Blunted THC Responses in Frequent Users Did Not Establish Why the Groups Differed
Frequent cannabis users showed smaller responses to several THC effects in a controlled experiment, but that comparison did not establish that acquired tolerance was the sole cause. Pre-existing differences remained another possible explanation.
The drug challenge was controlled
Thirty frequent users and twenty-two healthy controls were compared during a blinded, placebo-controlled intravenous THC study. Researchers assessed memory, attention, transient psychotomimetic and perceptual effects, subjective high, cardiovascular responses and endocrine measures.
Blunting was not uniform
The abstract reports THC effects in both groups, with smaller frequent-user responses in several cognitive, symptom and cortisol outcomes. Euphoric effects did not show the same relative blunting. The cortisol measurement was in serum, a distinct processed blood matrix.
Randomizing the challenge does not randomize use history
A controlled THC-versus-placebo comparison strengthens evidence about acute drug effects. It does not make frequent users and controls identical before their different cannabis histories developed.
The authors explicitly allowed both inherent blunting and acquired tolerance as explanations. Neither possibility establishes that frequent users are unaffected by THC or protected from psychiatric illness. The experiment also did not validate a personal impairment threshold. A careful account preserves the positive effects, the selectively smaller responses and the uncertainty about the origin of the group difference.
Related: interpreting cannabis tolerance claims.
Research cited
D'Souza DC; Ranganathan M; Braley G; Gueorguieva R; Zimolo Z; Cooper T; Perry E; Krystal J. Blunted psychotomimetic and amnestic effects of delta-9-tetrahydrocannabinol in frequent users of cannabis. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology (2008). doi:10.1038/sj.npp.1301643. Findings discussed from the study abstract.
