Introduction to Medicinal Cannabis
The use of medicinal preparations of cannabis can be traced back over five thousand years, making it one of the oldest medicinal plants.
Cannabis
More than 500 natural compounds have been identified and isolated from Cannabis sativa. This includes the medicinally important cannabinoids, terpenes, flavonoids, and other non-cannabinoid constituents. These compounds are produced in high concentration in the glandular trichomes, which are the hair-like, resin-secreting glands found on the surface of the female cannabis flower.
Cannabinoids
There are more than 100 cannabinoids in cannabis, which interact with the body’s cannabinoid receptors:
- Endocannabinoids – naturally produced in the body
- Phytocannabinoids – found in many plants, but in highest concentrations in cannabis
- Synthetic cannabinoids – includes pharmaceuticals that are analogues of THC (e.g., nabilone) or are mixtures of plant-extracted THC and CBD (e.g., nabiximols)
THC (delta-9-Tetrahydrocannabinol) is one of the main active ingredients in cannabis. It is responsible for many of the pharmacological effects of cannabis, including the psychoactive effect.
CBD (cannabidiol) is another of the major active compounds in cannabis, and is non-psychoactive.
Activation of Cannabinoids
Inactive delta-9-tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA) in the raw plant must be decarboxylated to the neutral phenols (THC and CBD) to interact with the endocannabinoid system. This occurs when dried cannabis flowers are heated. Many commercially available oils are decarboxylated.
Terpenes and flavonoids
These are responsible for the variety of scents and flavours of different cannabis varieties. Terpenes may have direct physiologic effects as well as interacting with cannabinoids to create the unique properties of individual cannabis varieties. This is known as the entourage effect, a theory that describes the potential interactions between major cannabinoids, minor cannabinoids, terpenes, and other plant constituents.
The Endocannabinoid System
The Endocannabinoid System (ECS) is a ubiquitous lipid signaling system that plays an important role in the regulation of homeostasis throughout the human body. The ECS consists of endogenous receptors, ligands, and metabolic enzymes.
It has been implicated in:
- neural development
- immune function
- inflammation
- appetite
- metabolism and energy homeostasis
- cardiovascular function
- digestion
- bone development and bone density
- synaptic plasticity and learning
- pain, reproduction
- psychiatric disease
- psychomotor behaviour
- memory
- wake/sleep cycles
- the regulation of stress and emotional state
Receptors
The ECS consists of the CB1 and CB2 receptors, two endogenous agonists (or endocannabinoids), and endocannabinoid synthesising and degrading enzymes. CB1 receptors are found in highest concentration in the central and peripheral nervous system and in the gastrointestinal tract. CB2 receptors are found primarily in the immune system, including the tonsils, spleen, lymph nodes, and circulating lymphocytes and neutrophils.
While present throughout the CNS, the concentration of cannabinoid receptors is low in the brainstem, specifically the area responsible for cardiorespiratory drive.
Activation of CB1 receptors
This schematic of a neuronal junction shows the activation of CB1 receptors by endocannabinoids. This retrograde signalling regulates neurotransmission in a precise spatio-temporal manner.
Reference
- Endocannabinoids are produced in the postsynaptic terminal in response to cellular demands.
- These ligands travel through the synaptic cleft and bind to cannabinoid receptors (e.g., CB1) on the cell surface of the presynaptic terminal.
- Once stimulated, cannabinoid receptors activate a signaling cascade that suppresses the release of neurotransmitters into the synaptic cleft (e.g., glutamate, GABA, dopamine, and cholecystokinin).
- Neurotransmitter suppression changes the frequency of postsynaptic neuronal firing.
Methods of Administration
Ingestion
Ingesting cannabis oil from an oral dosing syringe or packaged in softgels ensures accurate dosing.
Inhalation
Vapourising
Vapourising is a way to inhale the bioactive components of medicinal cannabis without burning the plant material. Cannabis is heated to a temperature that volatilises, without combusting, the cannabinoids and other plant constituents. Vapourising reduces the loss of cannabinoids, and is a more efficient way of extracting chemically active constituents.
Smoking
Smoking medicinal cannabis products is not recommended.
Side Effects
Like all other medicine, medicinal cannabis can also have side effects. The risk of dependence following prolonged use of medicinal cannabis has not been sufficiently studied, but the experience of drug research shows that cannabis is less addictive than comparable pain medication if misused (Ref.: Anthony, JC et al. (1994). Experimental and Clinical Psychopharmacology, 2 (3), 244-268).
Side effects from the use of medicinal cannabis include:
- Dry mouth
- Fatigue
- Impaired motor skills
- Dizziness
- Diarrhoea
- Nausea
- Impaired short-term memory and information processing
- Impaired attention
- Increased appetite
- Paranoia and anxiety (at high doses)
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