TY - JOUR
T1 - Pharmacokinetic and pharmacodynamic profile of supratherapeutic oral doses of D9-THC in cannabis users
AU - Lile, Joshua A.
AU - Kelly, Thomas H.
AU - Charnigo, Richard J.
AU - Stinchcomb, Audra L.
AU - Hays, Lon R.
PY - 2013/7
Y1 - 2013/7
N2 - Oral D9-tetrahydrocannabinol (D9-THC) has been evaluated as a medication for cannabis dependence, but repeated administration of acute oral doses up to 40 mg has not been effective at reducing drug-taking behavior. Larger doses might be necessary to affect cannabis use. The purpose of the present study was therefore to determine the physiological and behavioral effects of oral D9-THC at acute doses higher than those tested previously. The pharmacokinetic and pharmacodynamic profile of oral D9-THC, administered in ascending order in 15 mg increments across separate sessions, up to a maximum of 90 mg, was determined in seven cannabis users. Five subjects received all doses and two experienced untoward side effects at lower doses. D9-THC produced a constellation of effects consistent with previous clinical studies. Low cannabinoid concentrations were associated with significant effects on drug-sensitive measures, although progressively greater levels did not lead to proportionately larger drug effects. Considerable variability in Cmax and tmax was observed. Doses of oral D9-THC larger than those tested previously can be administered to individuals with a history of cannabis use, although given the pharmacokinetic variability of oral D9-THC and individual differences in sensitivity, individualized dose adjustment is needed to avoid side effects and maximize therapeutic response.
AB - Oral D9-tetrahydrocannabinol (D9-THC) has been evaluated as a medication for cannabis dependence, but repeated administration of acute oral doses up to 40 mg has not been effective at reducing drug-taking behavior. Larger doses might be necessary to affect cannabis use. The purpose of the present study was therefore to determine the physiological and behavioral effects of oral D9-THC at acute doses higher than those tested previously. The pharmacokinetic and pharmacodynamic profile of oral D9-THC, administered in ascending order in 15 mg increments across separate sessions, up to a maximum of 90 mg, was determined in seven cannabis users. Five subjects received all doses and two experienced untoward side effects at lower doses. D9-THC produced a constellation of effects consistent with previous clinical studies. Low cannabinoid concentrations were associated with significant effects on drug-sensitive measures, although progressively greater levels did not lead to proportionately larger drug effects. Considerable variability in Cmax and tmax was observed. Doses of oral D9-THC larger than those tested previously can be administered to individuals with a history of cannabis use, although given the pharmacokinetic variability of oral D9-THC and individual differences in sensitivity, individualized dose adjustment is needed to avoid side effects and maximize therapeutic response.
KW - Cannabis
KW - Digit-symbol-substitution task
KW - Marijuana
KW - Repeated acquisition task
KW - Subjective effects
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U2 - 10.1002/jcph.90
DO - 10.1002/jcph.90
M3 - Article
C2 - 23754596
AN - SCOPUS:84880297155
SN - 0091-2700
VL - 53
SP - 680
EP - 690
JO - Journal of Clinical Pharmacology
JF - Journal of Clinical Pharmacology
IS - 7
ER -