Psychopharmacology
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Randomized Controlled Trial
Opioid antagonism enhances marijuana's effects in heavy marijuana smokers.
Studies in laboratory animals strongly suggest reciprocal modulation of the opioidergic and endocannabinoid systems, a relationship that has not been demonstrated in humans. This study sought to clarify this interaction by assessing how a range of naltrexone doses altered the subjective, cognitive, and cardiovascular effects of marijuana. ⋯ In heavy marijuana smokers opioid-receptor blockade enhanced the subjective and cardiovascular effects of marijuana, suggesting that endogenous opioids dampen cannabinoid effects in this population. These findings demonstrate that a broad range of clinically used doses of naltrexone potentially increases the abuse liability and cardiovascular risks of cannabinoids.
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Randomized Controlled Trial
Human abuse liability assessment of oxycodone combined with ultra-low-dose naltrexone.
Prescription opioid abuse has risen dramatically in the United States as clinicians have increased opioid prescribing for alleviation of both acute and chronic pain. Opioid analgesics with decreased risk for abuse are needed. ⋯ The addition of ultra-low-dose NTX to OXY did not decrease abuse liability of acutely administered OXY in experienced opioid abusers.
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Randomized Controlled Trial Clinical Trial
Comparison of ketanserin, buspirone and propranolol on arousal, pupil size and autonomic function in healthy volunteers.
The human pupil may be a suitable physiological test system for the assessment of excessive daytime sleepiness (EDS), but pupillometric assessment could be confounded by medication for comorbid hypertension and mood disorders. ⋯ Ketanserin but not propranolol had a fully sedative profile and may confound pupillometric assessment of EDS. Beta adrenergic receptors do not appear to participate in arousal and pupillary functions, while 5HT1a receptors reduce pupil size without affecting arousal. Pupil size may not be used unequivocally as an index of the level of alertness in the case of drug-induced changes, when drugs interfere with the central pupil control mechanism in ways that are unrelated to their effects on arousal.
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Randomized Controlled Trial
Cognitive and psychomotor effects in males after smoking a combination of tobacco and cannabis containing up to 69 mg delta-9-tetrahydrocannabinol (THC).
Delta(9)-Tetrahydrocannabinol (THC) is the main active constituent of cannabis. In recent years, the average THC content of some cannabis cigarettes has increased up to approximately 60 mg per cigarette (20% THC cigarettes). Acute cognitive and psychomotor effects of THC among recreational users after smoking cannabis cigarettes containing such high doses are unknown. ⋯ Response time slowed down and motor control worsened, both linearly, with increasing THC doses. Consequently, cannabis with high THC concentrations may be a concern for public health and safety if cannabis smokers are unable to titrate to a high feeling corresponding to a desired plasma THC level.
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Randomized Controlled Trial
Preliminary evidence of cannabinoid effects on brain-derived neurotrophic factor (BDNF) levels in humans.
Acute and chronic exposure to cannabinoids has been associated with cognitive deficits, a higher risk for schizophrenia and other drug abuse. However, the precise mechanism underlying such effects is not known. Preclinical studies suggest that cannabinoids modulate brain-derived neurotrophic factor (BDNF). Accordingly, we hypothesized that Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the principal active component of cannabis, would alter BDNF levels in humans. ⋯ The effects of socially relevant doses of cannabinoids on BDNF suggest a possible mechanism underlying the consequences of exposure to cannabis. This may be of particular importance for the developing brain and also in disorders believed to involve altered neurodevelopment such as schizophrenia. Larger studies to investigate the effects of cannabinoids on BDNF and other neurotrophins are warranted.