information directly from their doctors, most reported that they were more likely to get information from sources outside of the healthcare system. "Cancer patients desire but are not receiving information from their cancer doctors about marijuana use during their treatment, so many of them are seeking information from alternate non-scientific sources," said Dr. Pergam. He stressed that marijuana may be dangerous for some cancer patients or lead to unwanted side effects. "We hope that this study helps to open up the door for more studies aimed at evaluating the risks and benefits of marijuana in this population. This is important, because if we do not educate our patients about marijuana, they will continue to get their information elsewhere."

https://www.sciencedaily.com/releases/2017/09/170925095431.htm

Medical students not trained to prescribe medical marijuana

Many states allow medical pot, but few med schools address it

September 15, 2017

Science Daily/Washington University School of Medicine

More than half of the states in the US now allow some type of legal marijuana use, primarily medical marijuana. But, in a survey of medical residents and deans at the nation's medical schools, researchers have found that the majority of schools are not teaching their students about medical marijuana, and the majority of students don't feel prepared to discuss the subject with patients.

Although 29 states and the District of Columbia allow marijuana use for medical purposes, few medical students are being trained how to prescribe the drug. Researchers at Washington University School of Medicine in St. Louis surveyed medical school deans, residents and fellows, and examined a curriculum database maintained by the Association of American Medical Colleges (AAMC), learning that medical marijuana is not being addressed in medical education.

Their findings are available online in the journal Drug and Alcohol Dependence.

"Medical education needs to catch up to marijuana legislation," said senior author Laura Jean Bierut, MD, the Alumni Endowed Professor of Psychiatry at Washington University and a member of the National Advisory Council on Drug Abuse. "Physicians in training need to know the benefits and drawbacks associated with medical marijuana so they know when or if, and to whom, to prescribe the drug."

Doctors are being asked to guide patients through areas in which most have no training, she explained.

The research team, led by first author Anastasia B. Evanoff, sent surveys to medical school curriculum deans at 172 medical schools in North America, including 31 that specialize in osteopathic medicine, and received 101 replies. Two-thirds (66.7 percent) reported that their graduates were not prepared to prescribe medical marijuana. A quarter of deans said their trainees weren't even equipped to answer questions about medical marijuana.

The researchers also surveyed 258 residents and fellows who earned their medical degrees from schools around the country before coming to Washington University School of Medicine and Barnes-Jewish Hospital in St. Louis to complete their training. Nearly 90 percent felt they weren't prepared to prescribe medical marijuana, and 85 percent said they had not received any education about medical marijuana during their time at medical schools or in residency programs throughout the country.

Using data from the AAMC database, the researchers found that only 9 percent of medical schools had reported teaching their students about medical marijuana.

"As a future physician, it worries me," said Evanoff, a third-year medical student. "We need to know how to answer questions about medical marijuana's risks and benefits, but there is a fundamental mismatch between state laws involving marijuana and the education physicians-in-training receive at medical schools throughout the country."

However, several states -- Missouri among them -- have not legalized medical marijuana, and published studies about potential risks and benefits of medical marijuana often are contradictory. So what are schools to teach?

"You address the controversy," said co-investigator Carolyn Dufault, PhD, assistant dean for education at Washington University and an instructor in medicine. "You say, 'This is what we know,' and you guide students to the points of controversy. You also point out where there may be research opportunities."

The authors argue that as more states legalize marijuana for medical and recreational use, doctors need to have at least enough training to answer patients' questions.

"More medical students are now getting better training about opioids, for example," said Evanoff. "We talk about how those drugs can affect every organ system in the body, and we learn how to discuss the risks and benefits with patients. But if a patient were to ask about medical marijuana, most medical students wouldn't know what to say."

https://www.sciencedaily.com/releases/2017/09/170915144132.htm

Marijuana may produce psychotic-like effects in high-risk individuals

September 13, 2017

Science Daily/Columbia University Medical Center

Marijuana may bring on temporary paranoia and other psychosis-related effects in individuals at high risk of developing a psychotic disorder, finds a preliminary study from researchers at Columbia University Medical Center (CUMC).

The study was published last month in an online edition of Psychiatry Research.

Individuals who have had mild or transient psychotic symptoms (such as unusual thoughts, suspiciousness, perceptual disturbances) without using substances such as marijuana or alcohol and have a family history of psychosis or other risk factors are considered at clinical high risk for psychotic disorder. Previous studies have found an association between marijuana use and psychosis in the general population, but none have rigorously examined marijuana's effects in those at greatest risk for psychosis.

"Many adolescents and young adults who are at high risk for psychosis smoke marijuana regularly or have a cannabis use disorder," said Margaret Haney, PhD, professor of neurobiology (in Psychiatry) at CUMC and senior author of the paper. "Yet researchers haven't studied the effects of marijuana in this population in a rigorous, controlled manner."

In this double-blinded, placebo-controlled laboratory study, the researchers looked at the effects of marijuana in six high-risk young adults and six controls, all experienced and current marijuana smokers who were physically healthy. Participants smoked half of an active or placebo marijuana cigarette, had psychological and physiological assessments before and after smoking, and then repeated this procedure with the opposite (active or placebo) cigarette.

After smoking active marijuana, both groups had signs of intoxication and increases in heart rate and arousal relative to the placebo. However, only the high-risk group experienced transient increases in paranoia and anxiety, as well as disrupted sensory perception and cognitive performance, after using active marijuana. Neither group experienced these effects after using the placebo.

"Although this was a small, preliminary study, it suggests that marijuana may affect individuals at high risk for psychosis differently than other marijuana users, by briefly inducing psychotic-like experiences and impairing their cognition," said Nehal Vadhan, PhD, a psychologist and associate professor in Psychiatry and Molecular Medicine at Hofstra Northwell School of Medicine and first author of the paper. "While larger studies are needed to confirm these findings, they may aid clinicians in their guidance to individuals at risk for psychosis about marijuana's potential effects."

Jeffrey Lieberman,MD, chair of psychiatry at CUMC and and former American Psychiatric Association president, noted that this report "demonstrates the convergent risks of adolescence and expanding cannabis use for the development of psychotic disorders, as well as the opportunity for preventive strategies."

https://www.sciencedaily.com/releases/2017/09/170913193010.htm

Oregon's marijuana legalization prompted big drop in sales in Washington's border counties

Economists find a reduction of legally purchased pot products moving illegally out of Washington

September 5, 2017

Science Daily/University of Oregon

Three days after recreational marijuana sales became legal in Oregon, sales across the border in Washington, where retail availability already existed, dropped by 41 percent, reports a team of University of Oregon economists.

The study also suggests that illegal cross-border movement, or diversion, of legally produced marijuana sold at retail outlets across state borders is a real concern but not occurring at alarming levels.

The National Bureau of Economic Research published the study this week as part of its working papers series.

"We found that the majority of marijuana sold in Washington is actually staying there," said study co-author Benjamin Hansen, a health economist at the UO. "We found that prior to Oregon's legalization 11.9 percent was potentially being diverted out of Washington overall, and it dropped to 7.5 percent after Oregon's legalization."

The research tapped a naturally occurring experiment to explore the issue of small-scale trafficking due to cross-border shopping by Oregon residents in Washington, said Caroline Weber, a professor in the UO's Department of Economics.

Washington was one of the first states to legalize recreational marijuana. The state's regulatory and tracking requirements covering production to sales provided a wealth of data, she said. The UO team studied Washington's sales for the two months before and after Oregon's legal market opened on Oct. 1, 2015.

In doing so, researchers were able to address one of the key concerns of the Cole Memorandum issued in 2013 by then-Deputy Attorney General James M. Cole. It called for federal law enforcement officials to monitor the diversion of sales across borders as states moved to legalize medical and recreational marijuana.

"There has been a lot of debate about a federal crackdown on marijuana," Hansen said, referring to signals expressed by the Trump Administration. "Our study says that 93 percent of marijuana sold in Washington is probably staying there now. There's probably not a lot you can do about the remaining share that is being diverted at this point. This is just the likely consequence of partial prohibition."

The diversion data also included the flow of retail-sold marijuana in Washington to neighboring Idaho and to British Columbia.

Because federal law still classifies marijuana as a Schedule 1 drug, grouped with heroin and methamphetamines, illegal cross-border movement could be targeted by law enforcement. One such method is by using randomized traffic searches along state borders.

Prior to Oregon's market opening, an average of 1,662 retail sales transactions occurred daily in Washington's Clark and Klickitat counties, just across the Columbia River from Portland. Given that 293,840 vehicles went between Oregon and those counties daily in 2015, according to the Oregon Department of Transportation, "a policy of randomly searching border-crossing vehicles could expect to find diverted recreational marijuana in just 0.47 percent of stops," the researchers concluded.

"You might expect larger diversion when states around a legalized one are not allowing recreational or medical market sales," Hansen said, adding that California, based on this study, likely will experience far less diversion because all of its neighboring states allow for some form of legal marijuana use.

The analysis by the team, which also included UO economist Keaton Miller, also found that randomized searches along Washington's Spokane and Whitman counties with Idaho, where marijuana is illegal, might expect to find illegally transported marijuana at most 4 percent of the time.

In the two months prior to the opening of Oregon's recreational market, 5,624 kilograms (12,398 pounds) of marijuana were sold in Washington; 670 kilograms (1,477 pounds), or 11.9 percent, went across state lines. Factoring in the 41 percent drop in sales along the Oregon border and no decline elsewhere in Washington implies that only 7.5 percent is illegally leaving Washington today, the research team concluded.

"Given the data available, we've been able to study this natural experiment to speak to a question that a lot of people in law enforcement and government care about," Weber said. "If we had instead found that 60 percent of Washington's marijuana was being diverted, then it would have suggested a whole different approach to thinking about legalization moving forward."

Small amounts of illegal, small-scale trafficking is to be expected as long as the U.S. does not have uniform policies, Hansen said.

Based on the data, the researchers concluded, people seem to prefer purchasing recreational marijuana in legal recreational markets instead of through the black market or as medical marijuana or growing their own.

"People value being able to go to a store, seeing the variety of products that are offered there and purchasing it in a retail store," Weber said.

Paper access: http://www.nber.org/papers/w23762

https://www.sciencedaily.com/releases/2017/09/170905134452.htm

Rethinking serotonin could lead to a shift in psychiatric care

September 4, 2017

Science Daily/Imperial College London

A better understanding of how a key chemical messenger acts in the brain could lead to a radical shift in psychiatric care, according to a new research paper.

Serotonin is a neurotransmitter which helps brain cells communicate with one another, playing important roles in stabilising mood and regulating stress.

Despite its importance, current models to explain serotonin's function in the brain remain incomplete.

Now, in a review paper published this month in the Journal of Psychopharmacology, researchers from Imperial College London suggest that serotonin pathways are more nuanced than previously thought.

They argue that the existing view should be updated to incorporate a 'two-pronged' model of how serotonin acts.

The researchers believe their updated model could have implications for treating recalcitrant mental health conditions, including depression, obsessive compulsive disorder and addiction, and could exploit the therapeutic potential of psychedelic drugs.

In the brain, serotonin acts via a number of sites called 'receptors' and serotonin has at least 14 of these. Brain drugs such antidepressants, antipsychotics and psychedelics are known to interact with serotonin receptors and two of these are thought to be particularly important -- the so-called serotonin 1A and 2A receptors.

For patients with depression, commonly prescribed drugs called SSRIs (Selective Serotonin Reuptake Inhibitors) can help to relieve symptoms by boosting levels of serotonin in the brain. Evidence suggests an important part of how they work is to increase activity at the serotonin 1A receptor, which reduces brain activity in important stress circuitry, thereby helping a person cope better.

In contrast, psychedelic compounds such as LSD and psilocybin (the psychoactive component of magic mushrooms), are thought to act primarily on the serotonin 2A receptor. Accumulating evidence suggests that psychedelics with psychotherapy can be an effective treatment for certain mental illnesses and, with a focus on the 2A receptor, the authors' paper attempts to explain why.

Writing in the review paper, the researchers say that while the traditional view of developing psychiatric treatments has been focused on promoting 1A activity and often blocking the 2A, the therapeutic importance of activating the 2A pathway -- the mechanism by which psychedelics have their effect -- has been largely overlooked.

"We may have got it wrong in the past," said Dr Robin Carhart-Harris, Head of Psychedelic Research at Imperial and lead author on the paper. "Activating serotonin 2A receptors may be a good thing, as it makes individuals very sensitive to context and to their environment. Crucially, if that is made therapeutic, then the combination can be very effective. This is how psychedelics work -- they make people sensitive to context and 'open' to change via activating the 2A receptor."

According to the researchers, the 1A and 2A pathways form part of a two-pronged approach which may have evolved to help us adapt to adversity. By triggering the 1A pathway, serotonin can make situations less stressful, helping us to become more resilient. However, they argue that this approach may not always be enough, and that in extreme crises, the 2A pathway may kick in to rapidly open a window of plasticity in which fundamental changes in outlook and behaviour can occur.

Growing evidence shows that in conditions such as treatment-resistant depression, obsessive compulsive disorder and addiction, certain brain circuitry may become 'stamped in' and resistant to change. The researchers suggest that in such cases, activating the 2A pathway -- such as through psychedelics -- could potentially offer a way to break the cycle, helping patients to change negative behaviours and thought patterns which have become entrenched.

By enabling the brain to enter into a more adaptive or 'plastic' state and providing patients with a suitably enriched clinical environment when they receive a drug treatment, clinicians could create a window for therapy, effectively making patients more receptive to psychotherapy.

According to the authors, their updated model of how serotonin acts in the brain could lead to a shift in psychiatric care, with the potential to move patients from enduring a condition using current pharmacological treatments, to actively addressing their condition by fundamentally modifying behaviours and thinking.

Professor David Nutt, Director of Neuropsychopharmacology in Imperial's Division of Brain Sciences, explained: "This is an exciting and novel insight into the role of serotonin and its receptors in recovery from depression that I hope may inspire more research into develop 5-HT2A receptor drugs as new treatments."

Dr Carhart-Harris added: "I think our model suggests that you cannot just administer a drug in isolation, at least certainly not psychedelics, and the same may also true for SSRIs. We need to pay more attention to the context in which medications are given. We have to acknowledge the evidence which shows that environment is a critical component of how our biology is expressed."

He added: "In psychiatry, as in science, things are rarely black and white, and part of the approach we're promoting is to have a more sophisticated model of mental healthcare that isn't just a drug or psychotherapy, it's both. I believe this is the future."

'Serotonin and brain function: a tale of two receptors' by Robin Carhart-Harris and David Nutt is published in the Journal of Psychopharmacology.

https://www.sciencedaily.com/releases/2017/09/170904093724.htm

Magic enzymes in 'magic' mushrooms analyzed

Enzymatic synthesis of psilocybin, the ingredient of magic mushrooms

August 25, 2017

Science Daily/Wiley

Little fungi pack a punch: "Magic mushrooms" of the Psilocybe species produce psychoactive compounds that alter perception when ingested. Recently, the effects on the neuronal system caused by their ingredient psilocybin have attracted the interest of pharmacologists. German scientists have now identified four of the enzymes responsible for the biosynthesis of psilocybin. In the journal Angewandte Chemie, they describe the biosynthetic pathway and introduce a synthetic route that could form the basis of biotechnological production.

For centuries, Central American cultures considered Psilocybe mushrooms to be divine and used them for spiritual purposes. More recently, they have been called magic mushrooms and used for their hallucinogenic effects. These mushroom drugs may soon also be in use as pharmaceuticals that treat the existential anxiety of advanced-stage cancer patients, depression, and nicotine addiction. Their effects stem from tryptamines, which are chemical derivatives of the amino acid L-tryptophan and structural relatives of the neurotransmitters serotonin and melatonin. Among these, psilocybin is the primary chemical mushroom component. Psilocybin is an inactive precursor that is rapidly activated when consumed: splitting off a phosphate group results in the actual active ingredient, psilocin.

Although the structure of psilocybin has been known for about 60 years, it has not been possible to decode the enzymatic basis of its biosynthesis. Researchers working with Dirk Hoffmeister at the Friedrich Schiller University of Jena have now figured this out. They have identified the four enzymes that transform the amino acidy L-tryptophan into psilocybin. Using genetic technology, the researchers were able to produce the enzymes in bacterial and mould fungi cultures and characterize them.

Based on this knowledge, they were also able to clarify the biosynthetic production route, which is different than previously supposed. In the first step of the biosynthesis, an unsusual type of tryptophan decarboxylase splits the carboxyl group off of the amino acid L-tryptophan. A monooxygenase then introduces an alcohol group, to which a kinase subsequently adds a phosphate group. Finally, a methyl transferase adds two methyl groups stepwise to the amino group.

Starting with 4-hydroxy-L-tryptophan and using three of the four fungal enzymes, the scientists were able to enzymatically synthesize psilocybin by a simple method in a combined reaction. Given the pharmaceutical industry's renewed interest in psilocybin, these results may lay the foundation for its biotechnological production.

https://www.sciencedaily.com/releases/2017/08/170825103955.htm

Does marijuana affect kidney function?

August 24, 2017

Science Daily/American Society of Nephrology

A new study found little evidence that marijuana use affects kidney function in healthy young adults. The analysis appears in an upcoming issue of the Clinical Journal of the American Society of Nephrology (CJASN).

Because marijuana is becoming increasingly accepted in the United States, there is a critical need for studies examining its risks and benefits. Regarding kidney health, animal studies suggest that marijuana might affect kidney function, but data in humans are limited.

In the first study of its kind, Julie Ishida, MD, MAS (University of California, San Francisco and San Francisco VA Medical Center) and her colleagues examined the potential links between marijuana use and kidney function in healthy young adults. Their analysis included data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, which contained repeated assessments of marijuana use and kidney outcomes.

The team found that at the start of the study, individuals with higher marijuana use had lower kidney function. Upon follow-up, however, marijuana use was not associated with change in kidney function over time or the appearance of albumin in the urine, which is a sign of kidney damage.

"Results from our observational study in young adults with normal kidney function may not translate into a clinically meaningful difference and may be insufficient to inform decision-making concerning marijuana use; however, it is possible that the association between marijuana use and kidney function could be different in other populations such as older adults or patients with kidney disease, so additional research is needed," said Dr. Ishida.

https://www.sciencedaily.com/releases/2017/08/170824182658.htm

Marijuana associated with three-fold risk of death from hypertension

August 9, 2017

Science Daily/European Society of Cardiology

Marijuana use is associated with a three-fold risk of death from hypertension, according to research published today in the European Journal of Preventive Cardiology.1

"Steps are being taken towards legalisation and decriminalisation of marijuana in the United States, and rates of recreational marijuana use may increase substantially as a result," said lead author Barbara A Yankey, a PhD student in the School of Public Health, Georgia State University, Atlanta, US. "However, there is little research on the impact of marijuana use on cardiovascular and cerebrovascular mortality."

In the absence of longitudinal data on marijuana use, the researchers designed a retrospective follow-up study of NHANES (National Health and Nutrition Examination Survey) participants aged 20 years and above. In 2005-2006, participants were asked if they had ever used marijuana. Those who answered "yes" were considered marijuana users. Participants reported the age when they first tried marijuana and this was subtracted from their current age to calculate the duration of use.

Information on marijuana use was merged with mortality data in 2011 from the National Centre for Health Statistics. The researchers estimated the associations of marijuana use, and duration of use, with death from hypertension, heart disease, and cerebrovascular disease, controlling for cigarette use and demographic variables including sex, age, and ethnicity. Death from hypertension included multiple causes such as primary hypertension and hypertensive renal disease.

Among a total of 1 213 participants, 34% used neither marijuana nor cigarettes, 21% used only marijuana, 20% used marijuana and smoked cigarettes, 16% used marijuana and were past-smokers, 5% were past-smokers and 4% only smoked cigarettes. The average duration of marijuana use was 11.5 years.

Marijuana users had a higher risk of dying from hypertension. Compared to non-users, marijuana users had a 3.42-times higher risk of death from hypertension and a 1.04 greater risk for each year of use. There was no association between marijuana use and death from heart disease or cerebrovascular disease.

Ms Yankey said: "We found that marijuana users had a greater than three-fold risk of death from hypertension and the risk increased with each additional year of use."

Ms Yankey pointed out that there were limitations to the way marijuana use was estimated. For example, it cannot be certain that participants used marijuana continuously since they first tried it.

She said: "Our results suggest a possible risk of hypertension mortality from marijuana use. This is not surprising since marijuana is known to have a number of effects on the cardiovascular system. Marijuana stimulates the sympathetic nervous system, leading to increases in heart rate, blood pressure and oxygen demand. Emergency rooms have reported cases of angina and heart attacks after marijuana use."

The authors stated that the cardiovascular risk associated with marijuana use may be greater than the cardiovascular risk already established for cigarette smoking.

"We found higher estimated cardiovascular risks associated with marijuana use than cigarette smoking," said Ms Yankey. "This indicates that marijuana use may carry even heavier consequences on the cardiovascular system than that already established for cigarette smoking. However, the number of smokers in our study was small and this needs to be examined in a larger study."

"Needless to say, the detrimental effects of marijuana on brain function far exceed that of cigarette smoking," she added.

Ms Yankey said it was crucial to understand the effects of marijuana on health so that policy makers and individuals could make informed decisions.

She said: "Support for liberal marijuana use is partly due to claims that it is beneficial and possibly not harmful to health. With the impending increase in recreational marijuana use it is important to establish whether any health benefits outweigh the potential health, social and economic risks. If marijuana use is implicated in cardiovascular diseases and deaths, then it rests on the health community and policy makers to protect the public."

https://www.sciencedaily.com/releases/2017/08/170809073246.htm

Can psychedelic drugs heal?

Psychologists explore potential benefits of hallucinogens for mental health disorders

August 9, 2018

Science Daily/American Psychological Association

Many people think of psychedelics as relics from the hippie generation or something taken by ravers and music festival-goers, but they may one day be used to treat disorders ranging from social anxiety to depression, according to research presented at the annual convention of the American Psychological Association.

"Combined with psychotherapy, some psychedelic drugs like MDMA, psilocybin and ayahuasca may improve symptoms of anxiety, depression and post-traumatic stress disorder," said Cristina L. Magalhaes, PhD, of Alliant International University Los Angeles, and co-chair of a symposium on psychedelics and psychotherapy. "More research and discussion are needed to understand the possible benefits of these drugs, and psychologists can help navigate the clinical, ethical and cultural issues related to their use."

Hallucinogens have been studied in the U.S. for their potential healing benefits since the discovery of LSD in the 1940s. However, research has mostly stalled since psychedelics were outlawed in the late 1960s.

A shift may be coming soon though, as MDMA, commonly known as ecstasy, is beginning its third and final phase of clinical trials in an effort to win Food and Drug Administration approval for treatment of post-traumatic stress disorder, said Adam Snider, MA, of Alliant International University Los Angeles, and co-chair of the symposium.

Findings from one study presented at the symposium suggested that symptoms of social anxiety in autistic adults may be treatable with a combination of psychotherapy and MDMA. Twelve autistic adults with moderate to severe social anxiety were given two treatments of pure MDMA plus ongoing therapy and showed significant and long-lasting reductions in their symptoms, the research found.

"Social anxiety is prevalent in autistic adults and few treatment options have been shown to be effective," said Alicia Danforth, PhD, of the Los Angeles Biomedical Research Institute at the HarborUCLA Medical Center, who conducted the study. "The positive effects of using MDMA and therapy lasted months, or even years, for most of the research volunteers."

Research discussed also explored how LSD, psilocybin (known colloquially as "magic mushrooms") and ayahuasca (a brew used by indigenous people of the Amazon for spiritual ceremonies) may benefit people with anxiety, depression and eating disorders.

Adele Lafrance, PhD, of Laurentian University, highlighted a study of 159 participants who reported on their past use of hallucinogens, level of spirituality and relationship with their emotions.

Using hallucinogens was related to greater levels of spirituality, which led to improved emotional stability and fewer symptoms of anxiety, depression and disordered eating, the study found.

"This study reinforces the need for the psychological field to consider a larger role for spirituality in the context of mainstream treatment because spiritual growth and a connection to something greater than the self can be fostered," said Lafrance.

Other research presented suggested that ayahuasca may help alleviate depression and addiction, as well as assist people in coping with trauma.

"We found that ayahuasca also fostered an increase in generosity, spiritual connection and altruism," said Clancy Cavnar, PhD, with Núcleo de Estudos Interdisciplinares sobre Psicoativos.

For people suffering from life-threatening cancer, psilocybin may provide significant and lasting decreases in anxiety and distress.

When combined with psychotherapy, psilocybin helped a study's 13 participants grapple with loss and existential distress. It also helped the participants reconcile their feelings about death as nearly all participants reported that they developed a new understanding of dying, according to Gabby Agin-Liebes, BA, of Palo Alto University, who conducted the research.

"Participants made spiritual or religious interpretations of their experience and the psilocybin treatment helped facilitate a reconnection to life, greater mindfulness and presence, and gave them more confidence when faced with cancer recurrence," said Agin-Liebes.

Presenters throughout the symposium discussed the need for more research to fully understand the implications of using psychedelics as an adjunct to psychotherapy as well as the ethical and legal issues that need to be considered.

https://www.sciencedaily.com/releases/2018/08/180809141223.htm

'Ego-dissolving' psychedelic drugs could assist with mental health

August 8, 2017

Science Daily/University of Adelaide

The altered state of consciousness and temporary lack of ego that results from using psychedelic drugs could help some mental health patients recover from their symptoms, according to academics at the University of Adelaide.

Researchers in the University's Department of Philosophy have been studying the body of evidence around the use of psychedelic drugs such as LSD and magic mushrooms, and the impact they have on people's sense of "self."

In a new article published online in Aeon (https://aeon.co/essays/psychedelics-work-by-violating-our-models-of-self-and-the-world), authors Professor Philip Gerrans and recent PhD graduate Dr Chris Letheby say there is growing evidence to suggest that psychedelic experiences can be truly "transformative" -- including helping some people with anxiety, depression, or addiction.

"We know quite a lot about the neurochemistry of psychedelic drugs and how they work on the brain. What's poorly understood is the more complex relationship between the brain, our sense of self, and how we perceive the world," says Professor Gerrans, who has been researching self-representation in psychiatric disorders.

In a recent paper published in the journal Neuroscience of Consciousness, Professor Gerrans and Dr Letheby explain how users of psychedelic drugs often report that their sense of being a self or 'I' -- distinct from the rest of the world -- has diminished or completely "dissolved."

"This 'ego dissolution' results in a moment of expanded awareness, a feeling in which the mind is put more directly and intensely in touch with the world," Professor Gerrans says.

"Through this experience it may be possible to re-engineer the mechanisms of self, which in turn could change people's outlook or world view. The profound sense of connection produced by this experience has the potential to be beneficial for people suffering from anxiety, depression, and some forms of addiction," he says.

Dr Letheby says one of the reasons why psychiatric disorders are so hard to shake is that it's almost impossible for sufferers to view things differently.

"People who go through psychedelic experiences no longer take it for granted that the way they've been viewing things is the only way," Dr Letheby says.

"Psychedelics can assist in enlightening people about the processes behind their subjectivity. Ego dissolution offers vivid experiential proof not only that can things be different, but that there is an opportunity to seek change."

The researchers do not advocate unsupervised recreational use of psychedelic drugs.

"These drugs were originally researched and used as treatments for various psychiatric conditions in the mid-20th century, with psychiatrists in the 1950s claiming success in treating alcoholism and other mental health conditions.

"It may be time for these drugs to make a psychiatric comeback, under controlled circumstances. More research would be needed to establish just how important they could be as part of an overall treatment program," Professor Gerrans says.

https://www.sciencedaily.com/releases/2017/08/170808145443.htm

Compound derived from marijuana interacts with antiepileptic drugs

August 7, 2017

Science Daily/Wiley

New research published in Epilepsia, a journal of the International League Against Epilepsy (ILAE), suggests that an investigational neurological treatment derived from cannabis may alter the blood levels of commonly used antiepileptic drugs. It is important for clinicians to consider such drug interactions during treatment of complex conditions.

Cannabidiol (CBD), a compound developed from the cannabis plant, is being studied as a potential anticonvulsant, and it has demonstrated effectiveness in animal models of epilepsy and in humans. An ongoing open label study (Expanded Access Program) conducted by investigators at the University of Alabama at Birmingham is testing the potential of CBD as a therapy for children and adults with difficult to control epilepsy. The study includes 39 adults and 42 children, all of whom receive CBD.

Because all of the participants are also taking other seizure drugs while they are receiving the investigational therapy, investigators checked the blood levels of their other seizure drugs to see if they changed. "With any new potential seizure medication, it is important to know if drug interactions exist and if there are labs that should be monitored while taking a specific medication," said lead author Tyler Gaston, MD.

Dr. Gaston and her colleagues found that there were significant changes in levels of the drugs clobazam (and its active metabolite N-desmethylclobazam), topiramate, and rufinamide in both adults and children, and zonisamide and eslicarbazepine in adults only. Except for clobazam/desmethylclobazam, however, the drug levels did not change outside of the normally accepted range. In addition, adult participants in the study taking clobazam reported sedation more frequently.

Tests also showed that participants taking valproate and CBD had higher ALT and AST (liver function tests) compared with participants not taking valproate. Very high ALT and AST indicate abnormal liver function, but significant ALT and AST elevation occurred only in a mall number of participants (4 children and 1 adult), and the levels returned to normal after discontinuation of valproate and CBD.

"While the interaction between CBD and clobazam has been established in the literature, there are currently no published human data on CBD's potential interactions with other seizure medications," said Dr. Gaston. "However, given the open label and naturalistic follow-up design of this study, our findings will need to be confirmed under controlled conditions."

The findings emphasize the importance of monitoring blood levels of antiepileptic drugs as well as liver function during treatment with CBD. "A perception exists that since CBD is plant based, that it is natural and safe; and while this may be mostly true, our study shows that CBD, just like other antiepileptic drugs, has interactions with other seizure drugs that patients and providers need to be aware of," said Dr. Gaston.

https://www.sciencedaily.com/releases/2017/08/170807080803.htm