CLINICAL
Side
Effects
BY
ADAM
ofSimultaneous
SULKOWSKI,
Alcohol
M.D.,
AND
LOUIS
and VACHON,
Marijuana
The subjects were young (aged 20-29) healthy male volunteers, screened by physical examination, psychiatric interview, and psychological questionnaire. All subjects signed a statement of informed consent that described the project in detail. The subjects all claimed that they were experienced social users (i.e. from once a month to twice a week) of both drugs and cornbined them frequently to increase the high. The following treatments were administered in randomized order to each subject. 1 A drink containing 1 g/kg of body weight of ethanol diluted in pure orange juice to a volume of 400 ml was consumed in 10-iS minutes. One hour later, a placebo marijuana cigarette (THC-exhausted) was smoked. 2. A placebo drink consisting of 400 ml of orange juice in a glass smeared with ethanol was drunk. This was followed 1 hour later by a cigarette containing active marijuana. 3. An “active” alcohol drink (as in number 1 above) was followed 1 hour later by a cigarette containing active marijuana. The dose of ethanol used in this study is known to produce a mild degree of intoxication and slight psychomotor impairment (3). The marijuana cigarettes were supplied by the National Institute on Drug Abuse. The analysis that accompanied the cigarettes indicated a content of 18 mg of-9-tetrahydrocannabinol. This dose has been found to produce a moderate social high in experienced users (4). The drugs were administered 1 hour apart; ethanol was given first because we expected that the subjects would ‘titrate’ their marijuana intake to reach their ‘optimum” level of intoxication. Specific instructions ,
.
‘
‘
Dr. Sulkowski ciate Professor cine, Division 02118.
is Instructor of Psychiatry and Dr. Vachon is Assoof Psychiatry, Boston University School of Mcdiof Psychiatry, 720 Harrison Ave. , Boston, Mass.
This
supported
in part
tal Health Administration tute on Drug Abuse.
grant
was
REPORTS
Use
to this effect had been included in the sent form and were repeated verbally subjects smoked. This strategy has been fully in studies of marijuana smoked schedule (5). Several performance tests tered before and after each treatment published elsewhere). Heart rate, blood conjunctival injection were monitored throughout the experiment. Incidence
Method
work
RESEARCH
M.D.
There is an increasing trend toward the simultaneous use of alcoholic beverages and marijuana as social intoxicants (1). Experimental data concerning the interaction of these drugs in humans are few and inconclusive (2). We recently began a study in which socially relevant doses of marijuana and ethanol are administered together and separately. We would like to report the unexpected occurrence of distressing nausea and vomiting in subjects who were given these two drugs simultaneously.
‘
AND
by Alcohol, Drug Abuse, and MenDA-00067 from the National Insti-
ofSide
informed conjust before the used successon an ad lib were adminis(results will be pressure, and and recorded
Effects
Four out of the 7 subjects who received both alcohol and marijuana (the number 3 treatment described previously) developed within 10 minutes a distressing nausea that progressed rapidly to vomiting which lasted for 30-90 minutes after the completion of smoking. One of these men complained of severe headache in “the center” of his head. Another felt totally incapacitated and unable to move because he was afraid of increasing his distress. The other 2 subjects appeared prostrated and could not perform simple psychomotor tasks for 2 hours. Marijuana-induced tachycardia (6) was seen immediately after completion of the smoking, but there was great variability among the subjects; increases ranged from 35 to 60 beats per minute (bpm). Unpredictable fluctuations were also observed within subjects. One individual’s heart rate went abruptly from 150 to 36 bpm. This bradycardia lasted 1 minute and disappeared when he was instructed to change his position from supine to semirecumbent. The same variable pattern was noted for blood pressure, but with more moderate increases. Intense reddening of the conjunctivae, marked skin pallor, and profuse cold sweating were also observed. The subjective distress and physiological signs dissipated slowly in 3 to 4 hours. The occurrence of this effect does not seem fortuitous. Let us make the conservative assumption that the incidence of nausea and/or vomiting for either drug used alone in these dosages is as high as 5%. (It is less than that in our laboratory setting.) The probability of occurrence of this adverse effect would then be 10% for the two drugs given together, assuming there is no interaction between them. The number of adverse reactions we observed (4 out of 7) exceeds this significantly (p
Side
Effects
BY
ADAM
ofSimultaneous
SULKOWSKI,
Alcohol
M.D.,
AND
LOUIS
and VACHON,
Marijuana
The subjects were young (aged 20-29) healthy male volunteers, screened by physical examination, psychiatric interview, and psychological questionnaire. All subjects signed a statement of informed consent that described the project in detail. The subjects all claimed that they were experienced social users (i.e. from once a month to twice a week) of both drugs and cornbined them frequently to increase the high. The following treatments were administered in randomized order to each subject. 1 A drink containing 1 g/kg of body weight of ethanol diluted in pure orange juice to a volume of 400 ml was consumed in 10-iS minutes. One hour later, a placebo marijuana cigarette (THC-exhausted) was smoked. 2. A placebo drink consisting of 400 ml of orange juice in a glass smeared with ethanol was drunk. This was followed 1 hour later by a cigarette containing active marijuana. 3. An “active” alcohol drink (as in number 1 above) was followed 1 hour later by a cigarette containing active marijuana. The dose of ethanol used in this study is known to produce a mild degree of intoxication and slight psychomotor impairment (3). The marijuana cigarettes were supplied by the National Institute on Drug Abuse. The analysis that accompanied the cigarettes indicated a content of 18 mg of-9-tetrahydrocannabinol. This dose has been found to produce a moderate social high in experienced users (4). The drugs were administered 1 hour apart; ethanol was given first because we expected that the subjects would ‘titrate’ their marijuana intake to reach their ‘optimum” level of intoxication. Specific instructions ,
.
‘
‘
Dr. Sulkowski ciate Professor cine, Division 02118.
is Instructor of Psychiatry and Dr. Vachon is Assoof Psychiatry, Boston University School of Mcdiof Psychiatry, 720 Harrison Ave. , Boston, Mass.
This
supported
in part
tal Health Administration tute on Drug Abuse.
grant
was
REPORTS
Use
to this effect had been included in the sent form and were repeated verbally subjects smoked. This strategy has been fully in studies of marijuana smoked schedule (5). Several performance tests tered before and after each treatment published elsewhere). Heart rate, blood conjunctival injection were monitored throughout the experiment. Incidence
Method
work
RESEARCH
M.D.
There is an increasing trend toward the simultaneous use of alcoholic beverages and marijuana as social intoxicants (1). Experimental data concerning the interaction of these drugs in humans are few and inconclusive (2). We recently began a study in which socially relevant doses of marijuana and ethanol are administered together and separately. We would like to report the unexpected occurrence of distressing nausea and vomiting in subjects who were given these two drugs simultaneously.
‘
AND
by Alcohol, Drug Abuse, and MenDA-00067 from the National Insti-
ofSide
informed conjust before the used successon an ad lib were adminis(results will be pressure, and and recorded
Effects
Four out of the 7 subjects who received both alcohol and marijuana (the number 3 treatment described previously) developed within 10 minutes a distressing nausea that progressed rapidly to vomiting which lasted for 30-90 minutes after the completion of smoking. One of these men complained of severe headache in “the center” of his head. Another felt totally incapacitated and unable to move because he was afraid of increasing his distress. The other 2 subjects appeared prostrated and could not perform simple psychomotor tasks for 2 hours. Marijuana-induced tachycardia (6) was seen immediately after completion of the smoking, but there was great variability among the subjects; increases ranged from 35 to 60 beats per minute (bpm). Unpredictable fluctuations were also observed within subjects. One individual’s heart rate went abruptly from 150 to 36 bpm. This bradycardia lasted 1 minute and disappeared when he was instructed to change his position from supine to semirecumbent. The same variable pattern was noted for blood pressure, but with more moderate increases. Intense reddening of the conjunctivae, marked skin pallor, and profuse cold sweating were also observed. The subjective distress and physiological signs dissipated slowly in 3 to 4 hours. The occurrence of this effect does not seem fortuitous. Let us make the conservative assumption that the incidence of nausea and/or vomiting for either drug used alone in these dosages is as high as 5%. (It is less than that in our laboratory setting.) The probability of occurrence of this adverse effect would then be 10% for the two drugs given together, assuming there is no interaction between them. The number of adverse reactions we observed (4 out of 7) exceeds this significantly (p
