Recreational cannabis, used often, increases risk of gum disease

May 24, 2017

Science Daily/Columbia University Medical Center

Columbia University dental researchers have found that frequent recreational use of cannabis -- including marijuana, hashish, and hash oil -- increases the risk of gum disease.

The study was published in the March issue of the Journal of Periodontology.

Periodontal (gum) disease is an inflammatory reaction to a bacterial infection below the gum line. Left untreated, gum disease can lead to receding gums and tooth loss. Longstanding periodontal disease has also been associated with a number of non-oral health issues, from preterm labor during pregnancy to heart disease.

Jaffer Shariff, DDS, MPH, a postdoctoral resident in periodontology at Columbia University School of Dental Medicine (CDM) and lead author, noticed a possible link between frequent recreational cannabis use and gum disease during his residency at a community-based dental clinic in Manhattan.

"It is well known that frequent tobacco use can increase the risk of periodontal disease, but it was surprising to see that recreational cannabis users may also be at risk," said Dr. Shariff. "The recent spate of new recreational and medical marijuana laws could spell the beginning of a growing oral public health problem."

Dr. Shariff and colleagues from CDM analyzed data from 1,938 U.S. adults who participated in the Centers for Disease Control's 2011-2012 National Health and Nutrition Examination Survey, administered in collaboration with the American Academy of Periodontology. Approximately 27 percent of the participants reported using cannabis one or more times for at least 12 months.

Periodontal exams focus on a patient's gum tissue and connection to the teeth. Among other assessments, periodontists look for plaque, inflammation, bleeding, and gum recession. The clinician uses a probe to measure the space between teeth and their surrounding gum tissue.

Healthy gums fit a tooth snugly, with no more than one to three millimeters of space, known as pocket depth, between the tooth and surrounding gum tissue. Deeper pockets usually indicate presence of periodontitis.

Among the study participants, frequent recreational cannabis users had more sites with pocket depths indicative of moderate to severe periodontal disease than less frequent users.

"Even controlling for other factors linked to gum disease, such as cigarette smoking, frequent recreational cannabis smokers are twice as likely as non-frequent users to have signs of periodontal disease," said Dr. Shariff. "While more research is needed to determine if medical marijuana has a similar impact on oral health, our study findings suggest that dental care providers should ask their patients about cannabis habits."

Commenting on the study, Dr. Terrence J. Griffin, president of the American Academy of Periodontology, said, "At a time when the legalization of recreational and medical marijuana is increasing its use in the United States, users should be made aware of the impact that any form of cannabis can have on the health of their gums."

https://www.sciencedaily.com/releases/2017/05/170524152634.htm

Cannabis reverses aging processes in the brain

Researchers restore the memory performance of Methuselah mice to a juvenile stage

May 8, 2017

Science Daily/University of Bonn

Memory performance decreases with increasing age. Cannabis can reverse these ageing processes in the brain. This was shown in mice by scientists at the University of Bonn with their colleagues at The Hebrew University of Jerusalem (Israel). Old animals were able to regress to the state of two-month-old mice with a prolonged low-dose treatment with a cannabis active ingredient. This opens up new options, for instance, when it comes to treating dementia. The results are now presented in the journal Nature Medicine.

Like any other organ, our brain ages. As a result, cognitive ability also decreases with increasing age. This can be noticed, for instance, in that it becomes more difficult to learn new things or devote attention to several things at the same time. This process is normal, but can also promote dementia. Researchers have long been looking for ways to slow down or even reverse this process.

Scientists at the University of Bonn and The Hebrew University of Jerusalem (Israel) have now achieved this in mice. These animals have a relatively short life expectancy in nature and display pronounced cognitive deficits even at twelve months of age. The researchers administered a small quantity of THC, the active ingredient in the hemp plant (cannabis), to mice aged two, twelve and 18 months over a period of four weeks.

Afterwards, they tested learning capacity and memory performance in the animals -- including, for instance, orientation skills and the recognition of other mice. Mice who were only given a placebo displayed natural age-dependent learning and memory losses. In contrast, the cognitive functions of the animals treated with cannabis were just as good as the two-month-old control animals. "The treatment completely reversed the loss of performance in the old animals," reported Prof. Andreas Zimmer from the Institute of Molecular Psychiatry at the University of Bonn and member of the Cluster of Excellence ImmunoSensation.

Years of meticulous research

This treatment success is the result of years of meticulous research. First of all, the scientists discovered that the brain ages much faster when mice do not possess any functional receptors for THC. These cannabinoid 1 (CB1) receptors are proteins to which the substances dock and thus trigger a signal chain. CB1 is also the reason for the intoxicating effect of THC in cannabis products, such as hashish or marihuana, which accumulate at the receptor. THC imitates the effect of cannabinoids produced naturally in the body, which fulfil important functions in the brain. "With increasing age, the quantity of the cannabinoids naturally formed in the brain reduces," says Prof. Zimmer. "When the activity of the cannabinoid system declines, we find rapid ageing in the brain."

To discover precisely what effect the THC treatment has in old mice, the researchers examined the brain tissue and gene activity of the treated mice. The findings were surprising: the molecular signature no longer corresponded to that of old animals, but was instead very similar to that of young animals. The number of links between the nerve cells in the brain also increased again, which is an important prerequisite for learning ability. "It looked as though the THC treatment turned back the molecular clock," says Zimmer.

Next step: clinical trial on humans

A low dose of the administered THC was chosen so that there was no intoxicating effect in the mice. Cannabis products are already permitted as medications, for instance as pain relief. As a next step, the researchers want to conduct a clinical trial to investigate whether THC also reverses ageing processes in the brain in humans and can increase cognitive ability.

The North Rhine-Westphalia science minister Svenja Schulze appeared thrilled by the study: "The promotion of knowledge-led research is indispensable, as it is the breeding ground for all matters relating to application. Although there is a long path from mice to humans, I feel extremely positive about the prospect that THC could be used to treat dementia, for instance."

https://www.sciencedaily.com/releases/2017/05/170508112400.htm

Evidence of a 'higher' state of consciousness?

Impact of psychedelics on neural signal diversity measured

April 19, 2017

Science Daily/University of Sussex

Scientific evidence of a 'higher' state of consciousness has been found in a study led by the University of Sussex.

Neuroscientists observed a sustained increase in neural signal diversity -- a measure of the complexity of brain activity -- of people under the influence of psychedelic drugs, compared with when they were in a normal waking state.

The diversity of brain signals provides a mathematical index of the level of consciousness. For example, people who are awake have been shown to have more diverse neural activity using this scale than those who are asleep.

This, however, is the first study to show brain-signal diversity that is higher than baseline, that is higher than in someone who is simply 'awake and aware'. Previous studies have tended to focus on lowered states of consciousness, such as sleep, anaesthesia, or the so-called 'vegetative' state.

The team say that more research is needed using more sophisticated and varied models to confirm the results but they are cautiously excited.

Professor Anil Seth, Co-Director of the Sackler Centre for Consciousness Science at the University of Sussex, said: "This finding shows that the brain-on-psychedelics behaves very differently from normal.

"During the psychedelic state, the electrical activity of the brain is less predictable and less 'integrated' than during normal conscious wakefulness -- as measured by 'global signal diversity'.

"Since this measure has already shown its value as a measure of 'conscious level', we can say that the psychedelic state appears as a higher 'level' of consciousness than normal -- but only with respect to this specific mathematical measure."

For the study, Michael Schartner, Adam Barrett and Professor Seth of the Sackler Centre reanalysed data that had previously been collected by Imperial College London and the University of Cardiff in which healthy volunteers were given one of three drugs known to induce a psychedelic state: psilocybin, ketamine and LSD.

Using brain imaging technology, they measured the tiny magnetic fields produced in the brain and found that, across all three drugs, this measure of conscious level -- the neural signal diversity -- was reliably higher.

This does not mean that the psychedelic state is a 'better' or more desirable state of consciousness, the researchers stress; instead, it shows that the psychedelic brain state is distinctive and can be related to other global changes in conscious level (e.g. sleep, anaesthesia) by application of a simple mathematical measure of signal diversity. Dr Muthukumaraswamy who was involved in all three initial studies commented: "That similar changes in signal diversity were found for all three drugs, despite their quite different pharmacology, is both very striking and also reassuring that the results are robust and repeatable."

The findings could help inform discussions gathering momentum about the carefully-controlled medical use of such drugs, for example in treating severe depression.

Dr Robin Cahart-Harris of Imperial College London said: "Rigorous research into psychedelics is gaining increasing attention, not least because of the therapeutic potential that these drugs may have when used sensibly and under medical supervision.

"The present study's findings help us understand what happens in people's brains when they experience an expansion of their consciousness under psychedelics. People often say they experience insight under these drugs -- and when this occurs in a therapeutic context, it can predict positive outcomes. The present findings may help us understand how this can happen."

As well as helping to inform possible medical applications, the study adds to a growing scientific understanding of how conscious level (how conscious one is) and conscious content (what one is conscious of) are related to each other.

Professor Seth said: "We found correlations between the intensity of the psychedelic experience, as reported by volunteers, and changes in signal diversity. This suggests that our measure has close links not only to global brain changes induced by the drugs, but to those aspects of brain dynamics that underlie specific aspects of conscious experience."

The research team are now working hard to identify how specific changes in information flow in the brain underlie specific aspects of psychedelic experience, like hallucinations.

https://www.sciencedaily.com/releases/2017/04/170419091624.htm

Cannabis-based medicine may cut seizures in half for those with tough-to-treat epilepsy

April 18, 2017

Science Daily/American Academy of Neurology

Taking cannabidiol may cut seizures in half for some children and adults with Lennox-Gastaut syndrome (LGS), a severe form of epilepsy, according to new information released today from a large scale controlled clinical study that will be presented at the American Academy of Neurology's 69th Annual Meeting in Boston, April 22 to 28, 2017. Cannabidiol is a molecule from the cannabis plant that does not have the psychoactive properties that create a "high."

Nearly 40 percent of people with LGS, which starts in childhood, had at least a 50 percent reduction in drop seizures when taking a liquid form of cannabidiol compared to 15 percent taking a placebo.

When someone has a drop seizure, their muscle tone changes, causing them to collapse. Children and adults with LGS have multiple kinds of seizures, including drop seizures and tonic-clonic seizures, which involve loss of consciousness and full-body convulsions. The seizures are hard to control and usually do not respond well to medications. Intellectual development is usually impaired in people with LGS.

Although the drop seizures of LGS are often very brief, they frequently lead to injury and trips to the hospital emergency room, so any reduction in drop seizure frequency is a benefit.

"Our study found that cannabidiol shows great promise in that it may reduce seizures that are otherwise difficult to control," said study author Anup Patel, MD, of Nationwide Children's Hospital and The Ohio State University College of Medicine in Columbus and a member of the American Academy of Neurology.

For the randomized, double-blind, placebo-controlled study, researchers followed 225 people with an average age of 16 for 14 weeks. The participants had an average of 85 drop seizures per month, had already tried an average of six epilepsy drugs that did not work for them and were taking an average of three epilepsy drugs during the study.

Participants were given either a higher dose of 20 mg/kg daily cannabidiol, a lower dose of 10 mg/kg daily cannabidiol or placebo as an add-on to their current medications for 14 weeks.

Those taking the higher dose had a 42 percent reduction in drop seizures overall, and for 40 percent, their seizures were reduced by half or more.

Those taking the lower dose had a 37 percent reduction in drop seizures overall, and for 36 percent, seizures were reduced by half or more.

Those taking the placebo had a 17 percent reduction in drop seizures, and for 15 percent, seizures were reduced by half or more.

There were side effects for 94 percent of those taking the higher dose, 84 percent of those taking the lower dose and 72 percent of those taking placebo, but most side effects were reported as mild to moderate. The two most common were decreased appetite and sleepiness.

Those receiving cannabidiol were up to 2.6 times more likely to say their overall condition had improved than those receiving the placebo, with up to 66 percent reporting improvement compared to 44 percent of those receiving the placebo.

"Our results suggest that cannabidiol may be effective for those with Lennox-Gastaut syndrome in treating drop seizures," said Patel. "This is important because this kind of epilepsy is incredibly difficult to treat. While there were more side effects for those taking cannabidiol, they were mostly well-tolerated. I believe that it may become an important new treatment option for these patients."

There is currently a plan to submit a New Drug Application to the FDA later this year.

https://www.sciencedaily.com/releases/2017/04/170418161907.htm

Cannabinoids may soothe certain skin diseases

Anti-inflammatory properties may be the key

April 18, 2017

Science Daily/University of Colorado Anschutz Medical Campus

Cannabinoids contain anti-inflammatory properties that could make them useful in the treatment of a wide-range of skin diseases, according to researchers at the University of Colorado Anschutz Medical Campus.

The new study, published online recently in the Journal of the American Academy of Dermatology, summarizes the current literature on the subject and concludes that pharmaceuticals containing cannabinoids may be effective against eczema, psoriasis, atopic and contact dermatitis.

Currently, 28 states allow comprehensive medical cannabis programs with close to 1 in 10 adult cannabis users in the U.S. utilizing the drug for medical reasons. As researchers examine the drug for use in treating nausea, chronic pain and anorexia, more and more dermatologists are looking into its ability to fight a range of skin disease.

"Perhaps the most promising role for cannabinoids is in the treatment of itch," said the study's senior author Dr. Robert Dellavalle, MD, associate professor of dermatology at the University of Colorado School of Medicine.

He noted that in one study, eight of 21 patients who applied a cannabinoid cream twice a day for three weeks completely eliminated severe itching or pruritus. The drug may have reduced the dry skin that gave rise to the itch.

Dellavalle believes the primary driver in these cannabinoid treatments could be their anti-inflammatory properties. In the studies he and his fellow researchers reviewed, they found that THC (tetrahydrocannabinol) the active ingredient in marijuana, reduced swelling and inflammation in mice.

At the same time, mice with melanoma saw significant inhibition of tumor growth when injected with THC.

"These are topical cannabinoid drugs with little or no psychotropic effect that can be used for skin disease," Dellavalle said.

Still, he cautioned that most of these studies are based on laboratory models and large-scale clinical trials have not been performed. That may change as more and more states legalize cannabis.

Dellavalle said for those who have used other medications for itch and skin disease without success, trying a cannabinoid is a viable option especially if it has no psychotropic effect. He did not recommend such medications for cancer based on current evidence.

"These diseases cause a lot of problems for people and have a direct impact on their quality of life," he said. "The treatments are currently being bought over the internet and we need to educate dermatologists and patients about the potential uses of them."

https://www.sciencedaily.com/releases/2017/04/170418094315.htm

Less fear: How LSD affects the brain

April 4, 2017

Science Daily/Universität Basel

Scientists at the University of Basel have shown that LSD reduces activity in the region of the brain related to the handling of negative emotions like fear. The results, published in the scientific journal Translational Psychiatry, could affect the treatment of mental illnesses such as depression or anxiety.

Hallucinogens have many different effects on the psyche; among other things, they alter perception, thought, and temporal and emotional experience. After the Basel-based chemist Albert Hofmann discovered lysergic acid diethylamide (LSD) in the 1940s, there was a huge amount of interest in the substance, particularly in psychiatry. It was hoped, for example, that it could provide insights into the development of hallucinations, and studies were conducted on its effectiveness on illnesses such as depression or alcohol dependency. In the 1960s, LSD was declared illegal worldwide, and medical research on it came to a standstill.

In the last few years, however, interest in researching hallucinogens for medical purposes has been revived. Psychoactive substances such as LSD, particularly in combination with psychotherapies, could offer an alternative to conventional medication. It is now known that hallucinogens bind to a receptor of the neurotransmitter serotonin; how the changes of consciousness influence the activity and connectivity of the brain, however, is not yet known.

LSD alters brain activity

Researchers at the University Psychiatric Clinics (UPK) and the Department of Pharmacology and Toxicology at the University Hospital Basel (USB) have now conducted a study into the acute effect of LSD on the brain. They used functional magnetic resonance imaging (fMRI) to measure the brain activity of 20 healthy people after taking 100 micrograms of LSD. During the MRI scan, the participants were shown images of faces portraying different emotional states such as anger, joy or fear.

Professor Stefan Borgwardt and his team showed that the depiction of fear under LSD led to a notably lower level of activity in the amygdala -- an area of the brain that is believed to be central to the processing of emotions. This observation could explain some of the changes in emotional experience that occur after taking hallucinogens.

Less fear after taking LSD

In a second step, the researchers, together with clinical pharmacologists at the University Hospital Basel, examined whether the subjective experience altered by LSD is associated with the amygdala. This appears to be the case: the lower the LSD-induced amygdala activity of a subject, the higher the subjective effect of the drug. "This 'de-frightening' effect could be an important factor for positive therapeutic effects," explains Doctor Felix Müller, lead author of the study. The researchers presume that hallucinogens may cause many more changes in brain activity. Further studies will investigate this, with a particular focus on their therapeutic potential.

https://www.sciencedaily.com/releases/2017/04/170404124640.htm

Cannabis use in people with epilepsy revealed: Australian survey

People with epilepsy resort to cannabis products when anti-epileptic drug side-effects are intolerable, epilepsy uncontrolled

March 9, 2017

Science Daily/University of Sydney

The first Australian nationwide survey on the experiences and opinions of medicinal cannabis use in people with epilepsy has revealed that 14 per cent of people with epilepsy have used cannabis products as a way to manage seizures.

The study showed that of those with a history of cannabis product use, 90 per cent of adults and 71 per cent of parents of children with epilepsy reported success in managing seizures after commencing using cannabis products.

Published in Epilepsy & Behaviour, the Epilepsy Action Australia study, in partnership with The Lambert Initiative at the University of Sydney, surveyed 976 respondents to examine cannabis use in people with epilepsy, reasons for use, and any perceived benefits self-reported by consumers (or their carers).

The survey revealed:

* 15 per cent of adults with epilepsy and 13 per cent of parents/guardians of children with epilepsy were currently using, or had previously used, cannabis products to treat epilepsy.

* Across all respondents, the main reasons for trying cannabis products were to manage treatment-resistant epilepsy and to obtain a more favourable side-effect profile compared to standard antiepileptic drugs.

* The number of past antiepileptic drugs was a significant predictor of medicinal cannabis use in both adults and children with epilepsy.

"This survey provides insight into the use of cannabis products for epilepsy, in particular some of the likely factors influencing use, as well as novel insights into the experiences of and attitudes towards medicinal cannabis in people with epilepsy in the Australian community," said lead author Anastasia Suraev from The Lambert Initiative.

"Despite the limitations of a retrospective online survey, we cannot ignore that a significant proportion of adults and children with epilepsy are using cannabis-based products in Australia, and many are self-reporting considerable benefits to their condition.

"More systematic clinical studies are urgently needed to help us better understand the role of cannabinoids in epilepsy," she said.

Co-author of the paper Carol Ireland, CEO of Epilepsy Action Australia, who was recently appointed to the Australian Government's new Australian Advisory Council on the Medicinal Use of Cannabis, said: "Cannabis products are often what people turn to when they have been unable to control their epilepsy with conventional medication."

"This highlights a growing need to educate consumers and health professionals on the use of cannabis by people with epilepsy, and to provide safe and timely access to cannabinoid medicine in order to lessen people's reliance on illicit black-market products" she said.

https://www.sciencedaily.com/releases/2017/03/170309120525.htm

Marijuana use associated with increased risk of stroke, heart failure

As marijuana legalization spreads, better understanding of side effects is needed

March 9, 2017

Science Daily/American College of Cardiology

Using marijuana raises the risk of stroke and heart failure even after accounting for demographic factors, other health conditions and lifestyle risk factors such as smoking and alcohol use, according to research scheduled for presentation at the American College of Cardiology's 66th Annual Scientific Session.

Coming at a time when marijuana, medically known as cannabis, is on track to become legal for medical or recreational use in more than half of U.S. states, this study sheds new light on how the drug affects cardiovascular health. While previous marijuana research has focused mostly on pulmonary and psychiatric complications, the new study is one of only a handful to investigate cardiovascular outcomes.

"Like all other drugs, whether they're prescribed or not prescribed, we want to know the effects and side effects of this drug," said Aditi Kalla, MD, Cardiology Fellow at the Einstein Medical Center in Philadelphia and the study's lead author. "It's important for physicians to know these effects so we can better educate patients, such as those who are inquiring about the safety of cannabis or even asking for a prescription for cannabis."

The study drew data from the Nationwide Inpatient Sample, which includes the health records of patients admitted at more than 1,000 hospitals comprising about 20 percent of U.S. medical centers. Researchers extracted records from young and middle-aged patients -- age 18-55 years -- who were discharged from hospitals in 2009 and 2010, when marijuana use was illegal in most states.

Marijuana use was diagnosed in about 1.5 percent (316,000) of more than 20 million health records included in the analysis. Comparing cardiovascular disease rates in these patients to disease rates in patients not reporting marijuana use, researchers found marijuana use was associated with a significantly increased risk for stroke, heart failure, coronary artery disease and sudden cardiac death.

Marijuana use was also linked with a variety of factors known to increase cardiovascular risk, such as obesity, high blood pressure, smoking and alcohol use. After researchers adjusted the analysis to account for these factors, marijuana use was independently associated with a 26 percent increase in the risk of stroke and a 10 percent increase in the risk of developing heart failure.

"Even when we corrected for known risk factors, we still found a higher rate of both stroke and heart failure in these patients, so that leads us to believe that there is something else going on besides just obesity or diet-related cardiovascular side effects," Kalla said. "More research will be needed to understand the pathophysiology behind this effect."

Research in cell cultures shows that heart muscle cells have cannabis receptors relevant to contractility, or squeezing ability, suggesting that those receptors might be one mechanism through which marijuana use could affect the cardiovascular system. It is possible that other compounds could be developed to counteract that mechanism and reduce cardiovascular risk, Kalla said.

Because the study was based on hospital discharge records, the findings may not be reflective of the general population. The study was also limited by the researchers' inability to account for quantity or frequency of marijuana use, purpose of use (recreational or medical), or delivery mechanism (smoking or ingestion).

Kalla suggested that the growing trend toward legalization of marijuana could mean that patients and doctors will become more comfortable speaking openly about marijuana use, which could allow for better data collection and further insights into the drug's effects and side effects.

https://www.sciencedaily.com/releases/2017/03/170309142318.htm

Experts ask: Can cannabis be made safer?

March 1, 2017

Science Daily/The Lancet

As cannabis laws become liberalised in many countries, experts writing in The Lancet Psychiatry argue that there is an urgent need to explore how cannabis use can be made safer.

The authors say that policy makers and researchers should consider regulating cannabis potency, reducing the use of tobacco (e.g. by using vapourisers), and exploring how the chemical composition of cannabis could be modified to reduce harm without altering the pleasurable effects of the drug.

In the past 40 years, the potency of cannabis has on average doubled worldwide and there is evidence of a greater number of people seeking help for cannabis use disorders in the UK, Europe, and USA.

Despite prohibitive laws on possession and use of cannabis being introduced in the 1960s, cannabis use has increased in most parts of the world, suggesting the laws have had little effect on use and abuse. Uruguay and a number of US states, including California, Oregon, Alaska, Maine, Massachusetts, Washington, Nevada, and Colorado allow cannabis to be sold for recreational purposes. Canada is set to legalise its recreational use in 2017 and several European countries, including Portugal, Spain and the Netherlands, have lessened or abolished sanctions on possession and use.

The main active compounds found in cannabis are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). High potency cannabis is high in THC with low (or absent) levels of CBD. This variety is commonly known as sinsemilla (Spanish meaning "without seed") or sometimes "skunk." Recent evidence suggests that CBD may protect against some of the detrimental effects of THC such as memory impairment and paranoia.

Writing in a Personal View, the authors, from the Institute of Psychiatry, Psychology and Neuroscience at King's College London and UCL (UK), argue that the time has come to consider harm reduction in cannabis use.

First, the authors say more focus on the harms of tobacco is needed since cannabis is frequently used with tobacco, particularly in Europe. For instance, smoke-free vapourisers could help reduce the harmful effects of smoke and avoid the highly addictive properties of tobacco.

Secondly, they say that in countries where cannabis is legalized, the potency of cannabis could potentially be addressed. In parts of the USA where cannabis is legalized, THC is not regulated and extremely potent cannabis products (up to 75% THC) have gained popularity. Some policy makers in the Netherlands and Uruguay have suggested introducing a cap to limit THC content to 15% and more evidence is needed on the effect of these measures. Alternative options might include taxing cannabis according to THC content.

However, the authors argue that these strategies might not be entirely successful, as cannabis users tend to prefer cannabis with a relatively high THC content. Instead, they argue that increasing the levels of CBD could reduce some of the harmful effects of cannabis, without compromising the effects users seek. More research into the harms posed by different levels of THC and CBD content is needed, and this information could potentially contribute to guidelines on safer cannabis use, similar to alcohol.

"Although most users will not develop problems from their cannabis use, it is vital, especially now that cannabis is becoming increasingly liberalised, that we explore alternative and innovative ways by which we can reduce and mitigate cannabis related harms" says Dr Amir Englund, lead author from King's College London. "With the rapidly changing political climate around cannabis, the demand to effectively reduce cannabis-related harms has never been greater, and more research is urgently needed to inform policy decisions. A strategy based on increasing the content of CBD in cannabis might be especially promising because CBD can offset several harms associated with cannabis without compromising its rewarding effects."

Dr Tom Freeman, a co-author and Senior Research Fellow for the Society for the Study of Addiction said: "In the last eight years, the number of people in the UK entering specialist treatment for cannabis increased by over 50%. During the same time period, street cannabis has become increasingly strong with high levels of THC and little or no CBD. Further research on CBD is now needed -- both to investigate its potential role in mitigating the harmful effects of THC in cannabis, but also as a potential treatment for the minority of people who develop problematic cannabis use. Efforts to reduce the common practice of mixing cannabis with tobacco could potentially prevent people progressing to nicotine dependence, providing a substantial benefit for public health."

https://www.sciencedaily.com/releases/2017/03/170301222148.htm

Neurobiologist illuminates the underexplored potential of cannabis to address opioid addiction

February 2, 2017

Science Daily/Mount Sinai Health System

Cannabinoids, extracts of cannabis legally sold as medical marijuana, could reduce cravings and ease withdrawal symptoms in heroin users, a number of animal studies and a small human pilot study have revealed.

A number of animal studies and a small human pilot study have revealed that cannabinoids, extracts of cannabis legally sold as medical marijuana, could reduce cravings and ease withdrawal symptoms in heroin users. In light of the opioid epidemic in the United States, this is a neglected area of research that quickly needs attention, argues Yasmin L. Hurd, PhD, the Ward-Coleman Chair of Translational Neuroscience at the Icahn School of Medicine at Mount Sinai and Director of the Center for Addictive Disorders for the Mount Sinai Behavioral Health System. Dr. Hurd, who studies the molecular and neurochemical effects of both cannabinoids and opioids, discusses her position in a brief review published February 2 in Trends in Neuroscience.

While both cannabinoids and opioids regulate the perception of pain, the two drugs affect different parts of the brain and also affect how the sensation is communicated between neurons. For example, previous research shows that cannabinoids have a stronger effect on inflammation-based chronic pain, while opioids are particularly good at relieving acute pain. Problematically, opioids can quickly lead to a deadly addiction.

"If you look at both drugs and where their receptors are, opioids are much more dangerous in part because of the potential for overdose. The opioid receptors are very abundant in the brainstem area that regulates our respiration so they shut down the breathing center if opioid doses are high," says Dr. Hurd. "Cannabinoids do not do that. They have a much wider window of therapeutic benefit without causing an overdose in adults. However, children have overdosed from consuming edible marijuana so that's something to consider when making decisions regarding medical use."

"Surprisingly, the scientific community has been largely missing from most conversations and policymaking decisions regarding the legalization of marijuana for medical purposes. Normally, preclinical models provide the foundation for clinical trials and then, after years of rigorous, structured scientific investigations, accrued evidence is evaluated by federal agencies to determine whether a particular compound should be approved for the treatment of specific symptoms/disease," explains Dr. Hurd. "For marijuana, such a bar has not been met. Decisions across the country have been driven, in large part, by anecdotal reports and lobbying efforts by a growing marijuana industry. Despite the challenges of prescribing the medical use of a plant without the normal, rigorous clinical study process and within our existing clinical structure, specific constituents of the plant could be more easily developed for medical indications."

Accumulating evidence suggests that cannabinoids could have long-lasting therapeutic effects. Preclinical animal models have long demonstrated that cannabidiol (CBD), a cannabinoid in the marijuana plant devoid of rewarding properties, reduces the rewarding properties of opioid drugs and withdrawal symptoms. Additionally, CBD directly reduces heroin-seeking behavior. A small pilot study in humans, led by Dr. Hurd, mirrored these animal findings. Dr. Hurd's human study revealed that CBD reduced heroin-related, cue-induced craving experienced by heroin users. Moreover, CBD's strongest effects were on the reduction of the anxiety induced by heroin cues.

Politicians are only beginning to acknowledge that an epidemic of opioid overdoses is taking place across the United States, particularly in suburban and rural areas, and the National Institute on Drug Abuse is asking researchers to think creatively about new strategies for pain relief. Marijuana has been a neglected option because there are restrictions on studying its effects in humans. While there has been a growing interest by the scientific community in cannabinoids since the legalization of medical marijuana, we still don't know much about how it could be used therapeutically, despite at least a million people having been issued prescriptions.

"We have to be open to marijuana because there are components of the plant that seem to have therapeutic properties, but without empirical-based research or clinical trials, we're letting anecdotes guide how people vote and how the policies are going to be made," says Dr. Hurd. "For one of the first times in US history, it is the general public and politicians, not scientists and physicians, who are determining the medical value of this drug in states where marijuana use has been legalized for medical purposes. Clearly, the legalization of marijuana has outpaced the science. But if we want to be able to accurately say something is medical marijuana, we have to prove that it is, indeed, medicinal."

https://www.sciencedaily.com/releases/2017/02/170202141322.htm

LSD alters perception via serotonin receptors

January 26, 2017

Science Daily/University of Zurich

Researchers from UZH have discovered how the perception of meaning changes in the brain under the influence of LSD. The serotonin 2A receptors are responsible for altered perception. This finding will help develop new courses of pharmacotherapy for psychiatric disorders such as depression, addictions or phobias.

Humans perceive everyday things and experiences differently and attach different meaning to pieces of music, for instance. In the case of psychiatric disorders, this perception is often altered. For patients suffering from addictions, for instance, drug stimuli are more meaningful than for people without an addiction. Or patients with phobias perceive the things or situations that scare them with exaggerated significance compared to healthy people. A heightened negative perception of the self is also characteristic of depressive patients. Just how this so-called personal relevance develops in the brain and which neuropharmacological mechanisms are behind it, however, have remained unclear.

Researchers from the Department of Psychiatry, Psychotherapy and Psychosomatics at Zurich University Hospital for Psychiatry now reveal that LSD influences this process by stimulating the serotonin 2A receptor, one of the 14 serotonin receptors in the brain. Before the study began, the participants were asked to categorize 30 pieces of music as personally important and meaningful or without any personal relevance. In the subsequent experiment, LSD altered the attribution of meaning compared to a placebo: "Pieces of music previously classified as meaningless suddenly became personally meaningful under the influence of LSD," explains Katrin Preller, who conducted the study in conjunction with Professor Franz Vollenweider and the Neuropsychopharmacology and Brain Imaging research team.

LSD works via the serotonin 2A receptors

Such excessive or exaggerated attributions of meaning to experiences and environmental stimuli occur in various psychiatric disorders. Conversely, a coherent self depends on a functioning network of so-called cortical mid-brain structure, as more recent studies reveal. According to this, the network is impaired in various psychiatric disorders. "LSD now seems to affect this very network and influence the experience of meaning," explains Preller.

With the aid of functional magnetic resonance imaging (fMRT), the scientists were also able to demonstrate that study participants attached greater meaning to previously irrelevant stimuli after taking LSD. If, on the other hand, the serotonin 2A receptor was blocked pharmacologically before LSD was taken, all other psychological changes triggered by LSD were also normalized. "This was very surprising," says Preller. "After all, studies on animals revealed that LSD also stimulates other receptors, such as the dopamine D2 system." It was previously assumed that this might be responsible for the euphoria triggered by LSD and that different receptor systems were involved in the development of experiencing meaning. The results of the current study, however, clearly indicate the key role of the serotonin 2A receptor in both the subjective experience under LSD and the changes in brain activity revealed using fMRT.

Possible approaches for courses pharmacotherapy to treat psychiatric problems

This observation sheds light on how LSD affects the brain neuropharmacologically and especially how the pharmacology of meaning perception works. While the serotonin 2A receptor seems to be responsible for generating new meaning, the dopamine system might regulate the relevance of stimuli we generally deem important. These results may therefore one day benefit people suffering from psychiatric disorders characterized by an altered perception of meaning, such as depression, phobias and addictions.

https://www.sciencedaily.com/releases/2017/01/170126123127.htm

Structure of LSD and its receptor explains its potency

January 26, 2017

Science Daily/Cell Press

Lysergic acid diethylamide -- more commonly known as "LSD" or simply "acid" -- is one of the longest lasting and most potent hallucinogens, but researchers have never understood why LSD's effects linger for 12 hours or more. The key to the drug's psychedelic longevity lies in how it fits into receptors in the brain, as reported in a study appearing January 26 in Cell.

"When I was younger, and The Grateful Dead was still around, I would occasionally go to Grateful Dead concerts. A lot of people took LSD and similar drugs during concerts, and it would be interesting to be in the parking lot hearing people wondering when their LSD experience was going to end," says Bryan Roth, a professor of pharmacology at University of North Carolina and a senior co-author on the study. "A lot of people who take the drug are not aware of just how long it lasts."

Scientists from Roth's lab at UNC captured crystallography images (images showing how a molecule's atoms are arranged) of an LSD molecule bound to a human serotonin receptor and discovered that the LSD molecule was wedged into the receptor's binding pocket at an angle no one had expected. On top of that, part of the receptor protein had folded in over the LSD like a lid, sealing the drug inside.

"Once LSD gets in the receptor, a lid comes over the LSD, so it's basically trapped in the receptor and can't get out," says Roth. "LSD takes a really long time to get on the receptor, and then once it gets on, it doesn't get off," he added.

This finding explains why LSD trips last for a full day, even though LSD doses are extremely small -- the average dose is 100 or so micrograms -- and LSD molecules are cleared from the bloodstream in a couple of hours. Given that there has been a tentative resurgence in testing LSD for some medical conditions, understanding the mechanism of its potent and long-lasting actions may help drug developers design more effective psychiatric drugs with fewer side effects, the researchers say.

While speculative, the study's results may help researchers think about how LSD micro-dosing could work. About 1 in 10 Americans have taken LSD at some point in their life, but increasingly, people are taking LSD at doses too small to cause hallucinations with the goal of boosting their creativity and countering depression. LSD micro-dosing has never been clinically tested, and many scientists have doubted that taking such small amounts of the drug would have any detectable effect. But when Roth's group exposed live cells in a Petri dish to micro-dose-sized amounts of LSD, those tiny doses of LSD affected the receptors' signaling. It's as yet unknown how this signaling would translate into an effect on a person's mood or perception, although the studies demonstrate LSD's remarkably potent actions on cellular signaling.

LSD's ability to fit in and let the receptor's "lid" close over it depends on the specific chemical structures of both the drug and the receptor. When the team exposed cells with mutant receptors that had floppier lids to LSD, the LSD bound more quickly and also exited the receptor much faster. Those short LSD binding events produced very different signaling patterns than the longer binding events.

"I think it's important for the pharmaceutical industry to understand that even if you modify just one tiny aspect of any compound, you may affect the way the entire compound sits in the receptor, and that affects the compound's performance," says study first author Daniel Wacker, a postdoctoral fellow at UNC.

The researchers stressed that they do not advocate LSD use, as it is an illegal and potentially dangerous drug. However, its potential medical applications, and its enormous impact on pop culture, warrant an understanding of its modes of action and ways in which they can be modified.

A separate study on LSD, published January 26 in Current Biology, found that one of the receptors the team tested plays a role in peoples' experience of music while on LSD.

This research was supported by the National Institutes of Health, the National Institute of Mental Health, a Terman Faculty Fellowship, and the Michael Hooker Distinguished Chair of Pharmacology.

https://www.sciencedaily.com/releases/2017/01/170126132541.htm

Answers to how our brains make meaning, with the help of a little LSD

January 26, 2017

Science Daily/Cell Press

We all have particular experiences or particular things -- a favorite song, for example -- that mean much more to us than others. Now, researchers who've studied how perceptions of meaning change when people take the psychedelic drug known as LSD have traced that sense of meaningfulness to particular neurochemicals and receptors in the brain. The findings are reported in Current Biology on January 26.

The findings add to our fundamental understanding of the human experience. They also point to potentially new targets for drugs to treat psychiatric illnesses or phobias, which come with abnormalities in the attribution of personal relevance to particular sensory experiences or cues, the researchers say.

"Our results increase our understanding of how personal relevance attribution is enabled in the brain," says Katrin Preller of the Zürich University Hospital for Psychiatry. "[We now know] which receptors, neurotransmitters, and brain regions are involved when we perceive our environment as meaningful and relevant."

Earlier studies showed that LSD alters the attribution of meaning and personal relevance to the environment, Preller explains. LSD also changes the way people perceive themselves, as the distinction between the self and the world outside the self blurs. But it wasn't clear exactly what parts of the brain and which neurochemicals were responsible.

Preller and colleagues first confirmed the usual effects of LSD on study participants' state of consciousness, mood, and anxiety in the lab. They found that those psychedelic effects of LSD were erased when participants took a second drug called ketanserin that blocked the ability of LSD to act on serotonin receptors known as 5-HT2ARs. That finding came as something of a surprise because LSD is also known to stimulate dopamine receptors, Preller says.

To explore LSD's influence on the way people attribute meaning to things in their world, the researchers asked participants taking a placebo, LSD, or LSD plus ketanserin to rank the meaning attached to a series of songs. Some of those songs were ones that participants told the researchers were particularly meaningful to them. Others were either neutral or without meaning.

The researchers found that musical pieces that were previously meaningless to participants took on special meaning when those individuals were under the influence of LSD. That effect was diminished when participants were given the second drug to counteract LSD's effects on the brain's serotonin receptors. Brain imaging studies also linked those changing attributions of meaning to particular brain areas.

"By combining functional brain imaging and detailed behavioral assessments using a specific experimental paradigm to investigate personal relevance or meaning of music pieces, we were able to elucidate the neurobiological correlates of personal relevance processing in the brain," Preller says. "We found that personal meaning attribution and its modulation by LSD is mediated by the 5-HT2A receptors and cortical midline structures that are also crucially involved in enabling the experience of a sense of self."

Preller says they now plan to explore whether they observe the same effects in response to visual or tactile stimuli. They also hope to explore the relevance of their findings to dysfunctional attributions of meaning in people with psychiatric disorders.

"Excessive stimulation of 5-HT2A receptors seems to underlay the experience of loosening of self/ego boundaries, disrupted self-referential processing and thus the related impairment of making meaning and attributing personal relevance to percepts and experiences seen in various psychiatric disorders," she says. "Therefore, it is important to consider this receptor subtype as potential target for the treatment of psychiatric illnesses characterized by alterations in personal relevance attribution."

A separate study in Cell on the structure of LSD and its receptor, and what this teaches us about the drug's potency, was also published on January 26.

This study was financially supported by grants from the Heffter Research Institute, the Swiss Neuromatrix Foundation, the Usona Institute, and the Swiss National Science Foundation.

https://www.sciencedaily.com/releases/2017/01/170126132544.htm

Testing breast milk for cannabinoids

January 11, 2017

Science Daily/American Chemical Society

With the legalization of medical and recreational marijuana spreading across the country, the drug's use is reportedly increasing among pregnant women. It stands to reason that many of these women will continue to use marijuana after they give birth. Now researchers have developed a new method to help determine what this means for infants' potential exposure to the active compounds in marijuana in breast milk. Their report appears in the journal ACS Omega.

Cannabinoids, marijuana's active compounds such as tetrahydrocannabinol (THC) and cannabinol, like to stick to fat, which is abundant in breast milk. This stickiness suggests that in women who use marijuana, these compounds can end up in breast milk, raising concerns about their potential effects on nursing babies. But the health risks to these infants largely remain undetermined. This is partly due to researchers' limited ability to precisely measure marijuana's active compounds in milk. Current analytical methods can detect THC at levels of 1.5 nanograms per milliliter or higher, but no current method can measure cannabinol or cannabidiol in milk.

Researchers at the Centers for Disease Control and Prevention developed a method that begins with saponification -- a process often associated with soap-making -- to separate cannabinoids from fat in milk. With this approach, the team can detect trace levels (picograms per milliliter) of active marijuana compounds, including cannabinol and cannabidiol, that they say could be present in milk due to second-hand exposure. The test is 100 times better at detecting THC in milk than previous techniques. The researchers say that their approach could contribute to future studies designed to determine potential health risks of a mother's marijuana exposure to her breastfeeding infant.

https://www.sciencedaily.com/releases/2017/01/170111102842.htm

Researchers urge caution around psilocybin use

Survey assesses both risky behaviors and positive outcomes

December 30, 2016

Science Daily/Johns Hopkins Medicine

In a survey of almost 2,000 people who said they had had a past negative experience when taking psilocybin-containing "magic mushrooms," Johns Hopkins researchers say that more than 10 percent believed their worst "bad trip" had put themselves or others in harm's way, and a substantial majority called their most distressing episode one of the top 10 biggest challenges of their lives. Despite the difficulty, however, most of the respondents still reported the experience to be "meaningful" or "worthwhile," with half of these positive responses claiming it as one of the top most valuable experiences in their life.

The results of the survey were published in the Dec. 1 print issue of the Journal of Psychopharmacology.

The researchers caution that their survey results don't apply to all psilocybin mushroom use, since the questionnaire wasn't designed to assess "good trip" experiences. And, the survey wasn't designed to determine how often bad trips occur.

"Considering both the negative effects and the positive outcomes that respondents sometimes reported, the survey results confirm our view that neither users nor researchers can be cavalier about the risks associated with psilocybin," says Roland Griffiths, Ph.D., a psychopharmacologist and professor of psychiatry and behavioral sciences and neurosciences at the Johns Hopkins University School of Medicine. Griffiths has spent more than 15 years conducting studies of psilocybin's capacity to produce profound, mystical-type experiences, treat psychological anxiety and depression and to aid in smoking cessation.

Psilocybin and use of other hallucinogens became popular in the U.S. in the 1960s due to charismatic proponents, who suggested anecdotally that users would experience profound psychological insights and benefits. But drugs such as psilocybin and LSD were banned for supposed safety reasons shortly thereafter, in the 1970s, without much scientific evidence about risks or benefits.

In recent years, Griffiths and his team have conducted more than a dozen studies confirming some of those benefits. The current study was designed, he said, to shed light on the impact of so-called "bad trips."

For the new survey, Griffiths' team used advertisements on social media platforms and email invitations to recruit people who self-reported a difficult or challenging experience while taking psilocybin mushrooms. The survey took about an hour to complete and included three questionnaires: the Hallucinogen Rating Scale, the Mystical Experience Questionnaire, developed by Griffiths and colleagues in 2006, and parts of the 5D-Altered States of Consciousness Questionnaire.

Participants were asked in the survey to focus only on their worst bad trip experience, and then to report about the dose of psilocybin they took, the environment in which the experience occurred, how long it lasted, and strategies available and used to stop this negative experience and any unwanted consequences.

Of 1,993 completed surveys, 78 percent of respondents were men, 89 percent were white, and 51 percent had college or graduate degrees. Sixty-six percent were from the U.S. On average, the survey participants were 30 years old at the time of the survey and 23 years old at the time of their bad trips, with 93 percent responding that they used psilocybin more than two times.

Based on the survey data that assessed each respondent's absolute worst bad trip, 10.7 percent of the respondents said they put themselves or others at risk for physical harm during their bad trip. Some 2.6 percent said they acted aggressively or violently, and 2.7 percent said they sought medical help. Five of the participants with self-reported pre-existing anxiety, depression or suicidal thoughts attempted suicide while on the drug during their worst bad trip, which the researchers say is indicative of requiring a supportive and safe environment during use, like those conditions used in ongoing research studies. However, six people reported that their suicidal thoughts disappeared after their experience on their worst bad trip -- the latter result coinciding with a recent study published by Griffiths showing the antidepressive properties of psilocybin in cancer patients.

Still, Griffiths said, a third of the participants also said their experience was among the top five most meaningful, and a third ranked it in the top five most spiritually significant experiences of their lives. Sixty-two percent of participants said the experience was among the top 10 most difficult ones in their lifetime; 39 percent listed it in their top five most difficult experiences; and 11 percent listed it as their single most difficult experience.

"The counterintuitive finding that extremely difficult experiences can sometimes also be very meaningful experiences is consistent with what we see in our studies with psilocybin -- that resolution of a difficult experience, sometimes described as catharsis, often results in positive personal meaning or spiritual significance," Griffiths says.

¬In all of Griffiths' clinical research, people given psilocybin are provided a safe, comfortable space with trained experts to offer support to participants. "Throughout these carefully managed studies, the incidence of risky behaviors or enduring psychological problems has been extremely low," Griffiths says. "We are vigilant in screening out volunteers who may not be suited to receive psilocybin, and we mentally prepare study participants before their psilocybin sessions."

"Cultures that have long used psilocybin mushrooms for healing or religious purposes have recognized their potential dangers and have developed corresponding safeguards," says Griffiths. "They don't give the mushrooms to just anyone, anytime, without a contained setting and supportive, skillful monitoring."

The researchers say that survey studies like this one rely on self-reporting that cannot be objectively substantiated, and that additional scientifically rigorous studies are needed to better understand the risks and potential benefits of using hallucinogenic drugs.

According to the Substance Abuse and Mental Health Services Administration's National Survey on Drug Use and Health, about 22.9 million people or 8.7 percent of Americans reported prior use of psilocybin. While not without behavioral and psychological risks, psilocybin is not regarded as addictive or as toxic to the brain, liver or other organs.

https://www.sciencedaily.com/releases/2016/12/161230180654.htm

Substance present in ayahuasca brew stimulates generation of human neural cells

Harmine increases the number of neural progenitors, cells that give rise to neurons, study suggests

December 7, 2016

Science Daily/D'Or Institute for Research and Education

Human neural progenitors exposed to harmine, an alkaloid presented at the psychotropic plant decoction ayahuasca, led to a 70 percent increase in proliferation of these cells. The effect of generating new human neural cells involves the inhibition of DYRK1A, a gene that is over activated in patients with Down syndrome and Alzheimer's Disease. Thus harmine could have a potential neurogenesis role and possibly a therapeutic one over cognitive deficits.

Ayahuasca is a beverage that has been used for centuries by Native South-Americans. Studies suggest that it exhibits anxiolytic and antidepressant effects in humans. One of the main substances present in the beverage is harmine, a beta-carboline which potential therapeutic effects for depression has been recently described in mice.

"It has been shown in rodents that antidepressant medication acts by inducing neurogenesis. So we decided to test if harmine, an alkaloid with the highest concentration in the psychotropic plant decoction ayahuasca, would trigger neurogenesis in human neural cells," said Vanja Dakic, PhD student and one of the authors in the study.

In order to elucidate these effects, researchers from the D'Or Institute for Research and Education (IDOR) and the Institute of Biomedical Sciences at the Federal University of Rio de Janeiro (ICB-UFRJ) exposed human neural progenitors to this beta-carboline. After four days, harmine led to a 70% increase in proliferation of human neural progenitor cells.

Researchers were also able to identify how the human neural cells respond to harmine. The described effect involves the inhibition of DYRK1A, which is located on chromosome 21 and is over activated in patients with Down syndrome and Alzheimer's Disease.

"Our results demonstrate that harmine is able to generate new human neural cells, similarly to the effects of classical antidepressant drugs, which frequently are followed by diverse side effects. Moreover, the observation that harmine inhibits DYRK1A in neural cells allows us to speculate about future studies to test its potential therapeutic role over cognitive deficits observed in Down syndrome and neurodegenerative diseases," suggests Stevens Rehen, researcher from IDOR and ICB-UFRJ.

https://www.sciencedaily.com/releases/2016/12/161207124115.htm

Beware: Children can passively 'smoke' marijuana, too

First study to successfully detect traces of marijuana chemicals in children's bodies

December 7, 2016

Science Daily/Springer

Relaxing with a joint around children is not very wise. Not only do youngsters inhale harmful secondary smoke in the process, but the psychoactive chemicals in the drug are taken up by their bodies as well. This warning comes from Karen Wilson of the Icahn School of Medicine at Mount Sinai and the American Academy of Pediatrics Julius B. Richmond Center of Excellence in the US. She led the first study showing that it is possible to pick up traces of THC, the primary psychoactive chemical in marijuana, in the urine of children exposed to secondary marijuana smoke. The findings are published in Springer Nature's journal Pediatric Research.

The two primary active components in marijuana are the psychoactive chemical delta9-tetrahydrocannabinol (THC), and the nonpsychoactive cannabidiol (CBD). Previous analytical methods were mostly developed to measure biomarkers of marijuana in users themselves. In this study, a new and more sensitive analytic method was developed and used by the US Centers for Disease Control and Prevention (CDC) to quantify the trace biomarkers resulting from secondhand marijuana smoke exposure.

The method was used to analyze the urine samples of 43 babies between the ages of one month and two years who were hospitalized with bronchiolitis in Colorado in the US between 2013 and 2015. Their parents also completed a survey about their marijuana smoking habits. The urine samples were analyzed for traces of marijuana metabolites (measured as levels of COOH-THC) and also for cotinine, a biomarker that indicates exposure to tobacco smoke.

COOH-THC was detectable in 16 percent of the samples, at concentrations between 0.04 and 1.5 nanograms per milliliter of urine. Higher concentrations were found in the urine of non-white children compared with white children.

"While documenting the presence of metabolites of THC in children does not imply causation of disease, it does suggest that, like tobacco smoke, marijuana smoke is inhaled by children in the presence of adults who are using it," says Wilson.

In 56 percent of children with detectable COOH-THC levels, more than 2.0 nanograms of cotinine per milliliter of urine were also measured. This indicates that children exposed to marijuana smoke are also more likely to be exposed to tobacco smoke, which increases their risk for cognitive deficits and respiratory ailments.

According to Wilson, more research is needed to investigate if secondhand marijuana smoke exposure is also a health risk. She believes that further high-sensitivity testing will give researchers the opportunity to do so more effectively, and that funds and human resources should be prioritized for such investigations.

"This research will help inform appropriate educational materials and outreach to parents and caregivers who use both marijuana and tobacco in the presence of their children," she says.

Wilson also supports the inclusion of a parent report screening question for institutions in areas where marijuana is legal, so that those who report household marijuana smoking can be counseled on how to reduce potentially harmful secondhand smoke exposure of their children.

https://www.sciencedaily.com/releases/2016/12/161207124123.htm

Hallucinogenic drug psilocybin eases existential anxiety in people with life-threatening cancer

December 1, 2016

Science Daily/Johns Hopkins Medicine

In a small double-blind study, Johns Hopkins researchers report that a substantial majority of people suffering cancer-related anxiety or depression found considerable relief for up to six months from a single large dose of psilocybin -- the active compound in hallucinogenic "magic mushrooms."

The researchers cautioned that the drug was given in tightly controlled conditions in the presence of two clinically trained monitors and said they do not recommend use of the compound outside of such a research or patient care setting.

The Johns Hopkins team released its study results, involving 51 adult patients, concurrently with researchers from New York University Langone Medical Center, who conducted a similarly designed study on 29 participants. Both studies are published in the Journal of Psychopharmacology on Dec. 1.

The Johns Hopkins group reported that psilocybin decreased clinician- and patient-rated depressed mood, anxiety and death anxiety, and increased quality of life, life meaning and optimism. Six months after the final session of treatment, about 80 percent of participants continued to show clinically significant decreases in depressed mood and anxiety, with about 60 percent showing symptom remission into the normal range. Eighty-three percent reported increases in well-being or life satisfaction. Some 67 percent of participants reported the experience as one of the top five meaningful experiences in their lives, and about 70 percent reported the experience as one of the top five spiritually significant lifetime events.

"The most interesting and remarkable finding is that a single dose of psilocybin, which lasts four to six hours, produced enduring decreases in depression and anxiety symptoms, and this may represent a fascinating new model for treating some psychiatric conditions," says Roland Griffiths, Ph.D., professor of behavioral biology in the Departments of Psychiatry and Behavioral Sciences and of Neuroscience at the Johns Hopkins University School of Medicine. He notes that traditional psychotherapy offered to people with cancer, including behavioral therapy and antidepressants, can take weeks or even months, isn't always effective, and in the case of some drugs, such as benzodiazepines, may have addictive and other troubling side effects.

Griffiths says his team's new study grew out of a decade of research at Johns Hopkins on the effects of psilocybin in healthy volunteers, which found that psilocybin can consistently produce positive changes in mood, behavior and spirituality when administered to carefully screened and prepared participants. The study was designed to see if psilocybin could produce similar results in psychologically distressed cancer patients.

"A life-threatening cancer diagnosis can be psychologically challenging, with anxiety and depression as very common symptoms," says Griffiths. "People with this kind of existential anxiety often feel hopeless and are worried about the meaning of life and what happens upon death."

For the study, the investigators recruited 51 participants diagnosed with life-threatening cancers, most of which were recurrent or metastatic. They were chosen from a total of 566 individuals reached through flyers, web advertisements and physician referrals. Most participants had breast, upper digestive, GI, genitourinary or blood cancer, and each had been given a formal psychiatric diagnosis, including an anxiety or depressive disorder.

Half of the participants were female with an average age of 56. Ninety-two percent were white, 4 percent were African-American and 2 percent were Asian.

Each participant had two treatment sessions scheduled five weeks apart, one with a very low psilocybin dose (1 or3 milligrams per 70 kilograms) taken in a capsule and meant to act as a "control" placebo because the dose was too low to produce effects. In the other session, participants received a capsule with what is considered a moderate or high dose (22 or 30 milligrams per 70 kilograms).

To minimize expectancy effects, the participants and the staff members supervising the sessions were told that the participants would receive psilocybin on both sessions, but they did not know that all participants would receive one high and one low dose. Blood pressure and mood were monitored throughout the sessions. Two monitors aided participants during each session, encouraging them to lie down, wear an eye mask, listen to music through headphones and direct their attention on their inner experience. If anxiety or confusion arose, the monitors provided reassurance to the participants.

In addition to experiencing changes in visual perception, emotions and thinking, most participants reported experiences of psychological insight and often profound, deeply meaningful experiences of the interconnectedness of all people.

The researchers assessed each participant's mood, attitude about life, behaviors and spirituality with questionnaires and structured interviews before the first session, seven hours after taking the psilocybin, five weeks after each session and six months after the second session. Immediately after the sessions, participants completed questionnaires assessing changes in visual, auditory and body perceptions; feelings of transcendence; changes in mood; and more.

Structured clinical interviews, such as the Hamilton Depression Rating Scale and the Hamilton Anxiety Rating Scale, and patient questionnaires, like the Beck Depression Inventory and the State-Trait Anxiety Inventory, assessed depression and anxiety. Other questionnaires assessed quality of life, death acceptance, meaningful existence, optimism and spirituality -- generally defined as a search for the meaning of life and a connection to something bigger than one's self. To measure the changes in attitudes, moods and behavior over time, the researchers administered a questionnaire that assessed negative or positive changes in attitudes about life, mood and behavior.

With regard to adverse effects, Griffiths says 15 percent of participants were nauseated or vomited, and one-third of participants experienced some psychological discomfort, such as anxiety or paranoia, after taking the higher dose. One-third of the participants had transient increases in blood pressure. A few participants reported headaches following the session.

"Before beginning the study, it wasn't clear to me that this treatment would be helpful, since cancer patients may experience profound hopelessness in response to their diagnosis, which is often followed by multiple surgeries and prolonged chemotherapy," says Griffiths. "I could imagine that cancer patients would receive psilocybin, look into the existential void and come out even more fearful. However, the positive changes in attitudes, moods and behavior that we documented in healthy volunteers were replicated in cancer patients."

Up to 40 percent of people with cancer suffer from a mood disorder, according to the National Comprehensive Cancer Network.

Anticipating wide interest in the psilocybin research from scientists, clinicians and the public, the journal solicited 11 commentaries to be co-published with the study results written by luminaries in psychiatry, palliative care and drug regulation, including two past presidents of the American Psychiatric Association, a past president of the European College of Neuropsychopharmacology, the former deputy director of the U.S. Office of National Drug Control Policy, and the former head of the U.K. Medicines and Healthcare Products Regulatory Authority. In general, the commentaries were supportive of the research and of using these drugs in a clinical setting as tools for psychiatry.

https://www.sciencedaily.com/releases/2016/12/161201094448.htm

Kratom may have medical benefit as opioid alternative

November 28, 2016

Science Daily/American Osteopathic Association

A delayed U.S. Drug Enforcement Administration ban on kratom would stifle scientific understanding of the herb's active chemical components and documented pharmacologic properties if implemented, according to a special report published in The Journal of the American Osteopathic Association.

The report cited the pharmacologically active compounds in kratom, including mitragynine, 7-hydroxymitragynine, paynantheine, speciogynine and 20 other substances, as one basis for further study. It also emphasized the extensive amount of anecdotal evidence and current scientific research that indicates kratom may be safer and less addictive than current treatments for pain and opioid withdrawal.

"There's no question kratom compounds have complex and potential useful pharmacologic activities and they produce chemically different actions from opioids," said author Walter Prozialeck, chairman of the Department of Pharmacology at Midwestern University Chicago College of Osteopathic Medicine. "Kratom doesn't produce an intense euphoria and, even at very high doses, it doesn't depress respiration, which could make it safer for users."

Kratom (Mitragyna speciosa) is indigenous to Southeast Asia, where the plant was used for centuries to relieve fatigue, pain, cough and diarrhea and aid in opioid withdrawal. Currently sold in the United States as an herbal supplement, kratom drew DEA scrutiny after poison control centers noted 660 reports of adverse reactions to kratom products between January 2010 and December 2015.

"Many important medications, including the breast cancer treatment tamoxifen, were developed from plant research," said Prozialeck.

"While the DEA and physicians have valid safety concerns, it is not at all clear that kratom is the culprit behind the adverse effects," said Anita Gupta, DO, PharmD and special advisor to the FDA.

Dr. Gupta, an osteopathic anesthesiologist, pain specialist and licensed pharmacist, has treated a number of patients who've used kratom. "Many of my patients are seeking non-pharmaceutical remedies to treat pain that lack the side effects, risk, and addiction potential of opioids," she said.

Kratom is currently banned in states including Alabama, Florida, Indiana, Arkansas, Wisconsin and Tennessee. The DEA is scheduled to decide whether to place kratom on its list of Schedule 1 drugs, a classification for compounds thought to have no known medical benefit. Marijuana, LSD and heroin are Schedule 1 drugs, which prevents the vast majority of U.S.-based researchers from studying those substances.

https://www.sciencedaily.com/releases/2016/11/161128132148.htm

THC in marijuana makes rats lazy, less willing to try cognitively demanding tasks

August 24, 2016

Science Daily/University of British Columbia

New research from the University of British Columbia suggests there may be some truth to the belief that marijuana use causes laziness -- at least in rats.

The study, published today in the Journal of Psychiatry and Neuroscience, found that tetrahydrocannabinol (THC), the main psychoactive ingredient in marijuana, makes rats less willing to try a cognitively demanding task.

"Perhaps unsurprisingly, we found that when we gave THC to these rats, they basically became cognitively lazy," said Mason Silveira, the study's lead author and a PhD candidate in UBC's department of psychology. "What's interesting, however, is that their ability to do the difficult challenge was unaffected by THC. The rats could still do the task -- they just didn't want to."

For the study, researchers looked at the effects of both THC and cannabidiol (CBD) on rats' willingness to exert cognitive effort.

They trained 29 rats to perform a behavioural experiment in which the animals had to choose whether they wanted an easy or difficult challenge to earn sugary treats.

Under normal circumstances, most rats preferred the harder challenge to earn a bigger reward. But when the rats were given THC, the animals switched to the easier option, despite earning a smaller reward.

When they looked at the effect of CBD, an ingredient in marijuana that does not result in a high, researchers found the chemical did not have any effect on rats' decision-making or attention. CBD, which is believed to be beneficial in treating pain, epilepsy and even cancer, also didn't block the negative effects of THC.

"This was surprising, as it had been suggested that high concentrations of CBD could modulate or reduce the negative effects of THC," said Catharine Winstanley, senior author of the study and an associate professor in UBC's department of psychology. "Unfortunately, that did not appear to be the case."

Given how essential willingness to exert cognitive effort is for people to achieve success, Winstanley said the findings underscore the importance of realizing the possible effect of cannabis use on impairing willingness to engage in harder tasks.

While some people view marijuana as a panacea that can cure all ailments, the findings also highlight a need for more research to determine what THC does to the human brain to alter decision-making. That could eventually allow scientists to block these effects of THC, allowing those who use medical marijuana to enjoy the possible benefits of cannabis without the less desirable cognitive effects.

At the beginning of each behavioural experiment, rats chose between two levers to signal whether they wanted an easy or hard challenge.

Choosing the easy challenge resulted in a light turning on for one second, which the rats could easily detect and respond to by poking it with their nose, receiving one sugar pellet as a reward. In the more difficult challenge, the light turned on for only 0.2 seconds, rewarding the rat with two sugar pellets if they responded with a nose poke.

Video:https://www.youtube.com/watch?v=jbR5Wen_b5Y

https://www.sciencedaily.com/releases/2016/08/160824144033.htm