Pharmacology

Pharmacodynamics

Medical cannabis contains several active compounds. THC is one of the most studied cannabinoid compound, showing activities as anesthetic, anti-inflammatory, antiemetic, antispasmodic, appetite stimulator and psychomodulator. CBD, another well-known cannabinoid, has strong therapeutical effects, such as anti-inflammatory, analgesic, anxiolytic, antiepileptic and anti-ischemic, in addition to neutralizing the psychoactive effects of THC, acting as a negative and competitive allosteric modulator of the CB1 receptor. Another cannabinoid compound, CBN acts as a weaker ligand for CB1 receptors (about 10% affinity, compared to THC) and has immunosuppressive effects, mostly. As for CBG, also with anti-inflammatory and analgesic activities, it acts as a partial agonist of cannabinoid receptors.¹

Safety

The safety level of cannabinoid extracts is quite favorable, especially when considering that of traditional therapeutic options. Compared to opioid derivatives, very popular in pain therapy, cannabis may have a superior sedative effect, but it has no potential to cause respiratory depression or addiction. Furthermore, its overdose is very difficult to be achieve, considered to be unlikely.

Adverse Effects – At a central level, possible adverse effects to cannabinoid medication are euphoria, dizziness, disorientation, temporary incoordination and drowsiness. At a peripheral level, adverse effects include tachycardia, hypotension, bronchodilation and muscle relaxation.²

Dosage

The dosing protocol is particular to each pharmacological composition, to each administration route, to the clinical condition considered and more importantly, to each organism. It is however crucial to keep in mind the pharmacokinetics of cannabis derivatives, when establishing such protocols.³

Administration Route Onset of Action Duration of Action Comments
Inhalation 5-10 minutes 0.5-4h Ideal for acute symptoms, for its fast penetration into bloodstream, ensuring immediate onset of action
Oral 60-120 minutes 5-8h Ideal for chronic diseases, as it ensures longer lasting effects
Sublingual 30-60 minutes 4-6h Fast onset of action and guarantee of longer lasting effects, ideal for chronic diseases
Topic >30-120 minutes 4-6h Safer route, due to its weak systemic effect, being of easy administration. Ideal for local symptoms

Drug interactions

Oral administration of cannabinoid extracts leads to hepatic metabolism, through enzymes of the CYP450 complex. The main enzymes involved are CYP2C9, CYP2C19 and CYP3A4, responsible for the hydroxylation of THC and CBD. On those enzymes, cannabinoids compounds act in an inhibitory manner. It is therefore important to consider the interaction with other compounds metabolized by this route when introducing cannabinoid derivatives into patient therapy.¹

Drugs that can lead to interaction with medical cannabis are:

  • Clobazam, Valproates, Warfarin, Opioids – which have their half-life increased by cannabinoid compounds;
  • Carbamazepine, Phenytoin and Topiramate – which reduce the half-life of cannabinoid compounds.

References

  1. Guia de Manejo de Cannabis Medicinal. V1, Julio 2021
  2. https://jamanetwork.com/journals/jamaoncology/fullarticle/2504173#crv160001r25
  3. https://www.onclive.com/view/a-primer-on-rising-medical-cannabis-use-in-oncology