&NA;The cytogenetic effects of subacute oral administration of &Dgr;‐9‐tetrahydrocannabinol, cannabidiol, cannabinol, and placebo were assessed in 27 subjects in a prospective double‐blind study. Both conventional chromosome aberration analysis and sister chromatid exchange were considered. A comparison group of 5 nondrug users was also investigated. The aneuploidy frequency decreased significantly following &Dgr;‐9‐tetrahydrocannabinol administration. By contrast, the frequencies of chromosome aberrations increased slightly for all three drug groups and decreased in the placebo and comparison groups although none of the predrug versus postdrug comparisons were statistically significant. No increase in the sister chromatid exchange frequency was found in any of the groups when predrug versus postdrug comparisons were made. The present study is the fourth short term prospective investigation failing to demonstrate a statistically significant increase in chromosome damage due to cannabinoid usage. However, it must be kept in mind that to date only gross chromosomal aberrations have been identified so that the more subtle chromosomal as well as molecular genetic damage has not been ruled out.