A second factor which influences the effect experienced by the user is the manner in which the substance is consumed. That is, whether it is smoked, swallowed or injected.

Isbell et al. (1967) demonstrated that smoked material is two and a half to three times as effective as orally consumed marihuana in the form of a 95% ethanolic solution in producing equivalent physiologic and subjective effects.

In addition, the oral time-action curve is extended with onset of symptoms one-half to one hour after administration. A peak effect is reached in two to three hours and the effect persists for three to five hours at low doses and six to eight hours at larger doses (Hollister et al., 1968; Isbell, et -al., 1967; Lemberger et al., 1971; Perez-Reyes, and Lipton, 1971).

In general, the effects produced by ingested THC or ingested marihuana extract are comparable to those produced by nearly one-third the amount of smoked and inhaled THC or marihuana (Hollister, 1971).

Recent work has been reported which clarifies these findings. Lemberger et a]. (1971) studied absorption into the blood utilizing radioactive labeled THC by three routes of administration: smoked, ingested in 95% ethanolic solution in cherry syrup, and intravenously injected. The first appearance of the drug into the, blood was immediate intravenously; almost immediate, by inhalation; and delayed for 15 to 30 minutes when ingested.

Perez-Reyes and Lipton (1971) using labeled AO THC demonstrated that rate of absorption by the gastrointestinal tract, and the duration of action is greatly influenced by the vehicle used to ingest the drug. Speed and completeness of absorption varied when the THC was dissolved in 100% ethanol or sesame oil or emulsified with a bile salt (sodium glycocholate), and administered to a subject who had fasted 12 hours. With the bile salt vehicle, the physiologic and subjective effects were noted between 15 to 30 minutes after ingestion and lasted two to three hours. In contrast, the effects, with ethanol or sesame oil, appeared after one ,hour and lasted four to six hours.

Hollister and Gillespie (1970) hypothesized that this delayed gastrointestinal absorption of THC might be accounted for by the nonpolar vehicle required to dissolve TUC or marihuana extracts.

Furthermore, Perez-Reyes and Lipton (1971) found that the peak levels and duration of radioactivity in the plasma paralleled the physiologic and subjective effects, although the plasma levels remained high for a longer period of time than the effect. Subjects receiving the drug emulsified in sodium glycocholate or dissolved in sesame oil had three times higher plasma levels of radioactivity with much less excreted in the feces than those receiving the drug dissolved in ethanol.

These results indicate that the THC was poorly absorbed from the gastrointestinal tract when given in all alcoholic solution. The sesame oil solution and the glycocholic acid preparation allowed more complete absorption and the latter preparation was much faster. It is of interest that the degree of subjective high after ingestion of 37 milligrams Delta 9 THC also parallels the plasma radioactivity.

Thus, the subjects reported their experience, as intense and unpleasant both with the bile salt and the sesame oil, and as moderate and entirely pleasant with ethanol. (Perez-Reyes and Lipton, 1971) This correlates well with earlier findings of Hollister et a]. (1968).