Can genetic tests help diagnose cannabinoid hyperemesis syndrome?

As awareness of cannabinoid hyperemesis syndrome (CHS) expands, both among medical doctors and patients, we are collectively becoming more and more able to identify a condition that has been historically hard to diagnose. After all, it seems counterintuitive that cannabis can cause many of the symptoms it’s used to treat. 

Researchers are taking the current understanding of this severe and often debilitating condition one step further by attempting to pinpoint genetic markers that could be used to more readily diagnose CHS. This could potentially prevent those who are vulnerable from developing it in the first place.

Below, find out how CHS relates to genetics and what is being done in the medical world to combat the onset of the cannabis-based condition. 

What is cannabinoid hyperemesis syndrome?

Still not widely known or completely understood, cannabinoid hyperemesis syndrome is a condition that is characterized by a strong, and often enduring, sensitivity to THC — and possibly other cannabinoids. CHS causes ongoing abdominal pain, cramping, nausea, and vomiting when cannabis is consumed.

What causes CHS?

While our understanding of the condition is still developing, CHS seems to occur most often in folks who consume high-potency cannabis and cannabis products regularly for long periods of time. What is happening in the body is a long-term and intense stimulation of the endocannabinoid system (ECS), along with other receptors and systems outside the ECS.

While medical science is still working to uncover the more complex and nuanced factors contributing to CHS, according to Dr. Ethan Russo, a renowned pioneer in cannabis research, it might be fair to say that CHS isn’t a functional gastrointestinal disorder so much as a “manifestation of gene and environmental interaction in a rare genetic disease, unmasked by excessive THC exposure.”

What doesn’t cause CHS? Pesticides. 

Dr. Russo thinks it’s important to dispel the myth that CHS is caused by the pesticides or neem oil used in plant cultivation. “That just doesn’t hold water as an explanation,” Dr. Russo said. “There are more pesticides in use now than when CHS was first discovered, and pesticide reactions are quite different to what we see with CHS. Additionally, it’s been shown that synthetic cannabinoids, which are quite potent, can induce CHS — and while they are not pure, they don’t have pesticides in them.”

The difficulty and high cost of diagnosing CHS

The primary symptoms of CHS — cyclic abdominal cramping, nausea, and vomiting — are not unique to this condition, making CHS hard to diagnose. Because of this, CHS is considered among doctors to be a “diagnosis of exclusion,” or a diagnosis that is made when all other probable causes are ruled out. 

According to an estimate made in a 2019 study, it took the average ER a whopping $76,920.92 in related testing expenses to diagnose CHS, while a 2018 paper estimated the average patient cost of a CHS-related emergency room visit to be over $4,600.

One thing that makes CHS easier to pinpoint is the habitual or ritualistic behavior of taking hot showers or baths, which patients learn tends to relieve their symptoms temporarily. Another is relief from the topical application of capsaicin cream, which in effect acts much in the same way, physiologically speaking, as taking a hot shower or bath.

While hot baths and showers, the topical application of capsaicin creams, and sometimes even antipsychotic drugs might be used to relieve symptoms, at present the only known cure for CHS is complete abstinence from cannabis.

How prevalent is CHS?

Historically, there has been inconsistent reporting around CHS diagnoses. People with CHS often end up in emergency rooms when cyclic vomiting becomes severe and their health becomes jeopardized. Due to the fact that CHS is not widely known or understood in the medical community, coupled with the reality that most doctors receive little to no education or training around the endocannabinoid system, CHS is often misdiagnosed or labeled as being caused by cannabis use disorder.

Not only is this troubling because it unfairly ties CHS to substance abuse in the medical community, but it also means that we don’t have a solid grasp on exactly how prevalent CHS is among cannabis consumers and patients. According to Dr. Russo, CHS is likely a lot more common than we realize.

One epidemiological study, conducted at Bellevue Hospital in New York City, surveyed over 2,000 patients admitted to the ER who presented with cyclical vomiting. They found that over 30% of these patients, who identified as consuming cannabis for more than 20 days per month and found relief with hot showers, likely suffered from CHS. When extrapolated to the US population, they estimated that 2.75 million Americans might suffer from CHS. 

What does genetics have to do with CHS?

The more we learn about cannabis, cannabinoids, and human physiology, the more refined our understanding becomes as to how the plants interact with and impact our bodies.

While there isn’t a substantial amount of research looking specifically at CHS, thanks to the forward-thinking work of geneticists and cannabis researchers, we are starting to put together a preliminary picture as to how genetics might impact the development of CHS.

In partnership with the cannabis genetics testing company, Endocanna Health, Dr. Russo looked at the genetics of 28 patients suffering from cannabis hyperemesis syndrome. What they found were five gene mutations, called single nucleotide polymorphisms (or SNPs) with plausible causative roles in CHS. 

These five genes impact everything from dopamine activity to pain responses, mood regulation, and gut disturbances:

COMT gene 

The COMT (catechol-O-methyltransferase) gene provides instructions for making an enzyme that helps break down stimulatory neurotransmitters like dopamine in the brain. When there is a malfunction in these genes, there might be an excess of dopamine, which can lead to more risk-taking behaviors and less inhibition around things like gambling or substance abuse, for example. 

According to Dr. Russo, COMT is also associated with depression, rumination of thought, OCD, ADHD, and psychosis. Fifty-six percent of the CHS patients in the study had mutations in this gene.

TRPV1 gene

This gene is involved in the development of TRPV1 receptors, which are activated by a wide variety of physical and chemical stimuli — most notably those involved in heat perception. 

Activation of the TRPV1 receptors often leads to painful and burning sensations, and it’s through interaction with TRPV1 that cannabinoids are able to offer pain relief. In Russo’s study, 71% of patients had mutations of this gene, which helps shed some light on the abdominal pain, gut disturbances, and the relief from capsaicin creams and hot showers that are common among folks suffering from CHS.

CYP2C9 gene

This gene provides instructions for making the CYP2C9 enzyme, which is involved in breaking down steroid hormones and fatty acids. It is also involved in metabolizing prescription drugs and THC. Forty-six percent of the patients in Russo’s study had mutations on this gene, and he hypothesizes that this mutation could inhibit the breakdown of THC, which would then lead to higher than normal concentrations in the body. 

At high concentrations, THC can create a biphasic response, which means it can create the exact opposite effects it does at lower concentrations or doses. This would make sense of the nausea and vomiting that we don’t typically associate with a cannabis experience.

DRD2 gene

The DRD2 gene is responsible for the creation of the dopamine receptor D2. This receptor is the target of many antipsychotic drugs and had mutations in 60% of CHS patients in Russo’s study. Drugs that target D2 receptors are pro-emetic, meaning they can induce nausea and vomiting, and they often affect gut motility, so it makes sense that a malfunction in the gene encoding this receptor would occur with CHS. 

These receptors are also associated with depression, anxiety, nicotine use, Tourette Syndrome, and chronic pain, which could point to other susceptibilities CHS patients might have.

ABCA1 gene

The ABCA1 gene is part of a family of genes responsible for creating proteins that act as carriers for other molecules to cross cell membranes, making them important to basic cell function along with our general metabolism and the creation of high-density lipoprotein (HDL) cholesterol. 

This gene mutation was present in 68% of the CHS patients in Russo’s study, and while more research would be needed, he believes it could signal that CHS patients might be more susceptible to coronary artery disease (CAD), heart attacks, type II diabetes, and Alzheimer’s.

The future of diagnosing CHS

Russo’s study is the first of its kind, and the largest study to date looking specifically at cannabinoid hyperemesis syndrome. 

While there is certainly more to uncover in and around the genetic underpinnings of CHS, this study provides us with several clues and a good battery of tests that can be used to more effectively and cost-efficiently screen folks for CHS, and to help heavy cannabis consumers understand if they might be susceptible to CHS. This could save both doctors and patients a lot of time and expense in the ER.

Companies like Endocanna Health are banking on the future of genetics testing in the cannabis space, for both patients and consumers. While Dr. Russo was a skeptic at first, he’s come around to the potential this field has in really helping people. He now serves as an unpaid scientific advisor at Endocanna, and sees promise in genetic testing.

“This is a relatively new technology but I have looked at a lot of reports, and the correlations seem to be very good. I am a believer that this is helpful to a lot of people. I started out as a skeptic, but I do think this is helpful technology at this point and it stands to improve the more it is utilized.”

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The designated driver role gets a modern update, covering dangers from COVID-19 to social media

The designated driver (DD) is a successful public health strategy dating back to the late 1980s. To better reflect the realities of today’s society, now is a good time to evolve the initiative to help mitigate the harms tied to broader substance use and beyond drinking and driving.

The promotion of “buddy circles,” as an expanded harm reduction strategy, is one possible way to achieve these ends. Similar to the DD, the aim of the proposed buddy circle initiative is to challenge norms and promote behaviour change in order to reduce harm.

The buddy circle concept, however, expands on that of the designated driver, taking into account other substances and risks — including COVID-19 and social media — in order to build a more comprehensive harm mitigation strategy for the 21st century.

The designated driver and beyond

In North America the concept of designated driving began in 1988 as part of Harvard University’s School of Public Health’s Alcohol Project. The project involved a partnership with major television networks and Hollywood studios. Over the past 30 years this program has achieved its goals, integrating the DD into our language and culture.

According to Jay Winsten, founding director of the Center for Health Communication at the Harvard T.H. Chan School of Public Health, there were two crucial elements involved in the successful promotion of the DD to the public. The first was that it was framed as a positive message, one that “lent social legitimacy to the option of refraining from drinking and created social pressure to conform.” The second was that the DD “needed to be viewed as an integral part of the evening’s fun and not as a bystander.”

Since its inception, the DD has been associated with alcohol consumption. That original focus still dominates our popular understanding of the program (for example see the online dictionary definition of DD).

Today, as an increasing number of countries explore relaxing their drug polices in response to and/or as a result of greater awareness of drug using behaviours and the harms associated with prohibitionist policies and practices, including Canada where recreational cannabis was legalized in 2018 and there is increasing pressure to decriminalize possession of all drugs — similar to Portugal, a broader approach to substance use behaviour and its associated risks is needed.

Program expansion

There are a variety of potential risks or harms that a buddy circle initiative may address. Four are highlighted here:

  • overconsumption of substances
  • unintended or non-consensual consumption of substances
  • social media exposure
  • COVID-19

The harms associated with over-consumption of substances include overdosing, passing out, vomiting, choking on vomit, sexual or physical assault or engaging in dangerous and/or embarrassing behaviour.

There is also a danger of unintended consumption, such as having a drink or other substance spiked by a more potent drug (for example, fentanyl-laced heroin) or via “date-rape” drugs (e.g., GHB and rohypnol).

Another area of risk in the 21st century is associated with smart phones and social media. Taking and posting photographs of oneself and one’s friends is an everyday occurrence. These include photos of intoxicated individuals, that can be (and often are) posted to social media sites by friends or by strangers.

Despite laws protecting privacy rights, such posts can have severe negative consequences for individuals. Elements of one’s social media behaviour that are viewed as evidence of questionable “honesty, maturity or moral character” can result in loss of jobs or job offers, loss of scholarships, rescinding of offers for school admission or other lost opportunities.

Now in 2020, COVID-19 adds an additional layer to evolving substance-use harm-mitigation strategies. As communities lift COVID-19 restrictions, we see young people in particular participating in social gatherings on beaches, at house partieson and off college campuses, and at bars, typically engaging in substance consumption and related behaviours that can increase the risk of COVID-19 transmission.

Buddy circles

The promotion of buddy circles as a harm reduction strategy can address these concerns. The idea builds on the successes of the DD, re-imagining how lessons learned can be applied to enhance the norms tied to socially responsible substance use behaviour. It also incorporates familiar elements from the more recent COVID-19 “social circle” campaigns, such as limiting our exposure to others to reduce risk.

Buddy circles are small groups of individuals who get together socially and look out for each others’ well-being. Buddy circles can work whether the group is staying in or going out, attending parties (small or large, indoors or outdoors), or going to bars or other indoor public venues.

On successive social occasions, members of the circle take turns playing the integral role of “buddy guard” (similar to the DD) — abstaining from substance use and taking the lead in encouraging the group to watch out for each other in order to mitigate harm. This can include reminding members to: stay together, maintain social distance, wear masks, clean their hands and avoid taking and sharing inappropriate photos of members. The buddy guard can also get help when needed and make sure that everyone arrives home safely at the end of the night, whatever the mode of transportation.

By Jacqueline Lewis, Associate Professor, Sociology, University of Windsor

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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Misinformation about illicit drugs is spreading on social media – and the consequences could be dangerous

We’re all familiar with the term “fake news” and have probably witnessed the speed at which these stories can circulate on social media. Fake news stories can be about almost any topic, but increasingly misinformation about illicit drugs is becoming common. But the consequences of such false information can be dangerous – even deadly.

There tends to be a high level of interest about drug use myths on social media, driven in part by curiosity, but also fear of the unknown as some new and bizarre threat is reported – but often without any evidence to back up the hysteria. Some of this interest will be amplified by algorithms used by social media platforms, which tailor content based on user search history.

However, this misinformation is also further spread by mainstream media news outlets that pick up on the popularity and publish stories repeating the false information. Misinformation on social media is also easy to access, engaging, and may be shared by friends and family, making it appear more trustworthy. And, for many people, social media is the only place they get their news.

Dangerous synthetic drugs are common subjects of misleading “fake” news spread on social media. Given their potential dangers, it’s understandable that many people are concerned. This misinformation could be harmful, especially to those who may take the drug.

One such example is the deadly drug fentanyl, an opiate that can be anywhere between 50 to 100 times stronger than morphine. A myth that you can overdose even by touching a small amount of this drug spread on social media – and was even perpetuated by the United States Drug Enforcement Administration, which claimed that touching or inhaling airborne fentanyl could be deadly. As this warning was issued by a government department, many people took this misinformation seriously. It spread quickly and widely on social media even after the medical community agreed that overdose due to fentanyl skin contact is impossible.

Researchers tracked the spread of information about fentanyl between 2015 and 2019 by using a media analysis tool which was able to track the number of fake news articles created on and spread by social media, and could also track the number of potential views by looking at article shares. They found that erroneous information had a reach 15 times greater than correct information. Some of this included the myth about how touching the drug could be toxic. Most of this misinformation about fentanyl originated from Facebook posts created in Texas and Pennsylvania, and potentially reached 67 million people.

While fentanyl use might not be common, this sort of misinformation could have dangerous consequences. For example, a person might not help someone who has overdosed if they believe any physical contract with them – even to administer chest compressions – could cause them harm, too.

Other synthetic drugs, including Krokodyl and “spice” (a type of synthetic cannabis) have also triggered widespread misinformation. Krokodyl has been portrayed on social media as a chemical which can eat your flesh, even after only one use. Spice, on the other hand, has been described in the media as a drug that causes users to rip off their clothes as if it’s given them “superhuman” strength.

While it’s unlikely someone would take a drug knowing it causes severe damage, the idea of using something to gain extraordinary physical strength might entice potential users. In both instances, this information was wrong, but that didn’t stop them from going viral on social media.

It is often the young or naive that are victims of misinformation about some new drug or using a drug to achieve an effect. This is illustrated in a recent case when information about the antihistamine Benadryl was circulated on social media. Users reported that consuming this drug caused hallucinations and would challenge each other to take the drug, sadly at least one person died as a result.

Beyond these extreme examples, it’s also becoming routine to see misinformation on social media about drugs such as cannabis. In particular, claims being made about cannabis-based medicinal products, which suggest that everything from pain to terminal cancer can be cured. These are made despite the lack of research and evidence that support these assertions. Tragically this type of misinformation offers false hope to people who are often at a very vulnerable point in their life. These false claims are harmful in themselves, but could be really damaging if people choose to stop traditional medical intervention and use these products in the belief that their health will improve.

Misinformation about illicit drugs may also make them sound more appealing to people who aren’t risk adverse. For them the appeal is in the risk that the drug poses. Widely circulated fake news may even be the reason they try these types of drugs to begin with.

Finding ways of reducing this type of misinformation is important to prevent any dangerous consequences. Social media platforms have an important role to play in regulating information – should they choose to. Educating people in how to spot fake news, and better education for young people in schools about drugs may also prevent the further spread of such harmful misinformation.

We need to accept that there will always be interest in drugs and that false information about them will accompany that curiosity. Social media platforms have the ability to mitigate misinformation, but they may not have the will if an action threatens their commercial interests. So young people and their families are left to separate fact from fiction as they try to reduce the potential risks some drugs pose.

By Ian Hamilton, Associate Professor of Addiction., University of York and Patricia Cavazos-Rehg, Professor of Psychiatry, Washington University in St Louis

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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Does cannabis really affect memory? Here’s what research currently says

Cannabis use has long been associated with memory loss. But until now, this notion was largely anecdotal. As researchers begin to look into cannabis and the effect that it has on human health, they’re beginning to better understand the effect it has on the human brain – and whether cannabis really does impair memory.

Memory is divided into both short-term and long-term memory. Short-term memory is where immediate events are temporarily stored, whereas long-term memory is where information is stored indefinitely.

Current evidence shows that cannabis intoxication may temporarily alter or distort short-term memory processing. This seems to be caused by compounds in cannabis that disrupt neural signalling when binding to receptors responsible for memory in the brain. Interrupted short-term memory can indeed impact on learning, and may also cause loss of interest or problems with concentration.

However, early research also shows that cannabis could have a positive impact on neurodegenerative diseases that affect memory, such as Alzheimer’s, Huntington Chorea, and epilepsy. In mainly animal studies, when researchers used components found in cannabis, they found it could slow or even prevent the advance of these diseases – essentially through the creation of neurons.

These apparently paradoxical effects from the same drug are best explained by two chemicals found in cannabis. Namely delta 9-tetrahydrocannabinol (THC) and cannabidiol (CBD). We all have naturally occurring cannabinoid receptors in our brains. THC is able to effectively bind to these receptors, creating euphoric effects. However CBD can interfere with this binding process, which dampens the feeling of euphoria.

Different ratios of these two chemicals are found in various types of cannabis. Consuming a cannabis product with THC but no CBD increases the risk of developing mental health problems, such as psychosis. However, CBD could actually be used to treat psychosis.

Cannabis with higher levels of THC and lower, or negligible, amounts of CBD appear to have a detrimental effect on short-term memory, particularly in adolescents. The main problem is their ability to retain and recall information. Fortunately this is not permanent.

But these recent discoveries about the role of THC and CBD in cannabis show that we can no longer simply say cannabis itself causes psychosis, or is detrimental to memory. Rather, it might be the type of cannabis, and the compounds it contains, that may have specific risks or benefits.

And while there’s little doubt that some people who use cannabis do experience impaired memory, establishing that cannabis is the cause is tricky. One reason for this is because it’s difficult to rule out the impact of other drugs that people may have used – and whether these drugs contributed to this memory impairment. For example, alcohol misuse can also cause brain damage and memory loss. Another obvious problem when researching this is when asking people with impaired memory to recall their past drug use and any associated problems. Their ability to recall these details could be compromised.

Recent research even suggests that any memory impairment associated with using cannabis can be reversed when people stop using cannabis. This effect was seen mainly in those who used cannabis at least once a week.

Just as higher doses of alcohol can potentially cause brain damage, higher doses or more frequent use of cannabis may also cause long-term memory problems – the ability to learn effectively and the ability to concentrate on a task for example. Some people will use both alcohol and cannabis, often at the same time, which may both worsen the potential impact on memory.

New research also suggests that it’s cannabis, rather than alcohol, that’s responsible for damage to developing teen brains. Though alcohol can destroy or severely damage brain neurons and their signalling functions, this study showed cannabis actually changes the neural brain tissue responsible for memory. But this change can be reversed within a matter of weeks if a person abstains. Though surveys suggest fewer young people are using both cannabis and alcohol, those teenagers that do use cannabis use it twice as frequently.

Research shows that young, frequent users of cannabis have thinner temporal and frontal cortices, which are both areas that help process memory functioning. Memory is a critical aid to learning and study – but cannabis doesn’t just effect memory, it can also reduce motivation to learn. This dual influence reduces a young person’s engagement in education and their ability to perform.

However, using cannabis later in life (age 50 and over) appears to have only a moderate impact on cognitive functioning, including on memory. These modest declines are not fully understood, and there is a lack of high quality research in this area. That will need to change as it’s not just young people that use cannabis. As more countries legalise cannabis, older people might also want to try it.

While there is likely to be no great harm to a person’s memory if they experiment with cannabis, current research seems to agree that the more frequent the use, the greater the risk. Though there is still a lot that researchers don’t yet know about cannabis use on memory, current evidence suggests that any memory impairment can be reversed if a person abstains from use.

By Ian Hamilton, Associate Professor of Addiction., University of York and Elizabeth Hughes, Professor of Mental Health, University of Leeds.

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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Cannabis use after work doesn’t affect productivity – new research

Musicians and artists have long used cannabis to enhance their creativity. But how does the drug affect more conventional nine-to-five jobs? With cannabis now legal in more places, including Canada and several US states, research is being carried out into how it affects people’s productivity at work.

recent paper found that using the drug after work did not hurt people’s performance or productivity the next day. The research explored how using cannabis at different times of the day affected people’s ability to complete assignments and meet their job requirements, as well as their behaviour toward colleagues and attitude toward their work.

Cannabis use after work did not affect any of the measures of workplace performance. Perhaps predictably, however, when people used cannabis before and during work, they did not fare so well.

The drug interfered with their ability to carry out tasks, affected their concentration and reduced their ability to solve problems. It had a negative effect on people’s “citizenship behaviour” – how likely they were to help colleagues or work in a team. And it also increased people’s propensity for counterproductive behaviour, such as daydreaming on the job and taking excessive time to perform a task.

Better than alcohol?

As with alcohol – where consuming a spirit compared to a beer will not only affect the speed of intoxication but the impact this has on functioning – the effect of cannabis will vary by product.

The study does not provide much detail about how much cannabis the participants consumed – just that they used it before, during or after work. So we know little about the point that cannabis consumption begins to negatively affect work performance. Nonetheless, it challenges stereotypes of cannabis users as lazy and unmotivated.

Research into the effects of alcohol on work performance is much more extensive. It shows how drinking after work and heavy drinking in particular negatively affects work in lots of ways. These include reduced productivity, greater levels of absenteeism, inappropriate behaviour and poorer relationships with work colleagues.

This new research on cannabis and productivity, while limited, is an important step forward into investigating the effects of the drug on society. It goes beyond the historically crude assessments of cannabis use, which would simply ask participants whether they had ever used cannabis or not then draw conclusions based on this simplistic grouping. This clearly missed the various doses and frequency of use.

Research in this area is tricky, however, as people that use cannabis are likely to also use or have a history of using other substances, such as alcohol. So untangling which substance is associated with an effect on performance is difficult, if not impossible in some cases.

Implications for drug testing

Cannabis use is not a niche activity. An estimated 20% of Americans are thought to have used the drug, while in Europe cannabis remains the most popular drug after alcohol, whether legal or not. Cannabis is well known to reduce stress and help people relax so it is likely to be an attractive antidote to a stressful day at work.

If companies have drug-related policies, they should be based on evidence and specific to the needs of the job. The effects of cannabis on coordination is one area that is more problematic. Like alcohol, the drug reduces people’s motor skills, reaction times and hand-eye coordination.

Unlike alcohol, there do not appear to be residual negative effects on coordination the day after using cannabis – unlike alcohol. But another study from earlier this year found that chronic, heavy cannabis use was associated with worse driving performance in non-intoxicated drivers. This is because the drug can impair the motor skills necessary for safe driving in the long term.

This evolving field of evidence makes it difficult for employers that do have drug-testing policies for their employees. Because most drugs break down very quickly in the body, tests are designed to identify chemicals called metabolites, which remain after the drug breaks down and can be detected weeks after use.

Verywell Mind

This means that an employee could have consumed cannabis on holiday, for example, then be subject to a work-based drug test weeks later and face disciplinary action when the test shows a positive result – even though the drug is not affecting their performance.

To fill this gap, there are apps that provide an alternative method of assessing impairment by measuring changes in task performance. This may prove to be a more reliable and efficient way to check if cannabis and other drugs are actually hurting someone’s work performance. Expecting an entire workforce to abstain is unrealistic and will restrict the talent pool from which employers can recruit.

By Ian Hamilton, Associate Professor of Addiction., University of York

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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An in-depth look at the study that discovered THCP, a cannabinoid more potent than THC

A new cannabinoid has been discovered, and the ramifications could be massive. Scientists funded by the UNIHEMP research project have discovered a new psychoactive molecule: Δ9-Tetrahydrocannabiphorol, or THCP; and they believe that there are great scientific implications for the phytocannabinoid

Phytocannabinoids are cannabinoid molecules that are specifically produced by plants. There are several types of cannabinoids, including endocannabinoids, synthetic cannabinoids, and phytocannabinoids. 

Endocannabinoids are compounds that are produced within the body by an organism’s endocannabinoid system; and synthetic cannabinoids are man-made chemicals that cannot be found in nature. Phytocannabinoids, on the other hand, are a different beast altogether. They are those that naturally occur in plants and are found in a variety, including echinacea. However, the plant species in which phytocannabinoids are most prominent is cannabis.

Because of cannabis’ status as a Schedule I controlled substance in the US, there are several barriers that prohibit the scientific study of the plant and its constituents. Thus, a considerable portion of cannabis research takes place abroad. Many clinical and laboratory studies of cannabis take place in Israel and Canada, where there is federal research funding to support this work; but, the newly discovered THCP was characterized by a group of Italian scientists.

Unlike the US, government funding for cannabis research is relatively commonplace in Europe. The discovery of THCP was enabled by the UNIHEMP project, which is sponsored by the European Regional Development Fund. A multi-disciplinary team of Italian scientists was responsible for the discovery of this novel cannabinoid, led by Giuseppe Cannazza of the University of Modena and Reggio Emilia.

The researchers’ findings were published in late 2019 in the journal Nature.

THCP is 33-times more active than THC

Throughout the duration of the project, the group studied a medicinal cannabis cultivar, dubbed FM2, which was supplied by the Military Chemical Pharmaceutical Institute in Florence. Using a variety of scientific characterization techniques, the researchers observed two novel cannabinoids, THCP and CBDP, and isolated them from other cannabinoids that were present. Following this discovery, the group artificially synthesized THCP and CBDP to create reference materials, and the synthesized versions were successfully used to verify the natural expression of the two cannabinoids in the FM2 cultivar.     

After the confirmation of the identity of the two cannabinoids, the group turned its focus to THCP. To study the compound, they pursued an in vitro experiment with cultured cells. This experiment tested the binding affinity of THCP with CB1 and CB2 receptors, using synthetic cannabinoids as reference materials. It was shown that, when comparing THCP-related results to the previously reported data of other cannabinoids against the CB1 receptor, THCP is 33-times more active than delta-9 THC. 

This finding is critical because the group also found that the chemical was present in FM2 at 0.0029%, whereas THC was found to be expressed at 3.9%; so, even in smaller amounts, THCP is more active than THC.

They also tested the cannabimimetic activity of the molecule. Cannabimimetic activity is a measure of how well a substance replicates the effects of more well-characterized cannabinoids which bind to the CB1receptor. An in vivo experiment involving mice was performed. Herein, the influence of THCP on body temperature, spontaneous activity, immobility, and pain was determined — the results of these tests confirmed that THCP acts similarly to other cannabinoids like delta-9 THC.

Will THCP be important?

According to the study, even at lower doses, THCP has more cannabimimetic activity than THC. Further, the group posits that THCP could account for the wide variability of patient responses in cannabis-based therapies, even amongst cultivars with equal THC doses. This means  that cannabis’  psychotropic effects, which the scientific community attributes to THC, may actually be due to the presence of THCP. 

Unfortunately, none of the original researchers could be reached for comment. However, experts in the field do have varying opinions regarding the study. Dr. Cecilia J. Hillard of the Medical College of Wisconsin said, “I think it is well designed.” She goes on, “[The study] has two important gaps, in my opinion. First, they should have compared the in vivo effects of THCP to that of THC ‘head to head’ so that relative potencies could be assessed. Second, I would like to know whether THCP has greater efficacy to activate the [CB1 receptor] in particular. THC is relatively safe because it has low efficacy at the receptor. If THCP has high efficacy (like the synthetic analogs that have also increased the tail length), it is a more concerning finding, as it would suggest that strains making a lot of THCP could be more dangerous to use than those that do not.” 

Expanding on how THCP could be more dangerous, Hillard continued, “The so-called ‘spice’ compounds are synthetic agonists of the CB1 receptor. They are full agonists, meaning that they are very strong activators of the CB1 receptor. Compared to THC, these drugs have significant adverse effects and produce significant dependence (addiction). So, my issue is that we do not know yet whether THCP is like THC, a partial agonist, or like the synthetic compounds, a full agonist. And my concern is that, if it is the latter, cannabis strains high in THCP will have more adverse effects than those that are low.”

Dr. Samuel Banister of The University of Sydney states, “[The study] was well designed and executed,” concurring with Dr. Hillard. However, he goes on to disagree with the group’s assessment that THCP may account for the variability of psychotropic effects across various cannabis cultivars: “While this possibility cannot be ruled out, the known potency differences for THC and THCP at cannabinoid receptors is relatively small, while the difference in abundance of each in cannabis is enormous. The same is true of CBD and CBDP, although CBD requires even higher doses to achieve many of its pharmacological effects. For this reason, I do not feel that minor or trace phytocannabinoids like THCP or CBDP contribute significantly to the psychoactive effects of different cannabis strains.” 

How this novel cannabinoid plays out in both medical and recreational use is yet to be determined, as much more research is needed. Nonetheless, this new evidence suggests that analytical laboratories in US regulated markets may need to expand their testing panel to include THCP.

Featured graphic by David Lozada/Weedmaps

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Smoking weed when you have Tourette Syndrome

In July 2019, Pennsylvania added Tourette syndrome to the list of conditions that qualify for medicinal cannabis use. Contributor Lorena Cupcake explains what Tourette syndrome is and looks at the place of cannabis when it comes to Tourette syndrome, using their own experiences as a medical cannabis patient.

Tourette Syndrome Awareness Month is recognized from May 15th to June 15th each year, inspiring some of the estimated 100,000 people living with Tourette Syndrome nationwide to share their stories with the hashtag #TouretteAwarenessMonth. As a medical cannabis patient — qualified due to my diagnosis — I’m sharing my experiences managing my condition with cannabis to help fill in the gaps in a field with little published research.

The research of neurology is hindered by the limitations of non-invasive techniques; my brain may only reveal some secrets after I’m dead. I’m telling my story while I’m still here so the conversation on the future role of cannabis in treating Tourette Syndrome can grow and gain momentum, leading to more high-quality studies, a better understanding of the behind-the-scenes biological functions, and increased access to decriminalized cannabis. Currently, only seven states including Arkansas, Illinois, Minnesota, Missouri, New Jersey, Pennsylvania, and Ohio have specifically approved Tourette Syndrome as a condition for medicinal cannabis use.

According to the National Institute of Neurological Disorders and Stroke, Tourette syndrome (often shortened to TS, or Tourette) is a neurological disorder characterized by involuntary movements and vocalizations known as “tics.” Every human experiences involuntary actions; we cringe when embarrassed, yelp when startled, and reflexively snatch our hands away from hot surfaces. These types of unconscious reactions are governed by the nervous system, which is divided into the sympathetic nervous system (SNS) and parasympathetic nervous system (PNS). 

To understand why people with TS have tics, and how cannabis may help with both tics and related medical conditions, it’s important to know the difference between the two divisions and the role in their body.

Fight, flight, or freeze

The SNS is most famously associated with “fight, flight, or freeze,” three evolutionary responses to danger tracing back to the caveman days. While this system can keep us out of danger, it’s overactive in people with TS, causing uncomfortable symptoms of anxiety, like rapid heartbeat, skin tingling, and chest tightness. The pressure builds unbearably until it’s released with an involuntary movement. Suddenly, there’s a wave of relief … until the pressure returns. 

It’s a cycle familiar to anyone with neurobiologically similar conditions like Obsessive-Compulsive Disorder (where the relief comes from giving in to a compulsion) or body-focused repetitive behavior disorders (which include conditions like Trichotillomania, a condition also called “hair-pulling disorder” by the Mayo Clinic). It’s important to realize that people with these medical issues aren’t simply lacking willpower; the basal ganglia, which would normally send inhibitory signals to suppress unwanted behaviors, isn’t functioning as effectively as it would in a neurotypical brain.

Pharmacological treatments for TS usually focus on suppressing dopamine, a messenger molecule your neurons use to initiate movements, both voluntary and not. I’ve personally had better results from cannabis, which has helped me learn to control and, more importantly, comfortably cope with tics through activation of the PNS.

Rest and digest

The parasympathetic nervous system, which slows the heart rate, increases saliva production, and stimulates the digestive tract, is nicknamed the “rest and digest” response. Many techniques exist to help activate this system, including mindfulness, meditation, and stimulation of the vagus nerve. 

This 2017 Iranian journal details how the endocannabinoid system modulates the release of GABA, a neurotransmitter with receptors found throughout the parasympathetic nervous system with the ability to decrease blood pressure, reduce stress, and stimulate appetite. Rather than directly blocking tics, the right type of cannabis-based product puts me in a relaxed state where tics are less likely to occur, easier to control, and less uncomfortable to endure.

Recognizing the importance of accessibility to this treatment, numerous states have approved medical marijuana as a treatment for TS. The key to gaining acceptance nationwide may lie in raising awareness of the many biological similarities between a relatively-rare syndrome and more well-known disorders that are widely recognized to be effectively regulated with cannabis.

Cannabis and movement

Movement disorders are neurological conditions that affect the ability to control movement. There’s evidence that cannabinoids produced naturally by the body assist in motor control, and that dysfunction of the endocannabinoid system plays a role in the pathophysiology of movement disorders like Parkinson’s Disease

Gina Coleman/Weedmaps

An anonymous survey conducted by the Prague Movement Disorder Centre found that one-quarter of the respondents had tried cannabis, with 45.9% of them going on to describe some sort of benefit. “Once I started taking CBD oil, I never had a sleepless night because I couldn’t relax my muscle groups,” septuagenarian Garry Griffin told CBD Denver following his participation in a University of Colorado study on the use of cannabidiol oil in patients with Parkinson’s Disease. “I’m not a stoner, but I am a proponent.”

The basal ganglia, mentioned earlier for its role in regulating unwanted movement, contains many endocannabinoid receptors. When cannabinoids bind with these receptors, they can help alleviate involuntary movements by assisting in the regulation of neurochemicals linked to signaling and movement.

Tics respond well to cannabis, with 82% of participants in a 1998 German study reporting improvement and one patient remaining symptom-free for an entire year. What’s missing is research that clearly explains the full role of cannabinoid receptors and the endocannabinoid system (ECS) in TS pathology and treatment, along with education, therapies, and medications that utilize those findings.

The potential of cannabis to calm spasticity, tremors, muscle tightness, muscle jerks, and pain associated with disorders like dystonia, epilepsy, and restless leg syndrome is documented, allowing insight into the significant biological impact of marijuana on movement. Until larger and more through studies can take place, the positive experiences with cannabis reported by many people with Parkinson’s, TS, and other movement disorders suggests that we have more to learn about the role of the ECS in governing movement.

Life on the spectrum

Tourette Syndrome is a spectrum disorder or a collection of conditions that share traits and characteristics. There are only so many different regions of the brain; only a limited array of neurochemicals used by the nervous system. Brain abnormalities and neurotransmitter dysfunction will often express themselves in diverse ways, with symptoms that may be associated with a range of different conditions.

People on the Tourette Syndrome Spectrum have much higher rates of Obsessive-Compulsive Disorder (OCD), Autism Spectrum Disorder, and learning disabilities like Attention-Deficit/Hyperactivity Disorder than the general public. They’re also more likely to have anxiety, personality, and mood disorders. Even if someone doesn’t qualify for dual diagnosis, they may still experience some symptoms; the reverse can be true for those with a primary diagnosis other than TS. For example, up to 50% of children with OCD experience tics.

Although these conditions are often considered separate, they share underlying biological mechanisms that link them together, which explains why cannabis may be beneficial in regulating all of them.

Looking Forward

Over the past couple of decades I’ve been living with TS, I’ve used cannabis alongside cognitive-behavioral techniques to cope. Cognitive-Behavioral Intervention for Tics (CBIT), a type of Habit-Reversal Training, teaches people with TS to identify the premonitory urges that come before a tic. They can then choose a low-impact and easy-to-disguise movement — like squeezing a fist— over tics that can be distressing, painful, or stigmatized.

Suppressing tics can be frustrating and physically uncomfortable, so I’m grateful to have a way to “get them out of my system” while minimizing unwanted attention and avoiding tics that might be dangerous or harmful. At the same time, daily cannabis use relaxes my body, reduces my anxiety, and balances my mood, making it easier to consciously activate my PNS and less stressful to manage my tics.

I’ve learned to accept that life on the Tourette Syndrome Spectrum means that every symptom is a puzzle piece that helps me figure out how and why my body works as it does. Cannabis doesn’t just improve my quality of life; it helps me gain insight into, and control over, the two divisions of my central nervous system. 

Featured image by Gina Coleman/Weedmaps

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Scientists Create New Method to Store Marijuana Pollen on a Long-Term Basis

Researchers have developed a way to determine the viability of pollen germination in marijuana plants, as well as a simple method of storing cannabis pollen for long periods of time, according to a new study.

For marijuana cultivators, the results could prove useful, helping them avoid potentially costly mistakes in the process and ensuring consistency and quality in their crops across growing cycles.

Ensuring long-term storage of pollen is important for cultivators because of the central role it plays in generating seeds. Taking pollen from a male plant and rubbing it on the hairs of a female plant—typically about halfway through the flowering cycle—will enable the female plant to produce buds that contains seeds, which along with cloning is one way to propagate and maintain strains.

The study, which was partly funded by the Canadian government, has “several implications,” co-author Igor Kovalchuk told Marijuana Moment.

First, the team created an “assay to test viability of such pollen before the use for pollination.”

They accomplished that by modifying an existing method of assessing germination viability, using a liquid media instead of a solid medium, which “resulted in better image acquisition and quantification of germination,” according to the study.

Perhaps even more consequential for growers, however, is the development of a long-term storage system for cannabis pollen.

“We have provided an easy protocol for cryopreservation using desiccation combined with baked wheat flour and subsequent long-term storage of cannabis pollen in liquid nitrogen.”

“This one is big,” Kovalchuk said. “Our protocol allows nearly indefinite storage,” which is “valuable for maintaining large collection of genetics.”

To preserve the pollen, the researchers removed any moisture, added the result to baked whole wheat flour and preserving agents and then froze it in liquid nitrogen. When they removed the mixture from the liquid nitrogen and applied it to flowering female plants, it resulted in successful seed formation in all of the subjects.

The team also discovered that pollen can be more or less viable at different stages of the flowering period. The optimal time to extract pollen seems to be during the mid-flowering stage. At that point, it retained “viability the longest with 22 percent of pollen grains successfully germinating after 21 days” of storage in a low-temperature environment.

“In conclusion, we have standardized a simple assay for quickly assessing pollen germination in Cannabis sativa,” the study states. “By using our [modified assay], we have demonstrated the loss of pollen viability over time when stored at 4 degrees Celsius, and suggested an optimal time during flower development for pollen collection to maximize longevity during storage.”

“Finally, we have provided an easy protocol for cryopreservation using desiccation combined with baked wheat flour and subsequent long-term storage of cannabis pollen in liquid nitrogen,” it concludes.

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This article has been republished from Marijuana Moment under a content-sharing agreement. Read the original article here.

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Setting the record straight about CBD and Coronavirus

A little more than a hundred years ago, the world faced a pandemic similar to the COVID-19  (coronavirus) that we confront today. According to The Centers for Disease Control (CDC), from 1918—1919, about 500 million people became infected with the H1N1 virus, which claimed the lives of 675,000 Americans and approximately 50 million worldwide. As of April 19, 2020, coronavirus has infected more than 2.4 million and killed 165,000 people.

Pandemics throughout history make people frantic for a cure, and snake oil salesmen have been hustling “cures” for millennia. During the 1918 pandemic, substances touted as such run the gamut: Vick’s VapoRub, Indian Herbs, and Miller’s Antiseptic Oil among them. 

Today is no different, and the proclivity to never let a good crisis go to waste thrives. Recently, a Southern California-based doctor was charged with fraud for selling COVID-19 “treatment packs” for a hefty price. Others looking to cash in on COVID fears are right-wing radio host Alex Jones, hawking COVID-curing gargle and toothpaste from his website. 

An air purifier company has claimed that their filters can remove coronaviruses from the air, and even others posit exposing contaminated surfaces to ultraviolet light, gargling warm salt water and taking hefty doses of Vitamins C and D. And what about all the claims in cannabis?

The ameliorative effects of CBD came into focus after CNN Chief Medical Correspondent Dr. Sanjay Gupta featured a young Charlotte Figi in the 2013 documentary Weed. Figi, who had an intractable form of epilepsy called Dravet Syndrome, practically eliminated her seizures by using a high-CBD cannabis strain produced by Colorado Springs growers who eventually named the strain after her, Charlotte’s Web. The US Food and Drug Administration (FDA) would approve Epilodilex, a CBD product aimed to reduce seizures from Lennox-Gastaut syndrome and Dravet syndrome, in 2018.    

Snake oil and the cannabis industry

Even the cannabis industry has some COVID-cure bandwagon hoppers, including retired NFL player and CBD evangelist Kyle Turley. In late March, Turley’s CBD company NeuroXPF received an FDA letter of warning for posting misinformation on their website and social media messages such as, “CBD can help keep your immune system at the top of its game … We want everyone to take CBD and take advantage of its potential to help prepare your body to fight a coronavirus infection.” 

While Turley’s CBD company’s social’s claim does not explicitly say that CBD can cure coronavirus, the word choice strongly suggests that taking CBD can protect you from infection. To make matters worse, Turley explicitly said CBD could cure and prevent coronavirus on his personal Twitter account. But is that true? Could an immune system enhanced by CBD keep you from getting coronavirus?

Martin A. Lee is the co-founder and director of Project CBD, a nonprofit whose mission is to promote and publicize research covering the medicinal uses of CBD and other cannabis compounds. “Potential is the keyword here because the research in this area is pre-clinical,” Lee told Weedmaps. “[Covid-19] is a disease that can express itself in different ways, and most people are having relatively mild experiences. But when it does threaten mortality, it does seem likely that what they’re dying from is how their body is reacting to the virus. And they are reacting to the cytokine storm. The immune system goes totally haywire.”

Cytokine storm is a term growing in familiarity as Americans look up their Google searches on how COVID-19 works in the body. According to WebMD, Cytokines are proteins that respond to an infection by triggering inflammation. However, the immune system can overreact to infection and release too many cytokines — ergo the term “cytokine storm” — resulting in hyper-inflammation, which can be deadly. 

What do the research and data say?

A study led by researchers at Mississippi State found in an in vitro setting using human and mouse cells that CBD” induced suppression of cytokine production.” However, it’s important to note that no study directly addresses CBD, cytokines, and COVID-19. Lee acknowledges that the gap between anecdotes and informal research about CBD’s effectiveness — some use CBD to self-treat autoimmune inflammatory conditions like multiple sclerosis — is conflicting. 

Mary Biles wrote in Project CBD, “A new wave of research and mounting anecdotal evidence points toward cannabinoids having an adaptive, immunomodulating effect, rather than just suppressing immune activity.” In other words, it’s possible that cannabinoids like CBD may keep inflammation at bay when healthy, but increase inflammation when getting sick  

But Lee reiterates that there is simply not enough evidence about cannabis and COVID-19 to draw any conclusions. “I think there’s enough evidence, given what we know about CBD, cannabis, and THC to suggest medical scientists should explore this [CBD] as a treatment for cytokine storm. To the extent of knowing if that would work, it’s pure speculation,” he added. 

Like Kyle Turley, those who have experienced the ameliorative effects of CBD firsthand often evangelize about the compound. However, how CBD works in partnership with the immune system lacks substantive, clinical research, leading people to rely heavily on anecdotal evidence. Researchers know even less about COVID-19, but what they do know is that cytokine storms likely contribute to COVID’s lethality.

Claims like Turley’s — in addition to being dangerously misleading — reflect poorly on the CBD industry at large, especially for companies attempting to run legitimate businesses in a mostly unregulated market. 

How some companies are doing it right

Degelis “Dege” Tufts and Kymberly “KymB” Byrnes are the co-founders of New York-based CBD and cannabis lifestyle company Tribe Tokes. Since COVID erupted, the ladies at Tribe Tokes say they have noticed an uptick in sales, but not because they’ve been peddling a cure. “In this era of legalization, we fought so hard to get legitimacy around [CBD] use, and so hard to fight stigma against the plant, making claims [about CBD] can unravel the legitimacy,” says Tufts. “We’re not here to make a profit off a somewhat vulnerable consumer right now.” 

The team at Tribe Tokes is keenly aware of what they can and cannot say about CBD on their labels, website, and social media. “There are pretty clear guidelines for CBD brands on what they can and can’t do,” Tufts explained. “We are not supposed to make claims about specific diseases. You can’t go near it, because the studies aren’t there. It’s really a red flag if brands are citing specific diseases, and coronavirus would fall under that umbrella.” 

Byrnes notes that there have been evangelists making healing claims about substances for eons, and CBD is no different. “But the most important thing for companies to do is have integrity. Our responsibility right now as a leader in CBD is to educate and elevate. We don’t have enough studies on corona and cannabis to understand how those two would have a relationship,” she added.

Many consumers have been rethinking their cannabis consumption during the pandemic, especially those who smoke or vape. Brynes and Tufts have noticed an increase in sales, especially from consumers looking to soothe feelings of anxiety during a time of increasing uncertainty, while Lee wonders if it’s safe to use CBD at all, even for consumers who have no symptoms and may be asymptomatic, given that we do not have a full understanding of how the compound may influence the immune system. “Would taking cannabis help [with Covid]? Would it be a good idea to consume CBD? Maybe not? We don’t have any data either way.” 

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CBD Prescription Drug Is No Longer A Federally Controlled Substance

The Drug Enforcement Administration (DEA) has removed a marijuana-based medication from the list of federally controlled substances.

GW Pharmaceuticals announced on Monday that Epidiolex, a prescription drug it developed that’s derived from cannabis and used in the treatment of epilepsy, had been taken off Schedule V of the Controlled Substances Act. Effectively immediately, the CBD medication is no longer a controlled substance, the company said.

That means individuals will be able to more easily obtain Epidiolex. GW said in its notice that it will “begin the process of implementing these changes at the state level and through the EPIDIOLEX distribution network.”

After that point, state reporting requirements under prescription drug monitoring programs will no longer be applicable. Like many non-controlled drugs, people will still need to get a prescription from a doctor, but those prescriptions will be valid for up to a year and can be transferred among pharmacies.

“This notification from DEA fully establishes that EPIDIOLEX, the only CBD medicine approved by FDA, is no longer a controlled substance under the federal Controlled Substances Act,” Justin Gover, CEO of GW, said in a press release. “We would like to thank DEA for confirming the non-controlled status of this medicine.”

“Importantly, the descheduling of EPIDIOLEX has the potential to further ease patient access to this important therapy for patients living with Lennox-Gastaut Syndrome and Dravet syndrome, two of the most debilitating forms of epilepsy,” he said.

The Food and Drug Administration (FDA) approved the medication in 2018. DEA said it would be placed in Schedule V, rather than Schedule I like marijuana and its derivatives.

FDA pushed back in a letter to the agency, arguing that CBD carries minimal risks and has established health benefits and so it shouldn’t be controlled at all. DEA replied that international treaty obligations warrant its control, albeit in the least restrictive category of Schedule V. FDA then said that if that changed, the agency should “promptly” revisit its status as a controlled substance.

Last year, the World Health Organization clarified that CBD containing no more than 0.2 percent THC is “not under international control.”

Meanwhile, FDA is in the process of developing regulations for hemp-derived cannabidiol products that aren’t approved as medications following the 2018 Farm Bill’s legalization of the crop and its derivatives. The agency said in a report to Congress last month that the rulemaking process is ongoing, but it is actively exploring pathways to allow for lawful sales of the cannabis compound as a dietary supplement, and it’s developing enforcement discretion guidance for products that are currently on the market.

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This article has been republished from Marijuana Moment under a content-sharing agreement. Read the original article here.

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