One of the first connotations when hearing the phrase “medical cannabis” usually relates to pain management and treatment, but why is this notion so prevalent? Historically the first use of cannabis for treating pain originated in Central Asia spreading to India, North Africa, and Sub-Saharan Africa. It was introduced to European markets only in the 19th century and in North America until it was classified as a dangerous illegal drug due to political, economic, and social reasons.

Cannabis and Pain

But do we all feel pain the same way? or are there Factors that determine the quality, level, and tolerance we humans have for pain? Factors such as anxiety, depression, culture, and personality can all influence pain perception and its effect on an individual's life, which makes medical cannabis an interesting option and opportunity to step inside the huge analgesic market, since:

• Cannabis can potentially be used for the treatment of both depression and anxiety
• Holds anti-inflammatory properties
• Possible synergic effect with other pharmaceutical drugs
• No recorded Over Dose or toxic repercussions compared to other mainstream pain killers, drugs (Opioids, NSAIDS)
• Mostly minimal and tolerable side effects

What types of pain exist and how do you differ?

Types of pain and the ways cannabis aids in:

Nociceptive pain

As mentioned above, nociceptive pain is the most common, followed by physical damage, due to inflammation, damaged tissues use your immune system to repair the damage via the recruitment of inflammation and immune cells, these cells release materials that cause activation of receptors that signal your brain through the spine to register the pain sensation. What can medical cannabis do to treat and reduce nociceptive pain? Cannabinoids such as CBD and THC can reduce this kind of pain since both possess anti-inflammatory qualities. study on rodents concluded that it is the CB1 receptor that is involved in nociceptive pain, although it was the activation of both CB1 and CB2 that was connected to inflammatory hypersensitivity, the activation of CB2 alone was enough to cause an anti-inflammatory and analgesic response. A study on rodents, demonstrated CBD's ability to reverse both thermal and mechanical pain in rodents through oral administration by reducing two symptoms of inflammation:

• Hyperalgesia
• Edema

CBD and THC are the main cannabinoids with analgesic qualities:

THC

• Through the activation of CB1 receptors in the brain and spinal cord.
• The activation of CB2 receptors on immune cells leads to a decrease in your body's pain response to injury
• THC's euphoric quality can improve the perception of pain, improved mood can might not physically decrease the pain, but allows us to cope with it mentally.
• Speculated to work in synergy with opioids such as Morphine in the spinal cord. (more in THC's article) – thus Indirectly increases the opioid analgesic potential and allows the use of smaller dosages.

CBD

• Reduces inflammation through the blocking of inflammation mediators such as Cytokines
• Increases levels of endogenous cannabinoids such as ANANDAMIDE, which behaves similarly to THC and works on CB1 receptors.
• Increases activity of receptors on GABA – the brain's primary inhibitory neurotransmitter, decreasing pain signals making their way to the brain.
• Benefiting mood
• Lowering anxiety

Neuropathic pain

What causes Neuropathic pain?

• Hyperstimulation of your neurons in the brain or PNS, thus generating abnormal or prolonged stimulation of pain.
• Diseases and conditions that can cause neuropathic pain such as: A. Multiple Sclerosis B. Diabetes C. Parkinson's D. AIDS E. Viral infections (post hepatic neuralgia) F. Brachial plexus lesion G. Fibromyalgia H. Cancer (including cancer treatment such as chemotherapy and radiation)

One of the most frequent symptoms of those listed is neuropathic pain, the options available for patients to treat themselves with medications are :

• Antidepressants such as (Tricyclic, SNRIs, and SSRIs)
• Anticonvulsants (Lyrica, Tegretol to name a few)
• Opioids

Medical cannabis steps in, how can cannabis benefit here? Clinical trials gathered in (see table 4) display the effectiveness of both THC and CBD in different scenarios reported.

CBD or THC for Neuropathic pain?

The lack of the entourage effect might explain why one of the first official cannabis-based drugs for the treatment of pain use both CBD and THC – together

Sativex (Nabiximols)

The first Cannabis-based medicine to be licensed, prescribed for treating Multiple Sclerosis related spasticity when other medications proved lacking in an individual. Sativex's effect on MS-related symptoms that were studied before gaining a license:

• Pain
• Bladder symptoms
• Tremors
• Sleep disturbances

How it is used? As an oral spray that delivers 2.7 MG of THC and 2.5 MG of CBD per spray.

Medical cannabis and tolerance in pain management

Similar to other medications/drugs, tolerance to cannabis exists, and is associated with CB1 receptors being activated by THC, which is why balancing THC with CBD is advised:

• CBD mitigates THC‘s action on CB1 therefore retention of efficacy and reducing the risk of developing tolerance in long-term pain management.

How to handle tolerance of cannabis building? The most "natural" way is normally to increase the dosage, but it has repercussions:

• Costly money wise in some countries
• The higher the dosage, the more side effects are possible

Our advice to deal with tolerance?

Reduction of dosage, gradually with your physician's knowledge for a period of time, letting your endocannabinoid system a chance to rest and reset, how long of a break? this is the tricky question.... a 2015 study shows that after 48 hours, the endocannabinoid receptors start to reset, so generally speaking, a 48 hour break is a good thresh hold. Another option is "Microdosing": As in, ingesting small amounts of THC to experience the desired effects and benefits, and at the same time, avoid psychoactive effects, edibles are a prime example for this, since it is easier to keep watch on the amount of THC used.