The mechanism of action of paracetamol is as follows:

• Inhibiting prostaglandin production in the brain: Prostaglandins are chemicals responsible for pain and inflammation, when when you take Paracetamol it inhibits the chemicals, thereby inhibiting the sensing of pain.

• Affecting the hypothalamic heat-regulating center: Another effective use of paracetamol is its ability to reduce fever. It achieves this by acting on the portion of the hypothalamus thats responsible for pain. 

• Acting on multiple neurotransmitter systems

  The neurotransmitters paracetamol acts on include

  • Serotonergic pathways: These are in serotonin secretions, a neurotransmitter that plays a key role in mood, pain perception, sleep, and more. so Paracetamol increases the secretion of serotonin in the central nervous system, especially in areas related to pain processing (like the spinal cord and brainstem). This in turn helps to reduce the sensation of pain, similar to how some antidepressants that increase serotonin can also relieve chronic pain.

  • Opioid receptors: These are part of the body’s natural pain-relief system. Endorphins (natural painkillers) bind to these receptors to reduce pain. Paracetamol indirectly activates it, but it is not considered an opoid because it has low affinity for it.

  • Cannabinoid system: This system helps regulate pain, appetite, mood, and memory. It involves CB1 and CB2 receptors, which are affected by substances like THC in cannabis—but also by natural body chemicals like anandamide. Paracetamol is metabolized into AM404, which prevents the breakdown of anandamide, a natural cannabinoid. By boosting anandamide levels, paracetamol may enhance the body’s own cannabinoid pain relief, without causing a “high.” This might contribute to its calming, pain-reducing effect.

  • Nitric oxide pathway: Nitric oxide is a gas and signaling molecule involved in blood vessel dilation, immune response, and pain processing in the brain and spinal cord. Paracetamol may inhibit nitric oxide synthase, the enzyme that produces nitric oxide during inflammation. This could reduce neurogenic inflammation and pain sensitization, helping ease discomfort without significant anti-inflammatory effects like NSAIDs.

Unlike NSAIDs (non-steroidal anti-inflammatory drugs), paracetamol does not have strong anti-inflammatory properties, making it gentler on the stomach and less likely to cause gastrointestinal side effects.