Cannabis has a long history of medical use. Recent archeological research has shown that humankind used this plant more than 12’000 years ago. In the 20th century, prohibition of cannabis started in 1913 in the state of California and extended rapidly to other states and countries around the world. It is only very recently, at the beginning of the 21st century, that cannabis has made its comeback in our society. Therefore, scientific studies in this area are still very limited. Many research papers and studies into the plant are now under development.

Many patients would like to know more about medical cannabis, but can feel embarrassed to talk to their doctor. Some patients already use it, but don't dare tell their doctors by fear to be judged or criticized.

The reason is that the whole medical community has been very dismissive of this plant during decades. How many times have we heard doctors complain that there was not enough evidence to recommend medical cannabis? In our opinion, there will be even less scientific evidence by keeping heads in the sand. Fortunately, many doctors are now trying to be informed and catch up with the therapeutic virtues of this plant.

Please note that cannabis used in an unsupervised manner is not considered medical cannabis. The same is true for cannabis that is authorized by a physician who does not adequately evaluate the patients, who does not prescribe cannabis as part of a wider care program, or who does not monitor the patients for subjective and objective outcomes or adverse events.

Our advice for patients:

Be entirely honest and open with your physicians and have high expectations of them. Tell them that you consider a medical cannabis treatment to be part of your care plan and that you expect them to be informed about it, and to be able to at least point you in the direction of the information you need.

Our advice for doctors:

Whether you are pro, neutral, or against medical cannabis, patients are embracing it, and although we don’t have rigorous studies nor a “gold standard” proof of its benefits and risks, we need to learn about it, be open-minded, and above all, be non-judgmental. Otherwise, patients will seek out other less reliable sources of information; they will continue to use it, not telling us, and there will be much less trust and strength in our doctor-patient relationship.

WHAT’S THC ?

THC (Delta-9-tetrahydrocannabinol) is the best-known cannabis compound. THC is the psychoactive neutral form of the carboxylic acid THCA, a non-intoxicating molecule found in cannabis plants, which is converted upon heating and being stored for a reasonable length of time. THC has a lot of properties: it is neuroprotective, anti-inflammatory and analgesic, and reduces intraocular pressure, spasticity, and muscle tension. Recent studies have shown that THC helps alleviate symptoms like pain, nausea, spasms and lack of appetite in patients suffering from various diseases.

THC, which has psychoactive effects, may have side effects such as tachycardia (rapid heartbeat), dry mouth, dizziness or lightheadedness, irritated eyes, and coughing among new users of cannabis medicines. These adverse effects, however, typically decline over a course of treatment.

WHAT’S CBD ?

CBD (Cannabidiol), unlike THC, is a non-psychoactive substance found in cannabis. Research indicates that it can eliminate some of THC’s unpleasant adverse effects like its psychoactivity, THC-induced sedation, anxiety and rapid heartbeat. CBDA, another acidic cannabinoid similar to THCA produced by the plant, can be converted to CBD by heat over time. CBD also has antiinflammatory, analgesic, anticonvulsant and antioxidant properties. While CBD is not intoxicating, patients using high- CBD / low-THC herbal cannabis have noted some effects akin to mild psychoactivity, an effect which could be caused by interactions between terpenes and CBD that are still to be understood.

Patients taking high doses of CBD should consult with a healthcare professional about potential interactions if taking other medications simultaneously.

Cannabis plants produce more than 700 chemical constituents, among which the principal ones are phytocannabinoids and terpenoids. Cannabinoids work in synergy with each other and with the cell receptors located in our bodies: this interaction is called the “entourage effect”. The human body also produces its own cannabinoids, called endocannabinoids, which interact with the endocannabinoid receptors and are responsible for a variety of functions such as, inter alia, memory, motor function, digestion, blood pressure, and immune response. Beside THC and CBD, the main cannabinoids found in cannabis plants, other important cannabinoids are, for example, CBG, CBC, and CBN.

CBG (Cannabigerol) is the third most prevalent cannabinoid produced by cannabis plants and is not psychoactive. Recent studies have shown that CBG has naturally strong healing properties such as anti-inflammatory, antibacterial, antioxidative and neuroprotective. Moreover, CBG is believed to boost anandamide, the endocannabinoid responsible for increasing dopamine levels and regulating appetite and sleep.

CBGA (the Cannabigerolic acid) appears to be accumulated more in fiber hemp than in drug cannabis varieties. Recent research has shown that CBGA has analgesic properties, stimulates appetite and contrast chemotherapy-induced cachexia. It is also being studied as a potential antibiotic, antiseptic and antitumoral.

CBC (Cannabichromene) is produced in the juvenile phase of the flowering cycle of the cannabis plant. The flowers are to be collected six weeks before floral maturity in order to have a cannabichromene content. CBC has shown a variety of effects: anti-inflammatory and analgesic, antibiotic, antifungal, but also antidepressant.

CBN (Cannabinol), in effect, is not produced by the cannabis plant but is found in cannabis resin or oil. It is one of the more common cannabinoids found in cannabis products. CBN has little psychoactivity but appears to be sedative when taken in synergy with THC. Recent studies show that CBN can be effective at treating MRSA infections and burns.

WHAT IS THE ENDOCANNABINOID SYSTEM ?

The endocannabinoid system (ECS) is a complex cell-signaling system identified in the early 1990s by researchers exploring THC, a well-known cannabinoid. Cannabinoids are compounds found in cannabis.

Experts are still trying to fully understand the ECS. But so far, we know it plays a role in regulating a range of functions and processes, including:

• sleep
• mood
• appetite
• memory
• reproduction and fertility

The ECS exists and is active in your body even if you don’t use cannabis. Read on to learn more about the ECS including how it works and interacts with cannabis.

HOW DOES IT WORK?

The ECS involves three core components: endocannabinoids, receptors, and enzymes.

Endocannabinoids

Endocannabinoids, also called endogenous cannabinoids, are molecules made by your body. They’re similar to cannabinoids, but they’re produced by your body. Experts have identified two key endocannabinoids so far:

• anandamide (AEA)
• 2-arachidonylglycerol (2-AG)

These help keep internal functions running smoothly. Your body produces them as needed, making it difficult to know what typical levels are for each.

Endocannabinoid receptors

These receptors are found throughout your body. Endocannabinoids bind to them in order to signal that the ECS needs to take action. There are two main endocannabinoid receptors:

• CB1 receptors, which are mostly found in the central nervous system
• CB2 receptors, which are mostly found in your peripheral nervous system, especially immune cells

Endocannabinoids can bind to either receptor. The effects that result depend on where the receptor is located and which endocannabinoid it binds to.

For example, endocannabinoids might target CB1 receptors in a spinal nerve to relieve pain. Others might bind to a CB2 receptor in your immune cells to signal that your body is experiencing inflammation, a common sign of autoimmune disorders.

Enzymes

Enzymes are responsible for breaking down endocannabinoids once they’ve carried out their function. There are two main enzymes responsible for this:

• fatty acid amide hydrolase, which breaks down AEA
• monoacylglycerol acid lipase, which typically breaks down 2-AG

WHAT ARE ITS FUNCTIONS?

The ECS is complicated, and experts haven’t yet determined exactly how it works or all of its potential functions. Recent research has linked the ECS to the following processes:

• appetite and digestion
• metabolism
• chronic pain
• inflammation and other immune system responses
• mood
• learning and memory
• motor control
• sleep
• cardiovascular system function
• muscle formation
• bone remodeling and growth
• liver function
• reproductive system function
• stress
• skin and nerve function

These functions all contribute to homeostasis, which refers to stability of your internal environment. For example, if an outside force, such as pain from an injury or a fever, throws off your body’s homeostasis, your ECS kicks in to help your body return to its ideal operation.

Today, experts believe that maintaining homeostasis is the primary role of the ECS.

How does THC interact with the ECS?

Tetrahydrocannabinol (THC) is one of the main cannabinoids found in cannabis. It’s the compound that gets you “high.” Once in your body, THC interacts with your ECS by binding to receptors, just like endocannabinoids. It’s powerful partly because it can bind to both CB1 and CB2 receptors.

This allows it to have a range of effects on your body and mind, some more desirable than others. For example, THC may help to reduce pain and stimulate your appetite. But it can also cause paranoia and anxiety in some cases.

Experts are currently looking into ways to produce synthetic THC cannabinoids that interact with the ECS in only beneficial ways.

How does CBD interact with the ECS?

The other major cannabinoid found in cannabis is cannabidiol (CBD). Unlike THC, CBD doesn’t make you “high” and typically doesn’t cause any negative effects.

Experts aren’t completely sure how CBD interacts with the ECS. But they do know that it doesn’t bind to CB1 or CB2 receptors the way THC does.

Instead, many believe it works by preventing endocannabinoids from being broken down. This allows them to have more of an effect on your body. Others believe that CBD binds to a receptor that hasn’t been discovered yet.

While the details of how it works are still under debate, research suggests that CBD can help with pain, nausea, and other symptoms associated with multiple conditions.

What about endocannabinoid deficiency?

Some experts believe in a theory known as clinical endocannabinoid deficiency (CECD). This theory suggests that low endocannabinoid levels in your body or ECS dysfunction can contribute to the development of certain conditions.

A 2016 article on https: reviewing over 10 years of research on the subject suggests the theory could explain why some people develop migraine, fibromyalgia, and irritable bowel syndrome.

None of these conditions have a clear underlying cause. They are also often resistant to treatment and sometimes occur alongside each other.

If CECD does play any kind of role in these conditions, targeting the ECS or endocannabinoid production could be the missing key to treatment, but more research is needed.

The bottom line

The ECS plays a big role in keeping your internal processes stable. But there is still a lot we don’t know about it. As experts develop a better understanding of the ECS, it could eventually hold the key to treating several conditions.

The above guide has been written by Crystal Raypole and medically reviewed by Alan Carter, Pharm. D. on 17.05.19 and published on: https://www.healthline.com/health/endocannabinoidsystem# takeaway for Healthline Media, a Red Ventures Company.

The most important difference between these two subspecies of cannabis lies in their medical effects and how they influence energy levels and productivity. Sativa plants require longer to grow and yield less medicine than Indica varieties. This is why Indica strains have traditionally dominated those available on the black market, where there is no concern for patient needs and the sole focus is profit. The fact that patients are given no choice of subspecies or strain when purchasing from the black market is a major reason it should be avoided. Patients should never trust or consume cannabis-based medicines without knowing their exact strain and whether they were properly grown, dried, cured, and laboratory tested for purity and potential contamination.

Sativa

A feeling of well-being and ease is often associated with Sativas, making them ideal for social situations. The high from Sativa strains is energizing, cerebral and well suited for daytime use. They are also said to promote deep conversation and enhance creativity. The highs from Sativa strains are often described as uplifting and energetic. A good Sativa should be about as stimulating as a strong cup of coffee.

INDICA

Indica plants are known to provide more of a body high. Some of the common benefits of Indica strains can be muscle relaxation, pain-relieving effects, and full body sedating effects. You can expect to feel the effects more heavily concentrated in your body and legs when medicating with Indica-dominant strains. Cannabis Indica is also known for its anti-panic and antianxiety properties along with being an effective treatment for insomnia.

Cannabis has been used for several years to treat patients for various ailments or symptoms. If you are looking into using medical cannabis, here is some useful information that may help you.

HOW THE FUTURE LOOKS LIKE

In light of recent Federal Council decisions, the legal framework is being modified to allow doctors to prescribe medical products with a high level of THC to their patients. Currently, there are a few thousand patients who are already treated with legal cannabis in Switzerland. This number is expected to increase significantly in the coming months and years.

In this regard, the FOPH will give a special license for production and manufacture of cannabis with a high level of THC to Swiss companies that fulfil specific requirements.

WHAT CANNABIS IS USED FOR

Your family doctor may have prescribed you medical cannabis to alleviate symptoms for a variety of conditions and disorders that have not responded to conventional medical treatments, such as:

• Anxiety and depression
• Nausea and vomiting related to chemotherapy
• Chronicpain
• Sleepdisorders
• Seizuredisorders
• MultipleSclerosis
• Parkinson’sdisease
• Post-TraumaticStressDisorder
• HIV/AIDS

INGESTION

Ingesting medical cannabis represents the most accurate method of administration. Precise doses may be consumed in the form of gel capsules, tablets or oils, making a controlled and repeatable treatment possible.

When ingested, the medical compounds of cannabis are broken down in the gastrointestinal tract before being absorbed into the bloodstream through the liver. This is the most effective method of administration. However, onset of the effects may take between 30 minutes and two hours.

ORAL ABSORPTION

Medical cannabis can be directly absorbed into the bloodstream through the mucous membranes in the mouth. The administration of lozenges or oils sublingually offers a more rapid onset of effects than ingestion and typically takes between 10 to 60 minutes to become effective.

INHALATION

Inhalation is one of the more commonly used methods for consuming cannabis in its raw plant form. There are two methods through which medical cannabis can be inhaled – vaporization and smoking. The active chemical compounds in cannabis must be heated in order to achieve the desired medical effect on the body. Both methods ensure the rapid onset of effects. However, smoking is not recommended because of the associated harmful effects of inhaling combusted plant material, which releases toxins and carcinogens.

Vaporizing allows for the consumption of the raw plant material without burning it. It works by heating the cannabis to a high temperature without reaching combustion thereby releasing the active compounds in a less harmful manner.

• Effectiveness
  Cannabis can reduce or increase anxiety, depending on its variety, its chemistry and dose, the mindset of the user and the setting in which the cannabis is used.
• Dosage
  Both THC and CBD are effective for relieving symptoms of anxiety, but it may be more effective to use each cannabinoid separately. THC dosage for anxiety is successful between 1 and 3 mg, while CBD dosage ranges between 2.5 and 10 mg.

• EFFECTIVENESS
  Many studies present scientific evidence on the effectiveness of the use of medical cannabis in cancer treatment. Positive effects are recognized on pain, chemotherapy-induced nausea (CIN) and vomiting, appetite stimulation, weight gain, and sleep. More recently, scientists reported that THC and other cannabinoids such as CBD slow growth and/or cause death in certain types of cancer cells growing in lab dishes. Some animal studies also suggest certain cannabinoids may slow growth and reduce spread of some forms of cancer.
• DOSAGE
  For all cancer symptoms please see the sections dedicated to each symptom.

• EFFECTIVENESS
  Researchers make a distinction among the various types of pain and their underlying mechanisms. The types of pain usually differentiated are: neuropathic (originating in the nerves, such as diabetic neuropathy or sciatica), visceral (originating in an organ, such as menstrual cramps), somatic, which is located in musculoskeletal tissues or the skin and underlies soft tissues (like arthritis or post-surgical pain), and psychogenetic (panic attacks or tension headaches, for example). Unlike other pain medication or treatment, medical cannabis has been proven effective for all types of pain.
• DOSAGE
  To establish the most effective dose of cannabis for pain, take the least amount of cannabis required to provide the level of effect needed. By taking less, rather than more, and carefully increasing the dose only until optimal effectiveness is reached, you may decrease the likelihood of developing a tolerance to the benefits of cannabis, while also minimizing intoxication from a dose.

• EFFECTIVENESS
  There are two primary types of nausea: acute and anticipatory. A substantial body of evidence supports the use of cannabis medicines in the treatment of acute nausea. Anticipatory nausea is especially difficult to treat via conventional medication, but strong preclinical evidence and observation reports support the use of cannabinoid-based medicines in anticipatory nausea. Since cannabinoids can reduce the impact of the traumatic memory’s imprinting mechanism in the brain and engage with receptors that modulate nausea, it is not surprising that cannabis is effective. Chronic nausea is often attended by anxiety, and CBD has been proven in human studies to be helpful.
• DOSAGE
  Oral and sublingual cannabis administration methods are both quite effective, with oral dosage providing longer lasting effects. When THC-based cannabis medicines are to be used for combating chemo-induced nausea, the right THC dose for nausea can cause intoxication, so it is often helpful to start with a small dosage and increase it over a week or two to the effective dosage range (10 to 12.5 mg THC) to give the patient the opportunity to get used to it.

• EFFECTIVENESS
  Medical cannabis can be used to treat a range of symptoms associated with HIV. Cannabis proves particularly effective in helping patients maintain weight during HIV treatment. It has been demonstrated that there is a positive link between moderate cannabis use, increased tolerance of antiretroviral therapy (ART) and common HIV symptoms relief. Cannabis is also being explored as a potential treatment for HIV-related inflammation. Studies have also demonstrated that medical cannabis can be used effectively against pain.
• DOSAGE
  The key for an effective dosage is to use the lowest effective dose for each symptom that is treated.

• EFFECTIVENESS
  Cannabis has proven effective in treating sleep disorders including insomnia. THC appears to act as a mild sedative while CBD acts as a stimulant. However, cannabis also shows anti-anxiety properties which can help to fall asleep. When using medical cannabis as a treatment for insomnia, timing is important due to the varying onset times of action of the different methods of administration.
• DOSAGE
  It is recommended to take 5 to 7.5 mg THC for treating insomnia.

• EFFECTIVENESS
  The effects of endocannabinoids and administered cannabinoids on multiple cellular levels in the brain make a convincing argument that cannabinoids are neuroprotective. In fact, cannabinoids reduce the inflammation that occurs when overstimulated macrophages and microglial cells (the brain’s own inflammatory cells) cause demyelination and cell death. Cannabinoids act as vasodilators resulting in increased blood flow to the injured cerebral areas. They also promote neurogenesis to encourage healing processes in the injured areas. Cannabinoids are powerful antioxidants, which could reduce the oxidative damage that leads to the death of neurons. While THC and CBD have independently demonstrated to be neuroprotective in animal studies, overall it is unclear whether combining THC and CBD leads to a greater neuroprotection than THC alone. There are even some concerns that CBD may reduce the neuroprotective effect of THC.
• DOSAGE
  Partial relief of nerve pain, muscle pain, cramps, dysphoria, anxiety, and insomnia are reasonable expectations from THC, whether inhaled, oral, mucosal, or edible preparations are used. Trials with multiple preparations and dosing are needed to achieve optimal results. MS patients should not be discouraged if the initial regimens are ineffective or hard to tolerate. To manage spasticity and pain, take 2 to 6 mg of both THC and CDB every three to four hours, sublingually or inhaled using a vaporization device. An 18:1 CBD to THC tincture in 5 mg doses is recommended for anxiety, as needed until 5 p.m. Take 5 to 7 mg THC orally for insomnia. If your goal is a disease modification, the most pragmatic regimen would be to take 3.5 mg of THC twice a day orally, with doses increasing by 3.5 mg weekly to a maximum of 28 mg, in twice daily doses or until side effects become intolerable.

• EFFECTIVENESS
  Research on medical cannabis as a treatment for Parkinson’s disease is still inconclusive, even though some studies have shown that cannabis can help control dyskinesias (uncontrolled movements). There is also some evidence that cannabis can help Parkinson’s patients with pain and tremors, as well as rigidity and slowness of movement and sleep issues, when conventional medicines are ineffective.
• DOSAGE
  The dosage for Parkinson’s disease depends on each of the symptoms being treated and can vary due to the disease’s progressive nature.

• EFFECTIVENESS
  Both endocannabinoids and cannabinoids reduce the acute response to stress, as well as the atypical response to perceived threats, while supporting the elimination of fears associated with PTSD. CBD has the potential to become a treatment for lingering traumatic memories and their impacts.
• DOSAGE
  1 to 5 mg THC are effective for anxiety when taken sublingually (or swallowed for a more potent effect). CBD cannabis is effective orally and sublingually at 5 to 10 mg. Light dosages of THC (typically about 2.5mg), taken sublingually, have relatively clear effects and have proven helpful to shift or elevate mood and relieve anxiety. This dosage can be increased to 5 mg, if needed. If taken in spray form or sublingually in a ratio of CBD:THC of 10:1 or higher, CBD can be taken in doses of 5 to 10 mg in the morning and again mid-afternoon. THC taken orally is recommended for sleep: swallow 5 mg THC one hour before bed or when bed rest is needed.

When recommending any therapy, a healthcare provider and patient need consider both the potential benefits and risks. What information is available to guide them when it comes to medical cannabis?

In 2013, the Canadian College of Physicians and Surgeons of Canada asked the federal government to develop explicit indications, precautions and counterindications for medical cannabis so doctors could evaluate which of their patients should, or should not, be given access to medical cannabis.(*)

Although it has an information document for practitioners on medical cannabis, Health Canada states upfront: “This document should not be construed as expressing conclusions from Health Canada about the appropriate use of cannabis (marihuana) or cannabinoids for medical purposes.”(**) Nevertheless, based on counterindications for existing synthetic cannabis medications (nabilone and dronabinol) and the cannabis extract dronabinol, Health Canada suggested the risk/benefit ratio of cannabis needs to be carefully and individually considered for people who:

• Are under the age or 18
• Have a history of hypersensitivity to any cannabinoid or to smoke (if the cannabis is smoked)
• Have severe cardio-pulmonary disease with occasional hypotension (low blood pressure), possible hypertension (high blood pressure), syncope (loss of consciousness) or tachycardia (rapid heart rate)
• Have respiratory diseases such as asthma or chronic obstructive pulmonary disease (COPD)
• Have severe liver or renal disease, including chronic hepatitis C
• Have a personal history of psychiatric disorders or a family history of schizophrenia
• Have a history of substance abuse
• Are women of childbearing age not using a reliable contraceptive, are planning to get pregnant, are pregnant, or are breastfeeding.

In addition, it suggests medical cannabis should be used with caution in people who have mood disorders or are taking sedatives or other psychoactive drugs.

In 2014, the College of Family Physicians of Canada (CFPC) produced its first guideline for physicians, focusing on cannabis for the treatment of chronic pain or anxiety.(***) In this document, the CPFC not only listed what sort of people might be inappropriate candidates for medical cannabis but also rated the level of the research evidence for their recommendations. Their rating scheme consisted of three levels: Level I evidence is the strongest (well-conducted controlled trials or meta-analyses), followed by Level II (well-conducted observational studies), and the weakest, Level III (consensus of the expert members of the committee writing the guidelines).

To summarize, in this document the CFPC advised doctors not to authorize medical cannabis to patients who:

• Are under the age of 25 (Level II)
• Have a personal history or strong family history of psychosis (Level II)
• Have a current or past cannabis use disorder or another active substance use disorder (Level III)
• Have cardiovascular or respiratory disease (Level III)
• Are pregnant, planning to become pregnant or are breastfeeding (Level II)

In addition, it said caution should be used in recommending cannabis for patients who:

• Have a mood or anxiety disorder (Level II)
• Smoke tobacco (Level II)
• Have risk factors for cardiovascular disease (heart disease and stroke) (Level III)
• Are heavy users of alcohol or take high doses of opioids, benzodiazepines (a class of tranquilizer) or other prescription or over- the-counter sedatives (Level III)

As this summary shows, because of gaps in research on medical cannabis, none of the recommendations were backed by the “gold standard” of evidence, randomized controlled trials (RCTs) or meta-analyses, a type of systematic review that combines and analyzes data from RCTs. Instead, most were based on observational studies or expert opinion. (To find out more about the type of research currently available to guide clinicians and decision-makers, you can check out our evidence summaries and reviews.)

The CFPC guidelines are a start, but pain and anxiety are only two of the potential indications for medical cannabis. Moreover, some of the possible counterindications listed in the Health Canada document are not addressed by the CFPC, which can be a point of confusion. More guidelines are needed to address all of the patient populations who may be eligible for medical cannabis, such as those with multiple sclerosis, HIV/AIDs, and cancer. In doing so, ethical and medical issues may arise. For example, should the counterindications in the CFPC report be applied to palliative-care patients? What about people with serious conditions who have tried but not benefited from conventional therapies? A lot of questions remain about the appropriate use of medical cannabis. The work of the Michael G. DeGroote Centre for Medicinal Cannabis Research will provide the sort of information and insights needed for better decision-making and health care.

The above article is from https://cannabisresearch.mcmaster.ca/news/2017/11/01/who-shouldn-tuse- medical-cannabis. The latest scientific evidence on this topic was reviewed by the Centre's leadership team. This evidence brief is written by Corinne Hodgson, D. Health, and assessed for accuracy by Medical Advisor Dr. Ramesh Zacharias, MD, a clinician with expertise in chronic pain. There are no conflicts of interest. Questions regarding this paragraph should be directed to Dr. Ramesh Zacharias (zacharias@hhsc.ca).

(*) College of Physicians and Surgeons of Canada. The College of Family Physicians of Canada Statement on Health Canada’s Proposed Changes to Medical Marijuana Regulations. February 2013.

(**) Health Canada. Information for Health Care Professionals: Cannabis (marihuana, marijuana) and the cannabinoids. 2013.

(***)College of Family Physicians of Canada. Authorizing Dried Cannabis for Chronic Pain or Anxiety. Preliminary Guidance. September 2014.