Cannabidiol for treating seizures show promise

Cannabidiol for treating seizures show promise

March 3, 2016

Science Daily/University of Alabama at Birmingham

Researchers have presented the first findings of a large study of cannabidiol for treating seizures.

Investigators with the University of Alabama at Birmingham Cannabidiol Program will present the first results drawn from the CBD oil studies underway at UAB and Children's of Alabama. Three abstracts will be presented at the annual meeting of the American Academy of Neurology in Vancouver, Canada.

The abstracts describe results from the first 51 subjects enrolled in the studies. Among other findings, the researchers report that approximately 50 percent of the subjects responded to the CBD oil therapy with overall sustained improvement in seizure control over a six-month period. Seizures declined between 32 and 45 percent in the responders, depending on the CBD dose. Two patients were seizure-free, and nine dropped out due to side effects or lack of efficacy.

UAB launched the studies of CBD oil as a treatment for severe, intractable seizures in April of 2015. The studies, an adult study at UAB and a pediatric study at Children's of Alabama, were authorized by the Alabama Legislature in 2014 by legislation known as Carly's Law.

The studies are designed to test the safety and tolerability of CBD oil in patients with intractable seizures. CBD oil, a derivative of the cannabis plant, is delivered orally as an oily liquid.

"The studies are ongoing, and we have a lot more to learn; but these preliminary findings are encouraging," said Jerzy Szaflarski, M.D., Ph.D., professor in the Department of Neurology, principal investigator of the adult study. "Among our goals was to determine the safety of CBD oil therapy, and it appears that, in many cases, patients tolerate the oil quite well. The evidence of seizure reduction gives us hope that, the more we learn about CBD oil, the better we will be able to tailor this therapy to provide relief for those with severe epilepsy."

The oil used in the studies is produced under stringent requirements of the United States Food and Drug Administration by a licensed pharmaceutical company. It contains only traces of THC, the psychoactive component of marijuana. The process developed by GW Pharmaceuticals guarantees the consistency of the product that is provided to study participants.

"The studies thus far show that the administration of CBD oil is a complex undertaking," said Martina Bebin, M.D., professor of neurology and principal investigator for the pediatric study. "Some patients respond well, but others either have no improvement or experience significant side effects. CBD is not a panacea, and it's not for everyone. But many patients do have a reduction in seizure activity, and we hope our efforts will further define how to best utilize CBD oil for maximum benefit to the appropriate patient population."

Tyler Gaston, M.D., a clinical neurophysiology fellow, led a study of potential interactions between CBD and clobazam, a commonly prescribed anti-epileptic medication. The investigators suspected that CBD treatment might cause an increase in the blood levels of clobazam and its metabolite, N-desmethylclobazam, leading to adverse events including sedation. Seventeen patients in the studies were taking clobazam, and investigators found clear evidence for an interaction, with rising clobazam levels during CBD therapy. This finding highlights the importance of monitoring clobazam and N-desmethylclobazam levels when treating patients with CBD, and the results underscore the importance of the new knowledge gained through the UAB CBD program.

A study headed by Leslie Perry, M.D., also a clinical neurophysiology fellow, looked at the effect of CBD oil therapy on electroencephalography, or EEG. EEG is the standard test to measure electrical activity in the brain. The same cohort of 51 patients received EEG tests prior to beginning CBD therapy and then again after CBD therapy had begun. The investigators report that CBD does not appear to have a negative effect on standard EEG parameters. However, the authors acknowledge that the conclusion is limited by the relatively short duration of both the EEG and the length of time from the tests done prior to beginning CBD therapy and then during therapy.

Another abstract, led by Jane Allendorfer, Ph.D., assistant professor of neurology, will be presented at the annual meeting of the Organization for Human Brain Mapping in Geneva, Switzerland. In her work, she evaluated the effects of CBD treatment on attention circuits in the brain using functional MRI. Eight patients underwent fMRI before treatment with CBD and while taking CBD. Their scanning showed improved activation of brain regions important for attention. The authors conclude that these preliminary results are promising and illustrate the potential of CBD treatment to improve not only seizure control but also cognition in patients with poorly controlled epilepsy.

The ongoing UAB CBD studies currently have 40 children and 39 adults enrolled.

https://www.sciencedaily.com/releases/2016/03/160303204007.htm

Psilocybin inhibits the processing of negative emotions in the brain

May 7, 2014

Science Daily/University of Zurich

Emotions like fear, anger, sadness, and joy enable people to adjust to their environment and react flexibly to stress and strain and are vital for cognitive processes, physiological reactions, and social behaviour. The processing of emotions is closely linked to structures in the brain, i.e. to what is known as the limbic system. Within this system the amygdala plays a central role -- above all it processes negative emotions like anxiety and fear. If the activity of the amygdala becomes unbalanced, depression and anxiety disorders may develop.

Researchers at the Psychiatric University Hospital of Zurich have now shown that psilocybin, the bioactive component in the Mexican magic mushroom, influences the amygdala, thereby weakening the processing of negative stimuli. These findings could "point the way to novel approaches to treatment" comments the lead author Rainer Krähenmann on the results which have now been published in the medical journal Biological Psychiatry.

Psilocybin inhibits the processing of negative emotions in the amygdala

The processing of emotions can be impaired by various causes and elicit mental disorders. Elevated activity of the amygdala in response to stimuli leads to the neurons strengthening negative signals and weakening the processing of positive ones. This mechanism plays an important role in the development of depression and anxiety disorders. Psilocybin intervenes specifically in this mechanism as shown by Dr. Rainer Krähenmann's research team of the Neuropsychopharmacology and Brain Imaging Unit led by Prof. Dr. Franz Vollenweider.

Psilocybin positively influences mood in healthy individuals. In the brain, this substance stimulates specific docking sites for the messenger serotonin. The scientists therefore assumed that psilocybin exerts its mood-brightening effect via a change in the serotonin system in the limbic brain regions. This could, in fact, be demonstrated using functional magnetic resonance imaging (fMRI). "Even a moderate dose of psilocybin weakens the processing of negative stimuli by modifying amygdala activity in the limbic system as well as in other associated brain regions," continues Krähenmann. The study clearly shows that the modulation of amygdalaactivity is directly linked to the experience of heightened mood.

Next study with depressive patients

According to Krähenmann, this observation is of major clinical importance. Depressive patients in particular react more to negative stimuli and their thoughts often revolve around negative contents. Hence, the neuropharmacologists now wish to elucidate in further studies whether psilocybin normalises the exaggerated processing of negative stimuli as seen in neuroimaging studies of depressed patients -- and may consequently lead to improved mood in these patients. .

Rainer Krähenmann considers research into novel approaches to treatment very important, because current available drugs for the treatment of depression and anxiety disorders are not effective in all patients and are often associated with unwanted side effects.

https://www.sciencedaily.com/releases/2014/05/140507095756.htm

Medical marijuana in treatment of certain brain diseases: Experts weigh in

April 28, 2014

Science Daily/American Academy of Neurology (AAN)

A review by the American Academy of Neurology of available scientific research on the use of medical marijuana in brain diseases finds certain forms of medical marijuana can help treat some symptoms of multiple sclerosis (MS), but do not appear to be helpful in treating drug-induced (levodopa) movements in Parkinson's disease. Not enough evidence was found to show if medical marijuana is helpful in treating motor problems in Huntington's disease, tics in Tourette syndrome, cervical dystonia and seizures in epilepsy. The review is published in the April 29, 2014, print issue of Neurology®, the medical journal of the American Academy of Neurology (AAN), and will be presented at the AAN Annual Meeting in Philadelphia, April 26-May 3, 2014, which is the world's largest gathering of neurologists.

"This review by the world's largest association for neurologists is intended to help neurologists and their patients understand the current research on medical marijuana for the treatment of certain brain diseases," said review author Barbara S. Koppel, MD, of New York Medical College in New York and Fellow of the American Academy of Neurology. "The AAN review also highlights the need for more high-quality studies of the long-term efficacy and safety of medical marijuana in the treatment of neurologic diseases."

The AAN review concluded that certain forms of medical marijuana (only in pill or oral spray form) can help treat some symptoms of MS. These include spasticity, certain types of pain (pain related to spasticity, including painful spasms, and painful burning and numbness) and overactive bladder.

Most of the MS studies examined pill or oral spray forms of medical marijuana. There were two studies that examined smoked medical marijuana for treating MS symptoms. However, the studies did not provide enough information to show if smoked medical marijuana is effective. "It's important to note that medical marijuana can worsen thinking and memory problems, and this is a concern since many people with MS suffer from these problems already due to the disease itself," said Koppel.

For Parkinson's disease, the AAN review concluded that medical marijuana in the form of synthetic tetrahydrocannabinol (THC) pills likely does not help relieve abnormal movements that can develop in the late stages of the disease from the drug levodopa, which is the main drug used to treat shaking, stiffness and slowness of movements.

The AAN review also concluded that there is not enough information to show if medical marijuana, including smoked medical marijuana, is safe or effective in these neurologic diseases: • Motor symptoms in Huntington's disease • Tics in Tourette syndrome • Cervical dystonia (abnormal neck movements) • Seizures in epilepsy

There are safety concerns with medical marijuana use. Side effects reported in at least two studies were nausea, increased weakness, behavioral or mood changes, suicidal thoughts or hallucinations, dizziness or fainting symptoms, fatigue, and feelings of intoxication. There was one report of a seizure.

Mood changes and suicidal thoughts are of special concern for people with MS, who are at an increased risk for depression or suicide. The studies showed the risk of serious psychological effects is about 1 percent, or one in every 100 people.

In general, medical marijuana is prescribed as a treatment for use only when standard treatment has not helped.

https://www.sciencedaily.com/releases/2014/04/140428163633.htm

Herbal cannabis not recommended for rheumatology patients

March 3, 2014

Science Daily/Wiley

Patients with rheumatic conditions are in need of symptom relief and some are turning to herbal cannabis as a treatment option. However, the effectiveness and safety of medical marijuana to treat symptoms of rheumatic conditions such as rheumatoid arthritis, lupus, or fibromyalgia is not supported by medical evidence. A new article published in Arthritis Care & Research, a journal of the American College of Rheumatology (ACR), explores the risks associated with using herbal cannabis for medicinal purposes and advises healthcare providers to discourage rheumatology patients from using this drug as therapy.

The reason for the medical interest in herbal cannabis is that the human body has an extensive cannabinoid system comprising molecules and receptors that have effects on many functions including pain modulation. Medical cannabis is commonly used to self-treat severe pain associated with arthritis and musculoskeletal pain. In fact, previous research reports that 80% of marijuana users in a U.S. pain clinic are treating myofascial pain with the drug. In population studies in the U.K. and Australia, up to 33% of individuals report using marijuana to treat arthritis pain. As of June 2013, estimates from the office of Information Commissioner of Canada list "severe arthritis" as the reason the 65% of Canadians who are allowed to possess marijuana for medicinal purposes.

"With the public outcry for herbal cannabis therapy, governments around the world are considering its legalization for medicinal use," explains lead investigator Dr. Mary-Ann Fitzcharles, a researcher and rheumatologist at the McGill University Health Centre (MUHC) and the Research Institute of the MUHC in Quebec, Canada. "Physicians caring for patients who are self-medicating with marijuana need to understand the health implications of using this drug. Our study aims to provide health care professionals with that medical evidence related to medical marijuana use in patients with rheumatic conditions."

In the U.S. twenty states, including the District of Columbia (DC), have legalized cannabis for medical purposes. The present study examines the dosing, administration, efficacy and risks of herbal cannabis in pain management for patients with rheumatic conditions. The health issues with recreational marijuana use in this patient population are not covered.

Concentrations of tetrahydrocannabinol (THC) -- the substance found in Cannabis sativa that provides pain relief and alters brain function (psychoactive effect) -- vary in the plant material by up to 33% and absorption rates are between 2% and 56%, making the dosing of herbal cannabis unreliable. While cannabis may be ingested, most users prefer to inhale the compound for a quicker response. However, smoking a "joint" is not recommended by the medical community due to adverse effects on the respiratory system from hydrocarbons, tar and carbon monoxide.

Furthermore, there is no formal short-term or long-term study of the effectiveness of herbal cannabis in patients with rheumatic diseases. Studies that show good efficacy of cannabinoids for cancer and neuropathic pain may not be extended to rheumatic diseases because of the differing mechanism in the types of pain.

The study authors highlight that use of medical marijuana comes with inherent risks such as compromised cognitive and psychomotor function. Long-term use of cannabis may lead to mental illness, dependence, addiction and memory issues. In fact, a prior U.S. study of 8,000 adults who used cannabis in the previous year found that the odds of depression were 1.4 times higher in cannabis users compared to non-users.

"At this time, we cannot recommend herbal cannabis for arthritis pain management given the lack of efficacy data, potential harm from the drug, and availability of other therapies for managing pain," concludes Dr. Fitzcharles. "Physicians should discourage rheumatology patients from using medical marijuana as a therapy."

https://www.sciencedaily.com/releases/2014/03/140303083543.htm

Study reveals how ecstasy acts on brain, hints at therapeutic uses

January 17, 2014

Science Daily/Imperial College London

Brain imaging experiments have revealed for the first time how ecstasy produces feelings of euphoria in users.

Results of the study at Imperial College London, parts of which were televised in Drugs Live on Channel 4 in 2012, have now been published in the journal Biological Psychiatry.

The findings hint at ways that ecstasy, or MDMA, might be useful in the treatment of anxiety and post-traumatic stress disorder (PTSD).

MDMA has been a popular recreational drug since the 1980s, but there has been little research on which areas of the brain it affects. The new study is the first to use functional magnetic resonance imaging (fMRI) on resting subjects under its influence.

Twenty-five volunteers underwent brain scans on two occasions, one after taking the drug and one after taking a placebo, without knowing which they had been given.

The results show that MDMA decreases activity in the limbic system -- a set of structures involved in emotional responses. These effects were stronger in subjects who reported stronger subjective experiences, suggesting that they are related.

Communication between the medial temporal lobe and medial prefrontal cortex, which is involved in emotional control, was reduced. This effect, and the drop in activity in the limbic system, are opposite to patterns seen in patients who suffer from anxiety.

MDMA also increased communication between the amygdala and the hippocampus. Studies on patients with PTSD have found a reduction in communication between these areas.

The project was led by David Nutt, the Edmond J. Safra Professor of Neuropsychopharmacology at Imperial College London, and Professor Val Curran at UCL.

Dr Robin Carhart-Harris from the Department of Medicine at Imperial, who performed the research, said: "We found that MDMA caused reduced blood flow in regions of the brain linked to emotion and memory. These effects may be related to the feelings of euphoria that people experience on the drug."

Professor Nutt added: "The findings suggest possible clinical uses of MDMA in treating anxiety and PTSD, but we need to be careful about drawing too many conclusions from a study in healthy volunteers. We would have to do studies in patients to see if we find the same effects."

MDMA has been investigated as an adjunct to psychotherapy in the treatment of PTSD, with a recent pilot study in the US reporting positive preliminary results.

As part of the Imperial study, the volunteers were asked to recall their favourite and worst memories while inside the scanner. They rated their favourite memories as more vivid, emotionally intense and positive after MDMA than placebo, and they rated their worst memories less negatively. This was reflected in the way that parts of the brain were activated more or less strongly under MDMA. These results were published in the International Journal of Neuropsychopharmacology.

Dr Carhart-Harris said: "In healthy volunteers, MDMA seems to lessen the impact of painful memories. This fits with the idea that it could help patients with PTSD revisit their traumatic experiences in psychotherapy without being overwhelmed by negative emotions, but we need to do studies in PTSD patients to see if the drug affects them in the same way."

https://www.sciencedaily.com/releases/2014/01/140117103941.htm

Non-hallucinogenic cannabinoids are effective anti-cancer drugs

October 14, 2013

Science Daily/University of St George's London

New research has shown that the non-hallucinogenic components of cannabis could act as effective anti-cancer agents.

The anti-cancer properties of tetrahydrocannabinol (THC), the primary hallucinogenic component of cannabis, has been recognised for many years, but research into similar cannabis-derived compounds, known as cannabinoids, has been limited.

The study was carried out by a team at St George's, University of London. It has been published in the journal Anticancer Research.

The team, led by Dr Wai Liu and colleagues carried out laboratory investigations using a number of cannabinoids, either alone or in combination with each other, to measure their anti-cancer actions in relation to leukemia.

Of six cannabinoids studied, each demonstrated anti-cancer properties as effective as those seen in THC. Importantly, they had an increased effect on cancer cells when combined with each other.

Dr Liu said: "This study is a critical step in unpicking the mysteries of cannabis as a source of medicine. The cannabinoids examined have minimal, if any, hallucinogenic side effects, and their properties as anti-cancer agents are promising.

"These agents are able to interfere with the development of cancerous cells, stopping them in their tracks and preventing them from growing. In some cases, by using specific dosage patterns, they can destroy cancer cells on their own.

"Used in combination with existing treatment, we could discover some highly effective strategies for tackling cancer. Significantly, these compounds are inexpensive to produce and making better use of their unique properties could result in much more cost effective anti-cancer drugs in future."

This latest research is part of a growing portfolio of studies into the medicinal properties of cannabis by the research team at St George's. The next step will be to examine in the laboratory these compounds in combination with existing anti-cancer treatments and study treatment schedules to identify strategies that will maximise their efficacy.

The study examined two forms of cannabidiol (CBD), two forms of cannabigerol (CBG) and two forms of cannabigevarin (CBGV). These represent the most common cannabinoids found in the cannabis plant apart from THC.

https://www.sciencedaily.com/releases/2013/10/131014094105.htm

'Yes' to one drug could become 'yes' for other drugs

October 8, 2013

Science Daily/Springer Science+Business Media

High school seniors who frown upon the use of drugs are most likely to be female, nonsmokers or hold strong religious beliefs, according to a study¹ by Joseph Palamar of New York University. Palamar examines how teenagers' attitudes toward marijuana influenced their thoughts on the further use of other illicit drugs. The work appears online in the journal Prevention Science², published by Springer.

The study was conducted as marijuana use continues to be on the upswing in the United States, along with more lenient legislation and diminishing public disapproval toward its use. Although previous research has shown that people who disapprove of a particular drug will in all likelihood not use it, little is known about how the use of one drug affects people's attitudes toward using other drugs.

Palamar therefore examined how demographics and a lifetime use of various drugs -- marijuana use in particular -- can predict if a person will become partial to using "harder" and more dangerous drugs, such as powder cocaine, crack, LSD, heroin, amphetamine and ecstasy, also known as "Molly." Data was obtained from 29,054 high school seniors who took part in the Monitoring the Future annual cross-sectional survey of approximately 130 public and private schools in 48 states between 2007 and 2011.

Palamar found that youths who smoked cigarettes or used more than one "hard" drug were consistently less critical of other drug use. The lifetime use of alcohol had no impact on people's attitudes. Those who used only marijuana tended to be less judgmental of further using such so-called "socially acceptable" drugs as LSD, amphetamine and ecstasy. They did not approve of cocaine, crack or heroin, however, most likely because of their perceived dangers and addictive qualities.

Unsurprisingly, female high school seniors consistently disapproved of using cocaine, crack, LSD and ecstasy. Compared to their male counterparts, females are generally less likely to use most drugs. Palamar was also not surprised by the finding that religiosity robustly increased attitudes against drug use, as it is a major force in societal values.

Youths from more advantaged socio-economic backgrounds with highly educated parents as well as those living in urban areas were much less disapproving of the use of the so-called "less dangerous" drugs. Palamar believes that the higher prevalence of illicit drug use in urban areas may be helping to normalize drug use in cities.

The finding that Black students are less disapproving of powder cocaine, crack and ecstasy is somewhat paradoxical as members of this group generally use such drugs less than White students do. This could, in part, be explained by their strong religious beliefs and the higher rates of arrests and incarceration among Blacks that may serve as a deterrent. The normalization of ecstasy, specifically in rap and hip-hop music, may explain why Black youths are less disapproving of it.

"Public health and policy experts need to ensure that the use of other drugs does not increase in light of the growing prevalence of marijuana use and more lenient policies surrounding it," Palamar explains. "Although it may be difficult to prevent an adolescent or a young adult from using alcohol, tobacco or marijuana, we need to prevent individuals from becoming users of multiple drugs."

https://www.sciencedaily.com/releases/2013/10/131008112434.htm

Sending multiple sclerosis up in smoke

October 7, 2013

Science Daily/American Friends of Tel Aviv University

In a new study, researchers demonstrate that some chemical compounds in marijuana can help treat multiple sclerosis and similar diseases in mice by preventing inflammation in the brain and spinal cord, holding promise for new treatments in humans as well.

Multiple sclerosis is an inflammatory disease in which the immune system attacks the nervous system. The result can be a wide range of debilitating motor, physical, and mental problems. No one knows why people get the disease or how to treat it.

In a new study published in the Journal of Neuroimmune Pharmacology, Drs. Ewa Kozela, Ana Juknat, Neta Rimmerman and Zvi Vogel of Tel Aviv University's Dr. Miriam and Sheldon G. Adelson Center for the Biology of Addictive Diseases and Sackler Faculty of Medicine demonstrate that some chemical compounds found in marijuana can help treat MS-like diseases in mice by preventing inflammation in the brain and spinal cord.

"Inflammation is part of the body's natural immune response, but in cases like MS it gets out of hand," says Kozela. "Our study looks at how compounds isolated from marijuana can be used to regulate inflammation to protect the nervous system and its functions." Researchers from the Weizmann Institute of Science co-authored the study.

Mind-altering findings

Israel has a strong tradition of marijuana research. Israeli scientists Raphael Mechoulam and Yechiel Gaoni discovered THC, or tetrahydrocannabinol, in 1964, kick-starting the scientific study of the plant and its chemical constituents around the world. Since then, scientists have identified about 70 compounds -- called cannabinoids -- that are unique to cannabis and have interesting biological effects. In the 1990s, Prof. Vogel was among the first researchers to describe endocannabinoids, molecules that act like THC in the body.

Besides THC, the most plentiful and potent cannabinoid in marijuana is cannabidiol, or CBD. The TAU researchers are particularly interested in CBD, because it offers medicinal benefits without the controversial mind-altering effects of THC.

In a 2011 study, they showed that CBD helps treat MS-like symptoms in mice by preventing immune cells in their bodies from transforming and attacking the insulating covers of nerve cells in the spinal cord. After inducing an MS-like condition in mice -- partially paralyzing their limbs -- the researchers injected them with CBD. The mice responded by regaining movement, first twitching their tails and then beginning to walk without a limp. The researchers noted that the mice treated with CBD had much less inflammation in the spinal cord than their untreated counterparts.

High hopes for humans

In the latest study, the researchers set out to see if the known anti-inflammatory properties of CBD and THC could also be applied to the treatment of inflammation associated with MS -- and if so, how. This time they turned to the immune system.

The researchers took immune cells isolated from paralyzed mice that specifically target and harm the brain and spinal cord, and treated them with either CBD or THC. In both cases, the immune cells produced fewer inflammatory molecules, particularly one called interleukin 17, or IL-17, which is strongly associated with MS and very harmful to nerve cells and their insulating covers. The researchers concluded that the presence of CBD or THC restrains the immune cells from triggering the production of inflammatory molecules and limits the molecules' ability to reach and damage the brain and spinal cord.

Further research is needed to prove the effectiveness of cannabinoids in treating MS in humans, but there are reasons for hope, the researchers say. In many countries, CBD and THC are already prescribed for the treatment of MS symptoms, including pain and muscle stiffness.

"When used wisely, cannabis has huge potential," says Kozela, who previously studied opiates like morphine, derived from the poppy plant. "We're just beginning to understand how it works."

https://www.sciencedaily.com/releases/2013/10/131007132253.htm

LSD and other psychedelics not linked with mental health problems

August 19, 2013

Science Daily/The Norwegian University of Science and Technology (NTNU)

The use of LSD, magic mushrooms, or peyote does not increase a person's risk of developing mental health problems, according to an analysis of information from more than 130,000 randomly chosen people, including 22,000 people who had used psychedelics at least once.

Researcher Teri Krebs and clinical psychologist Pål-Ørjan Johansen, from the Norwegian University of Science and Technology's (NTNU) Department of Neuroscience, used data from a US national health survey to see what association there was, if any, between psychedelic drug use and mental health problems.

The authors found no link between the use of psychedelic drugs and a range of mental health problems. Instead they found some significant associations between the use of psychedelic drugs and fewer mental health problems.

The results are published in the journal PLOS ONE and are freely available online after 19 August.

Symptoms and mental health treatment considered

The researchers relied on data from the 2001-2004 National Survey on Drug Use and Health, in which participants were asked about mental health treatment and symptoms of a variety of mental health conditions over the past year. The specific symptoms examined were general psychological distress, anxiety disorders, mood disorders, and psychosis.

Armed with this information, Krebs and Johansen were able to examine if there were any associations between psychedelic use and general or specific mental health problems. They found none.

"After adjusting for other risk factors, lifetime use of LSD, psilocybin, mescaline or peyote, or past year use of LSD was not associated with a higher rate of mental health problems or receiving mental health treatment," says Johansen.

Could psychedelics be healthy for you?

The researchers found that lifetime use of psilocybin or mescaline and past year use of LSD were associated with lower rates of serious psychological distress. Lifetime use of LSD was also significantly associated with a lower rate of outpatient mental health treatment and psychiatric medicine prescription.

The design of the study makes it impossible to determine exactly why the researchers found what they found.

"We cannot exclude the possibility that use of psychedelics might have a negative effect on mental health for some individuals or groups, perhaps counterbalanced at a population level by a positive effect on mental health in others," they wrote.

Nevertheless, "recent clinical trials have also failed to find any evidence of any lasting harmful effects of psychedelics," the researchers said, which supports the robustness of the PLOS ONE findings.

In fact, says Krebs, "many people report deeply meaningful experiences and lasting beneficial effects from using psychedelics."

"Other studies have found no evidence of health or social problems among people who had used psychedelics hundreds of times in legally-protected religious ceremonies," adds Johansen.

What's the bottom line on psychedelic use?

Psychedelics are different than most other recreational drugs. Experts agree that psychedelics do not cause addiction or compulsive use, and they are not known to harm the brain.

When evaluating psychedelics, as with any activity, it is important to take an objective view of all the evidence and avoid being biased by anecdotal stories either of harm or benefit, the researchers say.

"Everything has some potential for negative effects, but psychedelic use is overall considered to pose a very low risk to the individual and to society," Johansen says, "Psychedelics can elicit temporary feelings of anxiety and confusion, but accidents leading to serious injury are extremely rare."

"Early speculation that psychedelics might lead to mental health problems was based on a small number of case reports and did not take into account either the widespread use of psychedelics or the not infrequent rate of mental health problems in the general population," Krebs explains.

"Over the past 50 years tens of millions of people have used psychedelics and there just is not much evidence of long-term problems," she concludes.

Both researchers were supported by the Research Council of Norway.

https://www.sciencedaily.com/releases/2013/08/130819185302.htm

Evolutionary relationships among species of 'magic' mushrooms shed light on fungi

August 6, 2013

Science Daily/Canadian Science Publishing (NRC Research Press)

"Magic" mushrooms are well known for their hallucinogenic properties. Until now, less has been known about their evolutionary development and how they should be classified in the fungal Tree of Life. New research helps uncover the evolutionary past of a fascinating fungi that has wide recreational use and is currently under investigation for a variety of medicinal applications.

In the 19th century, the discovery of hallucinogenic mushrooms prompted research into the mushrooms' taxonomy, biochemistry, and historical usage. Gastón Guzmán, a world authority on the genus Psilocybe, began studying its taxonomy in the 1950s. In 1983, these studies culminated in a monograph, which is currently being updated as a team of researchers from the University of Guadalajara and the University of Tennessee collaborate with Guzmán to produce a hypothesis on how these mushrooms evolved. Some of their latest research is now published in the journal Botany.

Using new molecular and computational techniques, the team has produced the first multi-gene evaluation of the evolutionary development of Psilocybe, which constitutes a major step in classifying and naming "magic" mushrooms. Earlier work showed that species of Psilocybe did not commonly descend from a single ancestor. As a result, the hallucinogenic species (the genus Psilocybe) were typically separated from their non-hallucinogenic relatives (the genus Deconica). But this new work now places the two separate monophyletic -- meaning developed from a single ancestor -- groups into different families. Within Psilocybe (family Hymenogastraceae) and Deconica (family Strophariaceae s.str), the authors have discovered several strong infrageneric relationships.

According to the authors, their analysis of various morphological traits of the mushrooms suggests that these typically weren't acquired through a most recent common ancestor and must have evolved independently or undergone several evolutionary losses, probably for ecological reasons. Nevertheless, species of Psilocybe are united to some degree because they have the psychedelic compound psilocybin and other secondary metabolites, or products of metabolism. The authors say that former Psilocybe species that lack these secondary metabolites could also be found in Deconica.

https://www.sciencedaily.com/releases/2013/08/130806132852.htm

Perception of marijuana as a 'safe drug' is scientifically inaccurate, finds review of teen brain studies

August 27, 2013

Science Daily/Universite de Montreal

The nature of the teenage brain makes users of cannabis amongst this population particularly at risk of developing addictive behaviors and suffering other long-term negative effects, according to researchers at the University of Montreal and New York's Icahn School of Medicine at Mount Sinai.

"Of the illicit drugs, cannabis is most used by teenagers since it is perceived by many to be of little harm. This perception has led to a growing number of states approving its legalization and increased accessibility. Most of the debates and ensuing policies regarding cannabis were done without consideration of its impact on one of the most vulnerable population, namely teens, or without consideration of scientific data," wrote Professor Didier Jutras-Aswad of the University of Montreal and Yasmin Hurd, MD, PhD, of Mount Sinai. "While it is clear that more systematic scientific studies are needed to understand the long-term impact of adolescent cannabis exposure on brain and behavior, the current evidence suggests that it has a far-reaching influence on adult addictive behaviors particularly for certain subsets of vulnerable individuals."

The researchers reviewed over 120 studies that looked at different aspects of the relationship between cannabis and the adolescent brain, including the biology of the brain, chemical reaction that occurs in the brain when the drug is used, the influence of genetics and environmental factors, in addition to studies into the "gateway drug" phenomenon. "Data from epidemiological studies have repeatedly shown an association between cannabis use and subsequent addiction to heavy drugs and psychosis (i.e. schizophrenia). Interestingly, the risk to develop such disorders after cannabis exposure is not the same for all individuals and is correlated with genetic factors, the intensity of cannabis use and the age at which it occurs. When the first exposure occurs in younger versus older adolescents, the impact of cannabis seems to be worse in regard to many outcomes such as mental health, education attainment, delinquency and ability to conform to adult role," Dr Jutras-Aswad said.

Although it is difficult to confirm in all certainty a causal link between drug consumption and the resulting behavior, the researchers note that rat models enable scientists to explore and directly observe the same chemical reactions that happen in human brains. Cannabis interacts with our brain through chemical receptors (namely cannabinoid receptors such as CB1 and CB2.) These receptors are situated in the areas of our brain that govern our learning and management of rewards, motivated behavior, decision-making, habit formation and motor function. As the structure of the brain changes rapidly during adolescence (before settling in adulthood), scientists believe that the cannabis consumption at this time greatly influences the way these parts of the user's personality develop. In adolescent rat models, scientists have been able to observe differences in the chemical pathways that govern addiction and vulnerability -- a receptor in the brain known as the dopamine D2 receptor is well known to be less present in cases of substance abuse.

Only a minority (approximately one in four) of teenage users of cannabis will develop an abusive or dependent relationship with the drug. This suggests to the researchers that specific genetic and behavioral factors influence the likelihood that the drug use will continue. Studies have also shown that cannabis dependence can be inherited through the genes that produce the cannabinoid receptors and an enzyme involved in the processing of THC. Other psychological factors are also likely involved. "Individuals who will develop cannabis dependence generally report a temperament characterized by negative affect, aggressivity and impulsivity, from an early age. Some of these traits are often exacerbated with years of cannabis use, which suggests that users become trapped in a vicious cycle of self-medication, which in turn becomes a dependence," Jutras-Aswad said.

The researchers stress that while a lot remains unknown about the mechanics of cannabis abuse, the body of existing research has clear implications for society. "It is now clear from the scientific data that cannabis is not harmless to the adolescent brain, specifically those who are most vulnerable from a genetic or psychological standpoint. Identifying these vulnerable adolescents, including through genetic or psychological screening, may be critical for prevention and early intervention of addiction and psychiatric disorders related to cannabis use. The objective is not to fuel the debate about whether cannabis is good or bad, but instead to identify those individuals who might most suffer from its deleterious effects and provide adequate measures to prevent this risk" Jutras-Aswad said. "Continuing research should be performed to inform public policy in this area. Without such systematic, evidenced-based research to understand the long-term effects of cannabis on the developing brain, not only the legal status of cannabis will be determined on uncertain ground, but we will not be able to innovate effective treatments such as the medicinal use of cannabis plant components that might be beneficial for treating specific disorders," Dr Hurd said.

https://www.sciencedaily.com/releases/2013/08/130827091401.htm

Long-term cannabis use may blunt the brain's motivation system

July 1, 2013

Science Daily/Imperial College London

Long-term cannabis users tend to produce less dopamine, a chemical in the brain linked to motivation, a study has found.

Researchers found that dopamine levels in a part of the brain called the striatum were lower in people who smoke more cannabis and those who began taking the drug at a younger age.

They suggest this finding could explain why some cannabis users appear to lack motivation to work or pursue their normal interests.

The study, by scientists at Imperial College London, UCL and King's College London, was funded by the Medical Research Council and published in the journal Biological Psychiatry.

The researchers used PET brain imaging to look at dopamine production in the striatum of 19 regular cannabis users and 19 non-users of matching age and sex.

The cannabis users in the study had all experienced psychotic-like symptoms while smoking the drug, such as experiencing strange sensations or having bizarre thoughts like feeling as though they are being threatened by an unknown force.

The researchers expected that dopamine production might be higher in this group, since increased dopamine production has been linked with psychosis. Instead, they found the opposite effect.

The cannabis users in the study had their first experience with the drug between the ages of 12 and 18. There was a trend for lower dopamine levels in those who started earlier, and also in those who smoke more cannabis. The researchers say these findings suggest that cannabis use may be the cause of the difference in dopamine levels.

The lowest dopamine levels were seen in users who meet diagnostic criteria for cannabis abuse or dependence, raising the possibility that this measure could provide a marker of addiction severity.

Previous research has shown that cannabis users have a higher risk of mental illnesses that involve repeated episodes of psychosis, such as schizophrenia.

"It has been assumed that cannabis increases the risk of schizophrenia by inducing the same effects on the dopamine system that we see in schizophrenia, but this hasn't been studied in active cannabis users until now," said Dr Michael Bloomfield, from the Institute of Clinical Sciences at Imperial, who led the study.

"The results weren't what we expected, but they tie in with previous research on addiction, which has found that substance abusers -- people who are dependent on cocaine or amphetamine, for example -- have altered dopamine systems.

"Although we only looked at cannabis users who have had psychotic-like experiences while using the drug, we think the findings would apply to cannabis users in general, since we didn't see a stronger effect in the subjects who have more psychotic-like symptoms. This needs to be tested though.

"It could also explain the 'amotivational syndrome' which has been described in cannabis users, but whether such a syndrome exists is controversial."

Other studies have looked at dopamine release in former cannabis users and not seen differences with people who haven't taken cannabis, suggesting that the effects seen in this study are likely to be reversible.

https://www.sciencedaily.com/releases/2013/07/130701081053.htm

First trial to investigate magic mushrooms as a treatment for depression delayed by UK and EU regulations

April 7, 2013

Science Daily/British Neuroscience Association

The world's first clinical trial to explore the use of the hallucinogenic ingredient in magic mushrooms to treat depression is being delayed due to the UK and EU rules on the use of illegal drugs in research.

Professor David Nutt, president of the British Neuroscience Association and Professor of Neuropsychopharmacology at Imperial College London (UK), will tell the BNA's Festival of Neuroscience today (Sunday) that although the UK's Medical Research Council has awarded a grant for the trial, the Government's regulations controlling the licensing of illegal drugs in research and the EU's guidelines on Good Manufacturing Practice (GMP) have stalled the start of the trial, which was expected to start this year. He is calling for a change to the regulations.

He will tell the meeting at the Barbican in London, that his research has shown that psilocybin, the psychedelic ingredient in magic mushrooms, has the potential to alleviate severe forms of depression in people who have failed to respond fully to other anti-depressant treatments. However, psilocybin is illegal in the UK; the United Nations 1971 Convention on Psychotropic Substances classifies it as a Schedule 1 drug, one that has a high potential for abuse with no recognised medical use, and the UK has classified it as a Class A drug, the classification used for the most dangerous drugs. This means that a special licence has to be obtained to use magic mushrooms in research in the UK, and the manufacture of a synthetic form of psilocybin for use in patients is tightly controlled by EU regulations.

Prof Nutt will say: "The law for the control of drugs like psilocybin as a Schedule 1 Class A drug makes it almost impossible to use them for research and the reason we haven't started the study is because finding companies who could manufacture the drug and who are prepared to go through the regulatory hoops to get the licence, which can take up to a year and triple the price, is proving very difficult. The whole situation is bedevilled by this primitive, old-fashioned attitude that Schedule 1 drugs could never have therapeutic potential, and so they have to be made impossible to access."

"The knock-on effect is this profound impairment of research. We are the first people ever to have done a psilocybin study in the UK, but we are still hunting for a company that can manufacture the drug to GMP standards for the clinical trial, even though we've been trying for a year to find one. We live in a world of insanity in terms of regulating drugs at present. The whole field is so bogged down by these intransient regulations, so that even if you have a good idea, you may never get it into the clinic."

He will say that the regulations need to be changed. "Even if I do this study and I show it's a really useful treatment for some people with depression, there's only four hospitals in this country that have a licence to hold this drug, so you couldn't roll out the treatment if it worked because the regulations would make it difficult to use," he said.

Prof Nutt and his team at Imperial College London (UK) have shown that when healthy volunteers are injected with psilocybin, the drug switched off a front part of the brain called the anterior cingulate cortex, which is known from previous imaging studies to be over-active in depression. "We found that, even in normal people, the more that part of the brain was switched off under the influence of the drug, the better they felt two weeks later. So there was a relationship between that transient switching off of the brain circuit and their subsequent mood," he will explain. "This is the basis on which we want to run the trial, because this is what you want to do in depression: you want to switch off that over-active part of the brain.

"The other thing we discovered is that the major site of action of the magic mushrooms is to turn down a circuit in the brain called the 'default mode network', which the anterior cingulate cortex is part of. The default mode network is a part of the brain between the front and back. It is active when you are thinking about you; it coordinates the thinking and emotional aspects of you."

The researchers discovered that the 'default mode network' had the highest density of 5HT2A receptors in the brain. These are known to be involved in depression and are the targets for a number of existing anti-depressive drugs that aim to improve levels of serotonin -- the neurotransmitter [1] that gives people a sense of well-being and happiness. Psilocybin also acts on these receptors.

"We have found that people with depression have over-active default mode networks, and they are continually locked into a mode of thinking about themselves. So they ruminate on themselves, on their incompetencies, on their badness, that they're worthless, that they've failed; these things are not true, and sometimes they reach delusional levels. This negative rumination may be due to a lack of serotonin and what psilocybin is doing is going in and rapidly replacing the missing serotonin, switching them back into a mind state where they are less ruminating and less depressed," Prof Nutt will say.

The proposed trial will be for patients with depression who have failed two previous treatments for the condition. Thirty patients will be given a synthetic form of psilocybin and 30 patients will be given a placebo. The drug (or placebo) will be given during two, possibly three, carefully controlled and prepared 30-60 minute sessions. The first session will be a low dose to check there are no adverse responses, the second session will give a higher, therapeutic dose, and then patients can have a third, booster dose in a later session if it's considered necessary. While they are under the influence of the drug, the patients will have guided talking therapy to enable them to explore their negative thinking and issues that are troubling them. The doctors will follow up the patients for at least a year.

"What we are trying to do is to tap into the reservoir of under-researched 'illegal' drugs to see if we can find new and beneficial uses for them in people whose lives are often severely affected by illnesses such as depression. The current legislation is stopping the benefits of these drugs being explored and for the last 40 years we have missed really interesting opportunities to help patients."

Ethical approval for the trial was granted in March and Prof Nutt says he hopes to be able to start the trial within the next six months -- so long as he can find a manufacturer for the drug.

[1] Neurotransmitters are chemicals that transmit signals from neurons (nerve cells) to target cells.

[2] Funding: The Beckley Foundation has funded part of Prof Nutt's research, and the Medical Research Council has agreed a grant for the proposed clinical trial.

Abstract title: "Can we use psychedelic drugs to treat depressions?" Symposium: "Treating depression with antidepressants: where are we now and where are we going?"

https://www.sciencedaily.com/releases/2013/04/130407090832.htm

Potential of psilocybin to alleviate psychological and spiritual distress in cancer patients is revealed

January 31, 2013

Science Daily/New York University

Improvements in the diagnosis and treatment of cancers in recent years have led to a marked increase in patients' physical survival rates. While doctors can treat the physical disease, what is not well understood is how best to address the psychological needs of patients with cancer.

In addition to the physical pain associated with cancer, many patients also experience psychologically harmful symptoms of anxiety, depression, anger, and denial. Social isolation, in addition to hopelessness, helplessness and loss of independence, has also been associated with significant psychological suffering in patients coping with advanced-stage cancer.

A recently published book chapter "Use of the Classic Hallucinogen Psilocybin for Treatment of Existential Distress Associated with Cancer," reviews the potential of a novel psychoactive drug, psilocybin, in alleviating the psychological and spiritual distress that often accompanies a life-threatening cancer diagnosis.

The chapter, published in Psychological Aspects of Cancer: A Guide to Emotional and Psychological Consequences of Cancer, Their Causes, and Their Management, was co-written by Anthony P. Bossis, PhD, Clinical Assistant Professor of Psychiatry and Oral and Maxillofacial Pathology, Radiology, and Medicine at the New York University College of Dentistry (NYUCD) and Langone Medical Center.

The hallucinogen treatment model with psilocybin has been shown to induce a mystical or spiritual experience and is a unique therapeutic approach to reduce the anxiety of terminal cancer patients.

"Mystical or peak consciousness states in cancer patients have been associated with a number of benefits including improved psychological, spiritual, and existential well-being," said Dr. Bossis.

Psilocybin (a serotonergic psychoactive agent) is a naturally occurring active component of many species of mushrooms, and is rapidly metabolized to psilocin, a highly potent activator of serotonin receptors. In addition to receiving the psilocybin compound, patients enrolled in the study also receive psychological preparation prior to the psilocybin dosing followed by a brief series of integrative psychotherapeutic sessions.

The chapter includes a clinical case vignette of a patient in the ongoing Psilocybin Cancer Anxiety Study at the Bluestone Center for Clinical Research. Participants undergo two drug administration sessions in which psilocybin is administered on one occasion and a placebo on the other.

"The primary objective of this phase I, double-blind, controlled pilot study is to assess the efficacy of psilocybin administration on psychosocial distress, with the specific primary outcome variable being anxiety associated with advanced and/or recurrent cancer," said Bossis. "Secondary outcome measures will look at the effect of psilocybin on symptoms of pain perception, depression, existential/psychospiritual distress, attitudes toward illness, quality of life, and spiritual/mystical states of consciousness," said Bossis.

The clinical vignette describes a patient who, over the course of three years, experienced extreme fatigue, pain, overall body aches, discomfort and psychological distress due to cancer and intensive biweekly chemotherapy. The patient became increasingly anxious and depressed and was enrolled in two study sessions; in one he received psilocybin and the other placebo. Despite continuing the arduous chemotherapy schedule, suffering from illness, and undergoing additional surgical procedures, the patient continued to report a marked improvement in attitude, coping, and mood 18 weeks after his session and stated, "my quality of life is dramatically improved," the patient said.

Stephen Ross, MD, Assistant Professor of Psychiatry and Child and Adolescent Psychiatry at the NYU School of Medicine and Clinical Assistant Professor of Psychiatry and Oral and Maxillofacial Pathology, Radiology, and Medicine at the NYUCD is the principal investigator for the study; Dr. Bossis and Jeffrey Guss, MD, Clinical Assistant Professor of Psychiatry are co-principal investigators.

The co-authors of the chapter were: Charles S. Grob, MD, Professor of Psychiatry and Biobehavioral Sciences at Harbor-UCLA Medical Center and Roland R. Griffiths, PhD, Professor of Psychiatry and Behavioral Science and Neuroscience at Johns Hopkins University.

The Psilocybin Cancer Anxiety Study was also recently highlighted in a News article, "Opening Doors of Perception: Psychedelic Drugs and End-of-Life Care" in the Journal of the National Cancer Institute.

"The emotional, spiritual and existential distress that can often accompany a diagnosis of cancer often goes unidentified and untreated in cancer patients. Patients who have benefited from psilocybin clinical research have reported less anxiety, improved quality of life, enhanced psychological and spiritual well-being, and a greater acceptance of the life-changes brought on by cancer. It is a welcome development that this promising and novel clinical research model utilizing psilocybin has begun to gain clinical and academic attention," Bossis notes.

The Psilocybin Cancer Anxiety Study is currently recruiting additional subjects. To enroll or learn more, please visit BluestoneCenter.org or http://www.nyucanceranxiety.org/.

https://www.sciencedaily.com/releases/2013/01/130131095040.htm

Ecstasy harms memory with one year of recreational use

July 25, 2012

Science Daily/Wiley

There has been significant debate in policy circles about whether governments have over-reacted to ecstasy by issuing warnings against its use and making it illegal. In the UK, David Nutt said ecstasy was less dangerous than horseback riding, which led to him being fired as the government's chief drug advisor. Others have argued that ecstasy is dangerous if you use it a lot, but brief use is safe.

New research published online July 25 by the scientific journal Addiction, gives some of the first information available on the actual risk of using ecstasy. It shows that even in recreational amounts over a relatively short time period, ecstasy users risk specific memory impairments. Further, as the nature of the impairments may not be immediately obvious to the user, it is possible people wouldn't get the signs that they are being damaged by drug use until it is too late.

According to the study, new ecstasy users who took ten or more ecstasy pills over their first year of use showed decreased function of their immediate and short-term memory compared with their pre-ecstasy performance. These findings are associated with damage of the hippocampus, the area of the brain that oversees memory function and navigation. Interestingly, hippocampal damage is one of the first signs of Alzheimer's disease, resulting in memory loss and disorientation.

The study participants took an average of 32 pills each over the course of the year, or about two and a half pills per month. Some participants took as few as ten pills over the year and still showed signs of memory impairments.

Lead author Dr. Daniel Wagner says: "This study was designed to minimize the methodological limitations of earlier research, in which it was not possible to say whether cognitive impairments seen among ecstasy users were in place before drug use began. By measuring the cognitive function of people with no history of ecstasy use and, one year later, identifying those who had used ecstasy at least ten times and remeasuring their performance, we have been able to start isolating the precise cognitive effects of this drug."

https://www.sciencedaily.com/releases/2012/07/120725200258.htm

Speed and ecstasy associated with depression in teenagers

April 18, 2012

Science Daily/Montreal University

A five year study conducted with thousands of local teenagers by University of Montreal researchers reveals that those who used speed (meth/ampthetamine) or ecstasy (MDMA) at fifteen or sixteen years of age were significantly more likely to suffer elevated depressive symptoms the following year.

"Our findings are consistent with other human and animal studies that suggest long-term negative influences of synthetic drug use," said co-author Frédéric N. Brière of the School Environment Research Group at the University of Montreal. "Our results reveal that recreational MDMA and meth/amphetamine use places typically developing secondary school students at greater risk of experiencing depressive symptoms." Ecstasy and speed-using grade ten students were respectively 1.7 and 1.6 times more likely to be depressed by the time they reached grade eleven.

The researchers worked with data provided by 3,880 students enrolled at schools in disadvantaged areas of Quebec. The participants were asked a series of questions that covered their drug use -- what they had used in the past year or ever in their life -- and their home life. Depressive symptoms were established by using a standard epidemiological evaluation tool. 310 respondents reported using MDMA (8%) and 451 used meth/amphetamines (11.6%). 584 of all respondents were identified as having elevated depressive symptoms (15.1%). The range of questions that the researchers asked enabled them to adjust their statistics to take into account other factors likely to affect the psychological state of the student, such as whether there was any conflict between the parents and the participant. "This study takes into account many more influencing factors than other research that has been undertaken regarding the association between drugs and depression in teenagers," Brière said. "However, it does have its limitations, in particular the fact that we cannot entirely rule out the effects of drug combinations and that we do not know the exact contents of MDMA and meth/amphetamine pills."

The study's authors would like to do further research into how drug combinations affect a person's likelihood to suffer depression and they are keen to learn more about the differences between adults and adolescents in this area. "Our study has important public health implications for adolescent populations," said Jean-Sébastien Fallu, a professor at the University of Montreal and study co-author. "Our results reinforce the body of evidence in this field and suggest that adolescents should be informed of the potential risks associated with MDMA and meth/amphetamine use."

study received funding from Fonds Québécois de Recherche sur la Santé et la Société (FQRSC, 2007-NP-112947). Frédéric Brière is affiliated with the University of Montreal's School Environment Research Group. Jean-Sébastien Fallu is affiliated with the University of Montreal's School Environment Research Group, School of Psycho-Education, and Public Health Research Institute. The University of Montreal is officially known as Université de Montréal.

https://www.sciencedaily.com/releases/2012/04/120418203520.htm

Revisiting LSD as a treatment for alcoholism

March 8, 2012

Science Daily/SAGE Publications

Several decades ago, a number of clinics used LSD to treat alcoholism with some success. But until now, no research has pulled together the results of these trials to document exactly how effective LSD was. Now a new meta-analysis of randomized controlled trials of the drug, available in the Journal of Psychopharmacology, published by SAGE, provides evidence for a clear and consistent beneficial effect of LSD for treating alcohol dependency.

Teri Krebs and Pål-Ørjan Johansen are both affiliated with the Department of Neuroscience at the Norwegian University of Science and Technology (NTNU), Trondheim, Norway. During research fellowships at Harvard Medical School, Boston, USA, they spotted a gap in the understanding of lysergic acid diethylamide's (LSD's) potential for alcoholism treatment. No researcher had ever performed a quantitative meta-analysis of previous clinical trials using the drug.

Krebs and Johansen set out to independently extract data from previous randomized, controlled clinical trials, pooling their results. They identified six eligible trials, all carried out in the late 1960s and early 1970s. These included 536 participants, the vast majority of whom were male in-patients enrolled in alcohol-focused treatment programs. Individuals with a history of schizophrenia or psychosis were excluded from the original trials. The control conditions included low-dose LSD, stimulants, or non-drug control conditions. Each trial used clearly defined treatment-independent and standardized methods to assess outcomes on alcohol misuse.

While the experiments varied in the dosage used and the type of placebo physicians administered to patients, LSD had a beneficial effect on alcohol misuse in every trial. On average, 59 percent of LSD patients and 38 percent of control patients were improved at follow-up using standardized assessment of problem alcohol use. There was also a similar beneficial effect on maintained abstinence from alcohol. The positive effects of a single LSD dose -- reported both in these and in other, non-randomized trials -- lasts at least six months and appears to fade by 12 months.

Regarding the lasting effects of the LSD experience in alcoholics, investigators of one trial noted, "It was rather common for patients to claim significant insights into their problems, to feel that they had been given a new lease on life, and to make a strong resolution to discontinue their drinking." And investigators of another trial noted, "It was not unusual for patients following their LSD experience to become much more self-accepting, to show greater openness and accessibility, and to adopt a more positive, optimistic view of their capacities to face future problems."

LSD interacts with a specific type of serotonin receptors in the brain, which may stimulate to new connections and open the mind for new perspectives and possibilities, Krebs explains. LSD is not known to be addictive or toxic to the body, but the LSD has striking effects on imagination, perception, and memories and can elicit periods of intense anxiety and confusion.

"Given the evidence for a beneficial effect of LSD on alcoholism, it is puzzling why this treatment approach has been largely overlooked," says Johansen. The authors suggest a number of reasons for this: many of the individual trials did not have enough patients to confidently conclude that there was a beneficial effect of LSD, but when pooled together the trials shows a clear and consistent effect; trial authors expected unrealistic results from a single dose of LSD and tended to discount moderate or short-term effects and; earlier non-randomized clinical trials reporting promising results but had methodological problems, creating the misunderstanding that well-designed studies did not exist or failed to find a beneficial effect. Finally, the complicated social and political history of LSD meant that obtaining regulatory approval for clinical trials became laborious, although national and international drug control measures have never banned treatment development or medical use of LSD.

Its unusual for a psychiatric medication to have a positive treatment effect lasting for several months after a single dose. Krebs and Johansen suggest that repeated doses of LSD coupled with modern, evidence-based alcohol relapse prevention treatments might provide more sustained results. They also note that plantbased psychedelics such as mescaline and ayahuasca which are used by Native Americans to promote mental health and sustained sobriety, merit further investigation for alcoholism treatment.

https://www.sciencedaily.com/releases/2012/03/120308224524.htm

Magic mushrooms' effects illuminated in brain imaging studies

January 24, 2012

Science Daily/Imperial College London

Brain scans of people under the influence of the psilocybin, the active ingredient in magic mushrooms, have given scientists the most detailed picture to date of how psychedelic drugs work. The findings of two studies being published in scientific journals this week identify areas of the brain where activity is suppressed by psilocybin and suggest that it helps people to experience memories more vividly.

In the first study, published January 23 in Proceedings of the National Academy of Sciences (PNAS), 30 healthy volunteers had psilocybin infused into their blood while inside magnetic resonance imaging (MRI) scanners, which measure changes in brain activity. The scans showed that activity decreased in "hub" regions of the brain -- areas that are especially well-connected with other areas.

The second study, due to be published online by the British Journal of Psychiatry on January 24, found that psilocybin enhanced volunteers' recollections of personal memories, which the researchers suggest could make it useful as an adjunct to psychotherapy.

Professor David Nutt, from the Department of Medicine at Imperial College London, the senior author of both studies, said: "Psychedelics are thought of as 'mind-expanding' drugs so it has commonly been assumed that they work by increasing brain activity, but surprisingly, we found that psilocybin actually caused activity to decrease in areas that have the densest connections with other areas. These hubs constrain our experience of the world and keep it orderly. We now know that deactivating these regions leads to a state in which the world is experienced as strange."

The intensity of the effects reported by the participants, including visions of geometric patterns, unusual bodily sensations and altered sense of space and time, correlated with a decrease in oxygenation and blood flow in certain parts of the brain.

The function of these areas, the medial prefrontal cortex (mPFC) and the posterior cingulate cortex (PCC), is the subject of debate among neuroscientists, but the PCC is proposed to have a role in consciousness and self-identity. The mPFC is known to be hyperactive in depression, so psilocybin's action on this area could be responsible for some antidepressant effects that have been reported. Similarly, psilocybin reduced blood flow in the hypothalamus, where blood flow is increased during cluster headaches, perhaps explaining why some sufferers have said symptoms improved under psilocybin.

In the British Journal of Psychiatry study 10 volunteers viewed written cues that prompted them to think about memories associated with strong positive emotions while inside the brain scanner. The participants rated their recollections as being more vivid after taking psilocybin compared with a placebo, and with psilocybin there was increased activity in areas of the brain that process vision and other sensory information.

Participants were also asked to rate changes in their emotional wellbeing two weeks after taking the psilocybin and placebo. Their ratings of memory vividness under the drug showed a significant positive correlation with their wellbeing two weeks afterwards. In a previous study of 12 people in 2011, researchers found that people with anxiety who were given a single psilocybin treatment had decreased depression scores six months later.

Dr Robin Carhart-Harris, from the Department of Medicine at Imperial College London, the first author of both papers, said: "Psilocybin was used extensively in psychotherapy in the 1950s, but the biological rationale for its use has not been properly investigated until now. Our findings support the idea that psilocybin facilitates access to personal memories and emotions.

"Previous studies have suggested that psilocybin can improve people's sense of emotional wellbeing and even reduce depression in people with anxiety. This is consistent with our finding that psilocybin decreases mPFC activity, as many effective depression treatments do. The effects need to be investigated further, and ours was only a small study, but we are interested in exploring psilocybin's potential as a therapeutic tool."

The researchers acknowledged that because the participants in this study had volunteered after having previous experience of psychedelics, they may have held prior assumptions about the drugs which could have contributed to the positive memory rating and the reports of improved wellbeing in the follow-up.

Functional MRI measures brain activity indirectly by mapping blood flow or the oxygen levels in the blood. When an area becomes more active, it uses more glucose, but generates energy in rapid chemical reactions that do not use oxygen. Consequently, blood flow increases but oxygen consumption does not, resulting in a higher concentration of oxygen in blood in the local veins.

In the PNAS study, the volunteers were split into two groups, each studied using a different type of fMRI: 15 were scanned using arterial spin labelling (ASL) perfusion fMRI, which measures blood flow, and 15 using blood-oxygen level-dependent (BOLD) fMRI. The two modalities produced similar results, strongly suggesting that the observed effects were genuine.

The studies were carried out with a Home Office licence for storing and handling a schedule 1 drug and were approved by NHS research ethics committees. All the volunteers were mentally and physically healthy and had taken hallucinogenic drugs previously without any adverse response. The research involved scientists from Imperial, the University of Bristol and Cardiff University and was funded by the Beckley Foundation, the Neuropsychoanalysis Foundation, Multidisciplinary Association for Psychedelic Studies, and the Heffter Research Institute.

https://www.sciencedaily.com/releases/2012/01/120123152043.htm

Ecstasy drug produces lasting toxicity in the brain

December 12, 2011

Science Daily/Vanderbilt University Medical Center

Recreational use of Ecstasy -- the illegal "rave" drug that produces feelings of euphoria and emotional warmth -- is associated with chronic changes in the human brain, Vanderbilt University investigators have discovered.

The findings, reported online Dec. 5 in the Archives of General Psychiatry, add to the growing evidence that Ecstasy produces long-lasting serotonin neurotoxicity in humans, said Ronald Cowan, M.D., Ph.D., associate professor of Psychiatry.

"Our study provides some of the strongest evidence to date that the drug causes chronic loss of serotonin in humans."

The neurotransmitter serotonin, a critical signaling molecule, has roles in regulating mood, appetite, sleep, learning and memory.

The current study is important, Cowan said, because MDMA (Ecstasy's chemical name) may have therapeutic benefits and is now being tested as a treatment for post-traumatic stress disorder and anxiety associated with cancer.

"It's essential that we understand the risk associated with using Ecstasy," Cowan said. "If news keeps coming out that MDMA is being tested therapeutically and is safe, more people will tend to self-administer the drug. We need to know the dose at which this drug becomes toxic.

"Our studies suggest that if you use Ecstasy recreationally, the more you use, the more brain changes you get."

In the current study, Cowan and colleagues used positron emission tomography (PET) imaging to examine the levels of serotonin-2A receptors in various brain regions, in females who had used Ecstasy (but not in the 90 days prior to imaging) and in females who had never used the drug. They limited their studies to females because previous work has shown gender-specific differences in serotonin receptor levels.

They found that Ecstasy users had increased levels of serotonin-2A receptors and that higher lifetime use of the drug (higher doses) correlated with higher serotonin receptor levels. The findings are consistent with some studies in animal models, with receptor levels increasing to compensate for the loss of serotonin, Cowan said.

Cowan and colleagues reported earlier this year that Ecstasy increased brain activation in three brain areas associated with visual processing, which suggested a loss in brain efficiency. Together, the two studies provide compelling evidence that Ecstasy causes lasting changes in brain serotonin function, Cowan said.

"It's really critical to know whether or not this drug is causing long-term brain damage because millions of people are using it," he said.

The 2010 National Survey on Drug Use and Health estimated that 15.9 million individuals 12 years or older in the United States had used Ecstasy in their lifetime; 695,000 people had used Ecstasy in the month prior to being surveyed.

Cowan is interested in determining the doses of Ecstasy that are toxic, and whether there are genetic vulnerabilities to toxicity. If clinical trials show that the drug has therapeutic benefits, it's critical to know the risks, he said.

The research was supported by grants from the National Institute on Drug Abuse, the National Institute of Mental Health, and the National Center for Research Resources.

https://www.sciencedaily.com/releases/2011/12/111205165114.htm

Single dose of 'magic mushrooms' hallucinogen may create lasting personality change

September 29, 2011

Science Daily/Johns Hopkins Medical Institutions

A single high dose of the hallucinogen psilocybin, the active ingredient in so-called "magic mushrooms," was enough to bring about a measurable personality change lasting at least a year in nearly 60 percent of the 51 participants in a new study, according to the Johns Hopkins researchers who conducted it.

Lasting change was found in the part of the personality known as openness, which includes traits related to imagination, aesthetics, feelings, abstract ideas and general broad-mindedness. Changes in these traits, measured on a widely used and scientifically validated personality inventory, were larger in magnitude than changes typically observed in healthy adults over decades of life experiences, the scientists say. Researchers in the field say that after the age of 30, personality doesn't usually change significantly.

"Normally, if anything, openness tends to decrease as people get older," says study leader Roland R. Griffiths, a professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine.

The research, approved by Johns Hopkins' Institutional Review Board, was funded in part by the National Institute on Drug Abuse and published in the Journal of Psychopharmacology.

The study participants completed two to five eight-hour drug sessions, with consecutive sessions separated by at least three weeks. Participants were informed they would receive a "moderate or high dose" of psilocybin during one of their drug sessions, but neither they nor the session monitors knew when.

During each session, participants were encouraged to lie down on a couch, use an eye mask to block external visual distraction, wear headphones through which music was played and focus their attention on their inner experiences.

Personality was assessed at screening, one to two months after each drug session and approximately 14 months after the last drug session. Griffiths says he believes the personality changes found in this study are likely permanent since they were sustained for over a year by many.

Nearly all of the participants in the new study considered themselves spiritually active (participating regularly in religious services, prayer or meditation). More than half had postgraduate degrees. The sessions with the otherwise illegal hallucinogen were closely monitored and volunteers were considered to be psychologically healthy

"We don't know whether the findings can be generalized to the larger population," Griffiths says.

As a word of caution, Griffiths also notes that some of the study participants reported strong fear or anxiety for a portion of their daylong psilocybin sessions, although none reported any lingering harmful effects. He cautions, however, that if hallucinogens are used in less well supervised settings, the possible fear or anxiety responses could lead to harmful behaviors.

Griffiths says lasting personality change is rarely looked at as a function of a single discrete experience in the laboratory. In the study, the change occurred specifically in those volunteers who had undergone a "mystical experience," as validated on a questionnaire developed by early hallucinogen researchers and refined by Griffiths for use at Hopkins. He defines "mystical experience" as among other things, "a sense of interconnectedness with all people and things accompanied by a sense of sacredness and reverence."

Personality was measured on a widely used and scientifically validated personality inventory, which covers openness and the other four broad domains that psychologists consider the makeup of personality: neuroticism, extroversion, agreeableness and conscientiousness. Only openness changed during the course of the study.

Griffiths says he believes psilocybin may have therapeutic uses. He is currently studying whether the hallucinogen has a use in helping cancer patients handle the depression and anxiety that comes along with a diagnosis, and whether it can help longtime cigarette smokers overcome their addiction.

"There may be applications for this we can't even imagine at this point," he says. "It certainly deserves to be systematically studied."

Along with the National Institute on Drug Abuse, this study was funded by the Council on Spiritual Practices, Heffter Research Institute and the Betsy Gordon Foundation.

Other Hopkins authors of the research include Matthew W. Johnson, Ph.D, and Katherine A. MacLean, Ph.D.

https://www.sciencedaily.com/releases/2011/09/110929074205.htm