It belongs to ω-conopeptides which are 24–29 amino acid peptides isolated from cone snail venom. It blocks N-type calcium channels in the substantia gelatinosa. It also binds to the dorsal horn of the spinal cord, thus affecting presynaptic afferent fibres. It blocks transmitter release at the nerve terminal by blocking calcium influx. Systemic administration causes hypotension and thus it is administered intrathecally.100 % bioavailability is seen after intrathecal administration. It is cleared at the rate of 0.38 ml/min, primarily by diffusing into the systemic circulation where it is broken down by proteases and peptidases. Tolerance to antinociceptive effect is not seen unlike opioids. It is given at a dose of 2.4 mcg/day with dose titrations 2–3 times weekly. The onset of pain relief may take up to 1–2 h with peak effect seen in 8–12 h, and effect lasts for up to 2 days after the initial dosage.

Side effects seen are nausea, dizziness, nystagmus, confusion, somnolence, blurred vision, headache, infection and subarachnoid haemorrhage.

Cannabinoids are extracted from Cannabis sativa. The major active constituent is delta-9-tetrahydrocannabinol. Two receptors involved are CB1 and CB2. CB1 is in abundance everywhere whereas CB2 is seen in immunological system. The receptors on activation decrease cAMP via G proteins. CB1 receptors also block calcium channels. Cannabinoids are not licensed for chronic pain but are available for chemotherapy-induced emesis and appetite stimulation in AIDS patients. Studies have shown cannabinoids to be effective in reducing mechanical hyperalgesia. They also are effective in neuropathic pain in multiple sclerosis.