Parents of some autistic children have long reported that their kids calm down with cannabinoids, are better able to communicate, and can do more tasks by themselves. But because of the restrictions on cannabis research in the United States, there have been precious few real-world studies to confirm those anecdotal reports.
A recent study out of Israel, which approved cannabis research in 2007, gives parents new evidence to back up those claims. Published Jan 17. in the journal Nature, the study found that yes, cannabis can relieve some of the symptoms suffered by many autistic people, including seizures, restlessness, and rage attacks.
“Cannabis in ASD patients appears to be well tolerated, safe and effective option to relieve symptoms associated with ASD.”
The study, “Real Life Experience of Medical Cannabis Treatment in Autism; Analysis of Safety and Efficacy,” followed 188 autism spectrum disorder (ASD) patients over a six-month period. The subjects were mostly male (81.9%) and had a mean age of 12.9 years, with 14 of the participants younger than five, 70 patients between six and 10, and 72 patients between 11 and 18. Their autism symptoms included “restlessness, rage attacks, agitation, speech impairment, cognitive impairment, anxiety, incontinence, depression and more.”
“Although many with autism are being treated today with medical cannabis, there is a significant lack of knowledge regarding the safety profile and the specific symptoms that are most likely to improve under cannabis treatment,” wrote the study’s authors, Lihi Bar-Lev Schleider, Raphael Mechoulam, Naama Saban, Gal Meiri, and Victor Novack.
The aims of the study were straightforward: “to characterize the patient population receiving medical cannabis treatment for autism and to evaluate the safety and efficacy of this therapy.”
Its conclusion is emphatic: “Cannabis in ASD patients appears to be well tolerated, safe and effective option to relieve symptoms associated with ASD.”
Treatment and Findings
Parents have often reported that cannabis and CBD help calm their autistic children and help them focus. And for children who suffer from epileptic seizures, cannabis can help decrease the frequency. Parents such as Brandy Williams, a cannabis activist in Arizona, gave cannabis to her autistic son Logan, who experienced epileptic seizures, and noticed significant changes. He stopped rocking back and forth, and he was able to communicate more clearly.
Most of the subjects in the Israel study were given cannabis oil (30% CBD and 1.5% THC). One month into the trial, respondents were asked to rate their quality of life using the Likert scale “ranging from very poor to poor, neither poor nor good and good to very good,” and report side effects to provide a better yardstick for the final results.
At the end of the study’s six-month course, 155 subjects of the original 188 were still in active treatment. Others had dropped out or began a different treatment option. Of those 155 patients, 93 had been assessed through questionnaires.
Of those 93 patients, 28 (30.1%) reported a “significant” improvement, 50 patients (53.7%) reported a “moderate” improvement, and six (6.4%) reported a “slight” improvement. Only 8 patients (8.6%) showed no change in their condition.
Roughly a quarter of the assessed patients (25.2%) experienced some form of side effect, but most were minor. The most common was restlessness, which was reported by 6.6% of subjects. Others included sleepiness (3.2%), a psychoactive effect (3.2%), increased appetite (3.2%), digestion problems (3.2%), dry mouth (2.2%) and lack of appetite (2.2%).
The patients reported that their quality of life–that is “their mood and ability to perform activities of daily living”–had improved in six months. Prior to the study, 31.3% said they had a good quality of life. After, that figure more than doubled, rising to 66.8%.
“Quality of life” isn’t some nebulous thing. It has real-world meaning. For instance, the subject’s parents found that patients could dress themselves more easily after six months, an improvement of 21.5%.
Autism and Epilepsy
Nearly a third of autistic people are diagnosed with epilepsy–a condition that has been shown to respond well to cannabis treatment.
In the Israeli study, 14.4% of the participants had epilepsy. As in many studies involving autism, the subjects were usually taking other medications, which can make it more difficult to assess the effectiveness of cannabis treatment. Some of the patients in the study, for example, were also taking antipsychotic, antiepileptic, and antidepressant drugs.
Of the 93 patients who responded to the final questionnaire–about a third decreased or stopped some of those medications. After six months, 11 of the patients had stopped taking antipsychotic medication altogether.
The doses were not a one-size-fits all application–some patients received a drop of oil three times a day that contained 15 milligrams CBD and 0.75 mg THC. Others received up to 20 drops of oil three times a day.
Though the study is a step forward for demonstrating that cannabis can help autistic people, the researchers believe more work needs to be done. “While this study suggest that cannabis treatment is safe and can improve ASD symptoms and improve ASD patient’s quality of life, we believe that double blind placebo-controlled trials are crucial for a better understanding of the cannabis effect on ASD patients.”
Perhaps no other material has made as big of an impact on dabbing culture as quartz has over the past several years. Initially created as an alternative to materials like titanium and ceramics, quartz is now regarded as the gold standard for dabbing rig pieces.
Quartz can withstand and retain heat with less risk of breaking and it can preserve concentrate flavors better than other materials.
What makes quartz so great for dabbing cannabis concentrates? It can withstand and retain heat with less risk of breaking and it can preserve concentrate flavors better than other materials.
Here we look at what makes quartz so popular, how quartz nails and accessories have evolved, and best practices for quartz cleaning and maintenance.
What Is Quartz?
Silicon Dioxide (SiO2), also known as clear-fused quartz or fused silica, is a solid, amorphous (non-crystalline) material comprised of silicon and oxygen. While very similar to traditional glass, the two are distinct in that quartz contains no other materials.
In order to create fused quartz, pure silica sand containing quartz crystals must be melted or fused. This purity gives quartz a high thermal conductivity, and it’s also often used in laboratory-grade materials.
Why Dab With Quartz?
Quartz is great for low-temperature dabbing, the practice of using reduced temperatures when heating a nail in order to preserve terpene flavors during the sublimation and inhalation processes.
When used in conjunction with a carb cap or any other device designed to create convection, quartz nails preserve terpenes because they can maintain a lower temperature for a longer period of time before cooling off. This creates a much more robust and enjoyable dabbing experience compared to other nail materials, which can burn off terpenes with higher temperatures.
Quartz is also a champ when it comes to thermal conductivity. It can withstand high temperatures over time with less risk of breaking, and can also retain steadier temperatures for longer periods, making for easier and less rushed dabbing without the fear of cooling.
The amount of heat a quartz nail can retain depends on its thickness, and this is usually advertised by the retailer.
A Brief History of the Quartz Nail
Before 2010, low-grade flathead nails were easy to produce and often accompanied early versions of dab rigs. These impure glass nails would break easily, so quartz began to show up as a stronger, more resilient alternative.
The introduction of the quartz domeless nail was the turning point when quartz became a major contender for nails.
But the flathead design of early quartz nails was still imperfect. Although it fit well with early dab rigs that had domes for creating convection, concentrates would often melt off the ridges and go to waste. Cupped designs proved to be a better option with domed rigs, but these nails couldn’t retain heat long enough.
The introduction of the quartz domeless nail was the turning point when quartz became a major contender for nails. Designed to be used without a dome, these nails could hold concentrates easier and retain heat longer. Quartz domeless nails were quickly recognized for providing a better flavor when dabbing, compared to titanium and ceramic nails.
As it grew in popularity, several influential American glassblowers started custom designing nails with quartz. Out of this explosion of creativity came several designs, including the Honey Bucket model from Mothership Glass, the Quartz Club Banger from Quave Glass, and the Trough from Joel Halen.
While each of these designs are still popular today, the simplified banger nail has easily become the most popular for quartz enthusiasts because of its functionality, simple and sleek design, and easy replicability. Quartz nails complement glass more than other materials like titanium, bringing a more attractive aesthetic to expensive dab rigs.
Proper Quartz Hygiene
A fresh quartz nail, translucent and free of cloudiness and debris, will give you better dabs, allowing you to taste the flavors and terpenes of concentrates better.
Because of the amorphous nature of fused quartz, its atomic structure is in a perpetual state of imbalance. When heated to extreme temperatures, a process called devitrification occurs, when the atoms of quartz attempt to reorganize into a crystalline structure.
This can happen when cooled quartz is exposed to various elements, including extreme temperatures, like a red-hot torch flame, the introduction of contaminants like oil reclaim, or continued and prolonged exposure to oxygen as a byproduct of oxygenated torching.
When devitrification occurs, quartz becomes cloudy. This process is irreversible without lab-grade chemicals and it can negatively affect the function of the nail. To avoid this altogether, be proactive in taking care of your nail:
- Never expose a nail to extremely hot temperatures. This is the easiest way to ruin a fresh nail.
- Don’t dab on a hot quartz nail. Always wait for the nail to cool a bit before applying a concentrate.
- After each dab, immediately clean the nail with a cotton swab or similar material to rid the skillet of carbon residue or reclaim.
- Don’t leave a nail dirty for a prolonged period for risk of creating carbon build-up, which will devitrify the quartz on the next heating session.
- Don’t clean your nail with water, as this will also cause devitrification.
An old standard for nail care was seasoning–heating a new nail until it clouds and turns red, seasoning it like you would a cast iron skillet. But seasoning is, in fact, not considered a best practice for nail hygiene these days because the extreme temperatures cause devitrification.
Exciting New Quartz Technology
The world of quartz dabbing accessories continues to grow with new technologies, fueled by a never-ending pursuit to create a quality low-temperature dabbing experience. Here are some exciting innovations in quartz to look out for:
Thermal Banger Nails
Quartz bangers can create build-up and residue of concentrates inside the nail stem. This occurs when oil either bubbles over or solidifies within the stem when taking a dab. Thermal bangers mitigate this with their design: With a large cylinder to redirect airflow, residue can’t reach the downstem of the nail.
Bubble Carb and Directional Caps
Carb caps are designed to create convection when dabbing, allowing concentrates to sublimate more evenly over longer periods of time when exposed to lower temperatures. Bubble carb and directional caps help facilitate this process by siphoning airflow toward every corner of the skillet.
Their unique design allows the dabber to manipulate the direction of incoming air when taking a dab by moving the cap around. The result is less reclaim at the end of the dab and a better flavor when low-temperature dabbing.
One way to ensure that high-end quartz nails don’t suffer the fate of devitrification is to use a quartz insert or skillet. These skillets are designed to be pre-loaded with concentrates and placed in a heated flat-top nail. This lets the concentrate be sublimated inside of the skillet, leaving the nail basin free from the potential of residue buildup.
Rep. Tulsi Gabbard (D-HI) announced last week that she will be seeking the Democratic Party’s nomination for president in 2020. Here’s a look at where the congresswoman, who received a B+ grade from NORML as well as an earlier endorsement from the advocacy group, stands on marijuana reform.
Legislation And Policy Actions
Gabbard has cosponsored a large number of cannabis-related bills during her time in Congress, and she was the lead sponsor of a measure to require the federal government to study the impact of state marijuana legalization.
Gabbard signed onto far-reaching legislation to remove marijuana from the Controlled Substances Act (CSA) and withhold federal funds from states that disproportionately enforce cannabis laws.
Other bills she’s backed would shield medical marijuana states from federal interference, legalize industrial hemp, protect banks that service cannabis businesses, provide tax fairness for the cannabis industry, address various aspects of the federal-state marijuana policy gap, remove roadblocks to research and exempt CBD from the CSA.
She was the lead Democratic cosponsor of a measure to federally deschedule marijuana.
Gabbard, who served in a medical unit in the Hawaii Army National Guard, has also cosponsored several pieces of legislation aimed at expanding access to medical cannabis for veterans. That includes one bill that would block the U.S. Department of Veterans Affairs (VA) from denying benefits to patients who use marijuana and another that would require the VA to survey patients and caregivers on cannabis use.
She signed onto a House resolution last year that was meant to express the chamber’s sentiment that the drug war has failed and apologize to “individuals and communities that were victimized by this policy.” She also cosponsored a separate resolution calling on states to “address disparities in the cannabis marketplace participation and to address, reverse, and repair the most egregious effects of the war on drugs on communities of color, in particular to those who now hold criminal records for a substance that is now legal and regulated.”
Quotes And Social Media Posts
After then-Attorney General Jeff Sessions rescinded Obama-era Justice Department guidance on cannabis enforcement priorities in early 2018, she posted an extensive thread about why the move “will exacerbate an inhumane, ineffective system that tears families apart.
Later in the year, she turned her attention on Hawaii Gov. David Ige (D) after he vetoed legislation that would have made opioid misuse a qualifying condition for medical marijuana. Gabbard has repeatedly touted research demonstrating that legal access to cannabis can reduce opioid overdoses and prescriptions, potentially mitigating a national drug crisis.
“With such a stark increase in prescription opioid use and dependence, heroin and synthetic drug overdose, and emergency room visits over the last decade, we must allow legal access to medical marijuana to help prevent opioid addiction and opioid-related deaths,” Gabbard said in a press release. “Understanding that people’s lives are at stake, I urge Governor Ige to reconsider and sign this legislation into law now.”
She also talked about the relationship between marijuana laws and opioid overdoses on Joe Rogan’s podcast.
“There are states that have legalized, whether it’s just medical or full legalization, there has proven to be a direct correlation to a drastic reduction in opioid-related deaths in those states where people have access,” she said. “If we know this, and every one of the leaders in this country are so concerned about this opioid epidemic, why hasn’t this been brought forward?”
In a 2017 interview with SFGate, the senator discussed legislation she cosponsored to remove marijuana from the CSA, saying that current federal cannabis policies “have turned everyday Americans into criminals, torn families apart, and wasted huge amounts of taxpayer dollars to arrest, prosecute, and incarcerate people for nonviolent marijuana charges.”
“The reality is, whether or not any individual chooses to consume cannabis is irrelevant. The important question is, should we really be sending people to jail and turning them into criminals for using a substance that is far less dangerous and harmful than alcohol? The answer is no. The fiscal and social impacts of our current policy, are having devastating effects on individuals and our communities and are only perpetuating the problem.”
Touting her Marijuana Data Collection Act on the House floor, Gabbard said “federal policies should be based on actual science and fact, not misplaced stigma and outdated myths.”
“For decades, bad data and misinformation have fueled the failed War on Drugs that’s wasted billions of taxpayer dollars incarcerating Americans for non-violent marijuana charges,” she said. “Our outdated marijuana policies have turned everyday Americans into criminals, strained our criminal justice system, cost taxpayers tremendously, and torn families apart–all for a substance that’s proven to be far less harmful and dangerous than alcohol.”
Prior to the passage of the 2018 Farm Bill, which federally legalized industrial hemp, the senator spoke out in support of allowing farmers to cultivate the crop.
“Our nation should empower our local farmers by allowing them to grow, cultivate and research industrial hemp that will create opportunity and strengthen our economy,” she said in a press release. “The DEA must honor and uphold the Congressional intent of federal legislation that allows states, like Hawai’i, to establish programs to research the benefits, cultivation, and market of industrial hemp.”
Personal Experience With Marijuana
It’s not clear whether Gabbard has personal experience with marijuana besides meeting patients and veterans who’ve benefited from medical cannabis.
Marijuana Under A Gabbard Presidency
Gabbard’s cosponsorship of a long list of cannabis reform bills and continual focus on the issue in public statements and social media posts indicate she would be an especially marijuana-friendly president if she were to earn the Democratic nomination and win the 2020 election.
Photo element courtesy of Lorie Shaull.
The connection between cannabis and yoga stretches back centuries. Hindu scriptures hold that Shiva, the third god in the Hindu triumvirate, ingested a cannabis-infused drink called bhang to focus inward and harness his divine powers. Shiva is also known as the originator of yoga.
Bhang is not well-known in the West today but a growing number of people are turning to cannabis-enhanced yoga as a way to improve their mental and physical health. They say cannabis puts them in the right mindset for a yoga class and helps them get more out of the class itself.
Many yoga instructors are running cannabis-infused classes in North America and at least one, Dee Dussault, has written a book about it. “I found, for me, with my personal yoga practice, cannabis really enhances the connection to my body,” Dussault told a reporter. “I go deeper into the stretches. It helps me feel more present instead of multi-tasking.”
Juliane Nowe, a yoga instructor based in New Brunswick, began practicing yoga nearly a decade ago. She now teaches cannabis-infused classes to people who have experienced trauma with a particular focus on military veterans with post-traumatic stress disorder.
She says some of these veterans rely on medical cannabis to get through their days but shy away from situations in which they are criticized for using it. Because she is supportive of their medication, she says, these veterans feel at ease in her class and are able to enjoy the benefits of yoga.
Nowe started down this path by leading cannabis-infused yoga classes to her partner, a veteran with PTSD, and his peers in the military.
Thanks to the burgeoning interest in cannabis-enhanced yoga, Nowe says she will likely start running classes for recreational cannabis users in the not-too-distant future.
Her classes usually open with participants smoking or vaping cannabis before starting their poses. She urges them not to overdo it. “You don’t need to smoke a whole joint or eat an entire edible to benefit from the cannabis,” she says. “It’s not like you want to have this big experience before class. You just want to find the right strain, take it slow and connect with other people.”
Nowe says getting her students into a relaxed state of mind requires less effort when they have ingested cannabis. She believes the greatest benefit of cannabis in a yoga context is that it helps people move into each pose with a sense of relaxation that is otherwise difficult to achieve.
“If you show up to class feeling flustered and you haven’t ingested cannabis, you get on your mat and maybe by the end [of class] you have taken the edge off a little bit,” she says. “But if you use cannabis going into the process, you’re much more present, more focused and connected to start with. You get more out of that class.”
Nowe says cannabis is not necessary to enjoy the benefits of yoga for many enthusiasts but she says it can be a great option for those who have trouble letting go of stress during class.
There’s a myriad of ways cannabis can benefit people living with HIV. I can say this from personal experience.
New: This report is now available in Spanish and Japanese translations! See bottom of this article for downloads.
Project CBD, a California-based educational non-profit, has published an in-depth primer on Cannabinoid-Drug Interactions for health professionals, patients, and public policy-makers. The 33-page report, summarized below, is available for free download at the bottom of the page.
Drug interactions are a significant consideration in modern medicine. More than half of U.S. adults regularly take prescription meds and at least 75 percent of Americans take at least one over-the-counter drug. Many people, including most seniors (the fastest growing demographic of cannabis users), take multiple drugs, and these compounds can interact and affect the metabolism of each other.
Cannabis is one of the most widely consumed substances in the United States and throughout the world, and a huge number of cannabis users also consume pharmaceutical products. Given the increasing acceptance and prevalence of cannabis as a therapeutic option, it’s important for physicians and patients to understand how various cannabis components, including cannabidiol (CBD) and tetrahydrocannabinol (THC), the major phytocannabinoids, may interact with commonly consumed pharmaceuticals.
But pertinent information about cannabinoid-drug interactions is difficult to obtain because of marijuana prohibition and consequent restrictions on clinically relevant research. Hence the need for Project CBD’s primer, which was written not only to help health professionals and patients anticipate and avoid problematic outcomes but also to take advantage of situations where cannabis and pharmaceuticals can act synergistically in a positive way.
A complicated issue
“It’s a complicated issue,” says research chemist Adrian Devitt-Lee, the author of the Project CBD primer. “Although drug interactions are rarely so dangerous as to entirely preclude the use of a medication, they can have serious impacts on a patient’s treatment and wellbeing.”
The Project CBD primer includes a discussion of various “substrates” or drugs that are metabolized by cytochrome P450, a large family of non-specific enzymes that are involved in breaking down an estimated 60 to 80 percent of all pharmaceuticals. Cytochrome P450 enzymes may be inhibited or amplified by CBD, THC and other plant cannabinoids, thereby reducing or prolonging the activity of another drug.
By suppressing or inducing specific cytochrome P450 enzymes, CBD and THC can alter how one metabolizes a wide range of substances. Much depends on the particular substrate involved in the drug interaction. Some pharmaceuticals, known as “prodrugs,” don’t become functional until they are metabolized into an active component. If CBD or THC inhibits the breakdown of a prodrug, the latter will remain inactive – whereas inhibiting the metabolism of a regular drug will result in higher blood levels of the active substance.
Several variables make precise predictions about drug interactions difficult, even for practiced physicians. “It is much easier to assess whether drug interactions are likely than to predict their exact effect,” the Project CBD primer asserts.
The CBD paradox
Thus far, based on observations regarding the widespread use of raw cannabis flower and full-spectrum cannabis oil, it does not appear that there have been many problems because of cannabinoid-drug interactions. The clinical use of Sativex (a 1:1 CBD:THC sublingual tincture) and Marinol (a pure, synthetic THC pill) has resulted in few, if any, reported adverse events attributable specifically to interactions with pharmaceuticals.
To the extent that there have been problematic drug interactions with cannabinoids, these have involved high doses of nearly pure CBD isolates, not cannabis in general. Even though THC is an intoxicant and CBD is not, the fact that people tend to use much higher doses of pure CBD makes it a much riskier player in metabolic drug interactions.
Consider the numbers: Ten milligrams of THC in a cannabis product is a hefty dose for a naive patient and sufficiently psychoactive for the occasional recreational user. Ten mgs of THC combined with an equal amount of CBD in a Sativex tincture hit the analgesic sweet spot in clinical trials. These are moderate doses compared to the amount of single-molecule CBD administered to epileptic children in clinical trials – up to 50 mg per kilogram – with CBD doses as high as 2000 mg not uncommon among patients who obtain CBD isolates from internet storefronts and other unregulated sources.
THC has its own built-in guard rails – consume too much and you’ll know you’ve hit your limit. With CBD, there are no guard rails, no dysphoric feedback loop that says you’ve had enough. CBD is intrinsically safe, but when extracted from the plant and concentrated as an isolate, high doses are necessary for therapeutic efficacy – unlike whole plant CBD-rich extracts, which have a broader therapeutic window and are effective at lower doses than single-molecule CBD.
Drug interactions are much more likely with high dose CBD therapy than other forms of cannabis consumption. Physicians and patients should be concerned about this, given that the current regulatory regime privileges CBD isolates over artisanal, plant-derived, multicomponent formulations.
Mode & sequence of administration
The way cannabinoids are administered (smoking, eating, etc.) also has a major impact on whether or not drug interactions occur. Interactions are far more likely when both drugs are taken orally and processed by the liver before being distributed through the body. Cannabinoids are absorbed more if ingested on a full stomach. Ingested cannabinoids will have higher peak liver concentrations than inhaled cannabinoids, so ingested cannabinoids should have more potent drug interactions.
The Project CBD primer notes that the sequence as well as the route of administering cannabidiol can influence how another drug is metabolized. One study disclosed that CBD has a stronger inhibitory impact on a particular cytochrome P450 enzyme if it’s administered 20 minutes before the second drug.
CBD also interacts with THC. By taking CBD and THC together, individuals may find that the effects of THC are tempered but prolonged slightly. It is known that 11-OH-THC, a THC breakdown component, is more potent than THC at the CB1 cannabinoid receptor, which mediates psychoactivity. 11-COOH-THC, another THC metabolite, has anti-inflammatory effects without causing a high.
Some people can hardly tolerate any THC. The wide range of reactions to THC-rich cannabis may be influenced by genetic factors. A common polymorphism (or variant) of a gene that encodes a particular cytochrome P450 enzyme alters how one metabolizes THC so it breaks down more slowly and stays active longer, resulting in hypersensitivity to THC’s psychoactive effects.
That may be one of the reasons why some people find THC-rich cannabis to be unpleasant, while hundreds of millions smoke it to relax. This genetic variant exists among 20% in European & Middle Eastern populations, meaning one in five Caucasians are THC-averse. Less than 10% of Africans have this genetic variant and among Asians it’s less than 5%.
Other noteworthy findings in the Project CBD primer:
- THC v. lung cancer. When cannabis is smoked, cytochrome P450 enzymes in the lungs convert inhaled ash into potent carcinogens, including highly toxic polycyclic aromatic hydrocarbons (PAHs). But THC may protect against lung cancer by inhibiting the same metabolic enzymes that PAHs induce.
- Cannabinoid-opiate interactions. Supplementing an opioid-based pain-management regimen with cannabis could result in lower doses of opioids required for adequate analgesia. Lower doses of opioids will reduce the number of overdose deaths. This is an example of a potentially beneficial cannabinoid-drug interaction.
- CBD, THC & chemotherapy. Limited preclinical research indicates that administering CBD and/or THC in conjunction with first-line chemotherapy drugs could potentiate the latter, thereby reducing the dosage of highly toxic chemo necessary to treat the cancer. If this translates to human experience, it would be a huge benefit. But if pure CBD delays chemo metabolism, dangerously high levels of a toxic drug could accumulate unless the dose of chemotherapy is reduced and properly managed. The fact that cannabinoids make radiation and chemotherapy both more tolerable and seemingly more effective is an area worth studying.
- Blood thinners. Both THC and CBD delay the metabolism of warfarin, a widely prescribed blood thinner. Mis-dosing warfarin causes tens of thousands of ER visits every year because of excessive bleeding. The Project CBD primer reviews a recent case study as an example of how physicians can successfully adjust the dose of warfarin for a patient who is also taking a CBD isolate.
The information presented in the Project CBD primer is intended to help doctors and patients understand if and when drug interactions with cannabis or cannabinoids are likely. “It is not meant to stoke fears about drug interactions or add to decades of ill-advised, anti-marijuana hysteria,” the author emphasizes.
How dangerous are cannabinoid-drug interactions? As dangerous as mis-dosing the other drug(s) that a patient is taking. Problems are more likely to arise when a patient combines a high dose of an otherwise benign CBD isolate with a pharmaceutical that has a very narrow window between its therapeutic and toxic levels.
In GW Pharmaceuticals’ clinical trials of Epidiolex, an almost pure CBD compound, there were potentially dangerous interactions with Clobazam, an anti-epilpetic drug, which necessitated a dosage adjustment of the latter. The FDA recently approved Epidiolex as a medication for children with refractory seizure disorders. And the DEA classified Epidiolex as a schedule V substance in September 2018.
Epidiolex would surely command a lot of “off label” attention if not for the potent price tag. And just as surely a huge unregulated market for hemp-derived CBD isolates will continue to flourish in a tenuous legal environment. An already massive consumer demand for CBD products has far outpaced the gathering of clinical data on cannabinoid interactions with pharmaceuticals for pain, cancer, autism, heart disease and many other chronic ailments.
The longstanding barrier to requisite research is the Schedule I status of cannabis, a category reserved for dangerous substances with no medical value, according to federal law. But the paucity of federally sanctioned clinical research, a consequence of cannabis prohibition, should not be an excuse for physicians or patients to shun nonlethal cannabinoid therapies, which show promise for a wide range of conditions.
Project CBD hopes that “as cannabis therapeutics continues to gain acceptance among physicians and patients, adequate resources will become available for clinical studies involving drug interactions with CBD, THC and other plant cannabinoids.”
Project CBD: I’m Martin Lee with Project CBD, and this is another edition of Cannabis Conversations. Today, we’re very pleased to have Dr. Ethan Russo come back in the studio with us. Dr. Ethan Russo is a neurologist, a scientist, widely published author in many peer-reviewed journals and currently a director of research and development for the International Cannabis and Cannabinoid Institute, which is located in Prague, in the Czech Republic. Thanks for joining us, Ethan.
Russo: It’s a pleasure to be here.
Project CBD: Ethan, there’s been an explosion of interest in CBD lately. Explain what the excitement is about. What is CBD?
Russo: Well, first of all, this has been long in coming. For probably 40 years now the real concentration in breeding has been toward THC, the main psychoactive ingredient of cannabis. Unfortunately, a lot of that is a by-production of prohibition. The market was driven by people in the recreational sphere that were looking for escape or sometimes medical use. In the process, a lot of the benefit of cannabis was lost genetically because customarily, in many parts of the world where cannabis was grown, it was typically a plant that had equal amounts of tetrahydrocannabinol – the main psychoactive ingredient in cannabis – and cannabidiol.
So what is cannabidiol? Cannabidiol is frequently mischaracterized as being non-psychoactive. Rather, it is psychoactive. It is an anti-anxiety agent, and anti-psychotic agent. But it also complements a great number of the effects of THC, in that both are analgesics, painkillers, both are anti-inflammatory, and because cannabidiol has this ability to counteract some of the prominent side effects of THC it’s a very valuable thing to have in any cannabis preparation – whether it’s predominant or in conjunction with THC. It is a very versatile compound. It has a lot of effects. But unlike most drugs that have multiple effects, in this instance it’s very hard to pick out any particular side effect of CBD that’s problematic. The only thing that we can really point to is that in extreme doses, when it’s used in isolation, it can produce some drug-drug interactions such as producing sedation with drugs like Clobazam that are used to treat severe seizure disorders. But, on its own, it does not product anxiety – rather treats it. It’s really hard to come up with a significant side effect that we need to warn people about. Of course, it depends on the preparation, and other ingredients may be prone to side effects, so we have to be careful in that regard.
Project CBD: You refer to both THC (the high causer, so to speak) and CBD in the same breath. That suggests that they work together in some way. There’s this phrase, “the entourage effect” or “ensemble effect,” explain what that is in terms of the cannabis plant.
Russo: So, cannabis is a botanical. This is a way of saying that it’s a plant-based medicine. And, although the thrust of pharmaceutical development for decades has been on single molecules, often synthetic, this is the more common concept in medicine historically. What I mean is, traditionally people have used plant drugs to treat their problems. It’s only been in the last 75 years there’s been this shift toward synthetics. So, a botanical doesn’t rely on one compound to produce the beneficial effects. Rather there may be many – and that’s certainly the case in cannabis where we know that there are actually over 100 related molecules, we call cannabinoids, but in addition there are aromatic compounds, the same things that you’d find in lemon and pine needles called terpenoids that alter the effects of the cannabinoids in a way that often is synergistic. Synergy is a boosting of effect. So, it would be the idea that 2 + 2, instead to equaling 4, it gives you an 8 in terms of the benefit. So, for example, as we’ve mentioned, cannabidiol treats pain. But there are other ingredients in cannabis that also treat pain or may limit the side effects of other components and so it is sort of like an ensemble of musical instruments where you might think if THC as the soloist with an important part provided by cannabidiol, but you also have these other components producing a harmony that really increases the overall effect and makes hopefully the best possible medicine.
Project CBD: And you referred to pain: we are in the midst of a painkiller epidemic really. It’s well known now we have many overdoses due to addiction to opioids. Maybe you could talk a little bit about that in terms of what cannabis might bring to the table in terms of addressing this crisis.
Russo: This is an absolute medical crisis in that 72,000 Americans died of opioid-related overdoses in 2017. We have known – and this may come as a surprise to almost everyone – it’s been known for 150 years that cannabis is capable of acting in concert with opioids to treat pain and allowing what’s called “opioid sparing.” This means a lower dose producing the same or better level of pain control. Additionally, it was observed in the 19th century that cannabis could treat withdrawal symptoms from opioids and other addictive drugs, reduce craving, and allow people to get off of them entirely. The same thing has been observed for decades in people who have used cannabis medicinally. But, again, until recently that was primarily with THC predominant cannabis, which did work in this regard. But the real missing ingredient until say the last decade has been cannabidiol. Because cannabidiol on its own acts as an anti-addictive substance. It actually works on an area of the brain called the insula that reduces craving. Particularly in combination with THC, we’ve seen a really amazing response in patients to reduce their opioid doses and often get off of opioids that they may have used chronically. Additionally, there’s another component in cannabis, a terpenoid called caryophyllene, that also is anti-addictive through a totally different mechanism than CBD. It’s working on another receptor called the CB2 receptor that’s involved in addiction. So, a preparation that had THC, CBD, and caryophyllene may be an ideal way of dealing with chronic pain and particularly people who are addicted to opioids.
Project CBD: You mentioned CB2 receptor – you’re referring to a cannabinoid receptor which is part of something we refer to as the endocannabinoid system. Could you basically define that or describe what that is, and why it’s important.
Russo: So, we have this thing in our bodies and all mammals and a lot of lower animals, anything that has a spinal cord basically, has an endocannabinoid system. This came about through research on cannabis and specifically THC. So in 1998 it was discovered that there were endogenous cannabinoids; the first one was called anandamide (“Ananda” in Sanskrit means bliss), then a couple of years later it was observed that there was a cannabinoid receptor that was named CB1 (cannabinoid 1). Very shortly thereafter, a second receptor – a non-psychoactive receptor – called CB2 was discovered that is involved in inflammatory responses, pain control, and limiting fibrosis (the buildup of scar tissue in the body). So, THC works on CB1 and CB2. Caryophyllene works just on CB2 with no effect on CB1. Certainly, with adequate amounts of it, it has this ability to treat pain, inflammation, and addiction, without producing any unwanted psychoactive side effects. And when I say that, I mean anxiety, paranoia, the things that we associate with a situation where someone has too much THC.
Project CBD: What about CBD? Does it also bind or activate these receptors that you refer to? Or how does it work?
Russo: Well that’s really interesting – a little complicated. CBD does not bind directly to the regular sites on either CB1 or CB2. On CB1 it does bind to another site called the allosteric site (“allo” means other). When it does bind to these allosteric receptors it produces what’s called a negative modulation. Functionally what this means is when CBD is present it’s a little harder for THC to bind to the CB1 receptor. Now that really would make it sound like it’s going to interfere with the benefits of THC on pain and other conditions, but that’s not what we see. What we see, though, when CBD is combined with THC is a blunting of the peak high. If someone smoked material with both THC and CBD, they’re not going to get quite as high if they would with THC alone. But, much more importantly, the effect is prolonged. In medical settings, this is very important because it allows people to, say, dose with an oral preparation, perhaps two or three times a day, as opposed to smoking medicine where they might have to utilize it every two to three hours because of a higher peak and – peaks and valleys of activity – rather than a smoother contour of effect, which is much preferable in a medical setting.
Project CBD: I have lots of questions I’d love to ask, but I think we have time for one more. I believe in the Ayurvedic Indian medical tradition, and traditional Chinese medicine, there’s an emphasis on the gut. The idea that health is rooted in the gut. And we hear a lot these days, the buzzword about the microbiome, the bacteria beneficial or otherwise, in the gut and the role that that plays in terms of health. Does the endocannabinoid system play into this at all? And if so, how?
Russo: Well, yes it does in a very important way. There’s been some very interesting work done recently that shows that the microbiome, which is a collection of natural bacterium in the gut, has a great deal to do with our health overall. Whether someone has problems with inflammation or not, it provides neurotransmitters that go to the brain, effects our moods in a very key way, it’s very involved in autoimmune diseases. What it was found is that THC actually stimulates production of some of the more beneficial bacterium and suppresses the disease-causing bacteria like clostridia that produces severe diarrhea syndrome.
Project CBD: That’s THC in particular does that.
Project CBD: And CBD? Do they know how it plays into it?
Russo: We’ve got a little less knowledge. And yet, however, there seems to be a key role for the microbiome, or gut bacteria, in endocannabinoid tone. Endocannabinoid tone is a function of how many receptors, say CB1 receptors, are active in the brain. The amount of the endocannabinoids like anandamide and 2-Arachidonoylglycerol, and also the function of the enzymes that make these substances and break them down. So, it’s a very important concept. We can define it – right now we don’t have good methods of measuring it. We can do serum levels of endocannabinoids in the blood, but it might not reflect what’s going on in the brain. And today, I’m afraid we don’t have a scan of the brain yet to show the activity of the receptors. But these are research projects that hopefully are going to give us better diagnostics in the future.
Project CBD: The implication is that – and maybe it’s too obvious we don’t have to say it – but our diet is key to our health, and that the endocannabinoid system mediates that whether for good or ill in some way.
Russo: That’s absolutely right. And this is one of the reasons you see a lot of emphasis now, people may see ads on TV for what are called probiotics. This is a way of taking a supplement by mouth that’s going to provide, hopefully, more of these beneficial bacteria. But those beneficial bacteria need something to eat, and it isn’t always what we have in the American diet. The American diet, I’m afraid, with a lot of fried food and carbohydrates upsets the balance of the bacteria in the gut and favors the production of inflammation. If, however, people are eating certain foods called prebiotics, they tend to be non-digestible fibers. This is what the beneficial bacteria really like. And when they’re functioning well, we have good evidence now, it’s going to increase the endocannabinoid tone and really contribute to overall health.
Project CBD: I think that’s good food for thought. I want to thank you Dr. Russo, you’ve been a great educator for our community and when we appreciate it very much. It’s been another edition of Cannabis Conversations, hopefully we’ll do more with you in the future.
Russo: Thank you.
Dr. Ethan Russo can be contacted at www.icci.science.
Copyright, Project CBD. May not be reprinted without permission.
The federal government plans to award $1.5 million in grants during the 2019 fiscal year to researchers who study how components of marijuana other than THC affect pain.
In a notice about the funding opportunity published on Thursday, the National Center for Complementary and Integrative Health (NCCIH) said that it was seeking applications from researchers to conduct studies on “minor cannabinoids and terpenes.” The aim of the grants will be to learn how these components work–separately and when combined–as potential pain-relieving agents.
The research is especially important given the widespread use of addictive opioid-based painkillers for pain management, NCCIH said. While THC has known analgesic properties, very little is known about the hundreds of other constituents in cannabis, which could represent viable alternatives to popular painkillers.
“Early clinical data suggest that cannabis may enhance the potency of opioids in relieving pain; and the synergy from using these products together may result in more effective pain relief with lower doses of opioids,” the agency wrote. “Yet, it is unclear which components of cannabis may have these properties. In particular, few studies have examined whether and which cannabinoids and/or terpenes interact with the opioid pain pathways.”
NCCIH, which is part of the National Institutes of Health, said that of particular interest are studies looking at cannabidiol (CBD), cannabigerol (CBG), cannabinol (CBN), cannabichromene (CBC), nyrcene, ?-caryophyllene, Limonene, ?-terpineol, linalool, ?-phellandrene, ?-pinene, ?-pinene, ?-terpinene and ?-humulene.
“A growing body of literature suggests that the cannabis plant may have analgesic properties; however, research into cannabis’s potential analgesic properties has been slow,” the funding opportunity says. “One key mechanism to investigate is whether potential analgesic properties of cannabis can be separated from its psychoactive properties. To address this question, more research is needed into the basic biological activity of the plant’s diverse phytochemicals, specifically minor cannabinoids and terpenes.”
NCCIH listed 11 areas of interest for prospective applicants:
* To investigate the potential analgesic properties and adverse effects of minor cannabinoids, alone or in combination with each other or terpenes;
* To investigate the mechanisms by which minor cannabinoids and terpenes may affect pain pathways, including ascending and/or descending neural pathways, cellular and molecular signaling pathways, neuroimmune interactions, or other innovative regulatory pathways related to pain;
* To explore the impact of sex, age and ethnicity on potential analgesic properties of minor cannabinoids and terpenes;
* To explore analgesic potential of minor cannabinoids and terpenes for different pain types (e.g., acute pain, chronic pain, inflammatory pain, neuropathic pain);
* To investigate the pharmacology (pharmacokinetic and pharmacodynamic profiles) of minor cannabinoids and terpenes;
* To explore binding affinities of minor cannabinoids and terpenes to cannabinoid and opioid and other pain-related receptors;
* To investigate the impact of dose and/or route of administration on potential analgesic effects of minor cannabinoids and terpenes;
* To characterize if/how specific terpenes may influence potential analgesic properties of cannabinoids;
* To explore potential opioid sparing effects of minor cannabinoids and terpenes;
* To explore the interaction between the microbiome and minor cannabinoids or terpenes;
* To improve methods to quantify systemic levels of minor cannabinoids and terpenes
Applicants are encouraged to submit letters of intent about their research proposals 30 days before the March 15 application deadline. The $1.5 million will be distributed among four grant recipients.
The agency first announced its intent to launch the funding opportunity in November.
“The mechanisms and processes underlying potential contribution of minor cannabinoids and terpenes to pain relief and functional restoration in patients with different pain conditions may be very broad,” NCCIH said. “This initiative encourages interdisciplinary collaborations by experts from multiple fields–pharmacologists, chemists, physicists, physiologists, neuroscientists, psychologists, endocrinologists, immunologists, geneticists, behavioral scientists, clinicians, and others in relevant fields of inquiry.”
The research opportunity is one of several marijuana-related projects the federal government has recently promoted. For example, NCCIH has four other grants available to researchers to study “natural products” such as cannabis, the National Institute on Drug Abuse is calling for bulk marijuana cultivators to supply research-grade cannabis and the Agency for Healthcare Research and Quality has asked the public to send them information about marijuana and Alzheimer’s disease.
Photo courtesy of Brian Shamblen.
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