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Major Studies of Drugs and Drug Policy
Marihuana, A Signal of Misunderstanding - Table of Contents

Factors Influencing Psychopharmacological Effect


The problem in quantifying the THC dose delivered by different routes of administration has been clarified by several studies using radioactive compounds. However, until a method for determining the THC blood concentration is developed, only estimates oil amount delivered are possible.

Radioautographic studies clearly demonstrate that intravenous injection gives the, most complete and consistent delivery (Lemberger et a]., 1971; Me Isaac et M., 1971; Ho et a]., 1971; Kennedy and Waddell, 1971; Idanpaan-Heikkila, 1971). These investigators have demonstrated that THC is poorly absorbed from the injection site after intraperitoneal or subcutaneous injection.

As discussed earlier, the completeness of absorption ocurring after oral administration of THC appears to depend upon the vehicle. Judged by radioactivity levels, almost complete absorption of the THC occurs with an oil or bile acid vehicle, but absorption is incomplete with an alcohol vehicle. (Perez-Reyes et al., 1971)

Recent animal studies performed for NIMH indicated that the oral dose necessary to produce comparable gross behavioral changes in lab animals is about three times higher than the intravenous dose (Marihuana and Health. 1971: 171). Ferraro (1971) demonstrated the comparability of effective oral doses of THC in chimpanzees and humans. Furthermore, preliminary work performed in the laboratories of M. Isaac (1971) and Harris (1971) and Mechoulam (1971) appear to indicate that the intravenously administered dose of Delta 9 THC necessary to produce detectable behavioral changes in monkeys (20 to 50 microgram/ kg) on conditioned learning tasks is comparable to that in man. (Kiplinger et a]., 1971; Lemberger et al., 1971).

The dose of THC absorbed from natural marihuana extracts ingested orally is uncertain. THC is present as an acid in variable quantities in natural marihuana. THC acid has not presently been proven to be active. Claussen and Korte (1968) reported that the THC carboxylic acid is converted to free THC during the smoking process. Whether these, acids are active themselves; are absorbed from the gastrointestinal tract or converted there into THC; or are decarboxylated in the, body is unknown presently.

Because inhalation is the most widely used route of administration of marihuana, several laboratories have investigated the effect of combustion and smoking oil marihuana. Because techniques and conditions varied between laboratories, precise quantification of the delivery to the smoker's lungs is uncertain.

Manno, et al. (1970) calculated that about 50% of the THC contained in a marihuana cigarette would be delivered to the smoker's lungs for absorption if the entire cigarette were smoked in 10 minutes and each inhalation was retained for 30 seconds with no sidestream loss. Truitt (1971) and co-workers (Foltz et al., 1971) found that 50%c of THC was pyrolyzed and 6% was lost in the side stream while noting that almost 21% of the THC remained in the butt when three-fourths of the cigarette is consumed.

Agurell and Leander (1971) studied the transfer of THC using actual smoking subjects where only the main stream smoke was collected. They found that 14-29%% of the THC was transferred in the mainstream smoke for a cigarette and 45% for a pipe. However, they stated that this amount transferred would be comparable if no butt was left.

Agurell and Leander found that the amount transferred was not effected by depth of inhalation but that smokers using deep inhalation retained 80% of the transferred THC while those using superficial inhalation tended to exhale more than 20% of the transferred THC. Mikes and Waser (1971) also found about 22% in the mainstream smoke.

These divergent data appear to be comparable when corrected for loss to sidestream and retention in the unsmoked portion. Thus, the efficiency of delivery of THC by smoking and inhalation using good techniques, and smoking the entire cigarette approximates 40-50% of the original THC contained. A small fraction is lost in the uninhaled sidestream smoke, about 50% is destroyed during pyrolysis and a variable amount is exhaled from the respiratory dead space.

In apparent confirmation, Lemberger et al. (1971, 1972), using radiolabeled THC added to a marihuana cigarette, found that the initial plasma level of radioactivity after smoking was about onehalf the level after intravenous injection. Oral administration of the same dose of THC in an alcohol vehicle produced about one-half the peak level as smoking. However, Galanter et al. (1972) noted marked variability in the amount of THC absorbed using a standardized routine of inhaling, breath-holding and finishing the cigarette within a set time period.

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