Schaffer Library of Drug Policy

Marihuana: A Signal of Misunderstanding

Marijuana -- Factors Influencing Psychopharmacological Effect - Reverse Tolerance

US National Commission on Marihuana and Drug Abuse

Table of Contents
I. Marihuana and the Problem of Marihuana
Origins of the Marihuana Problem
The Need for Perspective
Formulating Marihuana Policy
The Report
II. Marihuana Use and Its Effects
The Marihuana User
Profiles of Users
Becoming a Marihuana User
Becoming a Multidrug User
Effects of Marihuana on the User
Effects Related to Pattern Use
Immediate Drug Effects
ShortTerm Effects
Long Term Effects
Very Long Term Effects
III. Social Impact of Marihuana Use
IV. Social Response to Marihuana Use
V. Marihuana and Social Policy
Drugs in a Free Society
A Social Control Policy for Marihuana
Implementing the Discouragement Policy
A Final Comment
Ancillary Recommendations
Legal and Law Enforcement Recommendations
Medical Recommendations
Other Recommendations
Letter of Transmittal
Members and Staff
History of Marihuana Use: Medical and Intoxicant
II. Biological Effects of Marihuana
Botanical and Chemical Considerations
Factors Influencing Psychopharmacological Effect
Acute Effects of Marihuana (Delta 9 THC)
Effects of Short-Term or Subacute Use
Effects of Long-Term Cannabis Use
Investigations of Very Heavy Very Long-Term Cannabis Users
III. Marihuana and Public Safety
Marihuana and Crime
Marihuana and Driving
Marihuana - Public Health and Welfare
Assessment of Perceived Risks
Preventive Public Health Concerns
Marihuana and the Dominant Social Order
The World of Youth
Why Society Feels Threatened
The Changing Social Scene
Problems in Assessing the Effects of Marihuana
Marihuana and Violence
Marihuana and (Non-Violent) Crime
Summary and Conclusions: Marihuana and Crime
Marihuana and Driving
History of Marihuana Legislation
History of Alcohol Prohibition
History of Tobacco Regulation
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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).

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