1. Study examines effect of THC on stress

    June 12, 2017 by Ashley

    From the University of Illinois at Chicago press release:

    Cannabis smokers often report that they use the drug to relax or relieve stress, but few studies provide clinical evidence of these effects.

    Now, researchers at the University of Illinois at Chicago and the University of Chicago report that low levels tetrahydrocannabinol, or THC, the main psychoactive compound in marijuana, does reduce stress, but in a highly dose-dependent manner: very low doses lessened the jitters of a public-speaking task, while slightly higher doses — enough to produce a mild “high” — actually increased anxiety.

    Cannabis is a highly regulated category 1 substance, and permits to study the drug are difficult to obtain. While it is common knowledge that many people use cannabis for its stress-relieving effects, “very few published studies have looked into the effects of THC on stress, or at the effects of different levels of THC on stress,” says Emma Childs, associate professor of psychiatry in the UIC College of Medicine and corresponding author on the study, published in the journal Drug and Alcohol Dependence.

    “We found that THC at low doses reduced stress, while higher doses had the opposite effect, underscoring the importance of dose when it comes to THC and its effects.”

    Childs and her colleagues recruited 42 healthy volunteers 18 to 40 years old who had some experience with cannabis use but who were not daily users.

    Participants were randomly divided into three groups: The low-dose group received a capsule containing 7.5 milligrams of THC; the moderate-dose group received a capsule containing 12.5 milligrams of THC; and a placebo group received a capsule containing none. Neither the participants nor the researchers knew who was in each group.

    “The doses used in the study produce effects that are equivalent to only a few puffs of a cannabis cigarette,” said Childs, noting that it is difficult to compare doses of smoked cannabis to doses of ingested THC. “We didn’t want to include a much larger dose, because we wanted to avoid potential adverse effects or cardiovascular effects that can result from higher doses of THC.”

    Participants attended two four-hour sessions at the University of Chicago, five days apart. At each session, they took their capsule and then relaxed for two hours to allow the THC to be absorbed into the bloodstream.

    During one session, participants were asked to spend 10 minutes preparing for a mock job interview. They were then subjected to a five-minute interview with lab assistants who did not offer any feedback, verbally or through body language, although video display was visible to the participant, showing their performance. Participants were then instructed to count backwards from a five-digit number by subtracting 13, for five minutes — a task that is “very reliably stress-inducing,” Childs said.

    In their second visit, participants were asked to talk to lab assistants about a favorite book or movie for five minutes and then play solitaire for another five minutes.

    Before, during and after each of the two activities, participants rated their stress levels and feelings about the tasks. Blood pressure, heart rate, and cortisol, a key stress hormone, were measured at intervals.

    The participants who received 7.5 milligrams of THC reported less stress after the psychosocial test than those given a placebo, and their stress levels dissipated faster after the test.

    Participants who received 12.5 milligrams of THC before the two tasks reported greater negative mood before and throughout the task, and were more likely to rate the psychosocial task as “challenging” and “threatening” beforehand. Participants who received this dose also had more pauses during the mock interview compared to those in the placebo group.

    There were no significant differences in participants’ blood pressure, heart rate or cortisol levels — before, during or after the doses or the tasks.

    “Our findings provide some support for the common claim that cannabis is used to reduce stress and relieve tension and anxiety,” Childs said. “At the same time, our finding that participants in the higher THC group reported small but significant increases in anxiety and negative mood throughout the test supports the idea that THC can also produce the opposite effect.”

    “Studies like these — examining the effects of cannabis and its pharmacological constituents under controlled conditions — are extremely important, considering the widespread use of cannabis for both medical and non-medical purposes,” she said. “Unfortunately, significant regulatory obstacles make it extremely difficult to conduct this type of research — with the result that cannabis is now widely available for medical purposes with minimal scientific foundation.”


  2. Study suggests cannabis reverses aging processes in the brain

    May 13, 2017 by Ashley

    From the University of Bonn press release:

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

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

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

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

    Years of meticulous research

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

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

    Next step: clinical trial on humans

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

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


  3. First atomic-level image of the human ‘marijuana receptor’ unveiled

    October 21, 2016 by Ashley

    From the Scripps Research Institute media release:

    marijuanaIn a discovery that advances the understanding of how marijuana works in the human body, an international group of scientists, including those from the Florida campus of The Scripps Research Institute (TSRI), have for the first time created a three-dimensional atomic-level image of the molecular structure activated by tetrahydrocannabinol (THC), the active chemical in marijuana.

    The new insights into the human cannabinoid receptor 1 (CB1) will provide an essential tool for understanding why some molecules related to THC have unexpectedly complex and sometimes harmful effects. The findings also have the potential to guide drug design for pain, inflammation, obesity, fibrosis and other indications.

    The new study, published by the journal Cell, was led by a quartet of scientists: TSRI’s Laura Bohn, Northeastern University’s Alexandros Makriyannis, Shanghai Tech University’s Zhi-Jie Liu and Raymond C. Stevens (also of the University of Southern California).

    At the beginning of the study, the team struggled to produce a crystal form — needed to obtain data to recreate the high-resolution structure — of the receptor bound with AM6538, a stabilizing a molecule that blocks the receptor’s action.

    The CB1 receptor proved as challenging for crystallization as it did for understanding its functional regulation and signaling,” said Bohn, who is a professor in TSRI’s Department of Molecular Therapeutics.

    When the scientists succeeded in crystalizing the receptor and collecting the data, the structure of the cannabinoid receptor complex revealed an expansive and complicated binding pocket network consisting of multiple sub-pockets and channels to various regions of the receptor.

    Cannabinoid receptors are part of a large class of receptors known as G protein-coupled receptors (GPCR), which account for about 40 percent of all prescription pharmaceuticals on the market, and play key roles in many physiological functions. When an outside substance binds to a GPCR, it activates a G protein inside the cell to release components and create a specific cellular response.

    AM6538, is an antagonist/inverse agonist that binds tightly to the receptor; it has a long half-life, making it potentially useful as a treatment of addiction disorders.

    As marijuana continues to become more common in society, it is critical that we understand how it works in the human body,” said Liu, who is professor and deputy director of the iHuman Institute of Shanghai Tech and is also affiliated with the Chinese Academy of Sciences.


  4. Study of fatal car accidents suggests medical marijuana may be helping curb opioid use

    September 17, 2016 by Ashley

    From the Columbia University Medical Center media release:

    marijuanaA study conducted at Columbia University’s Mailman School of Public Health found that there were fewer drivers killed in car crashes who tested positive for opioids in states with medical marijuana laws than before the laws went into effect. The study is one of the first to assess the link between state medical marijuana laws and opioid use at the individual level. Findings will be published online in the American Journal of Public Health.

    Researchers analyzed 1999-2013 Fatality Analysis Reporting System data from 18 U.S. states that tested for alcohol and other drugs in at least 80 percent of drivers who died within one hour of crashing. They looked at opioid positivity among drivers ages 21 to 40 who crashed their cars in states with an operational medical marijuana law compared with drivers crashing in states before those laws went into effect. There was an overall reduction in opioid positivity for most states after implementation of an operational medical marijuana law.

    We would expect the adverse consequences of opioid use to decrease over time in states where medical marijuana use is legal, as individuals substitute marijuana for opioids in the treatment of severe or chronic pain,” explained June H. Kim, MPhil, a doctoral student in the Department of Epidemiology at the Mailman School of Public Health, and lead author.

    Among the 68,394 deceased drivers, approximately 42 percent were fatally injured in states that had an operational medical marijuana laws, 25 percent died in states before an operational law went into effect, and 33 percent died in states that had never passed a medical marijuana law.

    In 1996, California was the first state to pass a voter-initiated medical marijuana law. Since then, 22 additional states and the District of Columbia have enacted their own medical marijuana laws either by voter initiatives or through state legislation. “The trend may have been particularly strong among the age group surveyed because minimum age requirements restrict access to medical marijuana to patients age 21 and older, and most medical marijuana patients are younger than 45,” noted Kim. According to the authors, they would expect to see similar reductions in opioid use among older cohorts if medical marijuana is increasingly embraced by older generations.

    “This study is about the possible substitution relationship between marijuana and opioids. The toxicological testing data for fatally injured drivers lend some suggestive evidence that supports the substitution hypothesis in young adults, but not in older adults,“said Guohua Li, MD, DrPH, Mailman School professor of Epidemiology, the founding director of the Center for Injury Epidemiology and Prevention at Columbia, and senior author.

    “As states with these laws move toward legalizing marijuana more broadly for recreational purposes, future studies are needed to assess the impact these laws may have on opioid use,” noted Kim.


  5. Long-term marijuana use associated with worse verbal memory in middle age

    February 10, 2016 by Ashley

    From the The JAMA Network Journals media release:

    marijuanaMarijuana use over time was associated with remembering fewer words from a list but it did not appear to affect other areas of cognitive function in a study of men and women followed up over 25 years, according to an article published online by JAMA Internal Medicine.

    Marijuana use is common among adolescents and young adults. It remains unclear whether there are long-term effects from low-intensity or occasional marijuana use earlier in life and whether the magnitude and persistence of impairment depends on the duration of marijuana use or the age of exposure.

    The Coronary Artery Risk Development in Young Adults (CARDIA) study includes 25 years of repeated measures of marijuana exposure starting in early adulthood. In year 25, CARDIA measured cognitive performance using standardized tests of verbal memory, processing speed and executive function.

    Reto Auer, M.D., M.A.S., formerly of the University of California-San Francisco and now the University of Lausanne, Switzerland, and coauthors used those measurements to study the association between cumulative years of exposure to marijuana use and cognitive performance in middle age among study participants who had marijuana exposures typical to the communities in which they live.

    Of the 3,499 participants assessed at the year 25 visit, 3,385 (96.7 percent) had data on cognitive function. Among the 3,385 participants, 2,852 (84.3 percent) reported past marijuana use but only 392 (11.6 percent) continued to use marijuana into middle age.

    Past exposure to marijuana was associated with worse verbal memory but does not appear to affect other domains of cognitive function. For every five years of past exposure, lower verbal memory corresponded to an average of 1 of 2 participants remembering one word fewer from a list of 15 words, according to the results.

    Limitations to the study include self-reported information that is not always reliable.

    “Future studies with multiple assessments of cognition, brain imaging and other functional outcomes should further explore these associations and their potential clinical and public health implications. In the meantime, with recent changes in legislation and the potential for increasing marijuana use in the United States, continuing to warn potential users about the possible harm from exposure to marijuana seems reasonable,” the study concludes.