Significant improvement of tics and compulsive behavior under delta(9)-THC compared to placebo, with significant correlation between tic improvement and 11-OH-THC plasma concentration.
Summary
Randomized, double-blind, placebo-controlled crossover study with single dose of delta-9-THC (5,0–10,0 mg) in n=12 adult Tourette patients. Significant improvement in tics (TSSL, p=0,015) and compulsive behavior (p=0,041) compared to placebo. Investigator rating: significant improvement of complex motor tics (p=0,015). No serious adverse events; 5 patients reported mild, transient side effects. Pilot character (n<20, single dose); long-term data pending.
P
PopulationAdults with Tourette syndrome, n=12
I
InterventionDelta-9-tetrahydrocannabinol (THC) oral, single dose 5,0 / 7,5 or 10,0 mg
C
ControlPlacebo (single dose, crossover)
O
OutcomeSignificant improvement in tics (TSSL, p=0,015) and obsessive-compulsive behaviors (OCB, p=0,041) under THC vs. placebo; significant improvement of complex motor tics in observer rating (p=0,015)
Confidence in the evidence
Very lowLowModerateHigh
Moderate
The third of four GRADE levels, the effect estimate is probably reliable.
Downgraded for
Imprecision
Quality profile
Sample size★★★★★
BlindingDouble-blind
Effect sizeClear benefit
Citations / year★★★★★
Authors
Müller-Vahl KR, Schneider U, Koblenz A, Jöbges M, Kolbe H, Daldrup T, Emrich HM
Anecdotal reports in Tourette's syndrome (TS) have suggested that Cannabis (cannabis sativa) and delta-9-tetrahydrocannabinol (Delta(9)-THC), the major psychoactive ingredient of Cannabis, reduce tics and associated behavioral disorders. We performed a randomized double-blind placebo-controlled crossover single-dose trial of Delta(9)-THC (5.0, 7.5 or 10.0 mg) in 12 adult TS patients. Tic severity was assessed using a self-rating scale (Tourette's syndrome Symptom List, TSSL) and examiner ratings (Shapiro Tourette's syndrome Severity Scale, Yale Global Tic Severity Scale, Tourette's syndrome Global Scale). Using the TSSL, patients also rated the severity of associated behavioral disorders. Clinical changes were correlated to maximum plasma levels of THC and its metabolites 11-hydroxy-Delta(9)-tetrahydrocannabinol (11-OH-THC) and 11-nor-Delta(9)-tetrahydrocannabinol-9-carboxylic acid (THC-COOH). Using the TSSL, there was a significant improvement of tics (p=0.015) and obsessive-compulsive behavior (OCB) (p = 0.041) after treatment with Delta(9)-THC compared to placebo. Examiner ratings demonstrated a significant difference for the subscore "complex motor tics" (p = 0.015) and a trend towards a significant improvement for the subscores "motor tics" (p = 0.065), "simple motor tics" (p = 0.093), and "vocal tics" (p = 0.093). No serious adverse reactions occurred. Five patients experienced mild, transient side effects. There was a significant correlation between tic improvement and maximum 11-OH-THC plasma concentration. Results obtained from this pilot study suggest that a single-dose treatment with Delta(9)-THC is effective and safe in treating tics and OCB in TS. It can be speculated that clinical effects may be caused by 11-OH-THC. A more long-term study is required to confirm these results.