Clinical Trial: THC/CBD Oil Significantly Reduced Use of Psychotropic Drugs in Patients With Severe Dementia

A combination of THC and CBD significantly reduced the use of as-needed psychotropic medications among older patients with severe dementia, while being well tolerated and causing no treatment-related serious adverse events, according to a randomized clinical trial.

The study, published in Age and Ageing by Oxford University Press on behalf of the British Geriatrics Society, was conducted by researchers from Geneva University Hospitals, the University of Geneva and Fondation pour l’accueil et l’hébergement de personnes âgées in Switzerland.

Researchers conducted a multicenter, randomized, double-blind, placebo-controlled crossover trial involving 25 residents of five long-term care facilities in Geneva. Participants had an average age of 83 and were diagnosed with severe dementia. Nineteen participants completed both treatment periods.

Participants received either a cannabis oil containing THC and CBD in a 1:2 ratio or a placebo for eight weeks before switching treatments following a one-week washout period. Doses were gradually increased to as much as 20 milligrams of THC and 40 milligrams of CBD per day, with the average dose following titration reaching 17.85 milligrams of THC and 35.7 milligrams of CBD.

The study’s primary outcome was agitation, measured using the Cohen-Mansfield Agitation Inventory. Researchers did not find a statistically significant advantage for THC/CBD over placebo in reducing agitation, and other major behavioral measures similarly failed to show significant differences.

However, researchers found a significant difference in the use of as-needed, or PRN, psychotropic medications.

Participants received 64 PRN psychotropic medication administrations during active THC/CBD treatment, compared with 153 during placebo treatment. The overall administration rate was 0.06 per participant per day during cannabis treatment compared with 0.14 during placebo treatment, a statistically significant difference.

Researchers said these medications typically included antipsychotics and benzodiazepines used for episodes of agitation, anxiety and insomnia. Because such medications can carry substantial risks for older adults with dementia, the researchers said reducing their use could itself represent an important clinical benefit.

The THC/CBD treatment was generally well tolerated, with no serious adverse events attributed to the study medication. Although blood pressure fluctuations were frequently recorded, average blood pressure and heart rate remained stable across the treatment and placebo periods.

Researchers also reported strong interest in continuing cannabis treatment after the trial. With one exception, representatives of every participant who completed the study requested continued access to THC/CBD oil. Six months later, all of those patients remained on the treatment, and 21% had been able to discontinue all other psychotropic medications.

The authors noted several limitations, including the small number of participants, substantial differences in individual responses, changing care staff conducting behavioral assessments and the lack of classification by dementia subtype. They also found cannabinoid metabolites remained detectable following the one-week washout period, indicating slower metabolism than anticipated in the elderly population and creating the possibility of carryover effects.

Researchers concluded that although THC/CBD oil was not superior to placebo for the study’s primary behavioral endpoint, its safety profile and association with reduced psychotropic medication use suggest cannabinoid-based medicine may have a role as an additional treatment option for some patients with severe dementia.

“Although further studies are needed to confirm efficacy,” the researchers said, the findings suggest “a potential role for cannabinoid-based medication as a safe therapeutic alternative” for behavioral and psychological symptoms of dementia.