Category: Education

As more states move to legalize cannabis, increasingly more people are warming up to cannabinoid-based therapies. At the same time, Δ9-tetrahydrocannabinol (THC) is gaining considerable interest in mental health. This is causing mixed reactions, with some questioning the long-term effects of cannabis use.

Dopamine is a neurotransmitter that mediates the feeling of pleasure, motivation, and satisfaction in the brain. The release of dopamine motivates one to pursue a pleasurable activity or occupation. A dopamine surge is what makes you feel good after achieving something significant. The right balance of dopamine is vital for both physical and mental wellbeing.

THC is a major cannabinoid of the cannabis plant with clear intoxicating effects. It binds to the CB1 receptor in the brain to elicit its psychoactive properties.

Anandamide, also known as the bliss molecule, is an endogenous cannabinoid that also binds the CB1 receptor. It is not surprising that both anandamide and THC are associated with a feeling of happiness and satisfaction. However, anandamide, unlike THC, is quickly broken down by enzymes and taken out of circulation. 

What’s the Link Between Cannabis and Dopamine?

The endocannabinoid system modulates the dopaminergic system through CB1 receptors and endocannabinoids. 

Endocannabinoids stimulate the release of dopamine. Certain CB1 antagonists can block this effect, demonstrating that CB1 receptors are involved in the dopaminergic effects of cannabinoids.

The link between cannabis and dopamine has to be the CB1 receptors (part of the endocannabinoid system). 

There is evidence of varying effects of acute vs. chronic THC exposure on the dopaminergic system.

Acute Vs. Long-term Cannabis Use

Animal studies have described the interactions that exist between amphetamine (promote dopamine release) and THC. These preliminary studies have demonstrated that the dose of THC consumed potentiates or antagonizes the effects of amphetamines. The researchers in this study proposed that dopamine is “a prime candidate for…the mode of action of Δ9-tetrahydrocannabinol”. 

Acute versus longer-term use of THC could have complex effects on dopamine synthesis and release.  While early studies with rodents show that low doses of THC increased dopamine synthesis and release, some studies show high doses of THC resulting in decreased dopamine synthesis. 

The results from human studies have not been consistent, however there is evidence that there may be reduced dopaminergic function among cannabis users. 

Indeed, THC has profound effects on the dopamine system, contributing to its recreational and harmful effects. Unfortunately, there are no randomized human trials that have been carried out to investigate this phenomenon. Additionally, inconsistencies between preclinical and clinical findings pose a significant challenge. One major inconsistency between animal and human studies is that THC, even in acute studies, was not administered to humans in the habitual manner in which it was typically consumed. 

The Crux of the Matter

THC’s rewarding properties are triggered by the firing of dopaminergic neurons and the release of dopamine in lower doses. Interactions with the CB1 receptors underpin this process.

Evidence suggests that acute vs. chronic THC exposure to the dopaminergic system will produce different effects; that is the crux of the matter.

Acute exposure to THC may cause increased dopamine release, which is associated with a feeling of pleasure.

On the other hand, chronic or long-term exposure to THC has been linked to blunting of the dopamine system. 

While acute exposure to THC may increase a sense of reward and satisfaction, long-term exposure may produce opposite effects. However, the premise of this argument is based on inconclusive, preliminary evidence. Future studies will shed more light on how cannabis affects dopamine over time.

Over 120 compounds have been isolated from Cannabis Sativa. Of these, the most studied are cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC); however research is expanding to discover the actions of additional cannabinoids such as cannabigerol (CBG).

CBG was first discovered and synthesized by Raphael Mechoulam and Yehiel Gaoni in 1964. It is derived from cannabigerolic acid (CBGA), which has been coined as the “mother of all cannabinoids” as it is a precursor of major cannabinoids that further decarboxylate to additional cannabinoids. In the cannabis plant, CBGA directly converts to cannabidiolic acid (CBDA), tetrahydrocannabinolic acid (THCA), and cannabichromenic acid (CBCA) through processes known as CBDA synthase, THCA synthase, and CBCA synthase. CBGA will also decarboxylate to CBG once heated, becoming a very stable molecule. 

Evidence from experiments show that CBG is devoid of the non-euphoric abilities of THC and that it has therapeutic potential for specific conditions.

Medical cannabis (THC) or nabilone can be recommended to cancer patients as a means to stimulate their appetite while undergoing conventional treatments. Although effective, there is the potential for undesirable, euphoric side effects. Data has demonstrated in animal tests that CBG significantly increases total food intake in that animals studied began feeding sooner, consumed more meals and consumed more during those meals. 

Animal studies have also shown CBG to reduce the effects of inflammatory bowel disease and the development and growth of colon cancer, hypothesizing that CBG may be a promising therapeutic agent for prevention and as a curative medicine. CBG has shown to increase the rate of tissue recovery in the colon, reduce inflammation, and reduce tumor formation and growth in a model of colorectal cancer. 

Several studies, in vitro and in animal models, have shown CBG to have neuroprotective potential for reducing the severity of neurological illnesses, such as Huntington disease (HD), amyotrophic lateral sclerosis (ALS), Parkinson’s disease, and multiple sclerosis (MS). The anti-inflammatory and antioxidant benefits contribute to reducing glutamate-induced oxidative stress and cell death, as shown in mouse models. 

Metabolic syndrome is considered a cluster of five conditions that may lead to heart disease, diabetes, and stroke. It is diagnosed when someone has three or more of the five conditions, being: high blood glucose, low levels of “good” cholesterol in the blood, high levels of triglycerides in the blood, a large waist circumference, and/or high blood pressure. It contributes to the highest rates of healthcare costs and preventable deaths. CBG has recently been compared to rosiglitazone, a pharmaceutical known to improve adipogenesis, a process essential for maintaining metabolic homeostasis. It was found that CBG and CBG/CBD combinations provided similar results as rosiglitazone, supporting the exploration of CBG as a potential therapeutic for metabolic syndrome and related conditions. 

Many cannabinoids have been confirmed to have antibacterial properties, however, CBG has been noted among the most potent cannabinoids when tested against strains of Staphylococcus aureus (the most dangerous of the staphylococcal bacteria responsible for causing skin infections, pneumonia, heart valve infections, and bone infections). 

Evidence from certain preliminary studies that indicate antidepressant activity show the possibility for CBG to have additional clinical applications for mood disorders, such as depression or anxiety as well as disorders of executive function, such as schizophrenia and ADHD. More studies are necessary to confirm these hypotheses. 

Although there is therapeutic promise for the potentials of CBG, there is much more research to be completed and considered to better understand the complete utility of CBG to include adverse events and how to administer so that therapy is effective. It is noteworthy to mention that there have been no published human studies with CBG to date. Much is left to learn and research recommends that the medical community invest in further CBG research as interest and popularity of the cannabinoid increases. 

◼

Disclaimer

The Realm of Caring Foundation specifically invokes the first amendment rights of freedom of speech and of the press without prejudice. These statements have not been evaluated by the food and drug administration. the products discussed are not intended to diagnose, cure, prevent or treat any disease. Realm of Caring always recommends when and wherever possible that licensed local healthcare professionals be consulted.

The Realm of Caring Foundation is an independent nonprofit with its own governing board. We do not produce or sell cannabinoid products, nor do we receive funds from the sale of other company’s products.

Many clients come to Realm of Caring looking for help in improving their quality of sleep. The great news is that research is continuing to show us that cannabinoid therapy may help. Certain cannabinoids have shown through studies the ability to benefit our sleep-wake cycles, decrease nightmares, lessen the conditions that interfere with our sleep, and assist in actually falling asleep. Depending on what sleep disorder one is suffering with, or what sleep benefit they are looking for, there are 3 main cannabinoids that have been studied for their sleep-enhancing qualities. Those cannabinoids to be discussed here are CBD, THC, and CBN. 

Before we go on, let’s get into some background information and understanding. 

Circadian rhythm is our biological rhythm in a 24-hour period, coming from the latin circa meaning around and dies meaning day. The most commonly known is the sleep-wake cycle, which in chronobiology, is tied to day and night or lightness and darkness. When our circadian rhythms are properly aligned and consistent, we can experience true restorative sleep. 

Insomnia is recognized by the American Psychiatric Association as the most common sleep disorder, involving problems getting to sleep or staying asleep with symptoms being episodic, persistent, and/or recurrent. The many types of insomnia are known to cause daytime tiredness, distress, irritability and/or impairment. 

Our Endocannabinoid System (ECS) is composed of endocannabinoids, as well as two distinct receptors known as CB1 and CB2, and enzymes responsible for the metabolism of endocannabinoids. It has been found that the expression pattern of CB1 and CB2 receptors are influenced by light-dark cycles and therefore appear to align with circadian rhythms. Furthermore, it has been shown in studies with rodents that the ECS may potentially modulate those rhythms to promote sleep. 

CBD Benefits

CBD is not a naturally sedative molecule. Research has shown that high quantities may have “sedative-like qualities”, potentially due to the effect on cortisol levels. So why is it that you might have heard from a friend that CBD helps them sleep?

There are two great reasons for this. 

CBD has therapeutic properties that have the potential to mitigate symptoms that interfere with sleep. It also has the potential to improve sleep-wake cycles leading to an increase in the percentage of total sleep overtime.

Among the several researched properties, CBD may benefit as an anxiolytic, anti-inflammatory, and analgesic. The anxiolytic properties of CBD may help to improve sleep by mitigating anxiety or stress-induced insomnia. Stress induces a sleep-related feature known as rapid eye movement (or REM) sleep rebound, this is an increase in REM sleep during the nightly sleep cycles. People experiencing REM sleep rebound may spend more time in REM than they would during a night of normal, healthy sleep.

Inflammation is a root cause of autoimmune disorders including arthritis, diabetes, irritable bowel syndrome (IBS), crohn’s disease, and others – all which have an effect on body clock function that can lead to sleep disorders. A study by Northwestern found in mice this link between inflammation and what controls the body clock. By limiting this inflammation, we may lessen the effects on our body clock functions and have more restful sleep. 

A study in 2005 showed that people reporting insomnia symptoms are at least 3 times more likely to have a chronic painful physical condition. These events may then become cyclical in that pain may disrupt sleep and sleep deprivation can increase pain perception. In the majority of animal studies, CBD has been known to exert analgesic effects; co-administering with THC may provide more benefit to this therapeutic action. 

Our circadian rhythm aligns our sleep and wakefulness with day and night to provide stability in restorative rest that enables increased daytime activity. Low doses of CBD may be associated with wakefulness to help our focus and cognition during the day. Studies show that therapeutic levels of CBD administration may increase total sleep time and decrease frequency of arousals at night – leading to an increase in total percentage of sleep overtime. 

THC Benefits

In comparison to CBD, THC has shown in studies as having an affect on mental and physical sedation, even in low amounts. THC also has positive therapeutic benefits that may lead to better sleep.

Nightmares are associated with post-traumatic stress disorder (PTSD) often resulting in this being considered a “treatment-resistant” condition. Initial research has shown the benefit cannabinoids can have in managing nightmares linked with PTSD. A study with military veterans and prison inmates receiving Nabilone, a synthetic form of THC, found a reduction in nightmare presence and intensity. This increased participants’ hours of sleep per night. 

Just as mentioned with CBD, THC is also beneficial for mitigating pain-induced insomnia or wakefulness. When it comes to pain studies and medical cannabis with significant THC content, benefits consistently show moderate to high symptom management of chronic pain. 

A normal amount of apneic events in a healthy individual is about 4 per hour while asleep. Sleep apnea is the most prevalent form of sleep-disordered breathing in the United States and a number of animal and human studies have been conducted to examine cannabinoids as potential therapeutic alternatives to continued positive airway pressure (CPAP) machines, which are currently being utilized.

THC shares properties of the endocannabinoid Oleamide, which benefits apneic events. Results in one animal study showed that both the endocannabinoid Oleamide and the exogenous cannabinoid THC reduced apneic events, suggesting therapeutic promise for those who suffer with sleep apnea. 

CBN and sleep

If you are new to CBN, this is a cannabinoid that is created as THC ages. 

It has been observed that there is a correlation between aged cannabis and sleepiness, therefore CBN was previously linked to sedation. However, there may be more to it than the CBN itself. What limited research there is, has shown that CBN alone does not provide sedating effects. However, the combination of THC and CBN has been researched to promote sleepiness. 

What also may be adding to the sleepiness as a result of taking CBN, are the sesquiterpenes that are left behind as cannabis ages. These may be naturally more calming than the monoterpenes that evaporate overtime. Neurologist Ethan Russo explains that in aged cannabis, monoterpenes begin evaporating after the live plant is cut from its growing medium as they are lighter in weight. Pinene is a monoterpene example. Once monoterpenes have evaporated, sesquiterpenes are left behind due to being heavier in weight. These terpenes are naturally more calming, such as nerolidol and caryophyllene oxide. 

As well, just as with CBD and THC, CBN has its own therapeutic benefits. For example, in a rodent study, CBN was shown to reduce arthritis-related inflammation. 

There is a lot to consider when starting cannabinoid therapy but, as always, a Realm of Caring care specialist is here to help with your questions. Contact us today by calling (719) 347-5400 or by emailing info@realmofcaring.org. 

◾

Disclaimer

The Realm of Caring Foundation specifically invokes the first amendment rights of freedom of speech and of the press without prejudice. These statements have not been evaluated by the food and drug administration. the products discussed are not intended to diagnose, cure, prevent or treat any disease. Realm of Caring always recommends when and wherever possible that licensed local healthcare professionals be consulted.

The Realm of Caring Foundation is an independent nonprofit with its own governing board. We do not produce or sell cannabinoid products, nor do we receive funds from the sale of other company’s products.

Update on June 29th, 2021: Our collective efforts to oppose and veto HB21-1317 have failed. Governor Polis signed the bill and now our friends at Cannabis Clinicians Colorado and Buscher Law are suing the State to stop this bill from becoming law. This must happen so that we can prevent HB21-1317 from ending medical cannabis. 

There is still time, but we need your action NOW. 

How?

You can still sign the veto request. 

Buscher Law is writing and filing this lawsuit and your letters are needed on how HB21-1317 will impact your practice or impact your healthcare. Please send your letters to info@realmofcaring.org as quickly as possible, there is no time to waste.

For more information, read the damaging impacts this bill will have below. 

Update on June 8th, 2021: On Friday, May 14th a bipartisan bill was introduced in the Colorado House to more strictly regulate high-potency THC products, imposing barriers to access for medical consumers as well as negatively affecting recreational buyers and cannabis businesses in Colorado. The proposed requirements aim to further regulate the legal purchase and sale of THC products, with damaging language that unfairly targets medical cannabis patients in the state. Members of the Colorado State Senate approved this legislation on June 3rd, 2021. The bill now will return to the House for a concurrence vote before advancing to the desk of Governor Polis. 

As an example to how these requirements would affect one, a medical cannabis patient in Colorado who is 20 years old would need four, in-person doctor visits per year who will need to assess the patient’s mental health history (in addition to physical health) prior to approval. Once this patient is approved for their card, they will only be allowed to purchase 2 grams of a concentrate product per day and their personal information would be tracked to ensure they do not “dispensary hop”. 

House Speaker Alex Garnett, a co-sponsor of this bill with Representative Yadira Caraveo (D-CO) has discussed combining this bill with an existing November ballot initiative seeking an additional tax on all recreational cannabis products sold in Colorado. 

HB21-1317 proposes:

• That The Colorado School of Public Health shall conduct a report of “High-Potency THC marijuana and marijuana concentrate research”. The research is to study the “effect of high-potency THC marijuana on the developing brain and the effect of marijuana concentrates on physical and mental health” by systematically curating and synthesizing existing research as well as identify evidence gaps and new research that is needed. The purpose is to find “sufficient scientific evidence to make a recommendation regarding appropriate regulatory measures”. 
• To limit concentrate purchases for medical and recreational consumers to 8 grams per day. Unless the patient is 18-20 years old, then their limit is 2 grams per day.
• Starting a new statewide tracking system to ensure that medical marijuana patients do not “dispensary hop” and buy their maximum allowed purchase amounts at multiple sites in the same day. 
• Medical cannabis concentrate and retail cannabis concentrate must be sold in a package containing one gram, separated into no less than 10, equally-portioned amounts. 
• Doctor’s who recommend medical cannabis must conduct a full assessment of their patients’ mental health history in addition to their physical health history. 
• Medical patients 18-20 years old would need two in-person visits every 6 months with doctors who diagnose them as “having a debilitating or disabling medical condition”. 
• Practitioners who make a medical cannabis authorization must include in their certification:
  • The date of issue and effective date of recommendation
  • The patient’s name and address
  • The recommending physician’s name, address, and federal drug enforcement agency number
  • The THC potency level recommended
  • The dosage form
  • The daily authorized quantity 
  • Directions for use
  • The recommending physician’s signature 
• That the Department of Public Health and Environment create a report from emergency room and hospital discharge data of patients who show conditions or a diagnosis that reflects cannabis use. 

Take action now! Click the following link to oppose HB21-1317!

Send a message to your lawmakers in opposition of this effort with The Action Network.