Medical Cannabis for Peripheral Neuropathy Treatment- Part 3 of 5

How Does Cannabis Work

by Dr. Rosemary Mazanet

In Part 2 of this series we described the history of cannabis and explained that there are two different species:  Cannabis Indica and Cannabis Sativa. This installment will describe how each of these strains are used as a peripheral neuropathy treatment.

Scientists have determined that genetic differences between the two strains result in the production of a predominant amount of a particular chemical (called a cannabinoid) such as THC or CBD. The amounts of THC or CBD, as well as the numerous secondary components present in smaller amounts that may also provide unique benefits determine how the cannabis plants are recommended for different medicinal purposes.  Today’s pharmaceutical grade medical cannabis (non flower) is usually designated by its THC:CBD ratio.

Main uses for THC:CBD Ratios

THC predominant

  • Analgesic/”Opiate Type Pain Relief”
  • Appetite Stimulant
  • Nausea
  • Sleep
  • Muscle Relaxation

CBD predominant

  • Neuropathic Pain Relief
  • Anti-Inflammatory
  • Anxiolytic
  • Cytotoxic
  • Antispasmodic
  • Anticonvulsant/Seizures

Cannabis effects on human physiology

It wasn’t until the mid-1990s that scientists discovered WHY marijuana exerts so many effects in the human body.  The body makes its own endocannabinoids (i.e. anandamide, 2-AG), which are part of a system, the Endocannabinoid System that influences multiple physiological processes such as:

  • Modulation of Pain
  • Seizure threshold
  • Appetite
  • Inflammation
  • Mood
  • Regulation of Immune system
  • Tumor surveillance
  • Intraocular pressure
  • Bone physiology
  • Digestion

These endocannabinoids circulate in the blood stream and bind to cannabinoid receptors in order to have their effect.  The amounts of endocannabinoids that are physiologic in humans is low enough to not have euphoric or central nervous system effects that are apparent.

There are currently two subtypes of cannabinoid receptors that are well characterized. The CB1 receptors are highly concentrated in the brain and nerve endings and the CB2 receptor is expressed mainly on cells of the immune system and blood forming cells.  There are also less well understood VR1 receptors.

Understanding the Endocannabinoid System

Cannabinoid Receptor-1 (CB1)

  • Highly expressed in the brain and CNS
  • Responsible for Neurotransmitter Release
  • Glutamate, GABA, Serotonin, Dopamine, Acetylcholine, Neuropeptides
  • Pain, motor control, memory processing, appetite, spasticity, circulatory effects, emesis, epilepsy, anxiety, etc.
  • Not prevalent in the brainstem, which may account for lack of cannabis-related fatalities (i.e. respiratory depression)
  • 10 times more prevalent in the CNS as compared to μ-opioid receptor for narcotics

Cannabinoid Receptor-2 (CB2)

  • Highly expressed in immune cells
  • Modulation of Cytokine Release
  • Immune Responses and Anti-inflammatory effects

Vanilloid Receptor (VR1) (also known as Transient Receptor Potential Vanilloid Receptor or TRPV1)

  • Highly expressed in the CNS
  • Responsible for Nociception

The cannabinoids in agricultural cannabis or marijuana (Phytocannabinoids, i.e. THC, CBD) bind and activate or inactivate these receptors in the body in much the same way as the human produced endocannabinoids do, at the receptor.  When THC enters the blood stream and reaches the brain, it binds to CB1 receptors much the same way as an endocannabinoid would (like in Figure 4), except at a pharmacological dose rather than a physiological dose.  This type of binding results in changes in the levels of various neurotransmitters (like dopamine and norepinephrine) released from the neurons.  The result for the patient is the acute effects of cannabis ingestion, such as euphoria and anxiety.

 

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