Activity of Δ
            <sup>8</sup>
            - and Δ
            <sup>9</sup>
            -Tetrahydrocannabinol and Related Compounds in the Mouse

Christensen, H.Dix; Freudenthal, Ralph I.; Gidley, JT; Rosenfeld, Roni; Boegli, G; Testino, L; Brine, Dolores R.; Pitt, Colin G.; Wall, Monroe E.

doi:10.1126/science.172.3979.165

Cited by 169 publications

(40 citation statements)

References 12 publications

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“…Investigations in animals (12) Comparison of THC and its 11-OH Metabolite . 4 1 mal species this compound was shown to be pharmacologically active (13)(14)(15)(16)(17). Previous studies in man (2) have suggested that metabolites of A9-THC were actually responsible for the psychologic effects of Y9-THC and cannabis.…”

Section: Resultsmentioning

confidence: 99%

Comparative Pharmacology of Δ9-Tetrahydrocannabinol and its Metabolite, 11-OH-Δ9-Tetrahydrocannabinol

Lemberger¹,

Martz²,

Rodda³

et al. 1973

J. Clin. Invest.

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Section: Resultsmentioning

confidence: 99%

Comparative Pharmacology of Δ9-Tetrahydrocannabinol and its Metabolite, 11-OH-Δ9-Tetrahydrocannabinol

Lemberger¹,

Martz²,

Rodda³

et al. 1973

J. Clin. Invest.

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“…Secondly, a major metabolite of A9-THC, 11-hydroxy-A9-THC, is thought to contribute significantly towards the pharmacological activity of its parent compound when the latter is administered to mice intravenously (Gill, Jones & Lawrence, 1973). However, when the parent compound is given intracerebrally or intraventricularly this is probably not so since conversion of A9-THC to its 11 -hydroxy metabolite in mouse brain is thought to be negligible (Christensen, Freudenthal, Gidley, Rosenfeld, Boegli, Testino, Brine, Pitt & Wall, 1971). …”

Section: Discussionmentioning

confidence: 99%

CHANGES IN BODY TEMPERATURE AND OXYGEN CONSUMPTION RATE OF CONSCIOUS MICE PRODUCED BY INTRAHYPOTHALAMIC AND INTRACEREBROVENTRICULAR INJECTIONS OF Δ⁹‐TETRAHYDROCANNABINOL

Fitton

Pertwee

1982

British J Pharmacology

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1 A9-Tetrahydrocannabinol (A9-THC) was injected into the preoptic area of the anterior hypothalamus or into the third or fourth cerebral ventricle of the conscious mouse through a chronically implanted cannula and the effects on body temperature and oxygen consumption rate were measured.2 At an ambient temperature of 22°C, injections of A9-THC into the fourth ventricle (5 and 10 plg) produced dose-dependent falls in rectal temperature. Hypothermia was also observed after injections of the drug into the hypothalamus (5 and 10 ltg) or into the third ventricle (10 jg).3 The hypothermia produced by 9-THC was associated with a fall in oxygen consumption rate.Falls in rectal temperature and in oxygen consumption rate were significantly greater after injection of A9-THC than after injection of the drug vehicle, Tween 80.4 The falls in rectal temperature and oxygen consumption rate produced by injection of A9-THC into the fourth ventricle were abolished by elevation of the ambient temperature from 22 to 32°C. 5 A pretreatment that consisted of subcutaneous injections of A9-THC (20 mg/kg) given once daily for three days produced tolerance to the hypothermic effect of the drug when injected on day 4 either into the fourth ventricle (10 plg) or into a lateral tail vein (2.0 mg/kg). 6 The results suggest that A9-THC acts centrally to alter thermoregulation in mice not only when it is injected directly into the hypothalamus or cerebral ventricles but also when it is given intravenously. After intraventricular or intravenous administration the drug may act at extrahypothalamic as well as at hypothalamic sites. The data also support the hypothesis that in mice, tolerance to the hypothermic effect of A9-THC is pharmacodynamic and does not depend on changes in metabolism or distribution of the drug.

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“…11-hydroxy-THC is rapidly formed by the action of hepatic microsomal oxidases, and plasma levels parallel the duration of observable drug action. 11-hydroxy-THC has been found to have psychotomimetic properties equal to THC (46)(47)(48). After smoking 1.75% and 3.55% THC cigarettes, this metabolite appears rapidly and peaks shortly after THC, approximately 15 min after the start of smoking (16).…”

Section: Metabolismmentioning

confidence: 99%

Pharmacokinetics of Cannabinoids

McGilveray

2005

Pain Research and Management

166

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Delta-9-tetrahydrocannabinol (∆-9-THC) is the main psychoactive ingredient of cannabis (marijuana). The present review focuses on the pharmacokinetics of THC, but also includes known information for cannabinol and cannabidiol, as well as the synthetic marketed cannabinoids, dronabinol (synthetic THC) and nabilone. The variability of THC in plant material (0.3% to 30%) leads to variability in tissue THC levels from smoking, which is, in itself, a highly individual process. THC bioavailability averages 30%. With a 3.55% THC cigarette, a peak plasma level of 152±86.3 ng/mL occured approximately 10 min after inhalation. Oral THC, on the other hand, is only 4% to 12% bioavailable and absorption is highly variable. THC is eliminated from plasma in a multiphasic manner, with low amounts detectable for over one week after dosing. A major active 11-hydroxy metabolite is formed after both inhalation and oral dosing (20% and 100% of parent, respectively). THC is widely distributed, particularly to fatty tissues, but less than 1% of an administered dose reaches the brain, while the spleen and body fat are long-term storage sites. The elimination of THC and its many metabolites (from all routes) occurs via the feces and urine. Metabolites persist in the urine and feces for several weeks. Nabilone is well absorbed and the pharmacokinetics, although variable, appear to be linear from oral doses of 1 mg to 4 mg (these doses show a plasma elimination half-life of approximately 2 h). As with THC, there is a high first-pass effect, and the feces to urine ratio of excretion is similar to other cannabinoids. Pharmacokineticpharmacodynamic modelling with plasma THC versus cardiac and psychotropic effects show that after equilibrium is reached, the intensity of effect is proportional to the plasma THC profile. Clinical trials have found that nabilone produces less tachycardia and less euphoria than THC for a similar antiemetic response.Key Words: Cannabinoids; Inhalation; Nabilone; Pharmacodynamics; Pharmacokinetics Pharmacocinétique des cannabinoïdesLe delta-9-tétrahydrocannabinol (∆-9-THC) est le principal ingrédient psychoactif du cannabis (marijuana). Le présent article de synthèse s'attarde à la pharmacocinétique du THC, mais inclut également des données sur le cannabinol et le cannabidiol, de même que sur les cannabinoïdes de synthèse sur le marché, soit le dronabinol (THC synthétique) et le nabilone. La variabilité des taux de THC dans la substance végétale (0,3 % à 30 %) donne lieu à des taux tissulaires variables de THC après l'inhalation, qui en soi, est déjà un processus hautement individuel. La biodisponibilité du THC est en moyenne de 30 %. Avec une cigarette dont la teneur en THC est de 3,55 % un pic plasmatique de 152 ± 86,3 ng/mL s'obtient environ 10 minutes après l'inhalation. D'autre part, le THC oral n'est biodisponible que dans une proportion de 4 à 12 % et son absorption est très variable. Le THC est éliminé du plasma de façon multiphasique, de faibles quantités étant décelables encore dans les sept jours suivant ...

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Activity of Δ ⁸ - and Δ ⁹ -Tetrahydrocannabinol and Related Compounds in the Mouse

Cited by 169 publications

References 12 publications

Comparative Pharmacology of Δ9-Tetrahydrocannabinol and its Metabolite, 11-OH-Δ9-Tetrahydrocannabinol

Comparative Pharmacology of Δ9-Tetrahydrocannabinol and its Metabolite, 11-OH-Δ9-Tetrahydrocannabinol

CHANGES IN BODY TEMPERATURE AND OXYGEN CONSUMPTION RATE OF CONSCIOUS MICE PRODUCED BY INTRAHYPOTHALAMIC AND INTRACEREBROVENTRICULAR INJECTIONS OF Δ⁹‐TETRAHYDROCANNABINOL

Pharmacokinetics of Cannabinoids

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Activity of Δ 8 - and Δ 9 -Tetrahydrocannabinol and Related Compounds in the Mouse

Cited by 169 publications

References 12 publications

Comparative Pharmacology of Δ9-Tetrahydrocannabinol and its Metabolite, 11-OH-Δ9-Tetrahydrocannabinol

Comparative Pharmacology of Δ9-Tetrahydrocannabinol and its Metabolite, 11-OH-Δ9-Tetrahydrocannabinol

CHANGES IN BODY TEMPERATURE AND OXYGEN CONSUMPTION RATE OF CONSCIOUS MICE PRODUCED BY INTRAHYPOTHALAMIC AND INTRACEREBROVENTRICULAR INJECTIONS OF Δ9‐TETRAHYDROCANNABINOL

Pharmacokinetics of Cannabinoids

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Activity of Δ ⁸ - and Δ ⁹ -Tetrahydrocannabinol and Related Compounds in the Mouse

CHANGES IN BODY TEMPERATURE AND OXYGEN CONSUMPTION RATE OF CONSCIOUS MICE PRODUCED BY INTRAHYPOTHALAMIC AND INTRACEREBROVENTRICULAR INJECTIONS OF Δ⁹‐TETRAHYDROCANNABINOL