Pharmacology of some Marijuana Constituents and Two Heterocyclic Analogues

Dewey, William L.; Harris, Louis S.; Howes, John F.; Kennedy, Julia; Granchelli, Felix E.; Pars, Harry G.; Razdan, Raj K.

doi:10.1038/2261265a0

Cited by 62 publications

(29 citation statements)

References 3 publications

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“…These results are within the range found by others; thus, ratios varying from 1:1 to 5; 1 (A9 -THC/ a 8 -THC) have been described for rats, mice, monkeys, pigeons and dogs, when the compounds were tested by several different techniques (19,20,21,31,32). The data of the present paper show also that humans quantitatively react to both isomers in a similar fashion.…”

Section: Discussionsupporting

confidence: 66%

See 1 more Smart Citation

Comparative Studies in Man and in Laboratory Animals on ▵8- and ▵9-trans-Tetrahydrocannabinol

Karniol

Carlini²

1973

Pharmacology

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The pharmacological activity of several doses of △⁸-THC and △⁹-TΗC was studied comparatively using rats (climbing rope test), mice (catatonia and spontaneous motor activity tests) and rabbits (Gayer test) and also human volunteers (pulse rate, time discrimination and subjective symptoms). △⁹-TΗC was twice as active as △⁸-THC in rats and mice; both compounds were equiactive in rabbits. In man △⁹-THC revealed to be nearly twice as active as its isomer. There were no qualitative differences between both drugs neither in man nor in the laboratory animals.

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Section: Discussionsupporting

confidence: 66%

“…Recently, Hollister (1971) stated 'quite likely, a8-THC will prove to be active in man when it becomes possible to test it' (18). Comparative studies with both THCs have been made in laboratory animals but not in man (19,20,21). In the present report we described our results comparing the activity of the two THCs in three animal species and man.…”

supporting

confidence: 52%

Comparative Studies in Man and in Laboratory Animals on ▵8- and ▵9-trans-Tetrahydrocannabinol

Karniol

Carlini²

1973

Pharmacology

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“…The reason for this increased mortality is currently unknown and needs to be determined in future experiments. As cannabinoids can cause pronounced hypotension and bradycardia (33,34), probably through activation of the CB1 receptor (35,36), it is conceivable that CB1 knockout mice may succumb to latent cardiovascular problems. Alternatively, CB1 Ϫ/Ϫ mice have an increased risk of developing neurological problems such as seizures.…”

Section: Discussionmentioning

confidence: 99%

Increased mortality, hypoactivity, and hypoalgesia in cannabinoid CB1 receptor knockout mice

Zimmer

Hohmann

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

962

693

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ABSTRACT⌬ 9 -Tetrahydrocannabinol (⌬ 9 -THC), the major psychoactive ingredient in preparations of Cannabis sativa (marijuana, hashish), elicits central nervous system (CNS) responses, including cognitive alterations and euphoria. These responses account for the abuse potential of cannabis, while other effects such as analgesia suggest potential medicinal applications. To study the role of the major known target of cannabinoids in the CNS, the CB1 cannabinoid receptor, we have produced a mouse strain with a disrupted CB1 gene. CB1 knockout mice appeared healthy and fertile, but they had a significantly increased mortality rate. They also displayed reduced locomotor activity, increased ring catalepsy, and hypoalgesia in hotplate and formalin tests. ⌬ 9 -THC-induced ring-catalepsy, hypomobility, and hypothermia were completely absent in CB1 mutant mice. In contrast, we still found ⌬ 9 -THC-induced analgesia in the tail-f lick test and other behavioral (licking of the abdomen) and physiological (diarrhea) responses after ⌬ 9 -THC administration. Thus, most, but not all, CNS effects of ⌬ 9 -THC are mediated by the CB1 receptor.

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“…-Tetrahydrocannabinol is the major active constituent of marijuana, a popular recreational drug of abuse [1]. In addition to its neurobehavioural effects, 9 -tetrahydrocannabinol elicits certain cardiovascular effects in experimental animals and humans [2,3].…”

Section: Introductionmentioning

confidence: 99%

Effect of chronic CB1 cannabinoid receptor antagonism on livers of rats with biliary cirrhosis

Yang

Lin

Huang³

et al. 2007

Clinical Science

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Recent studies have shown that the activated endocannabinoid system participates in the increase in IHR (intrahepatic resistance) in cirrhosis. The increased hepatic production of vasoconstrictive eicosanoids is involved in the effect of endocannabinoids on the hepatic microcirculation in cirrhosis; however, the mechanisms of these effects are still unknown. The aim of the present study was to investigate the effects of chronic CB(1) (cannabinoid 1) receptor blockade in the hepatic microcirculation of CBL (common bile-duct-ligated) cirrhotic rats. After 1 week of treatment with AM251, a specific CB(1) receptor antagonist, IHR, SMA (superior mesenteric artery) blood flow and hepatic production of eicosanoids [TXB(2) (thromboxane B(2)), 6-keto PGF(1alpha) (prostaglandin F(1alpha)) and Cys-LTs (cysteinyl leukotrienes)] were measured. Additionally, the protein levels of hepatic COX (cyclo-oxygenase) isoforms, 5-LOX (5-lipoxygenase), CB(1) receptor, TGF-beta(1) (transforming growth factor beta(1)), cPLA(2) [cytosolic PLA(2) (phospholipase A(2))], sPLA(2) (secreted PLA(2)) and collagen deposition were also measured. In AM251-treated cirrhotic rats, a decrease in portal venous pressure was associated with the decrease in IHR and SMA blood flow. Additionally, the protein levels of hepatic CB(1) receptor, TGF-beta(1), cPLA(2) and hepatic collagen deposition, and the hepatic levels of 5-LOX and COX-2 and the corresponding production of TXB(2) and Cys-LTs in perfusates, were significantly decreased after 1 week of AM251 treatment in cirrhotic rats. Furthermore, acute infusion of AM251 resulted in a decrease in SMA blood flow and an increase in SMA resistance in CBL rats. In conclusion, the chronic effects of AM251 treatment on the intrahepatic microcirculation were, at least partly, mediated by the inhibition of hepatic TGF-beta(1) activity, which was associated with decreased hepatic collagen deposition and the activated PLA(2)/eicosanoid cascade in cirrhotic livers.

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Pharmacology of some Marijuana Constituents and Two Heterocyclic Analogues

Cited by 62 publications

References 3 publications

Comparative Studies in Man and in Laboratory Animals on ▵<sup>8</sup>- and ▵<sup>9</sup>-<i>trans</i>-Tetrahydrocannabinol

Comparative Studies in Man and in Laboratory Animals on ▵<sup>8</sup>- and ▵<sup>9</sup>-<i>trans</i>-Tetrahydrocannabinol

Increased mortality, hypoactivity, and hypoalgesia in cannabinoid CB1 receptor knockout mice

Effect of chronic CB1 cannabinoid receptor antagonism on livers of rats with biliary cirrhosis

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