humulene and Hypothermia

The availability of delta 1-THC, the major psychoactive component of marihuana, in pure form offered an opportunity for better understanding of the mechanism of action of this drug. Two decades after the isolation of delta 1-THC its mode of action is still obscure despite the enormous amount of research invested in it. Studying cannabis content as a whole offers a different approach for better understanding of this ancient weed and its effects.

Topics: Animals; Behavior, Animal; Brain Chemistry; Cannabis; Dronabinol; Electroencephalography; Female; Humans; Hypothermia; Leydig Cells; Luteinizing Hormone; Male; Neurotransmitter Agents; Ovulation; Plant Extracts; Receptors, Drug; Stereoisomerism

Topics: Amphetamine; Animals; Body Temperature; Body Temperature Regulation; Cannabis; Cats; Chlorpromazine; Climate; Cold Temperature; Dogs; Fever; Guinea Pigs; Hot Temperature; Humans; Hypothermia; Metabolism; Pharmacology; Phenothiazines; Psychopharmacology; Rats; Sympathomimetics; Temperature; Time Factors; Toxicology

Topics: Animals; Antihypertensive Agents; Barbiturates; Behavior, Animal; Blood Pressure; Body Temperature Regulation; Cannabis; Cats; Central Nervous System; Dogs; Dronabinol; Drug Combinations; Drug Interactions; Drug Synergism; Drug Tolerance; Haplorhini; Heart Rate; Hypotension; Hypothermia; Macaca; Mice; Reserpine; Respiration; Sleep; Structure-Activity Relationship; Time Factors

Cannabidiol (CBD), a compound found in many strains of the Cannabis genus, is increasingly available in e-cigarette liquids as well as other products. CBD use has been promoted for numerous purported benefits which have not been rigorously assessed in preclinical studies.. To further validate an inhalation model to assess CBD effects in the rat. The primary goal was to determine plasma CBD levels after vapor inhalation and compare that with the levels observed after injection. Secondary goals were to determine if hypothermia is produced in male Sprague-Dawley rats and if CBD affects nociception measured by the warm water tail-withdrawal assay.. Blood samples were collected from rats exposed for 30 min to vapor generated by an e-cigarette device using CBD (100, 400 mg/mL in the propylene glycol vehicle). Separate experiments assessed the body temperature response to CBD in combination with nicotine (30 mg/mL) and the anti-nociceptive response to CBD.. Vapor inhalation of CBD produced concentration-related plasma CBD levels in male and female Wistar rats that were within the range of levels produced by 10 or 30 mg/kg, CBD, i.p. Dose-related hypothermia was produced by CBD in male Sprague-Dawley rats, and nicotine (30 mg/mL) inhalation enhanced this effect. CBD inhalation had no effect on anti-nociception alone or in combination with Δ. The vapor-inhalation approach is a suitable pre-clinical model for the investigation of the effects of inhaled CBD. This route of administration produces hypothermia in rats, while i.p. injection does not, at comparable plasma CBD levels.

Topics: Administration, Inhalation; Animals; Body Temperature; Cannabidiol; Cannabis; Cohort Studies; Dose-Response Relationship, Drug; Dronabinol; E-Cigarette Vapor; Electronic Nicotine Delivery Systems; Female; Hypothermia; Male; Models, Animal; Nicotine; Nociception; Plant Extracts; Rats; Rats, Sprague-Dawley; Rats, Wistar; Receptor, Serotonin, 5-HT1A

Topics: Atrial Fibrillation; Cannabis; Diagnosis, Differential; Drug-Related Side Effects and Adverse Reactions; Electrocardiography; Humans; Hypothermia; Male; Young Adult

The antidepressant action of cannabis as well as the interaction between antidepressants and the endocannabinoid system has been reported. This study was conducted to assess the antidepressant-like activity of Delta(9)-THC and other cannabinoids. Cannabinoids were initially evaluated in the mouse tetrad assay to determine doses that do not induce hypothermia or catalepsy. The automated mouse forced swim (FST) and tail suspension (TST) tests were used to determine antidepressant action. At doses lacking hypothermic and cataleptic effects (1.25, 2.5, and 5 mg/kg, i.p.), both Delta(9)-THC and Delta(8)-THC showed a U-shaped dose response with only Delta(9)-THC showing significant antidepressant-like effects at 2.5 mg/kg (p<0.05) in the FST. The cannabinoids cannabigerol (CBG) and cannabinol (CBN) did not produce antidepressant-like actions up to 80 mg/kg in the mouse FST, while cannabichromene (CBC) and cannabidiol (CBD) exhibited significant effect at 20 and 200mg/kg, respectively (p<0.01). The antidepressant-like action of Delta(9)-THC and CBC was further confirmed in the TST. Delta(9)-THC exhibited the same U-shaped dose response with significant antidepressant-like action at 2.5 mg/kg (p<0.05) while CBC resulted in a significant dose-dependent decrease in immobility at 40 and 80 mg/kg doses (p<0.01). Results of this study show that Delta(9)-THC and other cannabinoids exert antidepressant-like actions, and thus may contribute to the overall mood-elevating properties of cannabis.

Topics: Animals; Antidepressive Agents; Cannabidiol; Cannabinoids; Cannabis; Catalepsy; Depression; Dose-Response Relationship, Drug; Dronabinol; Hindlimb Suspension; Hypothermia; Immobility Response, Tonic; Male; Mice; Random Allocation; Swimming

In contrast to the numerous reports on the pharmacological effects of Δ(9)-tetrahydrocannabinol (THC), the pharmacological activity of another substituent of Cannabis sativa, cannabichromene (CBC) remains comparatively unknown. In the present study, we investigated whether CBC elicits cannabinoid activity in the tetrad assay, which consists of the following four endpoints: hypomotility, antinociception, catalepsy, and hypothermia. Because cannabinoids are well documented to possess anti-inflammatory properties, we examined CBC, THC, and combination of both phytocannabinoids in the lipopolysaccharide (LPS) paw edema assay. CBC elicited activity in the tetrad that was not blocked by the CB(1) receptor antagonist, rimonabant. Moreover, a behaviorally inactive dose of THC augmented the effects of CBC in the tetrad that was associated with an increase in THC brain concentrations. Both CBC and THC elicited dose-dependent anti-inflammatory effects in the LPS-induced paw edema model. The CB(2) receptor, SR144528 blocked the anti-edematous actions of THC, but not those produced by CBC. Isobolographic analysis revealed that the anti-edematous effects of these cannabinoids in combination were additive. Although CBC produced pharmacological effects, unlike THC, its underlying mechanism of action did not involve CB(1) or CB(2) receptors. In addition, there was evidence of a possible pharmacokinetic component in which CBC dose-dependently increased THC brain levels following an i.v. injection of 0.3mg/kg THC. In conclusion, CBC produced a subset of behavioral activity in the tetrad assay and reduced LPS-induced paw edema through a noncannabinoid receptor mechanism of action. These effects were augmented when CBC and THC were co-administered.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Camphanes; Cannabinoids; Cannabis; Catalepsy; Dose-Response Relationship, Drug; Dronabinol; Hallucinogens; Hypothermia; Inflammation; Male; Mice; Mice, Inbred ICR; Motor Activity; Piperidines; Pyrazoles; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; Rimonabant

Topics: Administration, Oral; Age Factors; Cannabis; Diagnosis, Differential; Humans; Hypothermia; Infant; Male; Poisoning; Reflex, Abnormal; Seizures

delta 9-Tetrahydrocannabinol (delta 9-THC), cannabinol, cannabidiol and cannabichromene were detected in commercially available cannabis seeds by silica gel TLC and gas chromatography. These cannabinoids existed in rather high content (0.10-2.02 mg/100 g of seeds) in the feed for birds especially bracts (82.3-441 mg/100 g). When the suspension prepared from the benzene washing solution of cannabis seeds, BenW, was administered at a dose of 3 mg/kg corresponding to delta 9-THC into a mouse, i.v., BenW caused hypothermia, catalepsy, pentobarbital-induced sleep prolongation and suppression of locomotor activity. These pharmacological activities of BenW were significantly higher than those of delta 9-THC (3 mg/kg, i.v.). These results may indicate the necessity to reconsider the present regulations on marihuana.

Topics: Animals; Cannabinoids; Cannabis; Catalepsy; Hypothermia; Locomotion; Male; Mice; Mice, Inbred Strains; Sleep

1 A cannabis extract (I) (in a concentration equivalent to 10 mg Delta(9)-tetrahydro-cannabinol(THC)/kg) prolonged pentobarbitone anaesthesia in mice maximally 20 min to 2 h after medication. The effect was still significant after 8 h, but less than at 2 hours.2 The cannabis extract (I) (equivalent to 10 mg Delta(9)-THC/kg) prolonged both pentobarbitone and ether anaesthesia in mice when administered 20 min before the anaesthetic. After eight consecutive daily doses of cannabis, the pentobarbitone anaesthesia was still significantly longer than a control group, while ether anaesthesia was not significantly prolonged.3 A second cannabis extract (II) with a different ratio of cannabinoids (also administered in dosage equivalent to 10 mg Delta(9)-THC/kg) failed to affect pentobarbitone anaesthesia in mice. This extract presented about 4% the dose of cannabidiol as extract I.4 Delta(8)-THC, Delta(9)-THC and cannabidiol prolonged pentobarbitone anaesthesia with cannabidiol being generally more active than Delta(9)-THC. Cannabinol (10 mg/kg) was inactive.5 The effects of cannabidiol and Delta(9)-THC were found to be additive, and there was a consistent trend for cannabinol to reduce the effectiveness of Delta(9)-THC and cannabidiol when given in combination.6 Premedication with phenoxybenzamine, phentolamine, propranolol, iproniazid, protriptyline, desipramine, reserpine, alpha-methyl tyrosine or parachlorophenylalanine did not affect the extract I-induced prolongation of pentobarbitone anaesthesia.7 It is concluded that cannabis may affect pentobarbitone and ether anaesthesia in mice at least partially by a direct depressant effect, and that the cannabis-induced prolongation of anaesthesia is probably unrelated to any effect on central 5-hydroxytryptamine or catecholamine neurones.

Topics: Anesthesia, General; Animals; Cannabis; Desipramine; Dronabinol; Drug Synergism; Ethyl Ethers; Fenclonine; Hypothermia; Iproniazid; Male; Methyltyrosines; Mice; Mice, Inbred Strains; Pentobarbital; Phentolamine; Preanesthetic Medication; Propranolol; Protriptyline; Reserpine

Topics: Body Temperature Regulation; Cannabis; Cold Temperature; Humans; Hypothermia; Skiing; Sports Medicine

Topics: Amphetamine; Animals; Appetite; Brain Chemistry; Cannabis; Histocytochemistry; Hypothalamus; Hypothermia; Male; Microscopy, Fluorescence; Norepinephrine; Rats; Smoke

Topics: Animals; Cannabis; Dronabinol; Drug Tolerance; Female; Fever; Hypothermia; Kinetics; Rats; Rats, Inbred Strains; Time Factors

Topics: Acetylcholine; Adipose Tissue; Analgesia; Animals; Benzopyrans; Body Temperature; Cannabis; Catalepsy; Depression, Chemical; Humans; Hypothermia; Mice; Nicotinic Acids; Pentobarbital; Phytotherapy; Plant Extracts; Sleep; Solubility; Time Factors; Tropanes

Administration of pure 1-delta(9)-tetrahydrocannabinol to mice had the following dose-dependent nzeurochemical and behavioral effects: a slight but significant increase in concentrations of 5-hydroxytryptamine in whole brain; a decrease in concentration of norepinephrine in brain after administration of low doses and an increase after high doses; diminished spontaneous activity, mloderate hypothermnia, hypersetisitivity to tactile and auditory stimiuli, and ataxia after low doses; and sedation, pronounced hypothermia, and markedly diminished spon taneous activity and reactivity after high doses. The duration of the effects on body temperature and spontaneous activity correlated generally with the changes in brain amines. The characteristic changes in brain amines do not correspond exactly to those observed with other psychotropic drugs.

Topics: Animals; Ataxia; Behavior, Animal; Benzopyrans; Brain; Cannabis; Female; Hydroxyindoleacetic Acid; Hyperesthesia; Hypothermia; Mice; Motor Activity; Norepinephrine; Serotonin