The Endocannabinoid System

Table of Contents

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The Endocannabinoid system is an ancient function that represents endogenous cannabinoid receptors throughout the human body. Through this system, Cannabis interacts with these receptors creating a range of benefits used to improve the human condition [1]. Some of these benefits have been found to impact our neural development, immune system, metabolism, cardiovascular function, digestive system, and our bone development and density. Additionally, the endocannabinoid system can balance the inflammation of our tissues and joints, our pain perceptions,  our appetites, our mood and energy levels.

This ancient system has two receptors and an amino acid that affect two markers in every nerve cell in the body[3], and it’s through this simple system that we have discovered how to interrupt negative processes with Cannabis and restore function as best as we can[4]. It doesn’t just show up in the nervous system, but is represented in many organs, and serves very important roles in their functioning[5].

Cannabis: What is it?

Cannabis Sativa (i.e. Cannabis) is a plant part of the hemp variety which is common to many temperate and tropical regions around the world[6]. The principle compounds of this plant are THC and CBD Their concentrations and the interplay between them, vary from strain to strain, region to region, and it’s this complex interaction between the two, also known as the ‘entourage effect’, that allows one strain to work better than others for particular sets of symptoms.

The active compound of THC has been closely analyzed due to the interests in its psychoactive effects on the human mind. [8]. Other compounds, present in varying trace amounts, have little of the mental effects common to THC. For reference, the dried Cannabis provided by Health Canada has a relative concentration of 12.5% THC.

Universality of Cannabis

The many beneficial properties of Cannabis are further enhanced by its peripheral properties: the ease of growing it[9], storing it, and the variety of ways of administering it, listed below:

Smoked Cannabis

Smoking Cannabis is one of the quickest delivery methods resulting in psychoactive effects. With an extremely rapid onset (within minutes) and higher concentrations detected in the bloodstream afterwards, it also presents a shorter duration of symptoms when compared to oral consumption[10]. Smoking Cannabis has a few uncontrollable variables that require extra observation and consideration beforehand: is the person smoking the Cannabis a regular user? If so, resistance is heightened and a higher dosage may be required. In some cases, the user has a natural resistance to the beneficial effects and, as before, a stronger or prolonged usage regimen is required. Occasionally the plant itself may have a variable concentration of THC: sometimes lower, sometimes higher. On average, this can be simplified through trial and error. Typically, between 25 and 27% of the total available THC is absorbed through smoking[11].

Vaporized Cannabis

Popular in recent years, vaporization of Cannabis (vaping) has been thoroughly explored as an alternative to smoking. There are many potential benefits to this mode: less carbon monoxide inhaled, less tar generated, and a far more efficient means of extracting THC from Cannabis[12]. The effects of vaping are similar to those of smoking without the smoke, smell, and coughing associated with it. In addition, vaporizing offers a quicker onset to users than smoking. As a bonus, it was reported that even among sensitive users, there were few, if any, adverse reactions and general tolerance was higher, with an overall preference over smoking[13].

Oral (food, drink, and pill)

Unlike the delivery methods of  smoking and vaporizing which only take minutes to feel the effects of Cannabis, the oral delivery can often take an hour or longer[14]. A slower onset, lower peak concentrations, longer durations: everything feels slower this way and, for some, this is precisely the effect desired[15]. The most common ways of taking Cannabis orally are via concentrated THC pills, in foods containing Cannabis (oils and butters, brownies and cookies), and least commonly, in tea brewed from the flowering tops of the Cannabis plant. In addition to this, and a relatively recent development, are Cannabis tinctures: the active ingredients distilled into an alcohol and administered with a dropper. This method is extremely easy to calculate the relative THC concentration and administer the dose that works best. Due to the relative potency in the tincture method, it doesn’t need to be administered as often as other delivery methods.

Topical Application

 One of the most promising methods of applying the active compounds in THC is through a cream or skin patch. Early tests show that CBD has a transfer rate ten times higher than THC when applied topically[16]. This encouraging result suggests that the pain-relieving properties of Cannabis can be delivered locally to chronic pains such as arthritis, without having to experience whole-body symptoms that would be associated with oral or smoked delivery methods. In fact, this method would bypass many of the mental effects that come with a relief of symptoms.

Pain Relief

Post-Operative

One of the most poorly managed types of pain is post-operative. The pain that lingers for weeks, sometimes months, after major surgery is difficult to address and treat under the best of circumstances, and to-date has received far too little attention. Cannabis offers an alternative to the existing drugs which are either ineffectual or come with unacceptable side-effects[17]. Preliminary studies have already begun to show that THC may have a promising future in managing this type of pain with treatment routes under development[18]. The earliest results are reporting that THC already shows moderate effectiveness at managing pain that traditional pharmaceuticals struggle to contain[19].

A preliminary trial that occurred over a period of just five days showed significant decreases in daily pain intensity[20]. Along with this important reduction in reported pain, statistics show significant improvement in the quality of sleep by the patients and an associated reduction in overall anxiety caused by ongoing pain. The most common side-effects are those typical to THC use: euphoria, dry eyes, numbness, and other common symptoms of Cannabis use.

Chronic Pain

Much like post-operative pain and the difficulties in managing it, chronic pain treatment often comes with prescription drugs that begin, or become, ineffectual, and side-effects that impact the overall quality of life of the user. Cannabis has been shown to reduce or eliminate many of the peripheral pains in individuals who are currently taking prescribed medication, further reducing the pain they experience[21]. Side-effects include: euphoria, mild intoxication, and increased hunger.

Cancer

Of all the diseases with complicated sets of symptoms, Cancer is the only where the treatment brings even more to bear on the patient. Loss of appetite, nausea and vomiting, chronic pain, and so many more. Cannabis is well-suited for the treatment of not just one of these symptoms, but many of them concurrently. One of the most common, and most distressing, symptoms of chemotherapy is the rapid onset of nausea and vomiting

Headaches and Migraines

Little scientific material has been collected in the treatment of migraines and headaches with Cannabis and the associated compounds, yet there is a history of evidence and reports to its efficiency[25]. There is evidence that an underlying endocannabinoid deficiency may be at the heart of some causes of migraines and chronic headaches[26]. One such case was found to be resolved when the patient began smoking Cannabis after the onset of the attack[27], while another patient suffering from cluster headaches found relief by using Cannabis as a preventative agent[28]. Caution is still advised, as a more-is-better situation hasn’t been found, and controlled doses function best during treatment[29].

Arthritis, Fibromyalgia, and Osteoporosis

 Preclinical trials showed reduced pain in the joints of subjects in many cases, both by a reduction in the activity of pain receptors and a noted reduction in the inflammation of tissue associated with the tests[30]. This is one of the most potent sources of relief for someone suffering from both rheumatoid or typical arthritis[31] [32].

A cross-sectional survey of patients suffering from intractable fibromyalgia found that there was a significant improvement in the quality of life for those who regularly used Cannabis, particularly in measured mental wellbeing[33], versus those who didn’t use Cannabis.

Additionally, Osteoporosis studies have discovered evidence linking the endocannabinoid system and the underlying mechanism that signals bones to manage their density and development. Clinical trials are currently underway but early results from preclinical studies have revealed two important points: stimulation of the endocannabinoid system can help prevent bone loss from ovariectomies[34], and there is evidence that Cannabis may help prevent age-related bone loss[35].

Inflammation and Skin Care

Endocannabinoids have been found to operate in anti-inflammatory systems, both through observed results in the treatment of other symptoms, and through clinical trial[36]. Several studies have concluded that these preliminary results suggest Cannabis as an avenue of treatment for symptoms such as inflammation The endocannabinoid system is found throughout the layers of the skin which helps keep skin components in balance. The important endocannabinoid system’s receptors are CB1, CB2, and TRPV1. The compounds of THC and CBD found in Cannabis mimic the natural endocannabinoid chemicals and can be used to treat many skin conditions such as psoriasis[38].

In direct histamine responses on the skin, the application of Cannabis-derived compounds was found to reduce swelling and flaring along with a reduction in the sensation of pain, burning, and itching[39]. These benefits came without any of the associated side-effects of Cannabis use, such as dizziness, or a general sense of being “high”[40].

Psychological Disorders

This avenue of exploration is one of the most studied areas of research, and has a lot of anecdotal and clinical data to support the belief that Cannabis is an effective treatment for a variety of psychological disorders, such as anxiety, depression, PTSD, and a variety of sleep disorders.

Long-term users self-report reductions in anxiety and an associated increase in their ability to relax, as well as a broad relief from tension[41]. A survey of over four thousand respondents showed overwhelming evidence that weekly use of Cannabis resulted in an improved quality of life[42]. Many psychological disorders are the result of a lack of our body’s endocannabinoid system’s receptors in the brain. The use of cannabis reintroduces these lacking receptors which in turn balances the function of the brain and diminishes symptoms of psychological disorders.

Among those suffering from anxiety, a study found a 93% improvement in anxiety with even short-term consumption, and an additional 86% of users reporting their associated depression was relieved[43]. This result is phenomenal when compared to current market pharmaceuticals which purport to treat the same symptoms, and have a considerable host of negative side-effects. These benefits extend to more serious instances of psychiatric distress, such as those suffering from PTSD. A thorough trial found that once-daily Cannabis usage before bedtime resulted in improvements in sleep time, daytime flash backs, and night sweats with 72% reporting a total cessation or lessening of severity of the nightmares that afflicted them[44].

Multiple Sclerosis and Spinal Cord Injury

There are over one hundred years of published reports suggesting that Cannabis can help alleviate spasticity in multiple sclerosis (MS) sufferers[45]. In the UK, 68% of people who suffer from MS have used Cannabis to alleviate some of the symptoms associated with the disease[46], and in Canada 43% of the people who responded to the survey reported using Cannabis to treat their symptoms. This number doesn’t include the 16% of sufferers in Alberta prescribed medical Cannabis[47] and a large population of sufferers in Nova Scotia prescribed the same[48]. The benefits are a reduction in stress and chronic pain as well as an overall reduction in depression, anxiety, and improvements in sleep.

For individuals who have suffered spinal cord injuries there is evidence that shows that the use of Cannabis has significantly improved a variety of associated pain symptoms. Many users have reported subjective improvements in quality of life[49], very likely related to the benefits in treating anxiety and depression Cannabis has been associated with, as well as direct clinical improvements in specific pain and spasticity, sleep, and a marked reduction in muscle spasms[50].

Palliative Care

The benefits of Cannabis are numerous, bringing relief to a wide set of individual and co-occurring symptoms. Incorporating Cannabis into mainstream medical use has been characterized as cautious yet its use appears to be gaining ground in palliative care settings, where the focus is on individual choice, patient autonomy and empowerment, comfort, and especially quality of life. Cannabis gives the choice of care and the level of comfort to the patient.

The evidence suggests Cannabis has great value and an appeal to its use in the alleviation of symptoms in palliative care settings, such as: intractable nausea and vomiting because of other treatments, anorexia and cachexia (typically caused by prolonged chronic illness), severe and intractable pain, severe and intractable depression, and insomnia[51] An added benefit of Cannabis in this environment is not only an improvement in the quality of life, but an overall reduction in the number of medications used in the treatment of any individual symptom; a reduction that certainly minimizes the chance of negative drug interactions for patients. These improvements in the quality of life have been clinically tested and measured in numerous clinical trials[53] [54].

Wasting syndrome and loss of appetite

It has been known for decades that Cannabis has a potent ability to increase appetite due to its THC component[55]. What isn’t recognized is that Cannabis users benefit from an increased intake of energy and nutrients[56]. Several tests show that Cannabis and THC, whether smoked or eaten, leads to increased food consumption, increased caloric intake, and increased body weight[57].

Stimulating Appetite and Weight Gain for Cancer and AIDS Patients

The ability for Cannabis to stimulate appetite and regulate the body’s production of sugar has been applied to clinical situations where this is of prime importance such as in HIV-associated muscle wasting and weight loss. Studies have reported that experienced Cannabis users who are HIV-positive and suffer from muscle loss have benefited from both synthetic Cannabis, such as oral dronabinol, and smoked Cannabis, which was the preferred treatment

Secondary Benefits and Emerging Potential Uses

Additional benefits associated with the use of Cannabis include relief of symptoms of glaucoma[59] and epilepsy[60], along with a host of generalized movement disorders[61] that become manageable with the anti-spasticity elements of Cannabis use. People suffering from asthma have seen improvements in the regulation of their airways with light Cannabis use[62], and people suffering from hypertension have found relief[63].

Finally, Cannabis has extremely well-documented properties in the prevention and control of the spread of a variety of different cancers[64]. THC, CBD, and both in combination have all been demonstrated to restrict the growth of tumors of certain cancer types[65] and in some select cases, cause a regression of the tumor[66]. There are many preclinical trials currently underway, each potentially offering a new direction of treatment for a variety of heart diseases[67], some which currently have no means of treatment.

Conclusions

The considerable clinical data alone represents the huge potential of Cannabis as an avenue for treatment across a huge spectrum of symptoms. It is clear there is potential here: potential for not just the relief of pain in a few cases, but of a radical rethinking of the means of relief we provide to those suffering from symptoms that had previously been considered impossible to treat. It is easy to grow, maintain, and cultivate almost anywhere in the world both indoors and out, with many ways it can be administered, with dosage and length of time being one of the most manageable factors in its efficacy. More than just a few isolated cases, Cannabis has been proven to have strong positive effects on many people suffering from a diverse set of symptoms, with evidence going back a century or longer. Cannabis is the clear way forward, and we’re already moving in that direction together.

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