Low-Dose THC in Dementia: Not Feeling High Did Not Mean No Measurable Effect
Older patients with dementia did not report significantly greater “high” after very low oral THC doses in a small crossover trial. Some physiological and balance measures nevertheless changed, showing why subjective intoxication and objective response must be considered separately.
Ten patients, repeated short treatment periods
The study involved ten patients with dementia, with a mean age of 77.3 years. Across a 12-week protocol, participants received THC or placebo during repeated three-day periods separated by washouts. Doses were 0.75 mg twice daily in the first half and 1.5 mg twice daily in the second half.
This was not continuous daily THC exposure throughout all 12 weeks. Treatment and placebo order was randomized within the crossover structure, while the lower-dose phase preceded the higher-dose phase. Clinical effects and plasma pharmacokinetics were assessed; the study did not test driving.
Several subjective measures were null
Feeling high, external perception, eyes-open body sway and diastolic blood pressure did not significantly differ from placebo. At 0.75 mg, internal-perception ratings and heart rate increased. At 1.5 mg, eyes-closed body sway increased.
Systolic blood pressure changed in opposite directions at the two doses. The investigators considered the measured effects small and not clinically relevant in this sample. Their interpretation should accompany the positive tests, while the positive tests should not disappear behind a general statement that THC had “no effect.”
Tolerability was observed under selected conditions
There were 98 adverse events across THC and placebo periods. Six were considered possibly related to THC and were mild and transient. No THC-related serious adverse event occurred.
These are repeated events in ten people, not 98 independently treated patients. The small sample and intermittent low doses cannot exclude rare reactions, quantify falls over prolonged treatment or establish safety of higher-potency products. The trial also excluded several high-risk clinical situations and interacting medicines.
Plasma exposure varied substantially
THC and 11-hydroxy-THC were measured in plasma separated from venous blood. Exposure generally increased with the higher dose, but differences between patients were substantial. One patient’s low-dose pharmacokinetic data were incomplete, leaving nine for that part of the analysis.
The absence of a strong subjective high did not imply no absorbed THC, and a detectable concentration did not independently establish functional impairment. The paper does not provide a concentration threshold or an efficacy conclusion for all dementia symptoms.
Its useful lesson is methodological: report the actual dose, intermittent schedule, specimen, specific positive and null endpoints, and the selected patient population before using “well tolerated” as a broad safety claim.
Related analysis: Concentration Is Not Impairment: THC Blood Levels in California Driving Cases.
Primary research
Amir I. A. Ahmed and colleagues. Safety, pharmacodynamics, and pharmacokinetics of multiple oral doses of delta-9-tetrahydrocannabinol in older persons with dementia. Psychopharmacology (2015). DOI: 10.1007/s00213-015-3889-y.
