The Latest in Cannabis Research: Winter/Spring 2019

As the summer heats up, it’s worth taking a look back in the year when cannabis research was just as hot. Exciting new studies continue to come out with the global trend toward legalization and acknowledging the therapeutic potential of cannabis.

Research so far this year encompasses finding the region in the brain that gets you high to the medicinal benefits of CBD. Below are some stand-out research papers from the first half of the year.

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Opponents of cannabis legalization claim that increasing access will increase problematic cannabis use. However, that idea is based more on gut feelings than scientific evidence.

Public health scientists put it to the test by comparing state-level policy liberalism rankings over the last couple decades with data collected regarding cannabis use and rates of cannabis use disorder. Notably, this assessment was limited to medical cannabis legalization and didn’t incorporate data relating to the legal recreational market now available in many states.

Overall, more people used cannabis in states with liberal cannabis policies than conservative-policy states, but the prevalence of cannabis use disorders was highest in conservative-policy states.

It’s uncertain at this point why conservative policy states would have higher cannabis use disorder rates, but it suggests that strict restriction of access to cannabis is not the solution to eliminating problematic use, and instead, increasing access may lead to safer overall use.

Looking for the Brain Region That Causes the High

People have been experiencing cannabis highs for thousands of years. Only recently, however, have scientists uncovered how this effect occurs in the brain.

THC was isolated in the 1960s and the CB1 receptor wasn’t fully discovered until the 1990s. Shortly after, it was confirmed that activation of CB1 receptors by THC causes the feeling of being high. However, where in the brain this feeling comes from remained elusive.

Recently, scientists working in the United Kingdom added to this story by revealing that the posterior cingulate cortex in the brain is a key contributor to THC’s high.

Discovering the seat of the high was likely not the scientist’s intention. Instead, they were looking at the brain activity of participants given either 8 mg of THC alone or THC with 10 mg of CBD. They revealed that THC disrupted activity in numerous brain regions, but the posterior cingulate cortex was specifically disrupted by THC alone, and less-so by THC with CBD.

Importantly, the degree of disruption positively correlated to the feeling of being stoned and high. So while THC’s actions across many brain regions are responsible for the numerous outcomes of using cannabis (e.g., memory, munchies, mood), your high can be traced to the posterior cingulate cortex.

So where is the posterior cingulate cortex? If you were to split the brain right down the middle, front to back, you’d slice through a large band of fibers called the corpus callosum that allows the two sides of the brain to communicate with one another. The brain’s outer layer that sits right above the corpus callosum on each side of the brain is the cingulate cortex, and the posterior end is the part toward the back of your head.

Adolescent Cannabis Consumers Don’t Have Structural Brain Abnormalities

Numerous studies have investigated whether cannabis use during adolescence changes the way the brain looks. However, these studies are often limited by a small sample size or only compare frequent consumers who consume more than three times per week. Few studies have looked at structural brain differences across different levels of cannabis consumption.

In this study, the brains of 781 adolescents aged 14-22 were compared. 109 participants were classified as occasional cannabis consumers (two or fewer uses per week) and 38 were classified as frequent consumers.

The Philadelphia-based scientists used brain MRIs to look at structural differences on a brain-wide and region-specific level. They concluded that neither occasional nor frequent cannabis use significantly affected the size of the whole brain or any of the specific regions of interest.

Further, there were no group differences in the number of brain cells, their connections, or in the thickness of the cortex–the surface of the brain that contributes to the unique cognitive abilities of humans and higher-order species.

While these findings suggest that adolescent cannabis consumption doesn’t affect the way the brain looks, it doesn’t address questions relating to the effect of cannabis on the way the brain functions. Nonetheless, this study serves as further support for the less-damaging effects of cannabis use compared to other drugs (such as alcohol), which have been shown to affect brain structure.

CBD Protects Against THC’s Effects on Learning and Memory

It turns out that CBD blocks some of the effects of THC, and it has become clear that the underlying reasons extend beyond just CBD’s actions on CB1 receptors. Since THC itself has numerous therapeutic benefits, understanding how CBD blocks some of THC’s negative effects, such as impairing learning and memory, could elevate the utility of THC-based therapies.

A collaborative effort of scientists across Spain and Japan revealed that CBD can block THC’s activating effects on CB1 receptors indirectly by increasing the activation of another type of receptor, the adenosine type IIa receptor. The adenosine receptor appears to oppose the actions of CB1 receptors–when the adenosine receptor is active, the CB1 receptor is not. By increasing adenosine activation, CBD can therefore block THC’s effects.

Intriguingly, this mechanism only influenced THC’s actions in the hippocampus region of the brain, which plays a critical role in laying down long-term memories. As one can predict, CBD prevented THC’s impairing effects on new memory formation.

Narrowing Down the Culprit of Cannabinoid Hyperemesis Syndrome

Cannabinoid hyperemesis syndrome (CHS) is a somewhat newly recognized condition that is characterized by cycles of severe stomach cramping and vomiting in frequent cannabis consumers. The number of cases is on the rise and while there is no confirmed cause, increasing THC potency in average recreational strains has usually been deemed the culprit.

To address whether high levels of THC are responsible for CHS, cannabinoid content in hair samples was analyzed from patients with CHS admitted to emergency departments in Ontario, Canada, and compared with two other groups: patients admitted to the emergency department for an unrelated condition, and recreational cannabis consumers without CHS.

The results revealed that THC levels were similar across the three groups, ruling out the possibility that CHS arises due to high levels of THC in the body. Intriguingly, the THC:CBN ratio was 2.6 times lower in the CHS group than in the recreational consumers without CHS, suggesting a potential protective role of additional cannabinoids.

If THC is not the sole cause of CHS, then what is? There are at least two remaining hypotheses. The first is that some patients experience a build-up of toxins, such as pesticides and molds, from repeated consumption, which triggers the body’s emetic response (i.e., vomiting) through activation of certain cells in the brainstem.

The second is that THC weakens the action of certain CB1 receptors in some people more than others. It turns out that activating CB1 receptors (as THC does) in the brain has anti-emetic effects–which explains THC’s well-known anti-nausea effect.

But it’s believed that CB1 receptors in the brain are more prone to weakening than those in the gut–therefore, heavy THC use in some people could lead to a weakening of the anti-emetic actions in the brain while leaving the pro-emetic actions in the gut unaffected. The result may be hyperemesis.

CBD Could Effectively Treat Related Symptoms of Autism

There is plenty of anecdotal support for cannabis-based therapies in Autism Spectrum Disorder (ASD), but those claims have lacked clinical support until now. ASD is characterized by core deficits in social, communication, and motor behaviors.

While these symptoms present their own challenges, comorbid symptoms such as self-injurious behavior, hyperactivity, anxiety, and sleep disorders are especially burdensome to the patient and their caregivers. Children with ASD are often on several medications to help relieve these comorbid symptoms, and not always successfully. Given CBD’s therapeutic range, it represents a single treatment strategy for combating these comorbid symptoms in ASD.

The effect of a 20:1 CBD:THC oil was assessed on comorbid ASD symptoms in 53 children between the ages of 4 and 22 years of age. Parents were free to administer as much of the oil as they wanted (recommended daily dose was 16 mg CBD per kilogram of body weight), but children ended up consuming around 90 mg of CBD each day.

Despite consuming less than the recommended amount, CBD reduced hyperactivity, lowered the number of self-injurious behaviors, improved sleep, and reduced anxiety in a majority of patients.

An overall improvement in at least one of the comorbid symptoms was observed in 75% of the participants and only worsened overall symptoms in 4%. Although CBD didn’t improve any one of the symptoms better than conventional treatments, it represents a single pharmaceutical approach that can target a myriad of symptoms simultaneously with limited adverse events.

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Marijuana Legalization Causes ‘Significant Decline’ In Opioid Overdoses, New Research Finds

Two new studies find that opioid-related deaths decline when states legalize access to marijuana. In fact, when adult-use cannabis laws are in place, the rate of opioid overdoses declines by at least 20 percent.

Both papers, published in the journal Economic Inquiry, not only show the impact of passing such laws, but also how dispensaries play a role in helping to quell these deaths.

The first study, helmed by researchers in Massachusetts and Colorado, claims to be the first to show the causal effects of access to recreational cannabis on opioid mortality.

“We find that marijuana legalization causes a significant decline in opioid mortality– especially deaths from synthetic opioids–with particularly pronounced benefits in states that have legalized recreational usage,” the study’s authors write. “Yet it is not legalization, per se, that produces these gains; rather, states that have legal access via dispensaries see the largest reductions in mortality.”

“We estimate that [recreational marijuana laws] reduce annual opioid mortality in the range of 20%-35%, with particularly pronounced effects for synthetic opioids.”

The study used three main sources of data: death rates involving all opiates, prescription opioids and synthetic opioids from January 1999 through the end of 2017; the history of marijuana legalization in each state (including when legislation was passed and when dispensaries opened for business) and state-level demographic information. During the study period, 29 states had approved medical cannabis, while recreational marijuana was legalized in eight states plus the District of Columbia. According to the Centers for Disease Control and Prevention, the number of opioid-related deaths has increased six times over between 1999 and 2017. Additionally, 36 percent of the 47,600 opioid overdoes in 2017 involved prescription opioids.

After running several statistical and mathematical models that included checks to ensure their results were consistent, the study’s authors found that broader adult-use laws reduce a state’s opioid death rate between 20 percent (for all opiates and prescription opioids) to 35 percent (for synthetic opioids).

“Recreational marijuana laws affect a much larger population than medical marijuana laws, yet we know relatively little about their effects,” study co-author Nathan W. Chan, PhD said in a press release. “Focusing on the recent wave of recreational marijuana laws in the U.S., we find that opioid mortality rates drop when recreational marijuana becomes widely available via dispensaries.”

“Our estimates are sizable,” the study itself states. “For reference, the average never-legalizer state has 4.82 fatalities per 100,000 people from All Opiates (Synthetic Opioids) annually, while for the average [medical marijuana law] state, these are 6.067 and 0.856 per 100,000 people. Thus, our estimates imply annual reductions in All Opioid mortality between 1.01 and 1.27 deaths per 100,000 people for non-[recreational marijuana law] states, on average. For a state with a population of 5 million (near the nationwide median), this would save on the order of 50 lives per year, or roughly 10 averted deaths from Synthetic Opioids alone.”

Those are conservative estimates, the authors add.

Additionally, models showed that white people and women saw the highest reductions in synthetic opioid deaths in states that legalized recreational cannabis: Whites experienced a 32 percent decrease, while the statistical effect for women was larger and “highly statistically significant” compared to what they found for men.

The authors did not identify what mechanism is responsible for this reduction in mortality rates, though past research suggests people who can legally access marijuana may substitute it for opioids. A recent study, for example, found the majority of people who shopped at cannabis retail shops reported using marijuana to help with pain and sleep.

The new study’s authors do stress, however, that the causal effect they identified is “highly robust.”

“Our bedrock findings remain unmoved by variations in modeling assumptions and selections of control variables, and our findings are further corroborated through placebo tests,” they write. “Our results show that there are substantial ancillary benefits to marijuana legalization, especially [recreational marijuana laws], and they offer important food for thought as many states continue to contemplate expansions to both medical and recreational marijuana access.”

Their findings support a growing body of research that has linked the availability of medical marijuana dispensaries with a drop in the rate of local opioid-related deaths.

In fact, that was the focus of the second cannabis-related study published recently in Economic Inquiry. According to its findings, after a medical cannabis dispensary opened in a county, prescription opioid deaths fell locally by approximately 11 percent. These results, the author writes, suggest “a substitutability between marijuana and opioids.”

“Furthermore,” the study concludes, “the unintended beneficial effects of allowing for marijuana dispensary operations should be considered by policymakers as they aim to curtail narcotic abuse and limit the impact of the opioid epidemic.”

New Analysis Explores Relationship Between Medical Marijuana And Opioid Overdoses

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Cannabis in Sports: Unpacking Exemptions for Therapeutic Use

For most adult Canadians, cannabis has never been easier to access. Meanwhile, our elite athletes must abstain while they are in competition or face aggressive fines or suspension.

Canadian MMA fighter, Elias Theodorou, suffers from bilateral neuropathic pain. He feels the pain from his condition in his upper extremities–his hands, wrists, and elbows are all affected.

When he fights, he says, the locations of these “flare-ups” come in direct contact with whatever he punches, elbows, and blocks. “Every time I punch there’s a shocking pain, it’s almost like a stinger.”

Sometimes Theodorou can’t feel these areas of his upper extremities and will push his training to the point of near-injury without realizing. This sort of overexertion could put any athlete into the danger zone.

Theodorou would like to add medical cannabis to his medicinal toolbox, but the rules set out by more than one anti-doping group bans cannabis in his sport.

Despite having a recommendation for medical cannabis from his long-time family doctor, Theodorou has been unsuccessful at securing a medical exemption from the US Anti-Doping Agency (USADA), which administers the UFC’s anti-doping program.

Theodorou has been training in mixed martial arts for the better part of a decade and fighting professionally for nearly six years, but some of the pain he feels today can be traced back to an adolescence spent skateboarding. He has arthritis in his wrists, likely due to a series of breaks and fractures sustained while skateboarding.

The aftermath of that damage leaves him with limited range of motion, and it has even forced him to change his fighting style. His access to medical marijuana in Canada helps, he says, but he must abstain for up to six weeks before a fight if he wants THC to be flushed from his body–the only way he can use cannabis and still qualify for his fights.

Fighters in the UFC are not tested for cannabis out of competition, as per the World Anti-Doping Agency code. But THC, the primary psychoactive compound in cannabis, is prohibited in the days leading up to the fight. If THC is detected in a fighter’s system close enough to the match–at the weigh-in, for example–they will face consequences.

Canada has a separate athletic organization that monitors athletes for potential doping. For both organizations, it is standard, under the World Anti-Doping Code, that they follow World Anti-Doping Agency (WADA) rules.

The Canadian Centre for Ethics in Sport (CCES) has several working groups and committees overseeing things like banned substance testing and issuing Therapeutic Use Exemptions (TUE) for banned substances, like cannabis.

Canadian athletes need to be careful not to confuse legalization of cannabis in Canada with permission to use cannabis in sport.

Canadian Centre for Ethics in Sports

The organization has–for years, they tell Leafly by email–recommended that cannabis be removed from the WADA Prohibited List because they do not believe it meets the standards to be included in the list.

“The CCES has in the past recommended to the WADA List Committee that cannabis [is] removed from the Prohibited List as we feel the evidence supporting its performance-enhancing properties is not conclusively supported by the scientific literature,” writes Paul Melia, CCES President and CEO in an email.

“The WADA List Committee has not followed our recommendation, and so cannabis use remains prohibited in sport. Therefore, even though cannabis was recently legalized in Canada, this does not affect the status of cannabis as a banned substance in sport.

“Canadian athletes need to be careful not to confuse legalization of cannabis in Canada with permission to use cannabis in sport. Canadian athletes also need to be aware that a positive test for cannabis use in competition may result in a significant sanction.”

A TUE application will be considered by the CCES if: “The use of the prohibited substance or method would produce no additional enhancement of performance other than that which might be anticipated by a return to a state of normal health following the treatment of a legitimate medical condition;” and, if “There are no reasonable therapeutic alternatives or other alternatives are ineffective.”

To apply for a TUE with either USADA or the CCES, extensive documentation of the athlete’s medical condition, assessments from several physicians, and proof that the athlete has explored to exhaustion all non-prohibited alternatives to prohibited medications is required.

Conventional prescription drugs, says Theodorou, don’t adequately address the sharp stinging pain and radiating heat he feels in his elbows and hands. As the intensity and frequency of his training ramps up before a fight, sometimes going five hours each day, he wishes more to have the option of using cannabis.

The irony of them telling me not to get hooked on opioids while telling me you need to try a lot more opioids before we can give you cannabis.

Elias Theodorou, Canadian MMA fighter

Despite his doctor’s recommendation, the legality of cannabis in Canada, and the legitimacy of his condition, Theodorou says he’s fighting an uphill battle with the USADA, an organization that receives funding from the Office of National Drug Control Policy (ONDCP), a US agency that must abide by the federal cannabis laws.

Without a TUE, Theodorou must rely on opioid painkillers six weeks before a fight, and laughs good-humouredly at “the irony of them telling me not to get hooked on opioids while telling me you need to try a lot more opioids before we can give you cannabis.”

Theodorou has made four attempts at a TUE from USADA, but they need him to exercise and exhaust all options of what they call “first-line medications,” which include the traditional antidepressants, opioids, and other medications that make up his pain management drug regimen.

“They never say no,” he says, describing the responses from USADA he receives by mail. “They just say you’re denied and we need more explanation.”

Both CCES and USADA are silent about whether any TUEs at all have been issued to athletes for the use of medical cannabis, but Theodorou isn’t giving up hope.

Beyond taking steps to further pursue his own TUE, he is watching the United States for changes to the nation’s federal laws regarding cannabis and whether that, in turn, encourages CCES to grant more (if any) TUEs in Canada.

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