Why 2021 Willl Be The Year For Marijuana Legalization The Fresh Toast
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A new study offers more data on the role cannabinoids play in the brain’s ability to extinguish traumatic memories. (AdobeStock)
The ability to forget fear is vital in allowing us to live normal lives. If we remembered every ounce of fear we’d ever felt, we wouldn’t be able to function. One of the hallmarks of post-traumatic stress disorder (PTSD) is impaired fear extinction—the process that helps our brains forget traumatic events.
A new study out of Leiden University in the Netherlands explores anandamide, a cannabinoid produced naturally by the human body, and its role in fear extinction. They did so by pioneering a technique that inhibits anandamide production in the brain.
The study could have profound implications for the use of cannabis in treating PTSD. Millions of military veterans and other trauma survivors already use medical cannabis to manage PTSD, but scientists are still exploring the mechanisms involved in the healing process.
At a basic level the endocannabinoid system is how THC gets you high. The intoxicating compound found in cannabis causes its iconic effects by binding to the cannabinoid receptor type 1 (CB1). THC’s more subtle effects, like immune modulation, are caused by its interaction with cannabinoid receptor type 2 (CB2).
The identification of CB1 and CB2 receptors in the early 1990s led to the discovery of compounds in our bodies that stimulate them naturally. These compounds are known as endocannabinoids—cannabinoids produced by our bodies. Over a dozen endocannabinoids have been identified. The two most commonly studied are anandamide (AEA) and 2-AG.
If you’ve ever worked out so hard that you feel totally blissed out for a few minutes, you’ve felt anandamide at work. That feeling is the reason anandamide was named after the Sanskrit word for ‘bliss.’ This light euphoria, sometimes called the runner’s high, lasts just a short period of time because anandamide is co-released with fatty acid amide hydrolase (FAAH), an enzyme that breaks down anandamide.
Think of the anandamide-FAAH relationship like the elements in a game of Hungry Hungry Hippos. If there aren’t that many FAAH hippos munching, the bliss-causing marbles of anandamide remain on the table a lot longer.
There’s a significant body of work that shows reducing FAAH expression makes all sorts of feel-good effects last longer. Anandamide makes us feel good by triggering the reward center of our brains, and the longer it sticks around, the longer we feel good.
The team at Leiden University, led by Mario van der Stelt, wondered what would happen if they did the opposite—if they reduced the amount of anandamide produced by the brain instead of reducing FAAH. Finding a specific tool to reduce anandamide production would paint a more detailed picture of what role it plays in our bodies. So that’s exactly what they did.
Van der Stelt’s team identified a chemical that reduces the production of anandamide by inhibiting the production of one of the enzymes that triggers its production. It didn’t block production completely, because the body produces anandamide in a number of ways. But by partially blocking anandamide production, they could test what role the endocannabinoid plays.
The researchers then compared behavior in normal mice and anandamide-suppressed mice. Mice with blocked anandamide production were way more stressed out—as evidenced by higher cortisol levels—than normal mice. The anandamide-suppressed mice also held onto conditioned fear for much longer than normal mice. The compound van der Stelt’s team developed isn’t targeted specifically at anandamide–it suppresses other endocannabinoids (OEA and PEA) as well. This means that their behavioral observations could be due to changes in any one of those closely related compounds, though anandamide seems the most likely culprit.
This is a highly technical discovery, but an important one. It’s the first study of its kind to prove that lowering anandamide levels has negative consequences on emotional behavior. This could explain why PTSD develops—those brains don’t produce enough anandamide to remain emotionally balanced. It could also explain why flashbacks feel so visceral to people with PTSD, they literally lack the mechanism to forget those traumatic memories.
Understanding anandamide’s role gives us more insight into why cannabis, with its ability to mimic the effects of anandamide, could help PTSD patients.
San Francisco Govt Gives Cannabis in A Harm Reduction Effort Plants Before Pills
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With the extract market burgeoning, there’s an increased focus on how those products are produced. Solvent extraction methods have advanced quickly over the past few years, with popular solvents including ethanol, CO2, and hydrocarbons—organic compounds containing only hydrogen and carbon atoms—which in cannabis are usually butane and propane. If you’ve used vape oil, edibles, or any number of products that incorporate extracts, you could well have been sampling the fruit of hydrocarbon extraction.
While they don’t sound like compounds you want to be ingesting, hydrocarbons have been used in food extraction for over five decades, for example, in the production of flavors and colorings. More recently, compounds like butane and propane are used to produce cannabis extracts with specific profiles. The purity and potency of hydrocarbon extracts vary greatly, but you can find THC-rich extracts that contain up to 90% of the plant’s original cannabinoids.
If carried out correctly, hydrocarbon extracts can be safe, both in terms of minimizing production risks and creating a product fit for consumption. Here we’ll talk about the details of hydrocarbon extraction processes, including their benefits and drawbacks, and we’ll also discuss which products are manufactured in this manner.
Hydrocarbon extracts can come in a variety of forms, including oil, glass, shatter, wax, and hash. These extracts are sometimes synonymous with Butane Hash Oil (BHO), which is often heated and inhaled in a process known as dabbing. That said, hydrocarbon extracts can be used in many other types of products, including edibles, vape cartridges, capsules, and topicals (including transdermal patches).
For extracts to be of high quality, you still need to start with a quality product. For example, nug runs—concentrates that use cannabis flower—are considered of higher quality than trim runs. Plus, the extraction process used, including any refinement steps, will determine the profile and quality of the final product.
Hydrocarbon extraction usually involves butane as the primary solvent, although other hydrocarbons or a blend of two or more may be used. When combined with cannabis plant material, the hydrocarbon dissolves desirable compounds present in the plants.
Butane is an ideal solvent for cannabis extraction—it has a low boiling point of 30.2°F (-1°C) and is used in extraction as a liquified gas. This allows you to avoid exposing temperature-sensitive terpenes and other delicate components to heat.
The boiling point of propane is even lower than that of butane at -43.6°F (-42°C). It’s common to see a blend of both used. Propane may provide benefits by stripping additional desirable compounds, such as terpenes, from the plant. It also allows for a more effective purging of leftover solvent.
Here are the general steps for hydrocarbon extraction:
- Cold, liquified butane (or hydrocarbon blend) is used to wash the plant matter, dissolving cannabinoids (such as THC and CBD) and terpenes (which provide aroma and flavor), often along with lipids and waxes.
- The resulting solution may then be refined using a number of methods, depending on the final product. For example, centrifugation can be used to remove terpenes and winterization can remove lipids from the concentrate. Dewaxing and decarboxylation are other common refinement steps.
- After refinement, the resulting solution is passed through a collection chamber to remove the majority of the residual solvent. The butane is often transported back to the start of the process to be reused.
Finally, the concentrated solution is further purged to get rid of any excess hydrocarbons. The process will depend on the final product but may involve drying in a vacuum oven or whipping.
While hydrocarbon extractions can technically be carried out anywhere, the dangers of dealing with butane gas can often produce disastrous results. Producers of legal extracts work in compliant environments and use equipment specially designed for this application. Do not try this at home.
Hydrocarbon extraction isn’t the only technique out there, and other extraction processes may be preferable depending on the desired outcome. Here are the main pros and cons of hydrocarbon extraction:
You can maintain the authenticity of the strain. Each strain has a unique chemical profile which other extraction methods can render unrecognizable. Hydrocarbon extraction can maintain the delicate makeup of the plant so that the original combination of cannabinoids and terpenes remains in the final product.
It offers versatility. There is a range of extract types that can be produced using hydrocarbon extraction because the levels of butane and propane can be tweaked to create the desired profile. Depending on the strain and how involved the production method is, you’ll find products at a broad range of price points.
You can use up trim. Due to the nature of hydrocarbon extraction, you can make use of the less desirable parts of the plant. For example, trim from cannabis harvests might otherwise be discarded as waste. However, these loose leaves still bear lots of resin that is rich in cannabinoids. These and other components can be extracted using hydrocarbon extraction, producing products known as trim runs.
Extractions can pose risks. If not carried out properly, hydrocarbon extraction methods can be very dangerous. Butane and propane are highly flammable so the equipment and environment must meet strict standards before being considered safe.
It’s possible to produce hazardous products. Similarly, if hydrocarbon extraction is not conducted properly, the consumer could be at risk. For example, some amateur products will use low-quality solvents that contain unknown contaminants. They might also fail to purge the final product of solvents at the end of the extraction, and sell items with residual solvent levels far above what is considered safe. This is one of the reasons it’s important to only purchase lab-tested products, so you know exactly what you’re getting.
We are currently living through anxiety provoking times. The coronavirus is the perfect recipe to turn even the most laid back and centred among us into worrying wrecks, imagining the most catastrophic (although unlikely) outcomes for ourselves and our loved ones.
And that, dear friends, is the day-to-day life of someone living with anxiety. I know because for the last fifteen years it’s an inner world I’ve inhabited. Only for me, it’s not a pandemic I’m freaking out about, but lesser evils such as whether I’m going to make a complete idiot of myself in some social gathering or my own favorite anxiety rabbit hole – feeling anxious about feeling anxious.
While there’s no magic bullet to banish anxiety for good, managing anxiety symptoms is a commonly stated reason why people take cannabis – medical or otherwise – with CBD showing particular promise in preliminary studies.
Anxiety disorders are a collection of mental health conditions characterized by disproportionate worrying about future events that brings about physiological responses in the body such as tightness in the chest, shortness of breath, muscle tension, sleep disturbance, excessive sweating, agitation, restlessness, irritability, and difficulty concentrating.
Avoidance behavior are common strategies amongst anxiety sufferers. If you’ve had a panic attack crossing a bridge, there’s a fair chance you’ll never make it to the other side of that river again. And for the socially anxious amongst us, myself included, not turning up to that party or after work drinks or a friend’s wedding are tactics regularly employed.
However, the more situations we avoid, the smaller our worlds eventually become, and it’s often at this point when an anxiety disorder is diagnosed. Right now, it’s estimated 264 million1 people worldwide have some kind of anxiety disorder, with approximately 40 million2 of them residing in the United States.
Anxiety disorders include generalized anxiety disorder (GAD) when anxiety is felt about a wide range of situations or issues; social anxiety disorder (SAD) – the fear of being negatively judged or rejected in social situations; panic disorder – sudden feelings of terror resulting in panic attacks; obsessive compulsive disorder (OCD) – unwelcomed repetitive thoughts and behaviour; phobias – an extreme fear triggered by a situation or object; and post-traumatic stress disorder (PTSD) – anxiety including flashbacks that develop after some kind of traumatic event.
Due to their complex and often individualized nature, there’s no one-size-fits-all approach to treating anxiety disorders. Talking therapies, such as cognitive behavioural therapy (CBT), are often combined with anti-anxiety drugs like SSRI antidepressants or benzodiazepines for a more immediate calming effect. Also known as tranquilizers, benzodiazepines include the likes of Xanax and Valium, and while they may lull patients into a state of anxiety-free calm, taken long term they can result in addiction.
It’s clear, therefore, that a new class of anti-anxiety medication, without risk of abuse or dependence and free from side effects, must be developed. And the big ‘green’ hope is that the cannabis plant might hold the key.
Stress, Anxiety & the Endocannabinoid System
Coping with stress or unwinding from a hectic day, is one of the major reasons millions of people consume cannabis. While your average recreational user isn’t interested in the biological mechanisms behind why they feel more relaxed after smoking a joint, the reason is almost certainly due to the direct activation of their endocannabinoid system (ECS).
The ECS comprises fatty ligands called endocannabinoids which bind to a vast network of cannabinoid receptor sites (CB1 and CB2) throughout the brain, central nervous system, immune system, and organs. Dynamic in nature, it is constantly working to ensure all our physiological systems remain in balance.
Life is filled with external stressors – pollution, poor sleep, that argument with your boss, the 24/7 news reports about the millions of people dying worldwide from the coronavirus. Thankfully the ECS works as a buffer to ensure our organisms don’t develop some kind of illness as a result. It also plays a crucial role in regulating fear, anxiety and how we cope with stress.3
Activating CB1 receptors in the brain and central nervous system has been found to calm feelings of anxiety, which explains why consuming cannabis tends to chill people out.4 However, it’s not a case of the more you smoke, the less anxious you feel as higher doses of THC, the main psychoactive compound in cannabis, can actually be anxiety inducing.5
Enhanced signaling between CB1 receptors and the endocannabinoid anandamide in the amygdala, an area of the brain key to processing fear, has been shown to help mice forget frightening experiences.6 That’s something of clinical interest for the treatment of anxiety disorders where frightening events of the past become indelibly marked in a patient’s memory, fueling future feelings of anxiety.
However, chronic stress itself can eventually impair our endocannabinoid system. Prolonged exposure to stress downregulates CB1 receptor signaling in brain regions involved in emotional processing.4 Chronic stress also increases levels of fatty acid amide hydrolase (FAAH), the enzyme that breaks anandamide down in the body, resulting in lower concentrations of the feel-good endocannabinoid.7
With weakened endocannabinoid signaling, we are more vulnerable to developing anxiety and depression. Indeed, one study showed a clear inverse relationship between anandamide levels and anxiety severity in women with major depression;8So in basic terms, the more anandamide deficient we are, the more anxious we may become.
Thus, boosting CB1 signaling could be a potential therapeutic target for both protecting against and treating anxiety disorders – a theory explored in a preclinical study on mice with low anandamide levels caused by stress-induced anxiety. Researchers observed how inhibiting FAAH reversed the animals’ anandamide deficiency, which in turn reduced their anxious behaviour.9
CBD: A Multi-Targeted Approach to Anxiety
While drug companies around the world are experimenting with synthetic FAAH inhibitors,10 hoping they’ll become the next big thing in anti-anxiety medication, cannabidiol (CBD), the non-intoxicating compound found in cannabis, has been shown to inhibit anandamide reuptake and delay its metabolism by FAAH.11 Several studies confirm that administering CBD enhances CB1 signaling, in turn promoting the creation of new neurons in the hippocampus,12 which scientists believe further contributes towards the compound’s anxiolytic effect.
However, CBD’s anti-anxiety action extends beyond increasing endocannabinoid signaling. Animal studies show how CBD interacts with serotonin 5-HT1A receptors in the brain, which are tried and tested targets for anti-anxiety medication.
In one study, administering CBD to rats submitted to 60 minutes of enforced restraint not only lowered their heart rate and mean arterial pressure, but also reduced anxiety levels. However, these results were not replicated when the rats were given a 5-HT1A antagonist, which blocked CBD from interacting with the serotonin receptors,13 What remains unclear is whether CBD elicits this effect by directly binding with 5-HT1A14 receptors or by indirectly facilitating 5-HT1A serotonin signaling.15
Neuroimaging in healthy subjects given 400mg of a CBD isolate suggested that the relaxation they reportedly experienced may have been caused by activity in the limbic and paralimbic brain system, areas of the brain associated with emotional processing, memory, and cognitive processes.16
CBD & Anxiety: Outside the Lab
While more still remains to be discovered about the mechanisms behind CBD’s anxiolytic effect, in certain US states and countries where medicinal use of cannabis is legal, doctors are treating their patients with CBD-rich cannabis strains for anxiety disorders. For the rest of us still condemned to the dark ages of prohibition, CBD oil derived from hemp has been our anti-anxiety salvation.
Consider the case of Emily Wilson, a 30-year-old British aid worker living in Greece. For the last three years, Emily has been education coordinator at a refugee camp on the outskirts of Athens, where 2800 displaced persons from countries like Syria, Afghanistan, Iraq, and Iran live side by side in converted shipping containers, many still suffering from severe trauma.
With limited resources, Emily was often left feeling stressed and frustrated by the limitations of the work she could do. After two years working at the refugee camp, her naturally buoyant and positive nature was no longer a protection against the physical and mental strain she endured on a daily basis.
“I remember a few times,” Emily recounted, “where I’d just be walking and I’d start to think about work and my chest would tighten and I’d have to start taking deep breaths because my chest was tightening so much and my eyes were watering like I was crying. But it was tears of frustration and tears of panic. This happened about once or twice a week for about three or four weeks until I realized there was something really wrong. It was so crippling that I didn’t go to work because I couldn’t get out of bed.”
Emily started taking full spectrum CBD oil, and after gradually building up the dose from one drop to three drops, three times a day, she started to feel her anxiety levels subside.
“I think the major benefit of it for me,” says Emily, “was it prevented the anxiety from becoming all encompassing. It didn’t take away the problems, but meant that they were there, I acknowledged them, I knew that I had to work through them, but they weren’t in my chest, they weren’t in my throat, and weren’t stopping me doing things. So there was a distance from them. I also felt a deep sense of calm and a deep sense of, OK, well, everything can be solved.”
Evidence With Limitations
Thousands of glowing anecdotal accounts are one thing, but without some randomised clinical trials, mainstream medical institutions will never take CBD seriously as an anti-anxiety treatment. Unfortunately, as with most areas of cannabinoid research, clinical research into CBD for anxiety still falls rather short.
Because anxiety is such a broad term, most research conducted so far has concentrated on just one type of anxiety disorder, namely social anxiety disorder. A well-established protocol for measuring the effectiveness of an anti-anxiety drug is its administration to socially anxious individuals before they take part in a public speaking test.
In one study, healthy and socially anxious subjects were both asked to perform a simulated public speaking test.17 Those with social anxiety disorder were either given a one-off dose of 600mg pure CBD or a placebo. The healthy subjects performed the test without any medication.
This hefty dose of CBD allowed the socially anxious participants to perform the task with “significantly reduced anxiety, cognitive impairment and discomfort in their speech performance,” as well as reducing their stress levels prior to the test. In comparison, the placebo group fared less well experiencing high levels of anxiety. No difference in anxiety or performance was noted between the CBD group and the healthy subjects, suggesting a one-off, high dose of CBD before public speaking may allow the socially anxious to perform just as well as someone without social anxiety disorder.
However, giving a single 600mg dose of purified CBD does not reflect the clinical experiences of doctors recommending medical cannabis to patients with anxiety or that of the millions of people around the world taking hemp-based CBD oil for anxiety-related conditions.
Purified Versus Whole Plant CBD
With a race on to find a new anti-anxiety drug potentially worth billions of dollars,18 there’s little financial gain to be enjoyed from developing medication based on whole plant cannabis. But purified CBD, while potentially more lucrative and easier to study in clinical trials, has its own therapeutic drawbacks that aren’t present in full spectrum CBD-rich cannabis extracts.
Anyone who’s tried a CBD isolate will vouch for the fact that a high dose is generally needed to get any therapeutic effect. This common experience was confirmed in a meta-analysis comparing CBD-rich products with purified CBD in patients with epilepsy.19 The study found much lower doses of CBD-rich cannabis were taken by patients to successfully control their seizures compared to the high amounts of purified CBD used in Epidiolex clinical trials.
Not only that, animal studies demonstrate how purified CBD has a ‘bell shaped dose-response’,20 whereby it only shows significant therapeutic benefit at a substantial dose, with little efficacy at lower or higher doses.
This inverted bell shaped dose-response was confirmed in the context of social anxiety when healthy volunteers undertaking a simulated public speaking test only experienced a reduction in anxiety when given 300mg of CBD, but no change with either 150mg or 600mg, suggesting a narrower therapeutic window compared to CBD-rich cannabis.21
Until recently, there’s been little evidence from human studies about the anti-anxiety effects of taking CBD over a prolonged period of time. However, just last year, a randomised placebo study was published in which Japanese teenagers with social anxiety and avoidant personality disorder were given 300mg of pure CBD or a placebo daily over four weeks.22 Not only did CBD significantly decrease their anxiety, but half of the participants given CBD expressed a wish to seek therapy or further treatment at the end of the study, while none of the placebo group mentioned such a desire.
In an open label retrospective study also published in 2019, 72 psychiatric patients with anxiety or sleep disorders were given between 25-175mg of CBD a day, alongside existing psychiatric medications.23 After two months of treatment, 78.1% of patients reported feeling less anxious and 56.1% experienced improved sleep.
A Clinician’s Experience
These encouraging results validate the experiences of clinicians who regularly prescribe medical cannabis to patients with anxiety. “For me, it’s a really good choice for treating anxiety in people,” says Dr. Rebecca Moore, a UK-based consultant psychiatrist who sees patients at The Medical Cannabis Clinics in London.
“I’ve seen some amazingly wonderful results. People who’ve had lifelong anxiety, who are doing all the right things in terms of their diet, their exercise, their supplements, but still have a fairly crippling anxiety, and within a couple of months they don’t have any anxiety at all and can’t quite believe what’s happened to themselves.
“One lady told me that she had been able to pick up a book and read for the first time in 20 years, focus and enjoy it. And another said she was planning her first holiday in 10 years. You know, it’s just life-changing differences for people.”
Dr. Moore has found medical cannabis – in particular CBD-rich oil, but also including small amounts of THC – to benefit patients with all types of anxiety disorders. In general, patients need far smaller doses than used in published preliminary studies, with some benefitting from as little as 30mg of CBD a day.
Patients usually arrive at Dr. Moore’s clinic because they find the anti-anxiety drugs they have been prescribed over the years don’t work well, and they struggle with the harsh side effects. “I’ve had people come in,” says Dr Moore, “on four or five different medications, who have managed to stop them all and just be on CBD. People who were on two antidepressants, plus a benzodiazepine, plus a sleeping tablet at night, plus an anti-hypertensive, and they stopped all of them.”
It’s in her treatment of PTSD using cannabinoids where Dr. Moore has seen some of the most fascinating changes in patients: “I think particularly with trauma memories, it’s so interesting the way it seems to impact on people’s recollection of their memory. People talk about feeling like their trauma memories are being deleted. And then I’ve had lots of people say they actually then start to remember positive memories, which they weren’t able to access before.”
Right now, a number of clinical trials to study the effectiveness of CBD for anxiety are in the process of recruiting, including one using 25mg of full spectrum CBD soft gel capsules over a period of twelve weeks;24 and a phase II clinical trial evaluating the efficacy of CBD for social anxiety, which will also measure changes in endocannabinoid levels.25 And a Harvard Medical School research project will compare whole-plant and single-extract CBD solutions for anxiety.
Unfortunately, though, with clinical research moving at a slow pace, we’re a long way from official approval of CBD as an anti-anxiety medicine.
In the meantime, in a bid to minimise any damage to our endocannabinoid system caused by current coronavirus stress which may make us more vulnerable to anxiety disorders now and in the future, we could do a lot worse than incorporating high quality, CBD-rich cannabis or a CBD oil into our self-care routine.
Mary Biles, a Project CBD contributing writer, is a journalist, blogger and educator with a background in holistic health. Based between the UK and Spain, she is committed to accurately reporting advances in medical cannabis research.
Copyright, Project CBD. May not be reprinted without permission.