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Cannabis

Up Close and Personal with the Science Behind Cannabinoids

Get to know the three different classes of cannabinoids: phytocannabinoids, endocannabinoids, and synthetic cannabinoids.

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Cannabinoids
PHOTO | Adobe Stock

The cannabis plant produces literally hundreds of specialized molecules — cannabinoids, terpenes, and flavonoids — that have been shown to deliver medicinal efficacy, lifestyle enhancement, and even performance enhancement to human beings. For those afflicted with disease, medical cannabis has been found to offer a wide range of health benefits, from killing cancerous tumors to alleviating the pain of arthritis to reducing the number of seizures experienced by epileptic children.

Of these molecules, cannabinoids are the most cited and understood. The most infamous cannabinoid is tetrahydrocannabinol (THC), the molecule responsible for most of the psychoactive (psychotropic) and euphoric effects of cannabis, but that also has been found to successfully treat serious conditions, such as PTSD and cancer. Another notable cannabinoid is cannabidiol (CBD), a mostly non-psychoactive chemical that has been found to provide a wide range of medicinal benefits, including reductions in pain, anxiety, and depression.

Endocannabinoids vs. Phytocannabinoids

First discovered in 1964 by Israeli researcher Raphael Mechoulam, phytocannabinoids from the cannabis plant interact with the human body by mimicking the molecular characteristics of chemicals produced internally. Called endocannabinoids, these internally manufactured molecules include anandamide and 2-AG.

Anandamide has been dubbed the “bliss molecule” because of its ability to decrease depression in humans. It plays a central role in the regulation and modulation of critical bodily functions such as mood, appetite, sleep, immune system efficiency, and one’s ability to deal with stress and anxiety.

Synthetic Cannabinoids

Synthetic cannabinoids emerged in the 1970s and are created in a laboratory. An example of it would be dronabinol (Δ9-THC synthetic), which is the active compound of Marinol, a medicine that comes in capsules and has been consumed in the US since 1985 to prevent nausea, vomiting, loss of appetite and loss of weight.

The Endocannabinoid System

All mammals, not merely humans, have evolved with a network of specialized cellular receptors throughout their bodies that are designed to bind with cannabinoids — both endocannabinoids such as anandamide and phytocannabinoids from cannabis — that is called the endocannabinoid system (ECS).

The fact that the ECS is present in all mammals is why companies and product lines dedicated to the health and wellness of household pets are beginning to emerge in legal cannabis markets. Dogs and cats suffering conditions such as arthritis, digestive issues, anxiety, and pain can gain significant benefit from the cannabinoids in cannabis and hemp.

Anandamide production has been found to increase and temporarily spike in those who engage in endurance exercise on a regular basis. However, it metabolizes quickly, exhibiting a relatively short duration of effect. Anandamide hints at the chemical underpinnings of the significant health benefits of frequent and intense exercise—and the fact that the mere consumption of cannabinoids is not enough to establish and sustain optimal health of the ECS (a condition called homeostasis that means “balance”).

Both internally produced endocannabinoids and plant-based phytocannabinoids interface with the ECS via specialized cellular receptors that were discovered in the 1990s and called CB1 and CB2. CB1 receptors are found mostly in the brain and central nervous system, whereas CB2 receptors are located primarily in the organs and tissues of the immune system—including the thymus, skin, bone marrow, lymph nodes, spleen, bowel, and the mucous membranes of the bladder, genitals, nose, and throat.

Major Cannabinoids + Acidic Precursors

More than 113 cannabinoids have been isolated and identified within the cannabis plant — which is, technically, also a vegetable. Beyond the two major cannabis-derived molecules, THC and CBD, are a plethora of healthful cannabinoids that deliver a slew of desirable and beneficial efficacies for lifestyle consumers and patients alike. Among these are cannabichromene (CBC), cannabigerol (CBG), cannabinol (CBN), and tetrahydrocannabivarin (THCV).

Additional healthful cannabinoids include tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA). These chemicals represent a class of cannabinoids dubbed acidic precursors. Think of acidic precursors as the larval caterpillar stage of what becomes the butterflies of THC and CBD.

While they provide significant benefits in terms of health and wellness, the exact effects of these molecules differ from their non-acidic versions. For example, while strains of cannabis that are potent in THC can exact a significant toll in terms of psychoactivity and euphoria, THCA delivers no such psychotropic effect. THCA does, however, offer anti-inflammatory and neuroprotective effects, making it helpful for conditions as wide-ranging as Alzheimer’s disease, arthritis, cancer, Crohn’s disease, fibromyalgia, multiple sclerosis, and Parkinson’s.

Understanding Decarboxylation

The process by which the transmogrification from the chemical state of acidic precursor (THCA) to its child molecule (THC) occurs is significant (and can be accurately controlled by anyone). A process called decarboxylation, this conversion involves the application of heat (via flame, as in combustion, or from a hot surface or airstream, as in vaporization) to catalyze a chemical reaction in which the THCA molecule drops a carbon and two oxygen atoms (called a carboxyl ring, or COOH) to become THC — and gain its euphoric effects based on its newfound binding affinity with the CB1 receptors of the ECS.

Technically, maximum decarboxylation for a sample of cannabis flowers occurs most effectively when exposed to 220 degrees F (104 degrees C) for a period of 30 to 45 minutes. Decarboxylation is easy and convenient because it can be accomplished using a standard consumer oven.

Thus, one who eats the raw flowers of cannabis will gain significant medicinal benefits, but no euphoria. The simple application of a flame or hot air, however, leads to the nearly instantaneous transformation of these molecules into their chemical cousins, delivering beneficial — but sometimes very different — effects.

The Research

A 2017 research study entitled “Medicinal Cannabis: History, Pharmacology, and Implications for the Acute Care Setting” that was published in the journal Pharmacy & Therapeutics found the cannabinoids of cannabis, such as THC and CBD, to be effective in the treatment of a wide range of diseases and conditions.

The study’s researchers stated, the “Beneficial cannabinoids exist, as evidenced by single-entity agents derived from cannabis containing the compounds THC and CBD.” The study concluded that “cannabis is relatively safe; therapy is self-titratable by the patient; and…therapy is relatively inexpensive compared with pharmaceutical agents.”

CBC is a powerful cannabinoid first isolated in 1964 by Israeli researcher Raphael Mechoulam. It is considered one of the “big six” cannabinoids that, according to Steep Hill Labs in Berkeley, California, is ten times more effective than CBD in treating anxiety and stress.

In a 2011 study conducted by cannabis research pioneer Ethan Russo entitled “Taming THC: Potential Cannabis Synergy and Phytocannabinoid-terpenoid Entourage Effects” and published in the British Journal of Pharmacology, Russo found that a CBC-extract displayed “pronounced antidepressant effect,” meaning it may be helpful for humans suffering from anxiety and depression.

Additional evidence of the medical benefits of cannabinoids derived from cannabis — this time for an ocular disease — was revealed in a 2008 study entitled “Possibilities of Applying Cannabinoids in the Treatment of Glaucoma” that was published in the journal Klinika Oczna. The study concluded that cannabinoids like CBG are “able to decrease intraocular pressure. These compounds are characterized by neuroprotection and vasodilatation properties that additionally substantiate their therapeutic utility in conservative treatment of glaucoma.”

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Cannabis

There Needs to Be More Research on How Cannabis Affects Dreams

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How Cannabis Affects Dreams
PHOTO | Jesse Barney

Most people forget their dreams shortly after waking. As soon as the eyelids flutter open, an entire evening of vivid adventures and abstract situations shuffle to an end, often leaving only lingering traces of their presence — a fragment of a dress here, the flashing face of a stranger there. While some individuals may be adept at remembering these mysterious nocturnal encounters, for the most part, the dreaming mind remains an enigma.

For those who consume cannabis, the dreaming self may remain even more elusive. The plant, you see, may prevent the sleeping mind from dreaming. Although cannabis has long been used as a meditation aid and sleep-inducer, preliminary research suggests the trance-inducing herb may suppress some forms of sleep consciousness. Of course, however, research on how cannabis affects dreams is far too premature to make any serious assessments.

The Purpose of Dreaming

Dream science over the past several decades provides more and more hints into the true nature of the dreaming mind. While the exact purpose of dreaming is unclear and dreams are particularly difficult to study, it is generally understood that the dreaming mind is also an emotional mind. While logic and rationality dominate during the day, the unique function of the dreaming mind is to help soothe and come to terms with emotional memories.

Most dreaming occurs during rapid eye movement sleep (REM sleep). The REM cycle is the closest sleep state to wakefulness when electrical activity in the brain increases, along with heart rate and breathing. During this time, levels of bodily stress hormones drop to their lowest levels. During the day, the hormone norepinephrine increased in the bloodstream in response to everyday stressors and anxieties. At night, however, norepinephrine levels slowly decrease as the dreaming mind takes over.

Brain scans suggest that the dreaming mind is very similar to the waking mind; visual areas of the brain are highly engaged, as well as areas related to memory and conscious thinking. A primary difference, however, is that the waking mind also responds to stress signals by releasing hormones like norepinephrine for fight-or-flight response. When dreaming, even strong emotions are distanced from this fight-or-flight impulse of the nervous system.

While the content of dreams may be very different than your visual memories from everyday life, it appears that emotional memory processing is a core function of REM sleep. The situations that your dreaming self is exposed to may be abstract or downright weird, but the emotional context of the dream may be what holds real value.

How Cannabis Affects Dreams

If dreams are the brain’s way of de-escalating and filing away emotional memories, then the effects of cannabis on dreams are well worth knowing. Thus far, a multitude of preclinical and small human trials show that cannabis consumption causes a reduction in REM sleep. This reduction is most strongly correlated with THC, although animal research thus far hasn’t determined whether or not the same effect occurs with CBD.

For individuals with recurring nightmares, this could be a positive benefit. Those with post-traumatic stress disorder (PTSD), for example, often demonstrate disturbed REM sleep patterns and may consistently remember their dreams. Healthy sleep is sleep that promotes feelings of restfulness upon waking. If a person plagued by chronic nightmares, it can have a distressing impact on the next wakeful day

In PTSD, patients are unable to delete fear-based experiences from their memories. Already, preclinical research suggests that cannabis medicines may be beneficial for those with the condition, potentially helping patients extinguish fear-based memories during the waking day.

And yet, for the everyday individual, the overall effect of cannabis on dreams remains unknown. Research suggests that the plant does, in fact, reduce dreams and limits the amount of time spent in REM sleep. Given that REM sleep is when the body records and desensitizes emotional memories, it’s possible that reducing time spent in REM may have a negative effect on emotional processing.

The catch? Very little research has been conducted on the aftermath of cannabis consumption on dreaming. Although cannabis is one of the most popular illicit sleep aids in the world, no high-quality or conclusive evidence exists on the impact of cannabis on sleep. Further, the bulk of research on the topic was conducted in the 1970s and 1980s, with isolated cannabis compounds and small participant numbers. As a result, the way in which cannabis affects dreaming and the implications this may have on waking life are simply unknown.

REM Rebound

The human brain does not like to go without enough REM sleep. While quality research on cannabis and dreaming is appallingly absent from the scientific literature, what is known, however, is that dreams come back with a vengeance after a brief period of abstinence from the plant. When regular cannabis consumers abstain from the herb, one of the most common side effects of withdrawal is the resurgence of very vivid and memorable dreams. This phenomenon has a proper name: REM rebound.

During REM rebound, a person is able to reach a state of REM sleep more quickly. They’re also more likely to remain in REM sleep for an extended amount of time. This dreaming rebound most often occurs after a person experiences sleep deprivation. The brain, it would seem, opens the floodgates of emotion once you’ve finally safe to hit the hay.

In terms of REM sleep, does cannabis produce similar effects to sleep deprivation? Without more research on how cannabis affects dreams, it’s hard to say.

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Wizard Stones: The Magic of Making Cannabis Diamonds

Aaron Palmer and Graham Jennings, founders of Oleum Extracts in Washington State, talk about Wizard Stones, their THCA isolate product.

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Wizard Stones
PHOTO | Oleum Extracts

Heat, pressure, and time. The three components required to form a diamond from carbon. But what about diamonds made from cannabis? The founders of Oleum Extracts, Aaron Palmer and Graham Jennings both agree that a good diamond product ultimately comes down to the flavor provided by its terpene fraction.

Diamonds is a slang term for the crystal formations of the cannabinoid THCA. The molecule’s lattice structure builds upon itself naturally as individual molecules clump together creating the faceted formations that resemble diamond or quartz.

When most people talk about cannabis diamonds, they’re talking about THCA structures that form in their own terpene sauce. So, it’s a little different technique than other isolation methods.

Oleum —While their chemical composition is the same, the process to make them is slightly different than the traditional diamonds mined from a raw extract. Instead, they use a specially formulated solvent mix to create a solution with a composition that encourages crystallization.

Due to Washington state’s regulations, Oleum is limited in the chemical solvents they can use. So that blend is the crucial variable to isolating THCA into their Wizard Stones product.

Growing cannabis diamonds within their original terpene fraction comes down to creating an environment with the right amounts of pressure and heat to encourage crystal growth.

Within the raw extract, the terpene and cannabinoid compounds are homogenized together, but as they settle and separate the mixture “crashes” — which is the start of crystallization.

Palmer explains that it “helps to create a seed because if there’s nothing for the THCA molecules to grab onto then they have a harder time starting the diamond formation.”

There are a few ways extractors seed a solution to start diamond growth, but Oleum prefers to use freezing temperatures to solidify and then thaw their extract, helping to create small groupings of THCA for other molecules to stack off.

Another common seeding technique is to drop a previously grown crystal into the extracted mixture of cannabis compounds, giving the THCA something to grow off of.

This technique is especially useful when filming a time-lapse of the crystal growth because it gives the camera a focal point knowing where the formation will grow from.

Creating Wizard Stones

The above timelapse video wasphotographed over a four day period by Dankshire. We can see diamonds begin to form almost immediately. However, the crystallization process can take a month if not longer to complete once a raw extract is jarred and waiting to crash.

Oleum utilizes custom-built isolation vessels for their production diamond runs but admits that the jar tech allows more visibility into the process.

Jennings points out, “You see the jars, we even do the jar stuff a lot. It’s more popular… and people know what it is compared to a large isolation vessel that no one can see into it but you know it’s growing 2,000 grams of crystals.”

Each batch can present a different ratio of diamonds to sauce and it seems like everyone wants a little different combination. “We just give ‘em what it makes,” Jennings said.

That’s the beauty of isolated products like cannabis diamonds and sauce; you can mix your own cocktail of cannabis compounds and really dial in the flavors and feelings that you’re after.

Cannabis diamonds grown in their own sauce create a potent, refined, and pronounce expression of the strain they are extracted from.

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Terpinolene: The Powerful Medicinal Terpene with Anti-Cancer Promise

Terpinolene (sometimes denoted as “TPO”) is considered a minor, or secondary, terpene and features an aroma resembling sweet pine.

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Terpinolene
PHOTO | Pexels

Few cannabis consumers are fully aware of the complex molecular chemistry of the herb they vaporize, smoke, or eat. Terpenes like terpinolene are the aromatic molecules responsible for the sometimes revealingly pungent aroma of many strains of cannabis. Although the chief purpose of this family of chemicals is an evolutionary defense mechanism against pests and predators, terpenes have been found to deliver medicinal efficacy that equals that of cannabinoids such as CBD and THC.

More than 20,000 terpenes exist throughout nature, about 200 of which have been identified in various strains of cannabis. Terpinolene (sometimes denoted as “TPO”) is considered a minor, or secondary, terpene and features an aroma resembling sweet pine.  It delivers a taste reminiscent of citrus and is produced in many plants in nature other than cannabis, including allspice, cumin, junipers, parsnip, rosemary, sage, and tea tree.

The Details of Terpinolene

In terms of medicinal efficacy, terpinolene kills cancer cells and acts as a sedative. In addition, it displays antibacterial properties and is both an anti-fungal and an anti-oxidant. It is employed as a flavoring agent by various segments of the food industry. It is also used to manufacture plastics and resins and is an effective repellent against pests such as mosquitoes and weevils.

A 2013 study found this special molecule to be a powerful anti-cancer agent. Concluded the study’s researchers, “Our findings clearly demonstrate that terpinolene is a potent antiproliferative agent for brain tumour cells and may have potential as an anticancer agent, which needs to be further studied.”

The Research

A 2013 study entitled “Anticancer and Antioxidant Properties of Terpinolene” that was published in the journal Arh Hig Rada Toksikol found terpinolene to be a “potent antiproliferative agent for brain tumour cells” and surmised that this powerfully medicinal terpene “may have potential as an anticancer agent,” an issue in obvious need of further research due to the 91 million people worldwide who suffer more than 100 types of cancers.

The researchers concluded, “Our findings clearly demonstrate that terpinolene is a potent antiproliferative agent for brain tumor cells and may have potential as an anticancer agent, which needs to be further studied.”

A 2012 study entitled “Terpinolene, a Component of Herbal Sage, Downregulates AKT1 Expression in K562 Cells” and published in the journal Oncology Letters found the terpene terpinolene to be an effective agent in the battle against a variety of cancers.

Concluded the study’s researchers, “Increased expression and/or activation of AKT is involved in a variety of human cancers. In cells treated with sage or rosemary extract, mRNA and protein expression levels of AKT1 were reduced compared with those of the control cells 48 hours after the herbal treatments. We found that terpinolene, a common component of sage and rosemary, markedly reduced the protein expression of AKT1 in K562 cells and inhibited cell proliferation.”

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