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Cannabis Research - Medical Uses - addiction withdrawal


Authors
Gilbert PE
Title
A comparison of THC, nantradol, nabilone, and morphine in the chronic spinal dog.
Source
Journal of Clinical Pharmacology
Date
1981 Aug-Sep
Issue
21(8-9 Suppl)
Pages
311S-319S
Abstract
Morphine and delta 9-tetrahydrocannabinol (THC) have been shown to have certain pharmacologic characteristics in common. Among these are antinociception, hypothermia, and the suppression of precipitated abstinence in morphine-dependent rats. In the present study the effects of morphine were compared with the effects of THC and two synthetic cannabinoids, nantradol and nabilone, in both nondependent and morphine-dependent chronic spinal dogs. Single doses of THC, nantradol, and nabilone depressed the flexor and skin twitch reflexes and had a calming effect after intravenous infusion. These effects are similar to those of morphine. Morphine, nantradol, and nabilone, but not THC, depressed rectal temperature. Unlike morphine, however, the cannabinoids produced mydriasis and an increased startle response, and these effects were not antagonized by naltrexone. THC, nantradol, and nabilone suppressed withdrawal abstinence in 40-hour and maximally abstinent morphine-dependent chronic spinal dogs. The results suggest that THC, nantradol, and nabilone share some properties with morphine since they increased the latency of the skin twitch reflex and suppressed withdrawal abstinence. It is doubtful, however, that these actions of the cannabinoids are mediated through opioid receptors since they were not antagonized by naltrexone.

Id Code
76054564
Authors
Hine B, Torrelio M, Gershon S
Title
Differential effect of cannabinol and cannabidiol on THC-induced responses during abstinence in morphine-dependent rats.
Source
Research Communications in Chemical Pathology & Pharmacology
Date
1975 Sep
Issue
12(1)
Pages
185-8
Abstract
The same dose of cannabinol (CBN) or cannabidiol (CBD) further increased the attenuation of precipitated abstinence signs observed in morphine-dependent rats that also received an acute dose of delta 9-THC. By contrast, rotational behavior (turning), which is observed concomitantly in THC-treated rats during morphine abstinence, was not increased by CBN, but was potentiated by CBD. These data illustrate differences between psychoinactive cannabinoids in their interaction with delta 9-THC that might be relevant to possible clinical use of Cannabis in narcotic detoxification.

Id Code
76177346
Authors
Hine B, Torrelio M, Gershon S
Title
Attenuation of precipitated abstinence in methadone-dependent rats by delta 9-THC.
Source
Psychopharmacology Communications
Date
1975
Issue
1(3)
Pages
275-83
Abstract
Racemic methadone hydrochloride was administered to male rats in daily subcutaneous injections of 10-30 mg/kg. Dependence, when assessed by naloxone challenge after 26 days, was quantitatively and qualitatively similar to that previously reported by us for rats implanted with a 75 mg morphine pellet for 72 hours. Abstinence scores in animals pretreated acutely with 10 mg/kg delta 9-THC one hour before naloxone were significantly less than those of a vehicle control group, and wet shakes and gastrointestinal signs of abstinence were blocked. These results extend previous observations of morphine abstinence attenuating properties of delta 9-THC to effects on animals dependent on methadone.

Id Code
75085639
Authors
Hine B, Friedman E, Torrelio M, Gershon S
Title
Morphine-dependent rats: blockade of precipitated abstinence by tetrahydrocannabinol.
Source
Science
Date
1975 Feb 7
Issue
187(4175)
Pages
443-5
Abstract
Male rats were implanted subcutaneously with a pellet containg 75 milligrams of morphine base or placebo, and naloxone hydrochloride (4 milligrams per kilogram of body weight) was administered 72 hours later. Treatment with delta-9-tetrahydrocannabinol (2, 5, or 10 milligrams per kilogram) 1 hour before maloxone administration significantly reduced the intensity of abstinence; the two higher doses blocked the appearance of wet shakes and escapes, diarrhea, and increased defecation. delta-9-Tetrahydrocannabinol did not induce abstinence itself, and prior treatment with cannabidiol was ineffective in reducing naloxoneprecipitated abstinence in animals with morphine pellets. These data suggest that delta-9-tetrahydrocannabinol may be of value in facilitating narcotic detoxification.

Id Code
79180703
Authors
Zaluzny SG, Chesher GB, Jackson DM, Malor R
Title
The attenuation of delta 9-tetrahydrocannabinol and morphine of the quasi-morphine withdrawal syndrome in rats.
Source
Psychopharmacology
Date
1979 Mar 22
Issue
61(2)
Pages
207-16
Abstract
The effect of delta 9-tetrahydrocannabinol (THC), morphine, haloperidol and chlordiazepoxide on the exhibition of the signs of the quasi-morphine withdrawal syndrome was studied in rats. In preliminary studies approximately equi-sedative doses of these drugs were chosen. Morphine and THC produced a very similar degree of suppression of the signs of the quasi-morphine withdrawal, but unlike morphine, the effects of THC were not reversed by the narcotic antagonist, naloxone. The dopamine receptor antagonist, haloperidol, produced a moderate suppression of the withdrawal syndrome and chlordiazepoxide was without significant effect. It is concluded that THC is of very similar potency to morphine in suppressing the quasi-morphine withdrawal syndrome, but its activity in this regard does not appear to be dependent upon the availability of opiate or dopamine receptors, nor is it due to sedation alone.

Id Code
78116101
Authors
Bhargava HN
Title
Time course of the effects of naturally occurring cannabinoids on morphine abstinence syndrome.
Source
Pharmacology, Biochemistry & Behavior
Date
1978 Jan
Issue
8(1)
Pages
7-11
Abstract
The effects of a single intraperitoneal injection (10 mg/kg) of delta9-tetrahydrocannabinol, delta8-tetrahydrocannabinol and 11-hydroxy-delta8-tetrahydrocannabinol on abstinence syndrome were investigated in mice rendered dependent on morphine by pellet implantation. In morphine dependent mice from which the pellets had been removed, delta9-tetrahydrocannabinol inhibited the naloxone-precipitated jumping response as evidenced by an increase in the ED50 of naloxone. This inhibition was evident for 24 hr, the most pronounced effect being produced between two to four hr after delta9-tetrahydrocannabinol administration. Withdrawal defecation was also inhibited for two hours. Similarly, in mice from which pellets were not removed, delta9-tetrahydrocannabinol suppressed the jumping response; however, the intensity of effect was less than when the pellets were removed. delta8-tetrahydrocannabinol and 11-hydroxy-delta8-tetrahydrocannabinol were not effective in suppressing morphine abstinence syndrome two hr following their administration. The suppression of jumping response was specific, since, the vertical jumping behavior induced by coadministration of amphetamine and l-dopa was not affected by cannabinoids. These results demonstrate that single injection of delta9-tetrahydrocannabinol is effective in controlling morphine abstinence syndrome for 24 hr, and that the drugs related to cannabinoids may show promise in narcotic detoxification.

Id Code
77079529
Authors
Bhargava HN
Title
Effect of some cannabinoids on naloxone-precipitated abstinence in morphine-dependent mice.
Source
Psychopharmacology
Date
1976 Sep 29
Issue
49(3)
Pages
267-70
Abstract
Mice were rendered morphine-dependent by the subcutaneous implantation of a pellet containing 75 mg of morphine base; 72 h after the implantation, the animals were injected intraperitoneally either with vehicle or with various doses of delta9-tetrahydrocannabinol, delta8-tetrahydrocannabinol, cannabidiol, cannabinol, or 11-hydroxy-delta8-tetrahydrocannabinol. Thirty minutes after injection of the cannabinoids, the antagonist, naloxone HC1, was administered to induce the stereotyped withdrawal jumping syndrome. The dose of naloxone needed to induce withdrawal jumping in 50% of the animals (ED50) was determined for each dose of the cannabinoids. All of the cannabinoids inhibited the naloxone-precipitated morphine abstinence as evidenced by an increase in the naloxone ED50. Two additional signs of morphine abstinence, defecation and rearing behavior, were also suppressed by the cannabinoids. The relative effectiveness of the cannabinoids in inhibiting morphine abstinence appeared to be in the following order: delta9-tetrahydrocannabinol greater than delta8-tetrahydrocannabinol greater than 11-hydroxy-delta8-tetrahydrocannabinol greater than cannabidiol greater than cannabinol. These data suggest that cannabinoids may be useful in facilitating narcotic detoxification.

Id Code
76165417
Authors
Bhargava HN
Title
Inhibition of naloxone-induced withdrawal in morphine dependent mice by 1-trans-delta9-tetrahydrocannabinol.
Source
European Journal of Pharmacology
Date
1976 Mar
Issue
36(1)
Pages
259-62
Abstract
The effects of various doses of 1-trans-delta9-tetrahydrocannabinol (delta9-THC) on naloxone-induced withdrawal were studied in mice rendered dependent on morphine by the pellet implantation procedure. When administered i.p., 30 min prior to naloxone, delta9-THC, inhibited the naloxone-induced withdrawal jumping response. Two other signs of morphine withdrawal (defecation and rearing behavior) were also suppressed by deltapTHC. It is suggested that delta9-THC or some of its derivatives may have potential use in narcotic detoxification.

Id Code
85298612
Authors
Chesher GB, Jackson DM
Title
The quasi-morphine withdrawal syndrome: effect of cannabinol, cannabidiol and tetrahydrocannabinol.
Source
Pharmacology, Biochemistry & Behavior
Date
1985 Jul
Issue
23(1)
Pages
13-5
Abstract
Delta-9-tetrahydrocannabinol (THC), the main psychoactive principle of cannabis, has been shown to attenuate the exhibition of signs of the quasi-morphine withdrawal syndrome in rats. Cannabinol (CBN) showed the same activity but required a dosage of approximately eight times that of THC to produce an equivalent effect. Cannabidiol was without effect at the dosage levels used. The efficacy of these cannabinoids and the potency differences recorded in this study are in accord with their effects on other behaviours, both in experimental animals and in man. The activity of THC and CBN was not affected by the narcotic antagonist, naloxone.