• Cannabis sativa appeared about 60 AD in the Pharmacopoeia of Pedanius Dioscorides (Greek physician, pharmacologist, botanist, and author of De materia medica), who served in the Roman army under Claudius and Nero.
• During sixteenth century England:

The Herbal of John Gerard (1597) in England recommended cannabis for easing the earache, and the Herbal of Nicholas Culpeper (1653) recommended its use to alleviate inflammations and ease the pain of gout and tumours

• In the 1960s, 49-tetrahydrocannabinol (THC) was first isolated and identified by Mechoulam and Gaoni in Israel
• The chemical synthesis of new potent cannabinoid derivatives and analogues allowed Devane to identify specific binding sites in the brain
• Definite proof of their existence came from the molecular cloning of the: Cannabinoid type 1 (CB₂) receptor in brain but also the heart and vasculature Cannabinoid type 2 (CB₂) receptor in immune cells

Devane WA, Dysarz FA, Johnson LS, Melvin LS, Howlett AC. Determination and characterization of a cannabinoid receptor in rat brain. Mol Pharmacol. 1988;34:605-613 Mechoulam R, Gaoni Y. The absolute configuration of delta-1-tetrahydrocannabinol, the major active constituent of hashish. Tetrahedron Lett. 1967:12:1109-1111 House of Lords Science and Technology- Ninth Report 1998. Science and Technology Committee Publications

Cannabis sativa – annual herbaceous flowering plant indigenous to eastern Asia

Cultivated throughout recorded history for: industrial fiber, seed oil, food, recreation, religious and spiritual moods and medicine

First classified by Carl Linnaeus in 1753

Constituents include than 500 compounds, such as:

• Strains are cultivated for specific ratios (sativa vs. indica)

Receptors:

Cannabinoid receptors

• CB1 – Psychoactive effects
• Expressed in the brain, heart, and vasculature

CB2-No psychoactive effects

• Expressed in the immune system

Endogenous ligands:

Endocannabinoids

• Derivatives of arachidonic acid
• Anandamide
• 2-arachidonoylglyercerol (2-AG)

Agonists:

• Anti-emetics
• Appetite stimulants (cancer)
• Analgesics for the relief of neuropathic pain

Antagonists:

• Obesity
• Metabolic disorder