High-strength cannabis linked to addiction and mental health problems

July 25, 2022

Science Daily/University of Bath

As the strength or potency of cannabis products has increased internationally over the years, so have rates of people being treated for cannabis addiction, say the authors of a new study.

Researchers from the Addiction and Mental Health Group at the University of Bath (UK) systematically analysed the relationship between the types of cannabis people use and their addiction and mental health problems. Their work draws on 20 studies involving almost 120,000 people.

After alcohol and nicotine, cannabis is the most widely used drug globally. Latest estimates from the UK suggest that over the last year around one in five 16-24 year olds had used cannabis.

Cannabis potency refers to the concentration of tetrahydrocannabinol (THC) in cannabis -- the key psychoactive drug it contains. Recent studies from the same team at Bath have found that the concentration of THC in cannabis has increased significantly over time meaning that cannabis used today is typically much stronger than previously.

The new study, published in The Lancet Psychiatry, suggests that people who use high potency cannabis are more likely to experience addiction than those using low potency products. It also suggests that people using high potency cannabis are more likely to experience a psychotic disorder, such as schizophrenia.

These findings may help to explain why more people have received treatment for cannabis problems over recent years. Data from the European Monitoring Centre for Drugs and Drug Addiction show a 76% increase in people entering treatment for cannabis addiction in the past decade.

Based on these new results, the authors argue that public health guidelines and policies to help make cannabis use safer should be encouraged.

Lead author, Kat Petrilli from the University of Bath's Department of Psychology explained: "Our systematic review found that people who use higher potency cannabis could be at increased risks of addiction as well as psychosis when compared to people who use cannabis products with lower potencies.

"These results are important in the context of harm reduction which aims to minimise the negative consequences associated with drug use. While the safest level of use for cannabis is of course 'no use', it is important to acknowledge that a significant number of people across the world use cannabis regularly and to ensure they can make informed decisions that could reduce any possible harms associated with it."

The authors point out that strategies to make cannabis use safer could inform how the drug is regulated in the UK and internationally. Recreational cannabis use remains illegal in the UK, but cannabis products are now legally sold for recreational use in Canada, Uruguay, and parts of the USA.

Several other countries appear set to follow this trend, including Germany. In the UK, the Liberal Democrats have argued that a legal regulated market could make cannabis use safer by enforcing a limit on the potency of cannabis products, and investing the revenue and savings from this into education and treatment for cannabis problems.

Senior author, Dr Tom Freeman explained: "Our findings suggest that people who use cannabis could reduce their risk of harm by using lower potency products. In places where cannabis is legally sold, providing consumers with accurate information on product content and access to lower potency products could help people to use cannabis more safely."

Despite anecdotal evidence of links between cannabis and anxiety and depression, the authors note that the links between cannabis potency and other mental health problems are unclear.

https://www.sciencedaily.com/releases/2022/07/220725203611.htm

Marijuana use is much more common in US states that have legalized recreational cannabis use

Highest rates among Americans who smoke cigarettes

July 19, 2022

Science Daily/Columbia University's Mailman School of Public Health

A study at Columbia University Mailman School of Public Health and The City University of New York found that the rates of cannabis use and daily cannabis use have increased across the U.S., and that current cannabis use and daily use are substantially higher among individuals residing in states that have legalized recreational cannabis use, relative to those where cannabis use remains illegal. The study also found that rates of cannabis use are even higher among Americans 12 and older who smoke cigarettes, and who reside in states with recreational cannabis laws, compared to those who live in states where cannabis was illegal in 2017.

"Based upon over a decade of data, cannabis use was markedly more prevalent in states where recreational use is legal for adults, relative to states where it was not in 2017. Yet, the increases in cannabis use during this time period were as fast, or faster, in states where cannabis use is prohibited by law, relative to states that had legalized for recreational use by 2017," said Renee Goodwin, PhD, adjunct associate professor of epidemiology at Columbia Mailman School and professor of epidemiology at CUNY, and lead author. "It remains to be seen how increased lawful accessi and growing use of cannabis among adults in all states -- almost regardless of legal status -- will impact the adolescent population. Recent trends, however, outline a potential explosion in both of-age and under-age use," she noted.

The researchers used data from the 2004-2017 National Survey on Drug Use and Health, a representative survey of U.S. individuals aged 12 and older. State of residence was used to determine state-level medical and recreational cannabis laws. The total sample was 784,293 respondents and for 2017 was 56,276 respondents.

The study found that cannabis use and daily cannabis use increased in the U.S with little difference in the speed of increase by state-level legal status of cannabis use from 2004 through 2017. Cannabis use and daily cannabis were much more common in states with recreationally legal cannabis use, relative to those with legal medical cannabis and those with no legal cannabis use.

Cannabis use was even greater among Americans who also smoke cigarettes in states that had adopted recreational cannabis laws, relative to those where cannabis use was not legal. In 2017, one in three (33 percent) daily cigarette smokers reported cannabis use in the past month in recreationally legal states and almost one in five (18 percent) reported daily cannabis use. In contrast, among non-smokers, one in ten reported any cannabis use in recreationally legal states and 3 percent of non-cigarette smokers in these states reported daily use.

The study found that among adolescents ages 12-17 who used cigarettes daily, the majority (73 percent) had used cannabis in the past month and almost one in three (30 percent) used cannabis daily. Among adolescents who did not smoke cigarettes, 5 percent used cannabis in the past month and one percent used cannabis daily.

The study is published online in the journal Drug and Alcohol Dependence.

Goodwin observes, "U.S. states are rapidly passing legislation, yet what should be requisite public education on how cannabis can be used safely has not accompanied these changes. For instance, retail licenses are being issued and it is expected that recreational retail outlets will open within the year in New York State, yet New York has not provided evidence-based guidance outlining safe cannabis use practices or informing the public of potential health risks associated with various levels of cannabis use."

https://www.sciencedaily.com/releases/2022/07/220719162133.htm

Emergency care and hospitalizations higher among cannabis users

Serious physical injury and respiratory-reasons the two leading causes of ED visits and hospitalizations among cannabis users

June 28, 2022

Science Daily/St. Michael's Hospital

Visits to the emergency department and hospitalizations are 22 per cent higher among individuals who use cannabis compared with those who do not, according to a new study.

The study, published in BMJ Open Respiratory Research and led by researchers at Unity Health Toronto and ICES, found serious physical injury and respiratory-reasons were the two leading causes of ED visits and hospitalizations among cannabis users.

The findings suggest an association between cannabis use and negative health events, which the researchers say should underline the need to educate and remind the public of the harmful impacts of cannabis on health. Recreational cannabis use has increased in Canada since decriminalization in October 2018.

"Our research demonstrates that cannabis use in the general population is associated with heightened risk of clinically serious negative outcomes, specifically, needing to present to the ED or be admitted to hospital," said Dr. Nicholas Vozoris, lead author, a respirologist at St. Michael's and an associate scientist at the hospital's Li Ka Shing Knowledge Institute.

"Unlike tobacco, there is some uncertainty or controversy regarding the adverse health impacts of cannabis. Some individuals may perceive that cannabis has some health benefits and is otherwise benign. Our research highlights to those using -- or considering to use -- cannabis, that this behaviour is associated with important negative health events."

To compare health outcomes among cannabis users and individuals who don't use cannabis, researchers used data collected in a survey of individuals who self-reported cannabis use and linked it with health administrative data from ICES for Ontario residents ages 12 to 65 years old.

Using propensity score matching -- a statistical matching technique -- researchers compared the health outcomes of nearly 4,800 individuals who reported any cannabis use in the preceding 12 months with the health outcomes of over 10,000 individuals who reported never having used cannabis, or having used cannabis only once and more than 12 months ago. Researchers incorporated 31 different variables while matching study participants to minimize an unfair comparison, including demographics, multiple physical and mental health diseases, and tobacco, alcohol and illicit drug use.

The primary goal of the study was to explore whether there was a link between cannabis use and respiratory-related hospitalization or ED visits. The researchers found no significant associations between cannabis use and respiratory-related ED visits, hospitalizations, or death from any cause. However, they did find that overall visits to the ED or hospitalizations for any reason was significantly higher among cannabis users.

In addition to having greater odds of going to the ED or being hospitalized, the findings show that one of every 25 people who use cannabis will go to the emergency department (ED) or be admitted to hospital within a year of using cannabis.

Among the reasons cannabis users went to the ED or were hospitalized, acute trauma -- defined as bodily injury -- was the most common, with 15 per cent of cannabis users who got medical attention receiving it for this reason, and 14 per cent receiving care for respiratory reasons.

"The results of our research support that health care professionals and government should discourage recreational cannabis consumption in the general population. Given the context of cannabis decriminalization in Canada, which has very likely facilitated the broader use of this product in the population, more efforts need to made from our health and political leaders to educate and remind citizens about the harmful impacts of cannabis on health," said Dr. Vozoris, who is also a scientist at ICES

https://www.sciencedaily.com/releases/2022/06/220628083257.htm

Cannabis products demonstrate short-term reduction in chronic pain, little else

In a systematic review of scientific literature, researchers find thin evidence that cannabis has clinical benefits

June 6, 2022

Science Daily/Oregon Health & Science University

Evidence behind the effectiveness of cannabis-related products to treat chronic pain is surprisingly thin, according to a new systematic evidence review by researchers at Oregon Health & Science University.

The federally funded review, which will be updated on an ongoing basis, was published today in the Annals of Internal Medicine.

Researchers did find evidence to support a short-term benefit in treating neuropathic pain -- caused by damage to peripheral nerves, such as diabetic neuropathy resulting in pain described as burning and tingling, involving two FDA-approved synthetic products with 100% tetrahydrocannabinol, or THC: dronabinol (under the trade name Marinol) and nabilone (Cesamet). Both products also lead to notable side effects including sedation and dizziness, according to the review.

Another product, a sublingual spray of equal parts THC and cannabidiol, or CBD, extracted from the cannabis plant, known as nabiximols, also showed evidence of some clinical benefit for neuropathic pain, although that product is not available in the U.S. This product also led to side effects, such as nausea, sedation and dizziness.

"In general, the limited amount of evidence surprised all of us," said lead author Marian S. McDonagh, Pharm.D., emeritus professor of medical informatics and clinical epidemiology in the OHSU School of Medicine. "With so much buzz around cannabis-related products, and the easy availability of recreational and medical marijuana in many states, consumers and patients might assume there would be more evidence about the benefits and side effects.

"Unfortunately, there is very little scientifically valid research into most these products," she said. "We saw only a small group of observational cohort studies on cannabis products that would be easily available in states that allow it, and these were not designed to answer the important questions on treating chronic pain."

Voters in Oregon, Washington and 20 other states have legalized medical and recreational marijuana, however the researchers found many of the products now available at U.S. dispensaries have not been well studied.

"For some cannabis products, such as whole-plant products, the data are sparse with imprecise estimates of effect and studies had methodological limitations," the authors write.

This situation makes it difficult to guide patients.

"Cannabis products vary quite a bit in terms of their chemical composition, and this could have important effects in terms of benefits and harm to patients," said co-author Roger Chou, M.D., director of OHSU's Pacific Northwest Evidence-based Practice Center. "That makes it tough for patients and clinicians since the evidence for one cannabis-based product may not be the same for another."

The living review, including a visual abstract summary of the findings, will also be shared on a new web-based tool launched by OHSU and VA Portland Health Care System early this year to help clinicians and researchers evaluate the latest evidence around the health effects of cannabis. Known as Systematically Testing the Evidence on Marijuana, or STEM, the project includes "clinician briefs" to help health care workers translate the clinical implications.

"This new living evidence review is exactly the type of resource clinicians need to clarify for patients the areas of potential promise, the cannabis formulations that have been studied and, importantly, the major gaps in knowledge," said co-author Devan Kansagara, M.D., M.C.R., professor of medicine in the OHSU School of Medicine and a staff physician at the VA Portland.

Reviewers searched more than 3,000 studies in the scientific literature as of January of this year and landed on a total of 25 with scientifically valid evidence -- 18 randomized controlled studies and seven observational studies of at least four weeks.

The effects of cannabis and related products are based on their ability to mimic the body's own endocannabinoid system. The system is composed of receptors and enzymes in the nervous system that regulate bodily functions and can affect the sensation of pain. In the evidence review, researchers sorted the types of product into high, comparable and low ratios of THC to CBD and compared their reported benefits and side effects.

Dronabinol and nabilone fit into the high THC to CBD ratio category, with 100% THC (no CBD), showing the most benefit among the products studied, with meta-analysis of the six randomized controlled studies demonstrating statistically valid benefits for easing neuropathic pain compared to a placebo.

"Honestly, the best advice is to talk to your primary care physician about possible treatments for chronic pain," McDonagh said. "If you want to consider cannabis, you need to talk to your doctor."

https://www.sciencedaily.com/releases/2022/06/220606181234.htm

Psychedelic experience may not be required for psilocybin's antidepressant-like benefits

So-called 'magic mushroom' drug seems to work through multiple brain mechanisms for its different effects

April 13, 2021

Science Daily/University of Maryland School of Medicine

University of Maryland School of Medicine (UMSOM) researchers have shown that psilocybin -- the active chemical in "magic mushrooms" -- still works its antidepressant-like actions, at least in mice, even when the psychedelic experience is blocked. The new findings suggest that psychedelic drugs work in multiple ways in the brain and it may be possible to deliver the fast-acting antidepressant therapeutic benefit without requiring daylong guided therapy sessions. A version of the drug without, or with less of, the psychedelic effects could loosen restrictions on who could receive the therapy, and lower costs, making the benefits of psilocybin more available to more people in need.

In all clinical trials performed to date, the person treated with psilocybin remains under the care of a guide, who keeps the person calm and reassures them during their daylong experience. This can include hallucinations, altered perception of time and space, and intense emotional and spiritual encounters.

Researchers in the field have long attributed psilocybin's effectiveness to the intense psychedelic experience.

"We do not understand the mechanisms that underlie the antidepressant actions of psilocybin and the role that the profound psychedelic experience during these sessions plays in the therapeutic benefits," says Scott Thompson, Ph.D., Professor and Chair, Department of Physiology at UMSOM and senior author of the study. "The psychedelic experience is incredibly powerful and can be life-changing, but that could be too much for some people or not appropriate."

Several barriers prevent the wide-spread use of psychedelic compounds. For example, there is fear that the psychedelic experience may promote psychosis in people who are predisposed to severe mental disorders, like bipolar disorder and schizophrenia, so the clinical therapy sessions performed to-date have been limited to a highly selected screened group without a family history of these disorders.

Dr. Thompson adds that there may also be an equity issue because not everyone can take several days off work to prepare and engage in the experience. The costs of staffing a facility with at least one trained guide per treated person per day and a private space may also be prohibitive to all but a few. He says it is conceivable that a depression treatment derived from psilocybin could be developed without the psychedelic effects so people can take it safely at home without requiring a full day in a care facility.

For their study, led by UMSOM MD/PhD student Natalie Hesselgrave, the team used a mouse model of depression in which mice were stressed for several hours a day over 2-3 weeks. Because researchers cannot measure mouse moods, they measure their ability to work for rewards, such as choosing to drink sugar water over plain water. People suffering from depression lose the feeling of pleasure for rewarding events. Similarly, stressed mice no longer preferred sugar water over plain water. However, 24 hours after a dose of psilocybin, the stressed mice regained their preference for the sugar water, demonstrating that the drug restored the mice's pleasure response.

Psilocybin exerts its effects in people by binding to and turning on receptors for the chemical messenger serotonin. One of these receptors, the serotonin 2A receptor, is known to be responsible for the psychedelic response. To see if the psychedelic effects of psilocybin were needed for the anti-depressive benefits, the researchers treated the stressed mice with psilocybin together with a drug, ketanserin, which binds to the serotonin 2A receptor and keeps it from being turned on. The researchers found that the stressed mice regained their preference for the sugar water in response to psilocybin, even without the activation of the psychedelic receptor.

"These findings show that activation of the receptor causing the psychedelic effect isn't absolutely required for the antidepressant benefits, at least in mice," says Dr. Thompson, "but the same experiment needs to be performed in depressed human subjects." He says his team plans to investigate which of the 13 other serotonin receptors are the ones responsible for the antidepressant actions.

"This new study has interesting implications, and shows that more basic research is needed in animals to reveal the mechanisms for how these drugs work, so that treatments for these devastating disorders can be developed" says Albert E. Reece, MD, PhD, MBA, Executive Vice President for Medical Affairs, University of Maryland Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor and Dean, University of Maryland School of Medicine.

This work was funded by the National Institute of Mental Health (R01 MH086828) and the National Institute of General Medical Sciences (T32 GM092237).

Although not approved yet, Dr. Thompson and the University of Maryland Baltimore have filed a patent on using psilocybin with drugs that block serotonin 2A receptors to treat depression.

https://www.sciencedaily.com/releases/2021/04/210413114107.htm

Ayahuasca fixings found in 1,000-year-old bundle in the Andes

New evidence that the mind-blowing brew goes back millennia

May 6, 2019

Science Daily/University of California - Berkeley

Today's hipster creatives and entrepreneurs are hardly the first generation to partake of ayahuasca, according to archaeologists who have discovered traces of the powerfully hallucinogenic potion in a 1,000-year-old leather bundle buried in a cave in the Bolivian Andes.

Led by University of California, Berkeley, archaeologist Melanie Miller, a chemical analysis of a pouch made from three fox snouts sewn together tested positive for at least five plant-based psychoactive substances. They included dimethyltryptamine (DMT) and harmine, key active compounds in ayahuasca, a mind-blowing brew commonly associated with the Amazon jungle.

"This is the first evidence of ancient South Americans potentially combining different medicinal plants to produce a powerful substance like ayahuasca," said Miller, a researcher with UC Berkeley's Archaeological Research Facility who uses chemistry and various technologies to study how ancient humans lived.

She is lead author of the study, published today (Monday, May 6) in the journal Proceedings of the National Academy of Sciences.

Miller's analysis of a scraping from the fox-snout pouch and a plant sample found in the ritual bundle -- via liquid chromatography tandem mass spectrometry -- turned up trace amounts of bufotenine, DMT, harmine, cocaine and benzoylecgonine. Various combinations of these substances produce powerful, mind-altering hallucinations.

The discovery adds to a growing body of evidence of ritualistic psychotropic plant use going back millennia, said Miller, a postdoctoral fellow at the University of Otago in New Zealand who conducted the research during her doctoral studies at UC Berkeley.

"Our findings support the idea that people have been using these powerful plants for at least 1,000 years, combining them to go on a psychedelic journey, and that ayahuasca use may have roots in antiquity," said Miller.

The remarkably well-preserved ritual bundle was found by archaeologists at 13,000-foot elevations in the Lipez Altiplano region of southwestern Bolivia, where llamas and alpacas roam. The leather kit dates back to the pre-Inca Tiwanaku civilization, which dominated the southern Andean highlands from about 550 to 950 A.D.

In addition to the fox-snout pouch, the leather bundle contained intricately carved wooden "snuffing tablets" and a "snuffing tube" with human hair braids attached, for snorting intoxicants; llama bone spatulas; a colorful woven textile strip and dried plant material. All the objects were in good shape, due to the arid conditions of the Andean highlands.

Though the cave where the artifacts were found appeared to be a burial site, an excavation did not turn up human remains. Moreover, the plants found in the bundle do not grow at those altitudes, suggesting the bundle's owner may have been a traveling shaman or another expert in the rituals of psychotropic plant use, or someone who was part of an extensive medicinal plant trading network.

"A lot of these plants, if consumed in the wrong dosage, could be very poisonous," Miller said. "So, whoever owned this bundle would need to have had great knowledge and skills about how to use these plants, and how and where to procure them."

Of particular fascination to Miller is the pouch made of three fox snouts. She describes it as "the most amazing artifact I've had the privilege to work with."

"There are civilizations who believe that, by consuming certain psychotropic plants, you can embody a specific animal to help you reach supernatural realms, and perhaps a fox may be among those animals," Miller said.

Ayahuasca is made from brewing the vines of Banisteriopsis Caapi and the leaves of the chacruna (Psychotria viridis) shrub. The leaves release DMT, and the vines release harmine -- and therein lies the secret of the ayahuasca effect.

"The tryptamine DMT produces strong, vivid hallucinations that can last from minutes to an hour, but combined with harmine, you can have prolonged out-of-body altered states of consciousness with altered perceptions of time and of the self," Miller said.

Once the drugs take effect, ayahuasca users typically enter a purgative state, which means they vomit a lot.

Though its use is currently fashionable among Silicon Valley techies, Hollywood celebrities and spiritual awakening-seekers worldwide, Miller says these latest archaeological findings pay homage to ayahuasca's ancient history.

Miller joined the Cueva del Chileno excavation project when archaeologists Juan Albarracín-Jordán of the Universidad Mayor de San Andrés in Bolivia and José Capriles of Pennsylvania State University sought her expertise to identify the plant matter they had found in the bundle.

She traveled for two days to reach the cave site near the remote south Bolivian village of Lipez and helped with the final phases of the excavation. The bundle was transported to a laboratory in La Paz and, once permits were in place, samples were exported to the lab of Christine Moore, chief toxicologist with the Immunalysis Corp. in Pomona, California.

Moore's lab provided the liquid chromatography tandem mass spectrometry technology needed to conduct toxicology tests on the samples. Once the contents of the Andean bundle tested positive for five kinds of psychotropic substances, Miller's research team was over the moon.

"We were amazed to see the incredible preservation of these compounds in this ritual bundle," said Miller. "I feel very lucky to have been a part of this research."

https://www.sciencedaily.com/releases/2019/05/190506151842.htm

Psilocybin rewires the brain for people with depression

April 11, 2022

Science Daily/University of California - San Francisco

Psilocybin fosters greater connections between different regions of the brain in depressed people, freeing them up from long-held patterns of rumination and excessive self-focus, according to a new study by scientists at UC San Francisco and Imperial College London.

The discovery points toward a general mechanism through which psychedelics may be acting therapeutically on the brain to alleviate depression and possibly other psychiatric conditions that are marked by fixed patterns of thinking.

Scientists analyzed fMRI brain scans from nearly 60 people who had participated in two psilocybin trials. In the first one, all the participants had treatment-resistant depression and knew they were being given psilocybin. In the second one, the participants were depressed but not as severely, and they were not told whether they had been given psilocybin or a placebo that turned out to be escitalopram, an SSRI antidepressant. In addition to the drugs, all the participants received the same type of psychotherapy.

The scans, which were done before and after treatment, showed the psilocybin treatment reduced connections within brain areas that are tightly connected in depression, including the default mode, salience, and executive networks, and increased connections to other regions of the brain that had not been well integrated.

Participants were also less emotionally avoidant and their cognitive functioning got better. The improvement in their depressive symptoms correlated with changes to their brains, and these changes lasted until the study ended three weeks after the second psilocybin dose. No such changes were seen in the brains of those who received escitalopram, suggesting that psilocybin acts differently on the brain than SSRIs.

Psilocybin and other serotonergic psychedelics like ayahuasca affect 5-HT2A receptors, which are plentiful in brain networks that become overactive in depression. One hypothesis is that the drugs briefly disrupt these connections, giving them a chance to reform in new ways in the ensuing days and weeks.

"In previous studies we had seen a similar effect in the brain when people were scanned whilst on a psychedelic, but here we're seeing it weeks after treatment for depression, which suggests a carry-over of the acute drug action," said Robin Carhart-Harris, PhD, who directs the Neuroscape Psychedelics Division at UCSF and is the senior author of the study, which appears April 11, 2022, in Nature Medicine.

"We don't yet know how long the changes in brain activity seen with psilocybin therapy last, and we need to do more research to understand this," said Carhart-Harris, who is the Ralph Metzner Distinguished Professor of Neurology, Psychiatry, and Behavioral Sciences and a member of the UCSF Weill Institute for Neurosciences. "We do know that some people relapse, and it may be that after a while their brains revert to the rigid patterns of activity we see in depression."

The authors caution that while these findings are encouraging, patients with depression should not attempt to self-medicate with psilocybin. The trials took place under controlled, clinical conditions, using a regulated dose formulated in a laboratory, and involved extensive psychological support before, during, and after dosing.

But the study points to a mechanism that, if it holds up, may explain both how psilocybin helps to alleviate depression and potentially other debilitating psychiatric conditions.

"For the first time we find that psilocybin works differently from conventional antidepressants -- making the brain more flexible and fluid, and less entrenched in the negative thinking patterns associated with depression," said David Nutt, DM, head of the Imperial Centre for Psychedelic Research. "This supports our initial predictions and confirms psilocybin could be a real alternative approach to depression treatments."

https://www.sciencedaily.com/releases/2022/04/220411113727.htm