Therapeutic Indication as an add on therapy

Cannabidiol oral Solution is indicated for the treatment of seizures associated with Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS) for 2 years of age and older and Tuberous sclerosis complex (TSC) in patients 1 year of age and older.

Mechanism of action

Cannabidiol (CBD) anti-seizure action mechanism remains not fully understood. CBD displays no effect on cannabinoid receptors (CB1 and CB2), compared to delta-9-tetrahydrocannabinol, and therefore has no psychotropic effects. Putative main mechanisms of CBD antiseizure action include modulation of intracellular calcium (via G protein-coupled GPRR55 receptors, transient receptor potential vanilloid type 1 TRPV1 channels, and voltage-dependent anion-selective channel protein 1 - VDAC1), leading to decreased neuronal excitability. Additionally, CBD influences anti-inflammatory adenosine-associated signaling pathways via equilibrative nucleoside transporter 1 - ENT-1 – inhibition and tumor necrosis alpha factor – TNF-alpha – so resulting in an antiepileptogenic effect.

Results and outcomes

  • In patients with Lennox gastaut syndrome, cannabidiol significantly reduces the frequency of drop seizures. A reduction in drop seizures was observed within 4 weeks of initiating treatment with cannabidiol and the effect remained generally consistent over the 14 weeks’ treatment period.
  • In patients with Dravet syndrome, cannabidiol significantly reduces in the frequency of convulsive seizures. A reduction in convulsive seizures was observed within 4 weeks of initiating treatment with cannabidiol and the effect remained generally consistent over the 14-week treatment period.
  • In patients with Tuberous sclerosis complex, cannabidiol significantly reduces in the frequency of TSC associated seizures. A reduction in TSC associated seizures was observed within 4 weeks of initiating treatment with cannabidiol and the effect remained generally consistent over the 12-week maintenance period.

Important safety information-

  • Hepatocellular Injury - Cannabidiol can cause dose-related elevations of liver transaminases (alanine aminotransferase [ALT] and/or aspartate aminotransferase [AST]).

 

  • Somnolence and Sedation - Cannabidiol can cause somnolence and sedation. Prescribers should monitor patients for somnolence and sedation and should advise patients not to drive or operate machinery until they have gained sufficient experience on Cannabidiol to gauge whether it adversely affects their ability to drive or operate machinery.

 

  • Suicidal Behavior and Ideation - Antiepileptic drugs (AEDs), including Cannabidiol, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with an AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, or any unusual changes in mood or behavior.

 

  • Hypersensitivity Reactions - Cannabidiol can cause hypersensitivity reactions. Cannabidiol is contraindicated in patients with a prior hypersensitivity reaction to cannabidiol or any of the ingredients in the product, which includes sesame seed oil.

 

  • Withdrawal of Antiepileptic Drugs (AEDs) - As with most antiepileptic drugs, Cannabidiol should generally be withdrawn gradually because of the risk of increased seizure frequency and status epilepticus. But if withdrawal is needed because of a serious adverse event, rapid discontinuation can be considered.