Δ7-TETRAHYDROCANNABINOL, A NON-PSYCHOTROPIC CANNABINOID: STRUCTURE-ACTIVITY CONSIDERATIONS IN THE CANNABINOID SERIES

Summary An improved synthesis, purification and spectroscopic data of (3R, 4R)-Δ 1(7) -tetrahydrocannabinol (Δ 7 -THC), a double bond isomer of Δ 1 -THC are described. The conformation of the isoprenoid ring of Δ 7 -THC was determined by nmr, based on model considerations. The ring is locked in a half chair conformation, the exocyclic methylene carbon being located ca 100 pm perpendicular above the plane of the aromatic ring. When tested for cannabinoid-like activity in the Rhesus monkey, Δ 7 -THC was found to be inactive in dosage up to 5 mg/kg i.v. Δ 7 -THC neither antagonized nor synergized the behavioural changes elicited by the standard Δ 1 -THC. Because of its close structural resemblance to the psychotropically active cannabinoids Δ 1 - and Δ 6 -THC, Δ 7 -THC is suggested as a model compound to differentiate the general effects produced by these cannabinoids from their specific psychotropic effects. The influence of side chain hydroxyl groups on the psychotropic activity of cannabinoids, determined for 4”-hydroxy-Δ 1 -THC, a microbial metabolite of Δ 1 -THC is discussed in relation to a hypothetical THC receptor.