Controlled clinical trials (evidence level = 1) |
Volicer et al.17
|
11 (72.7) |
AD mostly severe dementia |
Crossover, two arms: dronabinol 2.5 mg/day fixed dose (6 weeks) + placebo (6 weeks). Placebo (6 weeks) + dronabinol 2.5 mg/day fixed dose (6 weeks). |
Improvement of agitation and anorexia |
Mild euphoria; somnolence, tiredness; seizure (n = 1) |
Seizure was the most relevant adverse event (n = 1); causality unclear (dronabinol or disease progression); effect size not mentioned; p < 0.0005 for agitation (CMAI) and anorexia. |
Mahlberg et al.18
|
24 (79.0) |
AD severe dementia |
Two intervention groups vs. placebo for 2 weeks. Dronabinol 2.5 mg (n = 7), melatonin 3.0 mg (n = 7) or placebo (n = 10). |
Both treatment groups exhibited improvement of nocturnal agitation as measured by actigraphy |
Not reported |
Combined results of both intervention groups precludes identification of specific side effects from dronabinol; effect size not mentioned; p = 0.033 for agitation measured by NPI; p < 0.05 for actigraphic nocturnal activity. |
van den Elsen et al.19
|
22 (76.4) |
AD, VD, AD/VD severe dementia |
Δ9-THC formulation low- and high dose; equivalent to 0.75 mg or 1.5 mg/day of dronabinol vs. placebo for 12 weeks. |
No overall benefits for NPS, including agitation and aggression |
Well tolerated and safe |
Relatively mild NPS at baseline may have reduced the chance of detecting potential changes as outcomes; effect size not mentioned; p = 0.51 and 0.22 for NPI, CMAI, and ZBI. |
van den Elsen et al.20
|
50 dronabinol: 24 (79.0) placebo: 26 (78.0) |
AD, VD, AD/VD severe dementia |
Δ9-THC formulation (fixed-dose dronabinol 1.5 mg t.i.d. for 3 weeks) |
No benefits in agitation or aggression |
Well tolerated and safe |
Behavioral improvements in the placebo group possibly due to improved care during the trial; effect size not mentioned; p > 0.05 for NPI, CMAI, Barthel Index, CCGIC, QoL-AD. |
Herrmann et al.21
|
38 (87.0) |
AD moderate and severe dementia |
Randomized, double-blind, crossover design: nabilone 1.0-2.0 mg/day for 6 weeks; placebo for 6 weeks; 1-week washout between interventions. |
Decrease of agitation and reduction of caregiver burden |
Sedation |
Patients had resistant agitation, with inadequate response to psychotropics; effect size = 0.52, representing a medium effect; p = 0.003 for agitation (CMAI) and p = 0.001 for agitation (NPI); p = 0.009 for CGIC. |
Open-label and observational studies (evidence level = 2) |
Walther et al.22
|
6 (81.5) |
AD, VD severe dementia |
Δ9-THC (dronabinol) 2.5 mg/day for 2 weeks |
Improvement of agitation, aberrant motor behavior, nighttime behaviors, irritability, and appetite disorders |
Well tolerated |
No significant changes in psychotic symptoms (delusions, hallucinations) or apathy; effect size not mentioned; p < 0.05 for nocturnal motor activity (wrist actometer); p = 0.027 for NPI. |
Shelef et al.23
|
10 (73.2) |
AD moderate to severe dementia |
Medical cannabis oil containing THC extract and phytocannabinoids; 2.5-5.0 mg/day (7.5 mg/day subsequently if well tolerated) for 4 weeks. |
Improvement of agitation, aggression, aberrant motor behavior, delusions, sleep disorder, nighttime behavior, irritability, and apathy; decrease of caregiver distress. |
Dysphagia, confusion, and falls observed in three patients |
One patient had dysphagia and discontinued the treatment, another had recurrent falls, and a third patient became delirious with higher doses, but improved upon reduction (from 5.0 mg/day b.i.d. to 2.5 mg/day b.i.d.); effect size not mentioned; p < 0.05 to < 0.01 for NPI. |
Broers et al.24
|
10 (79.5), all female |
AD, VD, AD/VD |
THC/CBD-based oil preparation 7.6 mg/13.2 mg (respect.) for 2 weeks), followed by 9.0 mg/18.0 mg for 2 months); continuation phase thereafter. |
Improvement in global NPS, particularly, agitation; in motor rigidity, and performance of daily activities; patients became calmer and smiling more. |
Acceptable tolerability |
One particular feature of the study concerns the fact the authors prescribed natural cannabis extract, with a THC/CBD ratio of 1:2; unlike other studies, this used higher THC doses (9.0 mg vs. 5.0-7.0 mg/day); effect size not mentioned; no statistical analyses; only descriptive results |
Case reports (evidence level = 3) |
Passmore16
|
1 (72.0) male |
AD severe dementia |
Nabilone 0.5 mg b.i.d. for 6 weeks |
Improvement in agitation and aggressive behavior |
Well tolerated and safe |
After 6 weeks of substantial global improvement, NPS remained controlled for the following 3 months; effect size not mentioned; no statistical analyses. |
Walther et al.25
|
2 (patient A, 75.0; patient B, 81.0) |
AD moderate dementia |
Crossover, 2 weeks: A: dronabinol 2.5 mg/day followed by placebo; B: placebo followed by dronabinol 2.5 mg/day. |
Patient A: improvement in nighttime agitation; patient B improved only in the first week of dronabinol treatment. |
Well tolerated |
Short-lived or controversial benefits, but as dronabinol was well tolerated, the authors suggested new trials with higher dosages; effect size not mentioned; no statistical analyses. |
Amanullah et al.26
|
1 (79.0) male (case A) |
AD severe dementia |
Nabilone 0.5 mg q.d. up to 0.5 mg t.i.d. (1 week); extended period up to day 78. |
Decreased psychomotor agitation and aggression, including skin breakdown |
Well tolerated |
Nabilone alone may not be sufficient to control agitation since other drugs continued to be necessary; however, nabilone contributed to reducing doses of other antipsychotic drugs; effect size not mentioned; no statistical analyses. |
1 (60.0) male (case B) |
FTD severe dementia |
Nabilone 0.5 mg q.d. up to 0.5 mg t.i.d. (1 week); extended period up to day 63. |
Decreasing agitation and increasing cooperation with personal care; starting to smile; better communication. |
Well tolerated |
Zajac et al.27
|
1 (71.0) |
FTD severe dementia |
Nabilone 0.5-1.0 mg b.i.d. for 14 days; resumed after discontinuation and maintained for 3 months. |
Improvement in sexual disturbances in the initial phase; relapse upon discontinuation; sustained improvement with reintroduction of treatment. |
Sedation, lethargy, and delirium probably caused by drug interactions |
The brief period of sedation, lethargy, and delirium at the beginning of treatment may have been a result of side effects precipitated by an increased dosage of nabilone to 1.0 mg twice a day plus interaction with other medications, e.g., lorazepam and risperidone required to control behavioral disturbances; effect size not mentioned; no statistical analyses. |
Wilhelm et al.28
|
1 (78.0) male |
LBD severe dementia |
Dronabinol 2.5 mg/day to 12.0 mg/day |
No effect at lower doses; worsening of agitation at higher doses. |
Worsening of agitation |
Improved only after adding dextromethorphan; effect size not mentioned; no statistical analyses. |
Defrancesco and Hofer29
|
1 (79.0) female |
AD severe dementia |
Dronabinol (magistral formulation) equivalent to 4.9-6.7 mg/day for 8 months |
Improvement in agitation, disruptive behavior, aggression, and anxiety |
Well tolerated, no side effects |
Benefits of dronabinol for aggression and anxiety are mediated by activation of CB1 and activation of endocannabinoids; effect size not mentioned; no statistical analyses. |
Gopalakrishna et al.30
|
3 (63.0, 65.0, and 69.0) all female |
FTD severe dementia |
CBD (63 years) Medical marijuana (65 and 69 years) |
Improvement of mood and impulsive/intrusive behavior (CBD); improvement of anxiety (medical marijuana). |
No side effects reported |
Patient on CBD had vivid, unpleasant dreams which improved with addition of THC; effect size not mentioned; no statistical analyses. |