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.

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.

Assessment of the use of sialogogues in the clinical management of patients with xerostomia.

This study was conducted to assess the clinical efficacy and adverse effects of pilocarpine, bethanechol and cevimeline in patients with xerostomia. In this open-label crossover assessment in 20 patients with xerostomia, a one- to two-week course of each medication with a one-week washout period was prescribed. Side effects, symptoms, whole stimulated and unstimulated saliva were measured. Each sialogogue was found to increase saliva and decrease symptoms. A mixed-effects analysis showed a greater increase in stimulated saliva on bethanechol compared to pilocarpine (0.106, p = 0.0272). Increased sweating was the most common side effect, experienced more frequently with pilocarpine as compared to bethanechol (p = 0.0588) or cevimeline (p = 0.0143). A carryover effect beyond the washout period was seen. Effects on saliva and side effects vary between sialogogues, suggesting a benefit of trials with different sialogogues to determine individual patient preference. The observed carryover effect suggests that intermittent treatment may be an alternative to continuous treatment with sialogogues.

Longitudinal assessment of methylphenidate effects on oral word production and symptoms in first-episode schizophrenia at acute and stabilized phases.

BACKGROUND: Some studies have reported psychotic symptom exacerbation during "pharmacologic challenge" paradigms using dopamine agonists. Few studies, however, have examined the effects of these agonists on neurocognitive functions in patients with schizophrenia. This study assessed the effects of methylphenidate infusion on an oral word production test with demonstrated sensitivity to frontal lobe lesions, and on clinical state. METHODS: Patients were tested at two different phases; at the onset of their first-episode of schizophrenia (acute phase), and then again after they had responded to treatment and were clinically stable (stabilization phase). During each phase, patients were tested prior to and following methylphenidate infusion. Symptom clusters (i.e., positive, negative, and disorganization) were formed from SANS and SADS-C (+PD) ratings at each of these four timepoints. RESULTS: Patients produced significantly more words at preinfusion and while stabilized, suggesting that overall, decreased dopamine activity was associated with better word production. Redundant errors (i.e., perseverations of previously mentioned words and production of multiple words with the same roots) increased significantly following infusion in the stabilized phase. Disorganization symptoms increased significantly following infusion, regardless of study phase. CONCLUSIONS: These findings are consistent with previous theoretical and empirical findings relating dopamine activity to verbal output, a "redundancy bias" in cognitive control, and exacerbation of disorganization symptoms.

Use of a brief assessment examination in a study of subacute sclerosing panencephalitis.

Subacute sclerosing panencephalitis is a degenerative disease affecting children and young adults that remains a distinct and relatively frequent problem in developing countries worldwide. Recent advances in treatment prompted a study at King Faisal Specialist Hospital, Riyadh, Saudi Arabia, using oral isoprinosine and intraventricular alpha-interferon. Initially, the Neurological Disability Assessment and Index was used for tracking patient progress. However, an additional means of assessment was deemed necessary and the Brief Assessment Examination was devised. Largely cognitive based, the Brief Assessment Examination appeared to be more sensitive to mental status changes than the Neurological Disability Assessment and Index, though it correlated modestly with the Neurologic Disability Assessment and Index and more strongly with staging. In addition, the Brief Assessment Examination can be administered by technician-level staff with a minimum of training. Though more study is needed, preliminary findings suggest that the Brief Assessment Examination should be a useful tracking tool for subacute sclerosing panencephalitis, particularly in the developing world.

Observations on the clinical assessment of patients with motor neuron disease. Experience with a TRH analogue.

The need for improved assessment techniques in order to monitor the action of substances active in upper and lower motor neuron systems in motor neuron disease is discussed. A long-acting TRH analogue is shown to have detectable acute effects on bulbar symptoms, particularly speech, tone, fasciculations, and muscle force. Endocrine surveillance is essential in studies with TRH and analogues.

Behavioral toxicity associated with antiepileptic drugs: concepts and methods of assessment.

The BTB designed for the VA Epilepsy Cooperative Study is a conceptually organized and practical set of test procedures that can be utilized to assess change in the areas of motor integration, visual perception, speech and language, and mood that might be attributable to AED therapy. If the data warrant, these categories can be compressed into motor, attention-concentration, and mood. The unique methodological advantages of the VA Epilepsy Cooperative Study provide an opportunity to determine empirically the occurrence of behavioral toxicity for specific AED. The advantage of the BTB is the capacity to measure change from an objective baseline over an extended period during chronic AED treatment. The disadvantages are the requirements for apparatus, trained technicians, and additional time for the patient, which now limit its use to research. If BTB data confirm its sensitivity to behavioral toxicity often unappreciated during a neurological exam, the BTB will become a useful clinical tool. Additionally, a common vocabulary for communicating behavioral toxicity may emerge. This optimistic picture is presented with the simultaneous acknowledgment that a clear solution to the problem lies in accumulation of data in future studies which will have had the opportunity to examine the forthcoming results of this multicenter study.