Cannabis Therapy

Conclusive or Substantial Evidence Effectiveness

There is conclusive or substantial evidence that cannabis or cannabinoids are effective:

• For the treatment of chronic pain in adults.
• As antiemetics (anti-vomiting) in the treatment of chemotherapy-induced nausea and vomiting.

Moderate Evidence of Effectiveness

There is moderate evidence that cannabis or cannabinoids are effective for:

• Improving short-term sleep outcomes in individuals with sleep disturbance associated with obstructive sleep apnea syndrome, fibromyalgia, chronic pain, and multiple sclerosis.

Limited Evidence of Effectiveness

There is limited evidence that cannabis or cannabinoids are effective for:

• Improving anxiety symptoms, as assessed by a public speaking test, in individuals with social anxiety disorders.
• Improving symptoms of post-traumatic stress disorder.

Limited Evidence of Ineffectiveness

There is limited evidence that cannabis or cannabinoids are ineffective for:

• Improving symptoms associated with dementia. 
• Reducing depressive symptoms in individuals with chronic pain or multiple sclerosis. 

None or Insufficient Evidence

There is no or insufficient evidence to support or refute the conclusion that cannabis or cannabinoids are an effective treatment for:

• Cancers
• Symptoms of irritable bowel syndrome.

Cannabis

Cannabis is a broad term that refers to a group of three plants: Cannabis sativa, Cannabis indica, and the less common Cannabis ruderalis. The flowers of these plants can be dried and they yield the psychoactive drug known as marijuana, weed, or pot. There are more than 400 identified substances found in the cannabis flower including more than 120 components known as cannabinoids. While most of these cannabinoids are not well studied, two of them, cannabidiol (CBD) and tetrahydrocannabinol (THC) have been scientifically explored in good detail. CBD and THC have the exact same molecular structure made up of 21 carbon atoms, 30 hydrogen atoms, and 2 oxygen atoms, but the atoms are arranged in slightly different ways and it is this difference that results in the different effects each has on your body. [16] [17] 

Cannabidiol (CBD) is a psychoactive cannabinoid, meaning it affects your mind, but it does not produce a high. It is often used for medicinal purposes, particularly to help reduce inflammation and ease pain, and it is also used to manage nausea, migraines, seizures, and anxiety. 

Tetrahydrocannabinol (THC) is the primary psychoactive compound in cannabis and it is the source of the high that is associated with ingesting cannabis. 

Cannabis products may contain just CBD, just THC, or a combination of both. The dried flower from cannabis plants contains both CBD and THC although the ratio of CBD to THC can vary based on which type and strain of plant is used. Hemp, which is a type of cannabis plant, is defined by its low THC content. Hemp contains 0.3 percent or less THC content by dry weight, so it may have lots of CBD but it will not produce a high.

There are synthetic cannabinoids that are human-made and have cannabinoid-like action. These are known to potentially cause more intense and/or longer lasting (up to multiple days) effects and there is a higher chance that they will cause life threatening toxicity. This is the reason that the Lower-Risk Cannabis Use Guidelines (LRCUG) in the Recommendations Section above indicate that synthetic cannabinoids should be avoided. [7] 

The Endocannabinoid System (ECS)

In the early 1990’s researchers were studying THC and came across a body-wide system that appeared to regulate a broad range of functions and processes, including sleep, mood, appetite, memory and reproduction and fertility. This system is now called the endocannabinoid system (ECS) and it is a complex cell-signaling system that works to maintain stability, or homeostasis, in your body. [11] [12] [13] [14] 

The Endocannabinoid System ECS is a neuromodulatory system that plays important roles in central nervous system (CNS) development, synaptic plasticity, and the response to internal and external injuries. Plasticity is the ability of the brain to change and adapt to new information, and synaptic plasticity is change occurring at the synapses, which are the spaces between neurons that are used for communication. Generally, a neuromodulatory system consists of small groups of neurons located in the brain that can have a powerful effect on cognitive behavior and support many higher cognitive functions including attention, decision-making, emotion, and goal-directed behavior. Given this information, interest in the endocannabinoid system is growing but the research is still early and the working of this system is not well understood. [11] [15]

There are three components to the ECS: endocannabinoids, receptors, and specialized enzymes. 

Endocannabinoids, also called endogenous cannabinoids, are molecules made by your body (endogenous means ‘made within’). They’re similar to cannabinoids found in cannabis that you purchase from the pot store, but they’re produced by your body. These endocannabinoids help keep internal functions running smoothly and your body produces them as needed.

Endocannabinoid 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 types of endocannabinoid receptors:  CB1 and CB2 . CB1 receptors are mostly found in the central nervous system whereas CB2 receptors are mostly found in your peripheral nervous system. Your endocannabinoids can bind to either of these receptors and the effects vary based on which endocannabinoid binds to which receptor in which location. For example, your naturally-produced endocannabinoids might target CB1 receptors in a spinal nerve to relieve pain. 

There are more CB1 receptors in your brain than most other types of neural receptors and they have an important job – they control the levels and activity of most of the other neurotransmitters. They act to increase or decrease the activity of any of your body systems that need to respond to a stimulus such as your immune system adjusting to the presence of inflammation. [14] 

Finally, specialized enzymes work to break down your endocannabinoids once they have completed carrying their message to the receptors. [12] 

Cannabis and Your Endocannabinoid System

How does cannabis make you high?
Once you ingest THC it binds to both CB1 and CB2 receptors in your ECS in the same way that your endocannabinoids do. This causes the psychoactive effects, however these can be intended, such as pain or nausea reduction, or they can be unintended, such as paranoia and anxiety. Scientists are currently working on manufacturing synthetic THC cannabinoids that only produce positive and intended effects. 

CBD works in a different way than THC, in that it doesn’t bind to CB1 or CB2 receptors. One current hypothesis is that it works by preventing endocannabinoids from being broken down by enzymes, allowing them to circulate for longer in your system and have a longer or stronger effect on your body. Another hypothesis is that CBD binds to a receptor that has not yet been identified. [17]