Study design considerations in clinical trials with marihuana

Political and social pressures exist to make smoked marihuana available for treatment of a variety of seemingly unrelated medical disorders. Efficacy of smoked marihuana for any disorder remains unproven by scientifically valid techniques. Study design considerations for clinical trials with marihuana are considered. Marihuana is a plant with great variability. Although the clinical pharmacology of THC is well studied, relatively little medication development efforts have been devoted to marihuana itself. Control of delivered cannabinoid dose from smoked marihuana will be difficult. Protocols that require multiple dose levels and placebos will present problems. The availability of illicit marihuana may pose compliance problems in controlled trials, particularly with patients assigned to low-dose or placebo conditions. Some patients may consider the diversity of marihuana effects, particularly cognitive and cardiovascular effects, as adverse or unwanted. Decisions about the ultimate usefulness of marihuana should be based on relative benefits and risks. The risks of smoked marihuana for some medical applications may be greater than the risks posed by typical nonmedical use because of more frequent and regular dosing. Marihuana's utility as a medicine should be determined by generally accepted principles guiding medication development. Standards for determining the efficacy and safety of marihuana as a therapeutic agent should be equivalent to those used in other medication trials. Problematic study design issues are a consequence of the need to evaluate the therapeutic efficacy and safety of a smoked, crude natural product. Clinical trials with marihuana will be difficult, and fairly expensive to execute, but not impossible.