A single dose of cocaine enhances prospective memory performance

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Neurocognition and subjective experience following acute doses of the synthetic cannabinoid JWH-018: a phase 1, placebo-controlled, pilot study

BACKGROUND AND PURPOSE Synthetic cannabinoids (often sold as Spice or K2) have become a very popular alternative to cannabis due to their easy access and portrayed safety. Controlled studies on the behavioural effects of synthetic cannabinoids are currently lacking, which hampers risk assessments of these compounds. EXPERIMENTAL APPROACH This is a first attempt to assess the influence of a synthetic cannabinoid, JWH-018, on neurocognition and subjective experience in humans after controlled administration. JWH-018, 2 and 3 mg, was administered to six healthy cannabis-experienced volunteers in a placebo-controlled, cross-over study following an escalating dosing schedule. Participants weremonitored for 12 h after drug administration, and several neurocognitive measures and subjective questionnaires were taken. KEY RESULTS Serum concentrations of JWH-018 were highest after the 2 mg dose but generally low after administration of both doses. Both doses of JWH-018 were well tolerated, and no serious side effects were reported. Participants reported feelingmore ‘high’ at 1 and 2 h after administration, particularly after the 2 mg dose. Behavioural impairments also emerged despite the low serum concentrations of JWH-018. The low dose of JWH-018 impaired performance on the tracking, divided attention and stop signal task. CONCLUSION AND IMPLICATIONS JWH-018 dosing in the present study resulted in drug concentrations that were generally low and not fully representative of common use. Yet initial impairments of neurocognitive function and subjective feelings of high did emerge despite low levels of JWH-018 in serum. Higher doses are needed to obtain a more representative risk profile of JWH-018

Low Doses of LSD Acutely Increase BDNF Blood Plasma Levels in Healthy Volunteers

Despite preclinical evidence for psychedelic-induced neuroplasticity, confirmation in humans is grossly lacking. Given the increased interest in using low doses of psychedelics for psychiatric indications and the importance of neuroplasticity in the therapeutic response, this placebo-controlled within-subject study investigated the effect of single low doses of LSD (5, 10, and 20 μg) on circulating BDNF levels in healthy volunteers. Blood samples were collected every 2 h over 6 h, and BDNF levels were determined afterward in blood plasma using ELISA. The findings demonstrated an increase in BDNF blood plasma levels at 4 h (5 μg) and 6 h (5 and 20 μg) compared to that for the placebo. The finding that LSD acutely increases BDNF levels warrants studies in patient populations

Neurocognition and subjective experience following acute doses of the synthetic cannabinoid JWH-018: a phase 1, placebo-controlled, pilot study

BACKGROUND AND PURPOSE Synthetic cannabinoids (often sold as Spice or K2) have become a very popular alternative to cannabis due to their easy access and portrayed safety. Controlled studies on the behavioural effects of synthetic cannabinoids are currently lacking, which hampers risk assessments of these compounds. EXPERIMENTAL APPROACH This is a first attempt to assess the influence of a synthetic cannabinoid, JWH-018, on neurocognition and subjective experience in humans after controlled administration. JWH-018, 2 and 3 mg, was administered to six healthy cannabis-experienced volunteers in a placebo-controlled, cross-over study following an escalating dosing schedule. Participants weremonitored for 12 h after drug administration, and several neurocognitive measures and subjective questionnaires were taken. KEY RESULTS Serum concentrations of JWH-018 were highest after the 2 mg dose but generally low after administration of both doses. Both doses of JWH-018 were well tolerated, and no serious side effects were reported. Participants reported feelingmore ‘high’ at 1 and 2 h after administration, particularly after the 2 mg dose. Behavioural impairments also emerged despite the low serum concentrations of JWH-018. The low dose of JWH-018 impaired performance on the tracking, divided attention and stop signal task. CONCLUSION AND IMPLICATIONS JWH-018 dosing in the present study resulted in drug concentrations that were generally low and not fully representative of common use. Yet initial impairments of neurocognitive function and subjective feelings of high did emerge despite low levels of JWH-018 in serum. Higher doses are needed to obtain a more representative risk profile of JWH-018

Neurocognition and subjective experience following acute doses of the synthetic cannabinoid JWH-018: a phase 1, placebo-controlled, pilot study

BACKGROUND AND PURPOSE Synthetic cannabinoids (often sold as Spice or K2) have become a very popular alternative to cannabis due to their easy access and portrayed safety. Controlled studies on the behavioural effects of synthetic cannabinoids are currently lacking, which hampers risk assessments of these compounds. EXPERIMENTAL APPROACH This is a first attempt to assess the influence of a synthetic cannabinoid, JWH-018, on neurocognition and subjective experience in humans after controlled administration. JWH-018, 2 and 3 mg, was administered to six healthy cannabis-experienced volunteers in a placebo-controlled, cross-over study following an escalating dosing schedule. Participants weremonitored for 12 h after drug administration, and several neurocognitive measures and subjective questionnaires were taken. KEY RESULTS Serum concentrations of JWH-018 were highest after the 2 mg dose but generally low after administration of both doses. Both doses of JWH-018 were well tolerated, and no serious side effects were reported. Participants reported feelingmore ‘high’ at 1 and 2 h after administration, particularly after the 2 mg dose. Behavioural impairments also emerged despite the low serum concentrations of JWH-018. The low dose of JWH-018 impaired performance on the tracking, divided attention and stop signal task. CONCLUSION AND IMPLICATIONS JWH-018 dosing in the present study resulted in drug concentrations that were generally low and not fully representative of common use. Yet initial impairments of neurocognitive function and subjective feelings of high did emerge despite low levels of JWH-018 in serum. Higher doses are needed to obtain a more representative risk profile of JWH-018

Reduced responsiveness of the reward system is associated with tolerance to cannabis impairment in chronic users

Cannabis is the most commonly used illicit drug in the world. However, because of a changing legal landscape and rising interest in therapeutic utility, there is an increasing trend in (long‐term) use and possibly cannabis impairment. Importantly, a growing body of evidence suggests that regular cannabis users develop tolerance to the impairing, as well as the rewarding, effects of the drug. However, the neuroadaptations that may underlie cannabis tolerance remain unclear. Therefore, this double‐blind, randomized, placebo‐controlled, cross‐over study assessed the acute influence of cannabis on the brain and behavioral outcomes in two distinct cannabis user groups. Twelve occasional and 12 chronic cannabis users received acute doses of cannabis (300‐μg/kg delta‐9‐tetrahydrocannabinol) and placebo and underwent ultrahigh field functional magnetic resonance imaging and magnetic resonance spectroscopy. In occasional users, cannabis induced significant neurometabolic alterations in reward circuitry, namely, decrements in functional connectivity and increments in striatal glutamate concentrations, which were associated with increases in subjective high and decreases in performance on a sustained attention task. Such changes were absent in chronic users. The finding that cannabis altered circuitry and distorted behavior in occasional, but not chronic users, suggests reduced responsiveness of the reward circuitry to cannabis intoxication in chronic users. Taken together, the results suggest a pharmacodynamic mechanism for the development of tolerance to cannabis impairment, of which is important to understand in the context of the long‐term therapeutic use of cannabis‐based medications, as well as in the context of public health and safety of cannabis use when performing day‐to‐day operations