Nociception is enhanced after low doses and reduced after high doses of the serotonin receptor agonist 5-methoxy-N,N-dimethyltryptamine.

The effects on pain sensitivity of intracerebroventricular injections of 5-methoxy-N,N-dimethyltryptamine were tested by the tail-flick method. Following administration of 1.6, 3.1, 6.3, 12.5 and 25 micrograms (n = 8 for each dose), tail-flick latencies were reduced by 13-24%. Fifty and 100 micrograms caused a biphasic response (hyperalgesia followed by analgesia), whereas 400 micrograms increased mean latencies by 28-39%. The hyperalgesia observed after low doses was most likely due to reduced activity in descending serotonergic neurons following presynaptic stimulation. Higher doses caused analgesia, probably by stimulating spinal postsynaptic serotonergic receptors as well.