Psychomimetic activity

Tables 6.8-6.11 illustrate the wide range of C3 side-chain modified A -THC analogues that have been reported in the literature, together with associated in vitro and in vivo data. The affinity of classical cannabinoid analogues for the CBi receptor has been shown to correlate with depression of spontaneous activity and the production of antinociception, hypothermia and catalepsy in mice, and with psychomimetic activity in humans [93]. However, in some cases, there were unexplained differences between the observed trends in binding affinity and the trends in activity in mouse behavioural models. This may point to differences in efficacy among full agonists, partial agonists and antagonists/inverse agonists, or may reflect differences in in vivo metabolism or blood-brain barrier penetration or a combination of these factors.

In later investigations (1966) the impression that cyclazocine was not suitable as an analgetic was confirmed, but its use for the treatment of narcotic addicts was still favoured. The possibilities for pentazocine looked much brighter, and in 1967 pentazocine was released by the American Food and Drug Administration however, at very high doses some incidence of psychomimetic activity was observed. More recent investigations have demonstrated that, parenterally, the respiratory depression caused by pentazocine is equal to that shown by morphine, and also the absence of addictive properties has been questioned. Prolonged administration of pentazocine produces dependence like morphine. 

Sharp FR, Tomitaka M, Bernaudin M, Tomitaka S. 2001. Psychosis Pathological activation of limbic thalamocortical circuits by psychomimetics and schizophrenia Trends... 

Among the constituents of hemp Cannabis sativa), the tricyclic A -rra -tetrahydrocannabinol 13 possesses the strongest hallucinogenic activity (hashish, marijuana). Cannabinol 14, which possesses an aromatic C-ring, is psychomimetically inactive. 

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