Δ9-Tetrahydrocannabinol: EEG changes, bradycardia and hypothermia in the rhesus monkey

Matsuzaki, Motomichi; Casella, George; Ratner, Milton

doi:10.1016/0361-9230(87)90087-6

Cited by 16 publications

(19 citation statements)

References 29 publications

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“…This study also confirmed that the primary psychoactive ingredient in cannabis, Δ 9 -tetrahydrocannabinol (THC), reduces the body temperature of freely moving rhesus macaques. This confirms and extends two prior reports of rectal temperature change in chaired macaque monkeys (Matsuzaki et al, 1987, McMahon et al, 2005). The effect of THC was specific since the magnitude of change was determined by the dose administered and the hypothermia was attenuated by the co-administration of the CB 1 receptor antagonist SR141716/Rimonabant.…”

Section: Discussionsupporting

confidence: 92%

“…An early study of the effects of large, oral THC doses (3,000–9,000 mg/kg) did not report significant amounts of hypothermia (Thompson et al, 1973). The methods are not well specified in that work and more recent studies in chair restrained rhesus monkeys report (rectal) hypothermia of about 1–2°C with maximum effect observed about 2–3 hours after intraperitoneal or intramuscular injection (Matsuzaki et al, 1987, McMahon et al, 2005). We have shown, however, that thermoregulatory responses to 3,4-methylenedioxymethamphetamine (MDMA) in freely moving monkeys (Crean et al, 2006, Taffe et al, 2006), can be qualitatively different from thermoregulatory responses in chaired monkeys (Bowyer et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

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Δ9-Tetrahydrocannabinol attenuates MDMA-induced hyperthermia in rhesus monkeys

Taffe

2012

Neuroscience

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Background Cannabis is commonly consumed by Ecstasy (3,4-methylenedioxymethamphetamine; MDMA) users, including as an intentional strategy to manipulate the drug experience. The most active psychoactive constituent in cannabis, Δ9-tetrahydrocannabinol (THC), and other drugs with partial or full agonist activity at the CB1 receptor, produces a reduction of body temperature in rodents. Reports show that administration of THC can attenuate temperature increases caused by MDMA in mice or rats however a recent study in humans shows that THC potentiates MDMA-induced temperature elevations. Relatively little scientific evidence on the thermoregulatory effects of THC in monkeys is available. Methods The body temperature of male rhesus macaques was recorded after challenge with THC (0.1–0.3 mg/kg, i.m.) or combined challenge of THC with the CB1 receptor antagonist SR141716 (Rimonabant; 0.3 mg/kg, i.m.) or combined challenge of THC (0.1, 0.3 m/gkg, i.m.) with 3,4-methylenedioxymethamphetamine (MDMA; 1.78 mg/kg p.o.) using minimally-invasive, implanted radiotelemetry techniques. Results THC reduced the body temperature of monkeys in a dose-dependent manner with the nadir observed 3–5 hrs post-injection, however an attenuation of normal circadian cooling was also produced overnight following dosing. Hypothermia induced by THC (0.3 mg/kg, i.m.) was prevented by Rimonabant (0.3 mg/kg, i.m.). Finally, 0.3 mg/kg THC (i.m.) attenuated the elevation of body temperature produced by MDMA for about 4 hours after oral dosing. Conclusions As with rodents THC produces a robust and lasting decrement in the body temperature of rhesus monkeys; this effect is mediated by the CB1 receptor. THC also protects against the immediate hyperthermic effects of MDMA in monkeys in a dose-dependent manner. Nevertheless, a paradoxical attenuation of circadian cooling overnight after the THC/MDMA combination cautions that longer term effects may be critical in assessing risks for the recreational user of cannabis in combination with MDMA.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Δ9-Tetrahydrocannabinol attenuates MDMA-induced hyperthermia in rhesus monkeys

Taffe

2012

Neuroscience

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“…The present study demonstrates that intrapulmonary delivery of THC, using e-cigarette “vape” technology and propylene glycol as the vehicle, produces some of the major cannabinoid-typical effects in the rat. The vapor inhalation of THC significantly reduced the body temperature of male and female rats, just as it does when administered by injection in mice (Abel, 1973; Pertwee and Tavendale, 1977), rats (Taylor and Fennessy, 1977, 1982) or monkeys (Matsuzaki et al , 1987; McMahon et al , 2005; Taffe, 2012). The magnitude of hypothermia depended on the amount of time during which rats were exposed to vapor (Figure 1B) and the concentration in the vehicle (Figure 2), thereby demonstrating a dose-dependent relationship.…”

Section: Discussionmentioning

confidence: 90%

Inhaled delivery of Δ9-tetrahydrocannabinol (THC) to rats by e-cigarette vapor technology

et al. 2016

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Most human Δ9-tetrahydrocannabinol (THC) use is via inhalation, and yet few animal studies of inhalation exposure are available. Popularization of non-combusted methods for the inhalation of psychoactive drugs (Volcano®, e-cigarettes) further stimulates a need for rodent models of this route of administration. This study was designed to develop and validate a rodent chamber suitable for controlled exposure to vaporized THC in a propylene glycol vehicle, using an e-cigarette delivery system adapted to standard size, sealed rat housing chambers. The in vivo efficacy of inhaled THC was validated using radiotelemetry to assess body temperature and locomotor responses, a tail-flick assay for nociception and plasma analysis to verify exposure levels. Hypothermic responses to inhaled THC in male rats depended on the duration of exposure and the concentration of THC in the vehicle. The temperature nadir was reached after ~40 min of exposure, was of comparable magnitude (~3 °Celsius) to that produced by 20 mg/kg THC, i.p. and resolved within 3 hours (compared with a 6 hour time course following i.p. THC). Female rats were more sensitive to hypothermic effects of 30 min of lower-dose THC inhalation. Male rat tail-flick latency was increased by THC vapor inhalation; this effect was blocked by SR141716 pretreatment. The plasma THC concentration after 30 min of inhalation was similar to that produced by 10 mg/kg THC i.p.. This approach is flexible, robust and effective for use in laboratory rats and will be of increasing utility as users continue to adopt “vaping” for the administration of cannabis.

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“…The magnitude of the hypothermic effect in this group is consistent with the hypothermic effect reported by others in essentially drug-naive rhesus monkeys following similar i.p. doses of THC (Matsuzaki et al, 1987). However, in the intermittent group, the hypothermic effects of 3.2 mg/kg THC subsided even though blood levels of THC remained elevated compared with pre treatment levels.…”

Section: Discussionmentioning

confidence: 99%

Blood levels do not predict behavioral or physiological effects of Δ9-tetrahydrocannabinol in rhesus monkeys with different patterns of exposure

Ginsburg

Hrubá

Zaki

et al. 2014

Drug and Alcohol Dependence

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Background Recent changes in the legality of cannabis have prompted evaluation of whether blood levels of Δ9-tetrahydrocannabinol (THC) or its metabolites could be used to substantiate impairment, particularly related to behavioral tasks such as driving. However, because marked tolerance develops to behavioral effects of THC, the applicability of a particular threshold of blood THC as an index of impairment in people with different patterns of use remains unclear. Studies relevant to this issue are difficult to accomplish in humans, as prior drug exposure is difficult to control. Methods Here, effects of THC to decrease rectal temperature and operant response rate compared to levels of THC and its metabolites were studied in blood in two groups of monkeys: one received intermittent treatment with THC (0.1 mg/kg i.v.) and another received chronic THC (1 mg/kg/12 h s.c.) for several years. Results In monkeys with intermittent THC exposure, a single dose of THC (3.2 mg/kg s.c.) decreased rectal temperature and response rate. The same dose did not affect response rate or rectal temperature in chronically exposed monkeys, indicative of greater tolerance. In both groups, blood levels of THC peaked 20–60 min post-injection and had a similar half life of elimination, indicating no tolerance to the pharmacokinetics of THC. Notably, in both groups, the behavioral effects of THC were not apparent when blood levels were maximal (20-min post-administration). Conclusion These data indicate that thresholds for blood levels of THC do not provide a consistent index of behavioral impairment across individuals with different patterns of THC exposure.

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Δ9-Tetrahydrocannabinol: EEG changes, bradycardia and hypothermia in the rhesus monkey

Cited by 16 publications

References 29 publications

Δ9-Tetrahydrocannabinol attenuates MDMA-induced hyperthermia in rhesus monkeys

Δ9-Tetrahydrocannabinol attenuates MDMA-induced hyperthermia in rhesus monkeys

Inhaled delivery of Δ9-tetrahydrocannabinol (THC) to rats by e-cigarette vapor technology

Blood levels do not predict behavioral or physiological effects of Δ9-tetrahydrocannabinol in rhesus monkeys with different patterns of exposure

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