Factors Influencing Psychopharmacological Effect
Smith and Mehl’s (1970) clinical observations of many marihuana smokers suggest a J-shaped time curve of tolerance to marihuana. A novice marihuana smoker often reports feeling no high or requiring considerably more drug to get high on his first few trials with the drug than after he obtains more experience with the drug. This phenomenon has been called “reverse tolerance.” These clinicians believed this represented “learning to get high” or acquiring the ability to appreciate or become sensitive to the subtle aspects of the intoxication.
Goode (1971) found that more frequent and term marihuana smokers tend to require fewer “joints” to get high but differences were not statistically significant.
Weil et al. (1968) reported that experienced users of marihuana achieved a “high” after being given the same dose as naive (non-users) persons who did not experience a high but did demonstrate objective physiologic and psychomotor drug effects.
Meyer et al. (1971) found that heavy marihuana, users (daily for three years) were most sensitive to the “high” and required less marihuana to achieve a social high than infrequent intermittent users (use one to four times per month for less than two years).
Phillips et al. (1971) reported an increase in severity of symptoms after repeated administration of THC to rats. This “sensitization” may be a correlate of reverse tolerance.
Lemberger et al. (1971) supplied additional evidence for reverse tolerance based on the intravenous administration of 0.5 mg of THC to experimental subjects. Naive subjects experienced no effect from this small dose. However, daily marihuana users, who were told they were receiving a non-pharmacologically active dose of THC, reported a “marihuana high,” which lasted up to 90 minutes.
Lemberger et al. (1971, 1972) and Mechoulam (1970) suggested the possibility that enzymes necessary to convert THC to a more active compound require prior use of marihuana.
Reverse tolerance appears to be a complex phenomenon. Jones (1971) presented evidence which stressed the importance of expectation, setting and prior drug experience on learning to get “high.” As the user gains more experience with marihuana, the more the individual’s mind is able to respond to the expectation of the “high” by actually becoming high when given an inert material which smells and looks like marihuana.
Weil (1971) believes that the capacity to get “high” is an inherent characteristic of each individual’s mind. He, believes that marihuana facilitates the user’s abilitv to achieve this altered state of consciousness, that is, learn how to get high.
Mendelson et al. (1972) did not find evidence for reverse tolerance. In fact, the daily users were more likely than the intermittent users to smoke two cigarettes per occasion. Both groups had had an average of five years of marihuana use. Several other investigators did not obtain any evidence of reverse tolerance after repetitive daily use in experienced subjects (Hollister, 1971; Schuster and Renault, 1971; Fink et al., 1971).
Factors Influencing Psychopharmacological Effect REVERSE TOLERANCE Smith and Mehl’s (1970) clinical observations of many marihuana smokers suggest a J-shaped time curve of tolerance to