Cannabinoid pharmacokinetics in occasional users is well studied, but the interpretation of data from heavy users is difficult. In the present study, blood pharmacokinetic properties were investigated in occasional and heavy users in cannabis and placebo conditions. The results obtained with occasional users were in contrast to those of the heavy users who admitted cannabis use on 4-25 occasions during the previous week. Of the 12 heavy users, 10 exhibited up to 12.3 microg/L Delta(9)-tetrahydrocannabinol (THC) prior to smoking. During the 8 h after smoking, the distribution and elimination patterns were comparable to those of the occasional users and the concentrations returned to 68-196% (median 110%) of the initial values. However, the maximal concentration and the areas under the curves were significantly higher with marked interindividual variation. In contrast to the cannabis conditions, the THC concentrations in the placebo phase decreased more slowly (elimination half-life 17.5-43.5 h vs. 1.0-5.9 h) in accordance with a late elimination phase. The elimination half-lives of 11-hydroxy-THC and 11-nor-9-carboxy-THC in th cannabis conditions (medians 3.1 h and 6.2 h, respectively) were longer than those of THC, which was different in the placebo phase (medians 7.2 h and 13.0 h, respectively). From the results, it must be cautioned that cannabinoid blood concentrations from heavy users in a late elimination phase may be difficult to distinguish from concentrations measured in occasional users after acute cannabis use.