Effect of two oral formulations of cannabidiol on responses to emotional stimuli in healthy human volunteers: pharmaceutical vehicle matters

Objective: To compare plasma concentrations of cannabidiol (CBD) following oral administration of two formulations of the drug (powder and dissolved in oil), and to evaluate the effects of these distinct formulations on responses to emotional stimuli in healthy human volunteers. Methods: In a randomized, double-blind, placebo-controlled, parallel-group design, 45 healthy male volunteers were randomly assigned to three groups of 15 subjects that received either 150 mg of CBD powder; 150 mg of CBD dissolved in corn oil; or placebo. Blood samples were collected at different times after administration, and a facial emotion recognition task was completed after 150 min. Results: There were no significant differences across groups in the subjective and physiological measures, nor in the facial emotion recognition task. However, groups that received the drug showed statistically significant differences in baseline measures of plasma CBD, with a significantly greater difference in favor of the oil formulation. Conclusion: When administered as a single 150-mg dose, neither formulation of oral CBD altered responses to emotional stimuli in healthy subjects. The oil-based CBD formulation resulted in more rapid achievement of peak plasma level, with an approximate fourfold increase in oral bioavailability.

Cannabidiol presents an inverted U-shaped dose-response curve in a simulated public speaking test

Objective: Cannabidiol (CBD), one of the non-psychotomimetic compounds of Cannabis sativa, causes anxiolytic-like effects in animals, with typical bell-shaped dose-response curves. No study, however, has investigated whether increasing doses of this drug would also cause similar curves in humans. The objective of this study was to compare the acute effects of different doses of CBD and placebo in healthy volunteers performing a simulated public speaking test (SPST), a well-tested anxiety-inducing method. Method: A total of 57 healthy male subjects were allocated to receive oral CBD at doses of 150 mg (n=15), 300 mg (n=15), 600 mg (n=12) or placebo (n=15) in a double-blind procedure. During the SPST, subjective ratings on the Visual Analogue Mood Scale (VAMS) and physiological measures (systolic and diastolic blood pressure, heart rate) were obtained at six different time points. Results: Compared to placebo, pretreatment with 300 mg of CBD significantly reduced anxiety during the speech. No significant differences in VAMS scores were observed between groups receiving CBD 150 mg, 600 mg and placebo. Conclusion: Our findings confirm the anxiolytic-like properties of CBD and are consonant with results of animal studies describing bell-shaped dose-response curves. Optimal therapeutic doses of CBD should be rigorously determined so that research findings can be adequately translated into clinical practice.

Tolerability and effectiveness of fluoxetine, metformin and sibutramine in reducing anthropometric and metabolic parameters in obese patients / Tolerabilidade e eficácia da fluoxetina, metformina e sibutramina na redução de parâmetros antropométricos e metabólicos em pacientes obesos

The aim of this study is to assess the effects of sibutramine (S) 15 mg/day, fluoxetine (F) 60 mg/day, and metformin (M) 1,700 mg/day, as an adjunct therapy to a 1,500 kcal/day diet, in reducing anthropometric and metabolic parameters. S (n= 8), F (n= 9), and M (n= 8) were compared to placebo (n= 10) in 35 obese patients in a 90-day trial. Side effects were also studied during the treatment. The data demonstrated that F therapy resulted in a greater average reduction in BMI (11.0 percent), weight (10.0 percent), abdominal circumference (11.0 percent) and percentfatty-tissue (12.8). An elevation in HDL-cholesterol (25.8 percent) and a reduction in average triglyceride levels (28.3 percent) were also shown. S presented a 7.91 percent reduction in the abdominal circumference and a 9.65 reduction in percentfatty-tissue was also found. M group presented reductions in BMI (4.03 percent), waist circumference (6.92 percent), HOMA (23.5 percent) and blood pressure (6.08 percent in systolic and 2.08 percent in diastolic). In general, the three drugs can be considered well tolerated. We concluded that F and S demonstrated a greater mean reduction in anthropometric and metabolic parameters when compared to M, however all of them are useful for that purpose, when the subjectsÆ characteristics are considered.

O objetivo deste estudo foi avaliar o efeito da sibutramina (S) 15 mg/dia, fluoxetina (F) 60 mg/dia, e metformina (M) 1.700 mg/dia, associadas a uma dieta de 1.500 kcal/dia, na redução de parâmetros antropométricos e metabólicos. S (n= 8), F (n= 9) e M (n= 8) foram comparadas ao placebo (n= 10) em 35 pacientes obesos durante 90 dias de tratamento. As reações adversas também foram avaliadas durante o tratamento. O grupo F demonstrou uma redução no IMC (11,0 por cento), peso (10,0 por cento), circunferência abdominal (11,0 por cento) e por cento de tecido adiposo (12,8). Também foram observados um aumento nos níveis de HDL-colesterol (25,8 por cento) e uma redução nos níveis de triglicérides (28,3 por cento), no grupo F. O grupo S apresentou uma redução de 7,91 por cento na circunferência abdominal e de 9,65 na por cento de tecido adiposo. Já o grupo M apresentou reduções no IMC (4,03 por cento), circunferência abdominal (6,92 por cento), HOMA (23,5 por cento) e pressão arterial (6,08 por cento na sistólica, 2,08 por cento na diastólica). Os três fármacos analisados foram bem tolerados durante o tratamento. Concluímos que a F e a S demonstraram maior eficácia na redução dos parâmetros antropométricos e metabólicos dos pacientes obesos quando comparadas à M, entretanto todas podem ser prescritas para essa finalidade, desde que sejam consideradas as características individuais dos pacientes.