Safety and Tolerability of Namisol in the Elderly

Subjects will visit the site 5 times. The first visit, is a 2 hour screening visit for eligibility in which volunteers after signing informed consent will have a medical history, physical examination, ECG, hematological and biochemical blood tests, Mini Mental State Examination (MMSE), Geriatric Depression scale (GDS-30) and body sway test.

Eligible subjects will be randomly allocated to receive three doses Namisol® (3 mg or 5 mg or 6,5 mg) and placebo in double-blind crossover design (visit 1 to 4). The wash-out period between visits will be at least 2 weeks to a maximum of 4 weeks. Each visit will be preceded by baseline assessment measures. The safety and tolerability profiles of Namisol® will be evaluated on each intervention visit by using a standardized THC adverse effects checklist and self-reporting, vital signs, 12-lead ECG, body sway, Visual Analogue Scales (subtest feeling high), and Test for Attentional Performance (TAP, subtest alertness) and a follow up phone call the following day. Four blood samples will be collected on each visit to determine the relationship between the pharmacodynamic effects (VAS-feeling high, TAP-alertness and body sway) and the plasma concentrations of THC and its active metabolites 11-OH-THC and THC-COOH. In addition, a blood sample will be only collected on the first intervention day for genotyping of cytochrome P450 enzymes CYP2C9 CYP2C19 and CYP3A4.

Inclusion criteria

• Subject is a healthy old person as established by medical history, physical examination, electrocardiography, results of hematological and biochemical blood tests on screening.
• Age 65 years
• Body mass index between 18.0 and 30 kg m-2
• Subject is able and willing to sign the Informed Consent Form prior to screening evaluations

Exclusion criteria

• Regular cannabis user, defined as: smoking one or more joints per week
• Documented history of sensitivity/idiosyncrasy to cannabis
• Relevant history or presence of severe pulmonary disorders [e.g. COPD GOLD III or IV], serious cardiovascular disorders [e.g. myocardial infarction < 6 months ago; atrial fibrillation; heart failure NYHA III or IV; severe heart valve disease, orthostatic hypotension defined as systolic drop of 20 mm Hg Safety and Tolerability of Namisol in the Elderly Page 8 Version 2, 10 07 2012 or diastolic drop of 10 mm Hg], seizures, migraine, psychiatric disorders [e.g. depression (based on documented history or GDS-30 on screening ≥ 10); mania; psychosis; dementia], cognitive impairment [based on documented history or MMSE on screening < 28, significant renal (GFR < 30 ml/min) or hepatic disorders [e.g. cancer, cirrhosis. ALT or AST ≥ twice the upper limit of normal], diabetes mellitus, coagulation disorders
• Inability to understand the nature and extent of the trial and the procedures required
• Current alcohol abuse or use of more than 2 alcoholic consumptions daily
• History of, or current drug abuse
• Using drugs that are inhibitors of CYP2C9, CYP2C19 and CYP3A4 (see appendix 13.3)
• Participation in a drug trial within 60 days prior to the first intervention day
• Donation of blood within 60 days prior to the first intervention day
• Known lactose intolerance
• Using more than six units of (methyl)xanthine products per day (e.g. coffee, tea, cola, chocolate)
• Smoking more than ten cigarettes per day
• High fall-risk (based on body sway test)