In spite of the risky nature of some of the experiments (e.g., inducing addiction to opiates, alcohol, barbiturates, or new minimally tested pharmaceuticals, and then forcing immediate and severe withdrawal), there were apparently no fatalities, though there was at least one close call. Subjects sometimes dropped out in the middle of an experiment, although in one reported case a subject who wished to drop out after a severe negative reaction to a 180 microgram LSD dose ("He felt that he would die or would become permanently insane") required "considerable persuasion" to continue. The studies took place in a dedicated experimental ward. Given the hospital context, medical personnel were readily available. In general, the methodology appears scientifically sound (e.g., proper balancing of experimental conditions, within-subjects designs, single (sometimes double) blind procedures as appropriate, placebo conditions, careful documentation of the experimental procedures, appropriate awareness of potential confounding factors, etc.), although the small number of subjects in some of the experiments is a statistical concern. The general methodology for the addiction studies consisted of first getting subjects drug-free (with apparent exceptions for cigarettes and coffee), and then attempting to induce addiction by regular administration (orally or injected) of the substance of interest. Addiction was determined by the occurrence of abstinence symptoms when administration of the substance stopped. Sometimes a different substance (e.g., methadone) would be administered at the peak of withdrawal to determine if it alleviated symptoms. Following the evaluation of this cold turkey withdrawal, subjects were then usually more gradually weaned off of the substance being tested. Isbell also evaluated the "euphoric" effect of various drugs (typically opioids), evaluating various doses to see if they induced similar effects (e.g., talkativeness, comfort in the experimental situation, sedation in high doses) as 30 mg of morphine. The ability to induce euphoria is sometimes/often considered to be a component of addiction liability. In the psychedelic studies, subjects had the choice of staying in an individual room or mingling with other subjects in a common area. Observations and measurements were taken before the substance of interest was ingested, and hourly thereafter (following a 10-minute rest in bed). Physical measurements included pulse, blood pressure, rectal temperature, kneejerk reflex sensitivity, and pupil diameter (opiates cause constriction (miosis) while LSD causes dilation (mydriasis)). Psychological measurements consisted of a self-evaluation form with multiple statements (e.g., "I am confused"), as well as evaluation by experienced and trained observers.