Neuroscience

Articles and news from the latest research reports.

Posts tagged cannabis

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Smoking cannabis doesn’t make you more creative
People often think that smoking cannabis makes them more creative. However, research by Leiden psychologists Lorenza Colzato and Mikael Kowal shows that the opposite is true. They published their findings on 7 October in Psychopharmacology.
Strong cannabis doesn’t work
The findings show that cannabis with a high concentration of the psychoactive ingredient THC does not improve creativity. Smokers who ingested a low dose of THC, or none at all (they were given a placebo), performed best in the thinking tasks that the test candidates had to carry out.  A high dose of THC was actually shown to have a negative effect on the ability to quickly come up with as many solutions as possible to a given problem.
Increased creativity is an illusion
The research findings contradict the claims of people who say that their thinking changes and becomes more original after smoking a joint. There’s no sign of any increased creativity in their actual performance, according to Colzato. ‘The improved creativity that they believe they experience is an illusion.’
Too much dope is counterproductive
Colzato: ‘If you want to overcome writer’s block or any other creative gap, lighting up a joint isn’t the best solution. Smoking several joints one after the other can even be counterproductive to creative thinking.’  
The research method
Colzato and her PhD candidate Kowal were the first researchers to study the effects of cannabis use on creative thinking. For ethical reasons, only cannabis users were selected for this study. The test candidates were divided into three groups of 18. One group was given cannabis with a high THC content (22 mg), the second group was given a low dose (5.5 mg) and the third group was given a placebo. The high dose was equivalent to three joints and the low dose was equal to a single joint. Obviously, none of the test candidates knew what they were being given; the cannabis was administered via a vaporizer. The test candidates then had to carry out cognitive tasks that were testing for two types of creative thinking: 
Divergent thinking: generating rapid solutions for a given problem, such as: “Think of as many uses as you can for a pen?”
Convergent thinking: Finding the only right answer to a question, such as: “What is the link between the words ‘time’, ‘hair’ and ‘stretching’.  (The answer is ‘long’.)

Smoking cannabis doesn’t make you more creative

People often think that smoking cannabis makes them more creative. However, research by Leiden psychologists Lorenza Colzato and Mikael Kowal shows that the opposite is true. They published their findings on 7 October in Psychopharmacology.

Strong cannabis doesn’t work

The findings show that cannabis with a high concentration of the psychoactive ingredient THC does not improve creativity. Smokers who ingested a low dose of THC, or none at all (they were given a placebo), performed best in the thinking tasks that the test candidates had to carry out.  A high dose of THC was actually shown to have a negative effect on the ability to quickly come up with as many solutions as possible to a given problem.

Increased creativity is an illusion

The research findings contradict the claims of people who say that their thinking changes and becomes more original after smoking a joint. There’s no sign of any increased creativity in their actual performance, according to Colzato. ‘The improved creativity that they believe they experience is an illusion.’

Too much dope is counterproductive

Colzato: ‘If you want to overcome writer’s block or any other creative gap, lighting up a joint isn’t the best solution. Smoking several joints one after the other can even be counterproductive to creative thinking.’  

The research method

Colzato and her PhD candidate Kowal were the first researchers to study the effects of cannabis use on creative thinking. For ethical reasons, only cannabis users were selected for this study. The test candidates were divided into three groups of 18. One group was given cannabis with a high THC content (22 mg), the second group was given a low dose (5.5 mg) and the third group was given a placebo. The high dose was equivalent to three joints and the low dose was equal to a single joint. Obviously, none of the test candidates knew what they were being given; the cannabis was administered via a vaporizer. The test candidates then had to carry out cognitive tasks that were testing for two types of creative thinking: 

  • Divergent thinking: generating rapid solutions for a given problem, such as: “Think of as many uses as you can for a pen?”
  • Convergent thinking: Finding the only right answer to a question, such as: “What is the link between the words ‘time’, ‘hair’ and ‘stretching’.  (The answer is ‘long’.)

Filed under cannabis creativity divergent thinking convergent thinking neuroscience science

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Marijuana compound may offer treatment for Alzheimer’s disease

Extremely low levels of the compound in marijuana known as delta-9-tetrahydrocannabinol, or THC, may slow or halt the progression of Alzheimer’s disease, a recent study from neuroscientists at the University of South Florida shows.

Findings from the experiments, using a cellular model of Alzheimer’s disease, were reported online in the Journal of Alzheimer’s Disease.

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Researchers from the USF Health Byrd Alzheimer’s Institute showed that extremely low doses of THC reduce the production of amyloid beta, found in a soluble form in most aging brains, and prevent abnormal accumulation of this protein — a process considered one of the pathological hallmarks evident early in the memory-robbing disease. These low concentrations of THC also selectively enhanced mitochondrial function, which is needed to help supply energy, transmit signals, and maintain a healthy brain.

“THC is known to be a potent antioxidant with neuroprotective properties, but this is the first report that the compound directly affects Alzheimer’s pathology by decreasing amyloid beta levels, inhibiting its aggregation, and enhancing mitochondrial function,” said study lead author Chuanhai Cao, PhD and a neuroscientist at the Byrd Alzheimer’s Institute and the USF College of Pharmacy.

“Decreased levels of amyloid beta means less aggregation, which may protect against the progression of Alzheimer’s disease. Since THC is a natural and relatively safe amyloid inhibitor, THC or its analogs may help us develop an effective treatment in the future.”

The researchers point out that at the low doses studied, the therapeutic benefits of THC appear to prevail over the associated risks of THC toxicity and memory impairment.

Neel Nabar, a study co-author and MD/PhD candidate, recognized the rapidly changing political climate surrounding the debate over medical marijuana.

“While we are still far from a consensus, this study indicates that THC and THC-related compounds may be of therapeutic value in Alzheimer’s disease,” Nabar said. “Are we advocating that people use illicit drugs to prevent the disease? No. It’s important to keep in mind that just because a drug may be effective doesn’t mean it can be safely used by anyone. However, these findings may lead to the development of related compounds that are safe, legal, and useful in the treatment of Alzheimer’s disease.”

The body’s own system of cannabinoid receptors interacts with naturally-occurring cannabinoid molecules, and these molecules function similarly to the THC isolated from the cannabis (marijuana) plant.

Dr. Cao’s laboratory at the Byrd Alzheimer’s Institute is currently investigating the effects of a drug cocktail that includes THC, caffeine as well as other natural compounds in a cellular model of Alzheimer’s disease, and will advance to a genetically-engineered mouse model of Alzheimer’s shortly.

“The dose and target population are critically important for any drug, so careful monitoring and control of drug levels in the blood and system are very important for therapeutic use, especially for a compound such as THC,” Dr. Cao said.

Filed under alzheimer's disease neurodegeneration cannabis beta amyloid THC neuroscience science

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Schizophrenia and cannabis use may share common genes

Genes that increase the risk of developing schizophrenia may also increase the likelihood of using cannabis, according to a new study led by King’s College London, published today in Molecular Psychiatry

Previous studies have identified a link between cannabis use and schizophrenia, but it has remained unclear whether this association is due to cannabis directly increasing the risk of the disorder.

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The new results suggest that part of this association is due to common genes, but do not rule out a causal relationship between cannabis use and schizophrenia risk. 

The study is a collaboration between King’s and the Queensland Institute of Medical Research in Australia, partly funded by the UK Medical Research Council (MRC). 

Mr Robert Power, lead author from the MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre at the Institute of Psychiatry at King’s, says: “Studies have consistently shown a link between cannabis use and schizophrenia. We wanted to explore whether this is because of a direct cause and effect, or whether there may be shared genes which predispose individuals to both cannabis use and schizophrenia.”

Cannabis is the most widely used illicit drug in the world, and its use is higher amongst people with schizophrenia than in the general population. Schizophrenia affects approximately 1 in 100 people and people who use cannabis are about twice as likely to develop the disorder. The most common symptoms of schizophrenia are delusions (false beliefs) and auditory hallucinations (hearing voices). Whilst the exact cause is unknown, a combination of physical, genetic, psychological and environmental factors can make people more likely to develop the disorder.

Previous studies have identified a number of genetic risk variants associated with schizophrenia, each of these slightly increasing an individual’s risk of developing the disorder.  

The new study included 2,082 healthy individuals of whom 1,011 had used cannabis. Each individual’s ‘genetic risk profile’ was measured – that is, the number of genes related to schizophrenia each individual carried. 

The researchers found that people genetically pre-disposed to schizophrenia were more likely to use cannabis, and use it in greater quantities than those who did not possess schizophrenia risk genes.

Power says: “We know that cannabis increases the risk of schizophrenia. Our study certainly does not rule this out, but it suggests that there is likely to be an association in the other direction as well – that a pre-disposition to schizophrenia also increases your likelihood of cannabis use.”

“Our study highlights the complex interactions between genes and environments when we talk about cannabis as a risk factor for schizophrenia. Certain environmental risks, such as cannabis use, may be more likely given an individual’s innate behaviour and personality, itself influenced by their genetic make-up. This is an important finding to consider when calculating the economic and health impact of cannabis.”

(Source: kcl.ac.uk)

Filed under schizophrenia cannabis genes genetics neuroscience science

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Casual marijuana use linked to brain abnormalities in students

Young adults who used marijuana only recreationally showed significant abnormalities in two key brain regions that are important in emotion and motivation, scientists report. The study was a collaboration between Northwestern Medicine® and Massachusetts General Hospital/Harvard Medical School.

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This is the first study to show casual use of marijuana is related to major brain changes. It showed the degree of brain abnormalities in these regions is directly related to the number of joints a person smoked per week. The more joints a person smoked, the more abnormal the shape, volume and density of the brain regions.

"This study raises a strong challenge to the idea that casual marijuana use isn’t associated with bad consequences," said corresponding and co-senior study author Hans Breiter, M.D. He is a professor of psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine and a psychiatrist at Northwestern Memorial Hospital.

"Some of these people only used marijuana to get high once or twice a week," Breiter said. "People think a little recreational use shouldn’t cause a problem, if someone is doing OK with work or school. Our data directly says this is not the case."

The study will be published April 16 in the Journal of Neuroscience.

Scientists examined the nucleus accumbens and the amygdala — key regions for emotion and motivation, and associated with addiction — in the brains of casual marijuana users and non-users. Researchers analyzed three measures: volume, shape and density of grey matter (i.e., where most cells are located in brain tissue) to obtain a comprehensive view of how each region was affected.

Both these regions in recreational pot users were abnormally altered for at least two of these structural measures. The degree of those alterations was directly related to how much marijuana the subjects used.

Of particular note, the nucleus acccumbens was abnormally large, and its alteration in size, shape and density was directly related to how many joints an individual smoked.

"One unique strength of this study is that we looked at the nucleus accumbens in three different ways to get a detailed and consistent picture of the problem," said lead author Jodi Gilman, a researcher in the Massachusetts General Center for Addiction Medicine and an instructor in psychology at Harvard Medical School. "It allows a more nuanced picture of the results."

Examining the three different measures also was important because no single measure is the gold standard. Some abnormalities may be more detectable using one type of neuroimaging analysis method than another. Breiter said the three measures provide a multidimensional view when integrated together for evaluating the effects of marijuana on the brain.

"These are core, fundamental structures of the brain," said co-senior study author Anne Blood, director of the Mood and Motor Control Laboratory at Massachusetts General and assistant professor of psychiatry at Harvard Medical School. "They form the basis for how you assess positive and negative features about things in the environment and make decisions about them."

Through different methods of neuroimaging, scientists examined the brains of young adults, ages 18 to 25, from Boston-area colleges; 20 who smoked marijuana and 20 who didn’t. Each group had nine males and 11 females. The users underwent a psychiatric interview to confirm they were not dependent on marijuana. They did not meet criteria for abuse of any other illegal drugs during their lifetime.

The changes in brain structures indicate the marijuana users’ brains are adapting to low-level exposure to marijuana, the scientists said.

The study results fit with animal studies that show when rats are given tetrahydrocannabinol (THC) their brains rewire and form many new connections. THC is the mind-altering ingredient found in marijuana.

"It may be that we’re seeing a type of drug learning in the brain," Gilman said. "We think when people are in the process of becoming addicted, their brains form these new connections."

In animals, these new connections indicate the brain is adapting to the unnatural level of reward and stimulation from marijuana. These connections make other natural rewards less satisfying.

"Drugs of abuse can cause more dopamine release than natural rewards like food, sex and social interaction," Gilman said. "In those you also get a burst of dopamine but not as much as in many drugs of abuse. That is why drugs take on so much salience, and everything else loses its importance."

The brain changes suggest that structural changes to the brain are an important early result of casual drug use, Breiter said. “Further work, including longitudinal studies, is needed to determine if these findings can be linked to animal studies showing marijuana can be a gateway drug for stronger substances,” he noted.

Because the study was retrospective, researchers did not know the THC content of the marijuana, which can range from 5 to 9 percent or even higher in the currently available drug. The THC content is much higher today than the marijuana during the 1960s and 1970s, which was often about 1 to 3 percent, Gilman said.

Marijuana is the most commonly used illicit drug in the U.S. with an estimated 15.2 million users, the study reports, based on the National Survey on Drug Use and Health in 2008. The drug’s use is increasing among adolescents and young adults, partially due to society’s changing beliefs about cannabis use and its legal status.

A recent Northwestern study showed chronic use of marijuana was linked to brain abnormalities. “With the findings of these two papers,” Breiter said, “I’ve developed a severe worry about whether we should be allowing anybody under age 30 to use pot unless they have a terminal illness and need it for pain.”

(Source: eurekalert.org)

Filed under marijuana cannabis nucleus accumbens amygdala gray matter neuroscience science

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Discovery sheds new light on marijuana’s anxiety relief effects
An international group led by Vanderbilt University researchers has found cannabinoid receptors, through which marijuana exerts its effects, in a key emotional hub in the brain involved in regulating anxiety and the flight-or-fight response.
This is the first time cannabinoid receptors have been identified in the central nucleus of the amygdala in a mouse model, they report in the current issue of the journal Neuron.
The discovery may help explain why marijuana users say they take the drug mainly to reduce anxiety, said Sachin Patel, M.D., Ph.D., the paper’s senior author and professor of Psychiatry and of Molecular Physiology and Biophysics.
Led by first author Teniel Ramikie, a graduate student in Patel’s lab, the researchers also showed for the first time how nerve cells in this part of the brain make and release their own natural “endocannabinoids.”
The study “could be highly important for understanding how cannabis exerts its behavioral effects,” Patel said. As the legalization of marijuana spreads across the country, more people — and especially young people whose brains are still developing — are being exposed to the drug. Previous studies at Vanderbilt and elsewhere, Patel said, have suggested the following:
• The natural endocannabinoid system regulates anxiety and the response to stress by dampening excitatory signals that involve the neurotransmitter glutamate.
• Chronic stress or acute, severe emotional trauma can cause a reduction in both the production of endocannabinoids and the responsiveness of the receptors. Without their “buffering” effect, anxiety goes up.
• While marijuana’s “exogenous” cannabinoids also can reduce anxiety, chronic use of the drug down-regulates the receptors, paradoxically increasing anxiety. This can trigger “a vicious cycle” of increasing marijuana use that in some cases leads to addiction.
In the current study, the researchers used high-affinity antibodies to “label” the cannabinoid receptors so they could be seen using various microscopy techniques, including electron microscopy, which allowed very detailed visualization at individual synapses, or gaps between nerve cells.
“We know where the receptors are, we know their function, we know how these neurons make their own cannabinoids,” Patel said. “Now can we see how that system is affected by … stress and chronic (marijuana) use? It might fundamentally change our understanding of cellular communication in the amygdala.”
(Image: Shutterstock)

Discovery sheds new light on marijuana’s anxiety relief effects

An international group led by Vanderbilt University researchers has found cannabinoid receptors, through which marijuana exerts its effects, in a key emotional hub in the brain involved in regulating anxiety and the flight-or-fight response.

This is the first time cannabinoid receptors have been identified in the central nucleus of the amygdala in a mouse model, they report in the current issue of the journal Neuron.

The discovery may help explain why marijuana users say they take the drug mainly to reduce anxiety, said Sachin Patel, M.D., Ph.D., the paper’s senior author and professor of Psychiatry and of Molecular Physiology and Biophysics.

Led by first author Teniel Ramikie, a graduate student in Patel’s lab, the researchers also showed for the first time how nerve cells in this part of the brain make and release their own natural “endocannabinoids.”

The study “could be highly important for understanding how cannabis exerts its behavioral effects,” Patel said. As the legalization of marijuana spreads across the country, more people — and especially young people whose brains are still developing — are being exposed to the drug.
Previous studies at Vanderbilt and elsewhere, Patel said, have suggested the following:

• The natural endocannabinoid system regulates anxiety and the response to stress by dampening excitatory signals that involve the neurotransmitter glutamate.

• Chronic stress or acute, severe emotional trauma can cause a reduction in both the production of endocannabinoids and the responsiveness of the receptors. Without their “buffering” effect, anxiety goes up.

• While marijuana’s “exogenous” cannabinoids also can reduce anxiety, chronic use of the drug down-regulates the receptors, paradoxically increasing anxiety. This can trigger “a vicious cycle” of increasing marijuana use that in some cases leads to addiction.

In the current study, the researchers used high-affinity antibodies to “label” the cannabinoid receptors so they could be seen using various microscopy techniques, including electron microscopy, which allowed very detailed visualization at individual synapses, or gaps between nerve cells.

“We know where the receptors are, we know their function, we know how these neurons make their own cannabinoids,” Patel said. “Now can we see how that system is affected by … stress and chronic (marijuana) use? It might fundamentally change our understanding of cellular communication in the amygdala.”

(Image: Shutterstock)

Filed under anxiety cannabis cannabinoid receptors amygdala glutamate neuroscience science

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Global first: easing cannabis withdrawal

A world-first study led by the National Cannabis Prevention and Information Centre (NCPIC) at UNSW has revealed a breakthrough for dependent cannabis users, employing a cannabis-based medication, Sativex (nabiximols), that has been shown to provide significant relief from withdrawal symptoms.

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“One in ten people who try cannabis go on to become dependent. As cannabis use increases around the world and more people seek treatment to help them quit, it is surprising there is no approved medication to alleviate symptoms of withdrawal. The success of this study offers considerable hope for those struggling to get through a cannabis withdrawal and remain abstinent into the future,” said Professor Jan Copeland, Director of NCPIC and Chief Investigator of the study.

“One of the greatest barriers to quitting cannabis is withdrawal and while symptoms aren’t life-threatening, they are of a severity level that causes marked distress. For many people, symptoms including irritability, depression, cannabis cravings and sleep problems, can overcome their strong desire to quit and they find themselves using again.”

The study was conducted at inpatient services of South Eastern Sydney and Hunter New England Local Health Districts.

Associate Professor Nicolas Lintzeris, Director of Drug and Alcohol Services at South Eastern Sydney Local Health District and a trial investigator said: “The study found patients treated with Sativex stayed in treatment longer, and experienced a shorter and milder withdrawal than patients receiving placebo.”

Administered as an oral spray, Sativex is only licensed in Australia for the treatment of spasticity and pain in Multiple Sclerosis (MS) patients when other medications have failed. The spray contains the cannabis extracts, cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC), which is the substance primarily responsible for the psychoactive effects of cannabis.

The lead author of the paper and study investigator Dr David Allsop noted, “While most people who use cannabis do not become dependent, those who use regularly or for an extended period run that risk. Sativex is not licensed or available for treating cannabis users at this time. Our hope is that this study will lead to further research, and possibly approval of the drug for use as a treatment for people experiencing problematic cannabis use.”

The full findings of this study have been published in international psychiatry journal, JAMA Psychiatry.

(Source: newsroom.unsw.edu.au)

Filed under nabiximols cannabis cannabis withdrawal medicine science

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Molecule discovered that protects the brain from cannabis intoxication
Two INSERM research teams led by Pier Vincenzo Piazza and Giovanni Marsicano (INSERM Unit 862 “Neurocentre Magendie” in Bordeaux) recently discovered that pregnenolone, a molecule produced by the brain, acts as a natural defence mechanism against the harmful effects of cannabis in animals. Pregnenolone prevents THC, the main active principle in cannabis, from fully activating its brain receptor, the CB1 receptor, that when overstimulated by THC causes the intoxicating effects of cannabis. By identifying this mechanism, the INSERM teams are already developing new approaches for the treatment of cannabis addiction.
These results are to be published in Science on 3 January.
Over 20 million people around the world are addicted to cannabis, including a little more than a half million people in France. In the last few years, cannabis addiction has become one of the main reasons for seeking treatment in addiction clinics. Cannabis consumption is particularly high (30%) in individuals between 16 to 24 years old, a population that is especially susceptible to the harmful effects of the drug.
While cannabis consumers are seeking a state of relaxation, well-being and altered perception, there are many dangers associated to a regular consumption of cannabis. Two major behavioural problems are associated with regular cannabis use in humans: cognitive deficits and a general loss of motivation. Thus, in addition to being extremely dependent on the drug, regular users of cannabis show signs of memory loss and a lack of motivation that make quite hard their social insertion.
The main active ingredient in cannabis, THC, acts on the brain through CB1 cannabinoid receptors located in the neurons. THC binds to these receptors diverting them from their physiological roles, such as regulating food intake, metabolism, cognitive processes and pleasure. When THC overstimulates CB1 receptors, it triggers a reduction in memory abilities, motivation and gradually leads to dependence.
Increase of dopamine release
Developing an efficient treatment for cannabis addiction is becoming a priority of research in the fiend of drug addiction.
In this context, the INSERM teams led by Pier Vincenzo Piazza and Giovanni Marsicano have investigated the potential role of pregnenolone a brain produced steroid hormone. Up to now, pregnenolone was considered the inactive precursor used to synthesize all the other steroid hormones (progesterone, estrogens, testosterone, etc.). The INSERM researchers have now discovered that pregnenolone has quite an important functional role: it provide a natural defence mechanism that can protect the brain from the harmful effects of cannabis.
Essentially, when high doses of THC (well above those inhaled by regular users) activate the CB1 cannabinoid receptor they also trigger the synthesis of pregnenolone. Pregnenole then binds to a specific site on the same CB1 receptors (see figure) and reducing the effects of THC.
The administration of pregnenolone at doses that increase the brain’s level of this hormone even more, antagonize the behavioral effects of cannabis.
At the neurobiological level, pregnenolone greatly reduces the release of dopamine triggered by THC. This is an important effect, since the addictive effects of drugs involve an excessive release of dopamine.
This negative feedback mediated by pregnenolone (THC is what triggers the production of pregnenolone, which then inhibits the effects of THC) reveal a previously unknown endogenous mechanism that protects the brain from an over-activation of CB1 receptor.
A protective mechanism that opens the doors to a new therapeutic approach.
The role of pregnenolone was discovered when, rats were given equivalent doses of cocaine, morphine, nicotine, alcohol and cannabis and the levels of several brain steroids (pregnenolone, testosterone, allopregnenolone, DHEA etc..) were measured. It was then found that only one drug, THC, increased brain steroids and more specifically selectively one steroid, pregnenolone, that went up3000% for a period of two hours.
The effect of administering THC on the pregnenolone synthesis (PREG) and other brain steroids
This increase in pregnenolone is a built-in mechanism that moderates the effects of THC. Thus, the effects of THC increase when pregnenolone synthesis is blocked. Conversely, when pregnenolone is administered to rats or mice at doses (2-6 mg/kg) that induce even greater concentrations of the hormone in the brain, the negative behavioural effects of THC are blocked. For example, the animals that were given pregnenolone recover their normal memory abilities, are less sedated and less incline to self-administer cannabinoids.
Experiments conducted in cell cultures that express the human CB1 receptor confirm that pregnenolone can also counteract the molecular action of THC in humans.
Pier Vincenzo Piazza explains that pregnenolone itself cannot be used as a treatment “Pregnenolone cannot be used as a treatment because it is badly absorbed when administerd orally and once in the blood stream it is rapidly transformed in other steroids”.
However, the researcher says that there is strong hope of seeing a new addiction therapy emerge from this discovery. “We have now developed derivatives of pregnenolone that are well absorbed and stable. They then present the characteristics of compounds that can be used as new class of therapeutic drugs. We should be able to begin clinical trials soon and verify whether we have indeed discovered the first pharmacological treatment for cannabis dependence.”

Molecule discovered that protects the brain from cannabis intoxication

Two INSERM research teams led by Pier Vincenzo Piazza and Giovanni Marsicano (INSERM Unit 862 “Neurocentre Magendie” in Bordeaux) recently discovered that pregnenolone, a molecule produced by the brain, acts as a natural defence mechanism against the harmful effects of cannabis in animals. Pregnenolone prevents THC, the main active principle in cannabis, from fully activating its brain receptor, the CB1 receptor, that when overstimulated by THC causes the intoxicating effects of cannabis. By identifying this mechanism, the INSERM teams are already developing new approaches for the treatment of cannabis addiction.

These results are to be published in Science on 3 January.

Over 20 million people around the world are addicted to cannabis, including a little more than a half million people in France. In the last few years, cannabis addiction has become one of the main reasons for seeking treatment in addiction clinics. Cannabis consumption is particularly high (30%) in individuals between 16 to 24 years old, a population that is especially susceptible to the harmful effects of the drug.

While cannabis consumers are seeking a state of relaxation, well-being and altered perception, there are many dangers associated to a regular consumption of cannabis. Two major behavioural problems are associated with regular cannabis use in humans: cognitive deficits and a general loss of motivation. Thus, in addition to being extremely dependent on the drug, regular users of cannabis show signs of memory loss and a lack of motivation that make quite hard their social insertion.

The main active ingredient in cannabis, THC, acts on the brain through CB1 cannabinoid receptors located in the neurons. THC binds to these receptors diverting them from their physiological roles, such as regulating food intake, metabolism, cognitive processes and pleasure. When THC overstimulates CB1 receptors, it triggers a reduction in memory abilities, motivation and gradually leads to dependence.

Increase of dopamine release

Developing an efficient treatment for cannabis addiction is becoming a priority of research in the fiend of drug addiction.

In this context, the INSERM teams led by Pier Vincenzo Piazza and Giovanni Marsicano have investigated the potential role of pregnenolone a brain produced steroid hormone. Up to now, pregnenolone was considered the inactive precursor used to synthesize all the other steroid hormones (progesterone, estrogens, testosterone, etc.). The INSERM researchers have now discovered that pregnenolone has quite an important functional role: it provide a natural defence mechanism that can protect the brain from the harmful effects of cannabis.

Essentially, when high doses of THC (well above those inhaled by regular users) activate the CB1 cannabinoid receptor they also trigger the synthesis of pregnenolone. Pregnenole then binds to a specific site on the same CB1 receptors (see figure) and reducing the effects of THC.

The administration of pregnenolone at doses that increase the brain’s level of this hormone even more, antagonize the behavioral effects of cannabis.

At the neurobiological level, pregnenolone greatly reduces the release of dopamine triggered by THC. This is an important effect, since the addictive effects of drugs involve an excessive release of dopamine.

This negative feedback mediated by pregnenolone (THC is what triggers the production of pregnenolone, which then inhibits the effects of THC) reveal a previously unknown endogenous mechanism that protects the brain from an over-activation of CB1 receptor.

A protective mechanism that opens the doors to a new therapeutic approach.

The role of pregnenolone was discovered when, rats were given equivalent doses of cocaine, morphine, nicotine, alcohol and cannabis and the levels of several brain steroids (pregnenolone, testosterone, allopregnenolone, DHEA etc..) were measured. It was then found that only one drug, THC, increased brain steroids and more specifically selectively one steroid, pregnenolone, that went up3000% for a period of two hours.

The effect of administering THC on the pregnenolone synthesis (PREG) and other brain steroids

This increase in pregnenolone is a built-in mechanism that moderates the effects of THC. Thus, the effects of THC increase when pregnenolone synthesis is blocked. Conversely, when pregnenolone is administered to rats or mice at doses (2-6 mg/kg) that induce even greater concentrations of the hormone in the brain, the negative behavioural effects of THC are blocked. For example, the animals that were given pregnenolone recover their normal memory abilities, are less sedated and less incline to self-administer cannabinoids.

Experiments conducted in cell cultures that express the human CB1 receptor confirm that pregnenolone can also counteract the molecular action of THC in humans.

Pier Vincenzo Piazza explains that pregnenolone itself cannot be used as a treatment “Pregnenolone cannot be used as a treatment because it is badly absorbed when administerd orally and once in the blood stream it is rapidly transformed in other steroids”.

However, the researcher says that there is strong hope of seeing a new addiction therapy emerge from this discovery. “We have now developed derivatives of pregnenolone that are well absorbed and stable. They then present the characteristics of compounds that can be used as new class of therapeutic drugs. We should be able to begin clinical trials soon and verify whether we have indeed discovered the first pharmacological treatment for cannabis dependence.”

Filed under cannabis pregnenolone addiction dopamine neuroscience science

343 notes

Perception of Marijuana as a “Safe Drug” Is Scientifically Inaccurate 
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 dependant 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.
(Image: AP)

Perception of Marijuana as a “Safe Drug” Is Scientifically Inaccurate

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 dependant 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.

(Image: AP)

Filed under marijuana cannabis prefrontal cortex adolescence mental health neuroscience science

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Low Doses of THC Can Halt Brain Damage

Extremely low doses of marijuana’s psychoactive component protect brain before and after injury, says TAU researcher

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Though marijuana is a well-known recreational drug, extensive scientific research has been conducted on the therapeutic properties of marijuana in the last decade. Medical cannabis is often used by sufferers of chronic ailments, including cancer and post-traumatic stress disorder, to combat pain, insomnia, lack of appetite, and other symptoms.

Now Prof. Yosef Sarne of Tel Aviv University’s Adelson Center for the Biology of Addictive Diseases at the Sackler Faculty of Medicine says that the drug has neuroprotective qualities as well. He has found that extremely low doses of THC — the psychoactive component of marijuana — protects the brain from long-term cognitive damage in the wake of injury from hypoxia (lack of oxygen), seizures, or toxic drugs. Brain damage can have consequences ranging from mild cognitive deficits to severe neurological damage.

Previous studies focused on injecting high doses of THC within a very short time frame — approximately 30 minutes — before or after injury. Prof. Sarne’s current research, published in the journals Behavioural Brain Research and Experimental Brain Research, demonstrates that even extremely low doses of THC — around 1,000 to 10,000 times less than that in a conventional marijuana cigarette — administered over a wide window of 1 to 7 days before or 1 to 3 days after injury can jumpstart biochemical processes which protect brain cells and preserve cognitive function over time.

This treatment, especially in light of the long time frame for administration and the low dosage, could be applicable to many cases of brain injury and be safer over time, Prof. Sarne says.

Conditioning the brain

While performing experiments on the biology of cannabis, Prof. Sarne and his fellow researchers discovered that low doses of the drug had a big impact on cell signalling, preventing cell death and promoting growth factors. This finding led to a series of experiments designed to test the neuroprotective ability of THC in response to various brain injuries.

In the lab, the researchers injected mice with a single low dose of THC either before or after exposing them to brain trauma. A control group of mice sustained brain injury but did not receive the THC treatment. When the mice were examined 3 to 7 weeks after initial injury, recipients of the THC treatment performed better in behavioral tests measuring learning and memory. Additionally, biochemical studies showed heightened amounts of neuroprotective chemicals in the treatment group compared to the control group.

The use of THC can prevent long-term cognitive damage that results from brain injury, the researchers conclude. One explanation for this effect is pre- and post-conditioning, whereby the drug causes minute damage to the brain to build resistance and trigger protective measures in the face of much more severe injury, explains Prof. Sarne. The low dosage of THC is crucial to initiating this process without causing too much initial damage.

Preventative and long-term use

According to Prof. Sarne, there are several practical benefits to this treatment plan. Due to the long therapeutic time window, this treatment can be used not only to treat injury after the fact, but also to prevent injury that might occur in the future. For example, cardiopulmonary heart-lung machines used in open heart surgery carry the risk of interrupting the blood supply to the brain, and the drug can be delivered beforehand as a preventive measure. In addition, the low dosage makes it safe for regular use in patients at constant risk of brain injury, such as epileptics or people at a high risk of heart attack.

Prof. Sarne is now working in collaboration with Prof. Edith Hochhauser of the Rabin Medical Center to test the ability of low doses of THC to prevent damage to the heart. Preliminary results indicate that they will find the same protective phenomenon in relation to cardiac ischemia, in which the heart muscle receives insufficient blood flow.

(Source: aftau.org)

Filed under cannabis brain injury brain cells brain damage PTSD neuroscience science

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Mental illness associated with heavy cannabis use 
People with mental illnesses are more than seven times more likely to use cannabis weekly compared to people without a mental illness, according to researchers from the Centre for Addiction and Mental Health (CAMH) who studied U.S. data.
Cannabis is the most widely used illicit substance globally, with an estimated 203 million people reporting use. Although research has found links between cannabis use and mental illness, exact numbers and prevalence of problem cannabis use had not been investigated.
“We know that people with mental illness consume more cannabis, perhaps partially as a way to self- medicate psychiatric symptoms, but this data showed us the degree of the correlation between cannabis use, misuse, and mental illness,” said Dr. Shaul Lev-ran, Adjunct Scientist at CAMH and Head of Addiction Medicine at the Sheba Medical Center, Israel.
“Based on the number of individuals reporting weekly use, we see that people with mental illness use cannabis at high rates. This can be of concern because it could worsen the symptoms of their mental illness,” said Lev-ran, who conducted the research as a post-doctoral fellow with the Social Aetiology of Mental Illness (SAMI) Training Program at CAMH.
Researchers also found that individuals with mental illness were 10 times more likely to have a cannabis use disorder.
In this new study, published in the journal Comprehensive Psychiatry, CAMH researchers analyzed data from face-to-face interviews with over 43,000 respondents over the age of 18 from the National Epidemiologic Survey on Alcohol and Related Conditions. Using structured questionnaires, the researchers assessed cannabis use as well as various mental illnesses including depression, anxiety, drug and alcohol use disorders and personality disorders, based on criteria from the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV).
Among those will mental illness reporting at least weekly cannabis use, rates of use were particularly elevated for those with bipolar disorder, personality disorders and other substance use disorders.
In total, 4.4 per cent of individuals with a mental illness in the past 12 months reported using cannabis weekly, compared to 0.6 per cent among individuals without any mental illness. Cannabis use disorders occurred among 4 per cent of those with mental illness versus 0.4 per cent among those without.
Researchers also noted that, although cannabis use is generally higher among younger people, the association between mental illness and cannabis use was pervasive across most age groups.
They emphasize the importance of screening for frequent and problem cannabis use among those with mental illness, so that targeted prevention and intervention may be employed.

Mental illness associated with heavy cannabis use

People with mental illnesses are more than seven times more likely to use cannabis weekly compared to people without a mental illness, according to researchers from the Centre for Addiction and Mental Health (CAMH) who studied U.S. data.

Cannabis is the most widely used illicit substance globally, with an estimated 203 million people reporting use. Although research has found links between cannabis use and mental illness, exact numbers and prevalence of problem cannabis use had not been investigated.

“We know that people with mental illness consume more cannabis, perhaps partially as a way to self- medicate psychiatric symptoms, but this data showed us the degree of the correlation between cannabis use, misuse, and mental illness,” said Dr. Shaul Lev-ran, Adjunct Scientist at CAMH and Head of Addiction Medicine at the Sheba Medical Center, Israel.

“Based on the number of individuals reporting weekly use, we see that people with mental illness use cannabis at high rates. This can be of concern because it could worsen the symptoms of their mental illness,” said Lev-ran, who conducted the research as a post-doctoral fellow with the Social Aetiology of Mental Illness (SAMI) Training Program at CAMH.

Researchers also found that individuals with mental illness were 10 times more likely to have a cannabis use disorder.

In this new study, published in the journal Comprehensive Psychiatry, CAMH researchers analyzed data from face-to-face interviews with over 43,000 respondents over the age of 18 from the National Epidemiologic Survey on Alcohol and Related Conditions. Using structured questionnaires, the researchers assessed cannabis use as well as various mental illnesses including depression, anxiety, drug and alcohol use disorders and personality disorders, based on criteria from the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV).

Among those will mental illness reporting at least weekly cannabis use, rates of use were particularly elevated for those with bipolar disorder, personality disorders and other substance use disorders.

In total, 4.4 per cent of individuals with a mental illness in the past 12 months reported using cannabis weekly, compared to 0.6 per cent among individuals without any mental illness. Cannabis use disorders occurred among 4 per cent of those with mental illness versus 0.4 per cent among those without.

Researchers also noted that, although cannabis use is generally higher among younger people, the association between mental illness and cannabis use was pervasive across most age groups.

They emphasize the importance of screening for frequent and problem cannabis use among those with mental illness, so that targeted prevention and intervention may be employed.

Filed under cannabis mental illness psychatric disorders cannabis misuse health psychology neuroscience science

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